RFI Comments - Clinical and Translational Science | National Institute on Drug Abuse (NIDA)

Clinical and Translational Science

Glad to see that implementation science was listed (Public Health category). One suggested addition to this list: "Improve the understanding of how to personalize or adapt evidence-based prevention and treatment approaches to optimize their effectiveness"
Did not take the time to read current plan, but just in case you do not have the following covered, or need reinforcement:Naltrexone research that compares effectiveness to buprenorphine andmethadone: Naltrexone is being way too heavily marketed as effective for opioid use disorder by the manufacturer, which many of my colleagues and I object to. This was a failure in the 60s, 70s. Methadone, buprenorphine work, this does not. It pulls programs and patients away from the effective approaches.buprenorphine, methadone research. Goal, researched based guidelines that hopefully show which patients most appropriately start with buprenorphine, not methadone and which may need to start with methadone.Also, need more info out there to public where there is still so much misunderstanding on taking a drug to get off a drug.Cocaine not as heavily used as in the past, but still those with this disorder need a lot of help. Hearing bits and pieces on medications that address craving for this drug. Need to see something solid we can go with
Would love for you to include that all services must be delivered in a trauma informed manner
Hello NIDA, I'd like to offer a suggestion on where to focus future research. Much of my career has focused on school social work, as well as family systems. Consulting with an anthropologist, I've become aware of Robin Dunbar, author of "How Many Friends Does One Person Need," and creator of Dunbar's Number. DN is the proposed maximum number of people with which we can maintain substantial relationships. Once we have more contacts than the DN, the quality of our relationships may diminish. This is significant to me in the area of school social work, where we have a disproportional ratio of social workers / case managers to students. I believe that if we were to increase the number of social workers in schools, we could provide better services to students, and students would be less likely to turn to drugs as a means of coping / recreation. In a similar vein, I wonder what would happen if we were to max out the number of healthy relationships to current substance abusers. Would they be less likely to spend time with those who promote / enable their substance use? And how do we do so given prevalence of depression/isolation/addiction? I really think NIDA has the ability to make some great strides in preventative and responsive treatment if they pursue Dunbar's Number in their research of school and community resources. Thank you for your time and best of luck in your endeavors
1. Assessment of the effectiveness of 28-30 day Rehab Programs and Facilities to Determine if they work or not, e.g. do they have any positive impact on relapse following completion? Various types of rehabs could be explored as well as those with National acclaim (expensive) vs. inexpensive rehab facilities. If appropriate data is available, this research could be done as a retrospective study. Based on my experience all rehabs are just revolving door money machines for the owner which have no real impact on relapse for any meaningful period of time. Unfortunately, I have seen relapse just days following rehab program completion. If research supports this premise that a 28-day rehabs do not work, the public should be so advised and alternative approaches should be developed and explored. 2. Conduct research to assist in the early detection of potential addiction/alcoholism in young populations, e.g. under 18 years of age And, how to prevent addiction if detected early (or does addiction just have to run it's course, ODs, hospitalization, blood diseases, prison, criminal records and/or death?) 3. Assess the effectiveness of implanted Naltrexone to reduce craving and relapses. Apparently, this approach has been used in Europe for several years with some success. 4. Explore ways to increase the addiction research budget. It's interesting that Ebola got immediate national and international attention and funding yet addiction seems to always play 3rd or 4hh fiddle to just about every other disease. The reality is that addiction is so destructive to society but the public simply does not get it and proper funding never materializes. How do we get The Congress, White House and/or a celebrity involved. That is what it is going to take elevate the issue of addiction to give it the attention it needs
Something I'd like to see more research on is the efficacy of combining evidence-based treatment (IOP & NIOP) and Medicine Assisted Treatments, as opposed to providing MAT alone...And/or...The efficacy of providing a combination of Early Engagement (for low readiness clients still in some level of active use), IOP, NIOP, and Extended Aftercare treatment for AoD issues, as opposed to the traditional IOP/NIOP combination..
I appreciate the opportunity to comment on the FY 2016 - 2020 NIDA Strategic plan. While NIDA has. and will to, continue to play a vital role in understanding the neuroscience of drug use, addiction, and recovery; it has an opportunity to strengthen its role in delivery system improvement. In particular, there is a critical lack of outcome and quality measures pertaining to substance use disorders. States, programs, and payers are anxious to have better ways to hold their providers and payers accountable and to track the efficacy of their treatment programs. Substance use disorder quality measurement is a critical area where no Federal agency has taken a leadership role ( at least to my knowledge). It would be extremely useful for NIDA to enhance its portfolio of projects related to the development of valid and useful quality and outcome measures.
NSDUH data consistently show that 85% of persons needing treatment for a substance use disorder don’t receive treatment, AND don’t feel they need it. This fact is far more than just a tidbit that might receive a small nod in the plan; it should lead to a re-orientation of the entire enterprise. At present, it’s not even acknowledged. The overwhelming majority of persons meeting criteria for a drug use disorder are non-treatment seekers. Don’t build the entire plan around improving treatment.Current behavioral treatments are extremely difficult to disseminate with fidelity. This fact, combined with the first point (above), is part of why the overall burden of mental illness in general—including for the addictions in particular—is essentially unchanged despite all of our efforts (see Kazdin on this, as well as Chorpita). This of course means that we need more and better D & I research as well as far, far more pragmatic trials. (SRGs lean strongly toward explanatory vs. pragmatic trials. This is a mistake.) But we also need to think much more broadly (again, Kazdin is a key resource on this issue). Of the many alternatives to traditional behavioral therapies, technology is perhaps the most important: it is a crucial and growing trend that could do much to increase the reach of behavioral science, while also improving identification, treatment seeking, medication adherence, etc. It also is not mentioned in the current plan. Thank you for considering my comments
Dear NIDA. Thanks for the opportunity to weigh-in.Our research group is encouraged by the emerging field of personalized or adaptive intervention strategies (AIS).There is a need or a paradigm shift in prevention research with an emphasis on measuring variation in intervention impact and the circumstances under which response is or is not improved for a particular individual. Advances in developmental neuroscience, genetics, behavior change strategies, and descriptive development psychopathology have already contributed to the development and inital validation of personalized preventive intervention models. This promising line of research would benefit from a concentrated research effort among prevention scientists that cut across basic, translational and clinical science domains
I haven't found any evidence that degrees or certification or licensure make a difference in behaviorally treating addiction. The research evidence shows that when people are trained on the job with live clients to use specific therapy techniques (Motivational Enhancement Therapy for example) with observation and supervision and feedback, that makes a difference. It seems to me that with the cost of higher education burdening young people for decades and salaries so low that some type of research needs to be done to demonstrate that degrees and certification and licensure make a difference, otherwise, we keep doing the same things and expecting different outcomes. I've also noticed a decrease in treatment for the family of addicted individuals in both individual family counseling and multiple family group therapy. I suspect it has to do with money, decreased staff in agencies and lack of training. Addiction is a social disease and in my opinion families need to be treated in a social setting like multiple family group therapy where client, family and society.are represented. Some type of research to prove or disprove that families are being left out would be helpful. It's a great day here in the great state of South Carolina and the insurance companies are keeping lots of Medicaid money and the Governor and Tony Keck are happy
Just perusing the strategic plan...don't see any mention of Recovery Oriented Systems....Spirituality...or, Trauma Informed principles. Maybe I'm missing something.
Thank you for approaching me with this request. I am not working on drugs of abuse but I think that more attention needs to be paid to immunology and neuroimmunology of drugs of abuse. I do not recall seeing RFAs from NIDA on the role of immune system in mediating the effects of drugs on the brain (and other organs). Immune system is playing an enormous role in CNS function and unlike CNS it is accessible, fixable, drugable and even replaceable and, therefore, it has a huge therapeutic potential, which is yet largely unexplored. I hope NIDA will expand into neuroimmunology, at least as much as NINDS and NIMH are doing.I hope my comments are helpful (I am sure they are different :)Thank you again for reaching out!
Prevention is one of the strategic priorities. Investment into this direction has a clearly identifiable rationale and in the long run is likely to produce the biggest impact in terms of reducing drug abuse. Current objectives under this priority outline important directions in advancing basic science research to identify neurobiological mechanisms underlying addiction. The stated endpoint is development of strategies to “prevent people from ever taking drugs”. While this is likely achievable with purely recreational substances, the objective misses the mark in respect to clinically used medications with high addiction liability, e.g. opioid analgesics. Abuse of prescription medications is perhaps the biggest and most alarming source that leads to addiction. While a lot is being done to develop newer opioid painkillers with better pharmacological profiles and fewer side effects, all of the current drugs, as well as compounds in development, are fundamentally unsafe as they all trigger alterations in the reward pathways. We are making a great progress in understanding molecular and cellular basis of reward signaling and how drugs with addictive potential influence it. Thus, translating basic science discoveries into design of safer medications with reduced addiction liability is a worthy goal and perhaps can be included as a strategic objective.
Neuroscience is undergoing a transformation because of new technologies, including optogenetics and pharmacosynthetics (designer receptors). Designer receptors in particular have strong appeal as potential new clinical treatments for addiction and a host of disorders. This new technology allows direct application of knowledge in basic neuroscience to clinical disorders including addiction. My suggestion is for NIDA to join with other neuro-related NIH institutes to focus effort on developing this new technology for human clinical application. This would involve microinjections of AAV vectors into human brain to express these receptors in target neurons. There are 13 current clinical trials ongoing using AAV vectors in express other proteins in brain, indicating the feasibility of this vector approach. The DREADD designer receptor has the advantage of being essentially a human muscarinic receptor with 2 point mutations in the binding pocket, but within the membrane of the cell, limiting potential immunogenic problems. The DREADDs have recently been successfully tested in monkeys without untoward effects but with expected and significant behavioral actions (Barry Richmond group, SFN 2014). Numerous animal studies (including from my own lab) have shown efficacy of DREADDs in a variety of behavioral functions, including animal models of disease. Therefore, the time has come to make a major effort to rive this exciting new technology into the yuma to treat a host of brain disorders. Thank you for your consideration.
Yes, please investigate the efficacy of 12 Step programs. In particular, whether they actually cause depression and suicide. As well: bingeing behavior and crime. Also please don't suppress the data even if it makes AA look bad.
As the President and on behalf of the National Alliance for Recovery Residences (NARR), I am submitting comments on the proposed FY2016-2020 Strategic Plan for the National Institute on Drug Abuse (NIDA). Specifically, I would like to strongly encourage the committee to formally incorporate research on recovery from addiction into the FY2016-2020 Strategic Plan.NARR is a 501 (c) 3 nonprofit and recovery community organization (RCO) that currently serves 25 regional affiliate organizations. These affiliate organizations collectively support over 25,000 persons in addiction recovery who are living in over 2,500 certified recovery residences throughout the United States. Our mission is to support persons in recovery from addiction by improving their access to quality recovery residences through standards, support services, placement, education, research and advocacy.It is now widely acknowledged, in large part through the efforts of the NIDA, that addiction is a chronic, relapsing brain disease. Treatment is often essential to helping individuals struggling with addiction begin to address their disease, but long-term and community-based recovery support services are equally important to helping individuals maintain their sobriety and prevent relapses.Recovery support services are such an integral component to the management of addiction that both the Office of National Drug Control Policy (ONDCP) and the Substance Abuse and Mental Health Services Administration (SAMHSA) have formally incorporated recovery into their strategic plans through expanding support for recovery services. However, it is imperative that services for those in recovery from addiction be based on the best available evidence on factors that promote recovery and empirically tested for their effectiveness.As the stated mission of the NIDA is to lead the nation in bringing the power of science to bear on drug abuse and addiction, NIDA must lead the charge in developing a research agenda for understanding and developing addiction recovery services and interventions. This has heretofore been lacking. For example, in the Strategic Plan issued in 2010, the word recovery appeared just three times in the entire document (in a small section discussing treatment goals and objectives, page 28). In the draft of the FY 2016-2020 Strategic Plan outlined in this RFI, it appears four times, but only in the context neurobiological aspects and biomarkers of recovery.Recovery and recovery support services need to be included in the list of strategic priorities. Such a strategic priority might look something like the following:Recovery and Recovery Support Services: Enhance the scientific understanding of recovery and support the development and testing of interventions and services to reduce relapse and promote recovery from addictionIdentify factors (biological, behavioral, environmental, and developmental factors) that promote recovery and reduce relapse among those who have achieved sobriety;Promote the development of novel, evidence-based interventions and services to support recovery;Develop techniques to measure and monitor recovery;Support research investigating cost savings and cost-effectiveness of recovery support services.NARR works with a number of scientists studying aspects of recovery (and we would happily refer you to them) who might be in a better position to outline objectives within this priority, but we offer the above suggestions because research in these areas is critical to the work that NARR does. NIDA is the most logical Institute at NIH to support and champion this research, and we encourage you to consider adding recovery more formally to the 2016–2020 Strategic Plan.
Dear Strategic Planning Committee Member:As Founder and Executive Director of the Pennsylvania Alliance of Recovery Residences (PARR), I am submitting comments on the proposed FY2016-2020 Strategic Plan for the National Institute on Drug Abuse (NIDA). Specifically, I would like to strongly encourage the committee to formally incorporate research on recovery from addiction into the FY2016-2020 Strategic Plan. PARR is a 501(c) 3 nonprofit and Eastern Regional Affiliate of the National Alliance of Recovery Residences (NARR) that has currently certified over 41 recovery residences serving over 501 persons in recovery in Philadelphia PA, Bucks County PA, Harrisburg PA, Pottstown PA, York PA and New Jersey. Our mission at PARR is to create, evaluate and improve standards and measures of quality for all levels of recovery residences. PARR provides a forum for exchanging ideas to include developing uniformity for our field, problem solving and advocacy.It is now widely acknowledged, in large part through the efforts of the NIDA, that addiction is a chronic, relapsing brain disease. Treatment is often essential to helping individuals struggling with addiction begin to address their disease, but long-term and community-based recovery support services are equally important to helping individuals maintain their sobriety and prevent relapses.Recovery support services are such an integral component to the management of addiction that both the Office of National Drug Control Policy (ONDCP) and the Substance Abuse and Mental Health Services Administration (SAMHSA) have formally incorporated recovery into their strategic plans through expanding support for recovery services. However, it is imperative that services for those in recovery from addiction be based on the best available evidence on factors that promote recovery and empirically tested for their effectiveness.As the stated mission of the NIDA is to lead the nation in bringing the power of science to bear on drug abuse and addiction, NIDA must lead the charge in developing a research agenda for understanding and developing addiction recovery services and interventions. This has heretofore been lacking. For example, in the Strategic Plan issued in 2010, the word recovery appeared just three times in the entire document (in a small section discussing treatment goals and objectives, page 28). In the draft of the FY 2016-2020 Strategic Plan outlined in this RFI, it appears four times, but only in the context neurobiological aspects and biomarkers of recovery.Recovery and recovery support services need to be included in the list of strategic priorities. Such a strategic priority might look something like the following:Recovery and Recovery Support Services: Enhance the scientific understanding of recovery and support the development and testing of interventions and services to reduce relapse and promote recovery from addictionIdentify factors (biological, behavioral, environmental, and developmental factors) that promote recovery and reduce relapse among those who have achieved sobriety;Promote the development of novel, evidence-based interventions and services to support recovery;Develop techniques to measure and monitor recovery;Support research investigating cost savings and cost-effectiveness of recovery support services.The goal of PARR is to ensure that individuals in recovery have access to safe and supportive housing and to provide advocacy for recovery residences of all types and we support the above suggestions because research in these areas is vital to the work PARR does. NIDA is the most logical Institute at NIH to support and champion this critical research, and we encourage you to consider adding recovery more formally to the 2016-2020 Strategic Plan.
My name is [PII Redacted] and am the owner of 3 NARR certified recovery residences in New Jersey. I am currently in litigation with the state for "operating boarding homes without a license". It is imperative that we have more research showing the outcomes of recovering addicts that live in recovery residences as opposed to those that don't. I have 8 years of data showing the success of those that have lived in our houses and am happy to share that. It is a crime that the state is forcing us to spend legal dollars to defend houses that are saving lives. Thank you so much for your time and please feel free to contact me at [PII Redacted].
I represent a group of nearly 900 people who have gotten together to support Dr. Kim Janda's and Dr. George Koob's heroin vaccine research at The Scripps Research Institute in La Jolla, California. If education and awareness were sufficient to keep people from using drugs we would not have the increase in deaths from heroin overdoses that we are seeing. If rehab or therapy or AA were enough, we would not see the number of relapses that we do. It is clear there needs to be another tool in the arsenal of addiction treatment tools to help those that suffer from this addiction. On our own, we have raised nearly $20,000 for the vaccine research which while essentially insignificant, hopefully signals the depth of our commitment to see that this research goes forward. We hope that you will continue to support this research as you have done in the past.
I am responding to your request with regard to input from NIDA constituent organizations, such as AATOD, in developing a future strategic agenda for NIDA and its research initiatives. Thank you for giving us this opportunity. We have several suggestions for your and your associates to consider.Impact of Providing Access to Medication Assisted Treatment for Opioid Addiction and when Access is Denied or CompromisedThis is an extremely dynamic period for opioid addiction treatment in the US. Many reports have been published about prescription opioid use and abuse and the transition from the use of prescription opioids to heroin. SAMHSA has found that almost 80% of current heroin using individuals have used prescription opioids in the past.We also have different policies being executed depending on what state a patient happens to be in. Illustratively, Governor LePage in Maine appears to be unalterably opposed to the use of methadone to treat opioid addiction. OTPs have struggled against Medicaid cutbacks and other policies which limit access or duration of treatment.On the other hand, the State Alcohol and Drug Abuse Director in North Dakota, with her state associates, is about to open the state's first OTPs to provide access to care. It appears that there is a significant amount of prescription opioid and heroin abuse among individuals working on the oil pipelines there.While I could provide other illustrations, such as the innovative Hub and Spoke model in Vermont as well as some of the most interesting initiatives with regard to OTPs and Health Homes in Rhode Island, the point is to learn the impact that such dramatic differences in policy has on residents in those states. I do not believe that such comprehensive research has been done in the past. The bottom line is that such research would reveal the tale of different states and the impact that such different policies have on the health and well being of their residents during a time of such public health crisis. We are requesting that NIDA consider1this kind of research initiative, which could guide effective public policy for the future.At the federal level, it would be important to understand how the ACA has expanded access to the use of medications to treat opioid addiction. There are still a significant number of states that have not supported this federal initiative, however, half of the states have engaged in implementing various aspects of the ACA. We still do not know the impact that this initiative has had on increasing access to care through OTPs or DATA 2000 practices.What Do We Know About the Use of Buprenorphine in DATA 2000 Practices?There has been a significant policy debate over the course of the past year with regard to increasing treatment access to approved DATA 2000 services, which operate under the aegis of SAMHSA. At the present time, there is a restriction in the number of patients in DATA 2000 practices to 100. There has been a fair amount of policy debate to increase this number to some other reference point. The bottom line is that we do not know much about what transpires with regard to patient care in DATA 2000 practices. We do not even have an idea what percentage of practices are at this limit. It is our understanding that SAMHSA has approved approximately 8,000 physicians to treat up to 100 patients each as part of their registered DATA 2000 practices. SAMHSA does not know what number of physicians are at the limit. Dr. Wilson Compton brought this point up during the September 22-23, 2014 "Buprenorphine Summit", which had been organized through SAMHSA and NIDA. There was no answer to Dr. Compton's question.I believe you already have the AATOD position paper which was published on July 2, 2014 (see attached). This policy paper asks some basic questions about what actually occurs in a DATA 2000 practice. What percentage of such physicians access PDMP databases either before or during a patient's treatment? What percentage of practitioners conduct toxicology reports to guide therapeutic decision making? What percentage of such practices refer the patients for any kind of counseling or other medical care to treat co-morbid conditions?We are recommending that NIDA consider developing research initiatives which will better answer such questions. In effect, the existing policy debates about changing the number of patients that a DATA 2000 practitioner can treat, is completely absent any foundation since we do not have the answers to those questions. We believe that NIDA could go a long way to help provide such information to guide effective and thoughtful public policy.Psychomotor Skills and Medication Assisted Treatment for Opioid AddictionThere have been only a few and now outdated studies that address the issue about Medication Assisted Treatment for opioid addiction and an impairment of psychomotor skills. We believe that it would be helpful-ifNIDA were to refocus some initiatives to further explore this complicated matter. This is a significant issue in policy discussions since there are a number of policy officials who have resisted the use of Medication Assisted Treatment for opioid addiction based on the view that such treatment will impair psychomotor skills. This is still an issue in the Department of Transportation where there is a prohibition with regard to the use of methadone for individuals wishing to obtain a commercial driver's license. This matter comes to surface in a number of actions in state enforcement authorities, drawing upon the lessons of the federal Department of Transportation regulations in this regard. We believe that such research would help guide more informed evidence based policy in this area.The Use of Telemedicine in Increasing Access to Medication Assisted Treatment for Opioi<l AddictionThe Substance Abuse and Mental Health Services Administration is about to release its Accreditation Guidelines for the use of medications to treat opioid addiction in Opioid Treatment Programs. There is a section on the use of telemedicine services through the OTPs. There is little known about the effectiveness of utilizing such telemedicine services through established Opioid Treatment Programs. As a result of such limited research information in this area, there is some question in how federal and state regulatory authorities go about the process of encouraging the use of telemedicine services through OTPs. In our judgment, NIDA would provide excellent guidance in ftmding such research initiatives to best determine how to use telemedicine services through OTPs most effectively, especially in increasing access to care. There are a number of rural states which have major opioid addiction problems and too few addiction treatment services. An informed understanding of how to best use telemedicine services in this area would be extremely helpful in providing necessary guidance to such regulatory authorities.The Use of Medication Assisted Treatment in the Criminal Justice Setting This is the last major area of public policy research that we are asking NIDA toconsider for its 2015 future initiatives. There has been considerable andadvanced policy discussion about the efficacy of using Medication Assisted Treatment for opioid addiction in the criminal justice setting. NIDA has been incredibly forward thinking in a number of its publications.NADCP has also included recommendations to use the three federally approved medications to treat chronic opioid addiction in the US through its 2013 Adult Drug Court recommendations.SAMHSA has also produced an influential Einstein Report during 2014 which provides additional guidance in this area. They are also about to publish a fact sheet on the use of MAT, which will specifically target criminal justice entities.The Legal Action Center published a groundbreaking paper on this topic in 2011 (Legality of Denying Access to Medication Assisted Treatment in the Criminal Justice System). It is a major policy report, providing additional encouragement for the use of medications to treat chronic opioid addiction in this country.Finally, the Bureau of Justice Assistance within the DOJ also published a training curriculum on the use of MAT for people under supervision in 2013.In spite of all of this policy support, there have been a small number of correctional facilities offering such treatment to inmates during their incarceration. Drug Courts and correctional facilities have been slow to adopt the use of such medications. We realize that NIDA has been extremely supportive of providing access to MAT during incarceration and to serve as a bridge to OTPs and DATA 2000 practices in the community upon the release of the inmate. It has been long established that providing such linkages to treatment contributes to reduction of relapse and overdose. We believe that this point needs to be made more forcefully through ongoing research efforts.We believe it would be helpful for NIDA to conduct a series of research initiatives in order to better understand the most effective models that are being used to increase access to the use of MAT in the criminal justice system so that it will guide future policymaking in this area. It is still fraught with ideologic conflict and individuals who still take the view that MAT should not be used in such criminal justice settings.These are five topics which we think NIDA should take up in developing its own future research initiatives. We realize that there are many other competing challenges to resources and there could be even more topics added to this list. For the sake of simplicity and focus, we believe that these policy areas make the best sense given the current debates on the use of MAT for opioid addiction in the US. Thank you once again for giving us this opportunity to comment and please let me know if you have any other questions.
As NIDA considers its Clinical and Translational Science portfolio, some individuals in our research community have expressed concern that 1) NIDA may begin working on the “next” promising treatment modality before fully exploring the value of one already found to be efficacious (e.g., agonist replacement therapies for stimulant use disorders and contingency management); and 2) that NIDA tends to identify a new compound and allocates resources towards assessing its efficacy all at once (i.e., conducting preclinical, human lab and clinical trials simultaneously) rather than using a step-wise screening pipeline progressing from preclinical to human laboratory to clinical trials for the most promising compounds (a recent example cited was the evaluation of buspirone). The recommendation from our community would therefore be to increase resource allocation towards dissemination and use of efficacious treatments before investing in the evaluation of new treatment interventions and, when evaluating new treatment interventions, employing a more systematic approach to establish efficacy.
The Association of Recovery in Higher Education (ARHE) represents forty-five Collegiate Recovery Programs (CRPs) and Collegiate Recovery Communities (CRCs) across the nation. The longest standing CRP was originated in 1983. A collegiate recovery program (CRP) is a supportive environment that offsets campus “party” culture and reinforces the decision to disengage from addictive behavior. Collegiate Recovery Programs are designed to provide educational opportunities alongside recovery supports to ensure that students do not have to sacrifice one for the other. Our institutional members represent the professionals, faculty, researchers, and the students who are invested in these programs. The primary goal of ARHE is to provide strategic guidance to enhance the work on university campuses that support recovering students to find success in college. We applaud the foresight of universities who have adopted CRPs and who have recognized the tremendous impact of these programs and who continue to prioritize the efforts on their campuses. The collegiate recovery movement is alive and well across the nation. We are on the cusp of a movement experiencing exponential growth in the last five years. Adding to the fifty established programs in existence, at least fifty more are emerging in various stages of development. We invite you to review the research evidence supporting the efficacy of these programs. Data suggests that CRPs effectively promote recovery, prevent relapse, and improve educational outcomes for the individuals participating in these programs (Cleveland, Harris, Baker, Herbert, & Dean, 2007). Researchers have indicated that peer-to-peer recovery support, together with the infrastructure of a university program, is an essential component to the continuum of care. Institutions are finding that providing supports is necessary for the subset of the student population to achieve success in an otherwise abstinence hostile environment.Since many of our communities require abstinence as criteria for membership or participation, we maintain that the science of abstinence-based approaches to recovery is meaningful and should not be discounted within National Institute on Drug Abuse (NIDA) priorities. The purpose of our letter is to offer suggestions after reviewing the 2016-2020 strategic plan for NIDA. The following points represent the ARHE suggestions for your strategic plan: The voice of recovery is underrepresented in NIDA’s strategic priorities and approaches toward addressing addiction. We suggest that funding research on recovery be included as a major priority. As addiction is a chronic brain disease for some, we also suggest NIDA prioritize understanding the benefit of extending the continuum of care well beyond treatment. For those who engage in a lifetime endeavor of recovery, the support offered and research conducted should reflect the chronic nature of the disease. More specifically, we suggest increased funds to investigate the mechanisms of why CRPs are so effective. The support provided within the priorities could increase the growing body of evidence emerging in the field of collegiate recovery—research which, if properly funded, would change the trajectory of even more students’ lives. To this end, we suggest that NIDA formally support this movement. We hope that NIDA will encourage the efforts that students and universities are making to sustain recovery in a high-risk environment. In implementing these suggestions, you will not only support the universities and the professionals providing these resources, but the students whose successes and education attainments speak for themselves.
Young People in Recovery (YPR) would like to submit this comment in response to your Request for Information (RFI). YPR is a national advocacy organization aimed at improving access to resources for young people in or seeking recovery from addiction. We believe more research needs to emerge in the following areas:Expanding current addiction treatment processes to a more individualized approach, rather than a one-size-fits-all approach. Focusing research efforts on determining the efficacy of various treatment methodologies will inform policy and improve standards of care across the states. harm reduction: research needs to inform a more comprehensive plan than what currently is available; in other words, providing more than strictly medication management, such as incorporating a comprehensive plan for life skills and cognitive improvement. Currently, no follow up support services to maintain efforts to promote healthy living exist. natural recovery: more research needs to emerge on natural recovery; that is, people who recover on their own, without attending mutual aid support groups (Martin, 2008). Additionally, how does the concept of "recovery capital" fit into natural recovery and how can it be replicated/reproduced in both a clinical setting and community support services. Youth peer-to-peer support. More research needs to emerge on youth peer support for young people seeking recovery from addiction. As of now, the research on youth peer support is inconclusive. We appreciate the opportunity to comment. We are confident that our suggestions will help inform your research efforts in the coming years.
We are responding to the invitation of NIDA to provide a single input as an organization. This response was crafted by [PII Redacted]. As with any healthy organization, we have diverse opinions that have been debated over decades. Therefore, this response represents a consensus rather than complete agreement. Our overarching message is that psychoanalysis has a contribution to make in the understanding and treatment of addiction that has been shut out of NIDA’s strategic plan. This should end. Addiction, Psychoanalysis and NIDA – A current perspectiveUnfortunately, NIDA and NIH in general, conflate non-biological behavioral concepts and neurobiology. The “reward system” imbricates the RDoC criteria used for researching biological systems underlying mental illness. The NIDA approach uses concepts or “reward, self control and conditioning” that are taken from this non-neurological behavioral psychology and applied to NIDA’s research agenda as basic assumptions that blunt the ability of that agenda to make discoveries regarding the nature of human addiction. Normal development and function across the lifespan is a central preoccupation of psychoanalysis. Dr. Dodes (1990, 1996, 2002, 2011) has written extensively about the psychology that explains both the function and drive behind the behavior we call addiction. Patients with addiction have many complicated issues that constantly interact. A simple focus on teaching recovery skills ignores the complexity of human motivations. Psychoanalysts have also considered the role of neurobiological concepts of addiction. Dr. Johnson has been involved in the neuropsychoanalytic movement that uses Panksepp’s animal research and evo-devo thinking-derived neural pathways to explain addictive behaviors and opioidergic human relatedness that is altered by some addictive drugs, but not others (Johnson 2010, 2013, 2014). For a more detailed version of Dr. Johnson’s work, see document also attached--Addendum. Psychoanalysis has a tradition of applying its concepts to the understanding of cultural phenomena. Johnson (2009, 2013) has described the psychological strategies of the addictive drug industry to capture the brains of children via an alteration of dopaminergic function so that the industry can harvest money from people until they die from addiction decades later. Dodes (2014) has suggested that NIDA reconsider the use of the behaviorist paradigm, and consider testing outcomes of cognitive behavioral treatment against psychodynamic treatment. Robert Gregrory M.D., Chair of Psychiatry at SUNY Upstate, showed that at 30 month follow up comparing 12 month psychodynamic treatment of alcoholic borderline patients with “optimal community care,” drug use completely remitted with psychodynamic treatment by the end of treatment and remained in remission for all 15 subjects treated psychodynamically while it worsened by the end of the 30 month follow up for behaviorally treated subjects (Gregory et al 2010).Our experience as psychoanalysts is that our contributions to thinking about addiction have been dismissed – to the detriment of NIDA and the people they serve. We suggest that in terms of strategic planning that the complexity of human experience be considered in both conceptualizing and treating addiction. Our overarching message is that psychoanalysis has a contribution to make in the understanding and treatment of addiction that has been shut out of NIDA’s strategic plan. ReferencesAmerican Academy of Addiction Psychiatry (2013) - Opioid-Induced Hyperalgesia (OIH) (http://www.pcss-o.org/online-module-4) By Brian Johnson M.D. Assoc Prof Psychiatry and Anesthesia SUNY Upstate Medical UniversityBlondell RD, Ashrafioun L, Dambra CM, Foschio EM, Zielinski AL, Salcedo D M. (2010) A clinical trial comparing tapering doses of buprenorphine with steady doses for chronic pain and co-existent opioid and co-existent opioid addiction. J Addiction Medicine 4:140-46. Carroll KM (1998) A cognitive behavioral approach: Treating cocaine addiction. NIH Pub 98-4308. Rockville, Md:NIDA.Carroll KM et al. (2014) Computer-assisted delivery of cognitive-behavioral therapy: Efficacy and durability of CBT4CBT among cocaine-dependent individuals maintained on methadone. Am J Psychiatry 171:436-44.Colace C. (2014) Drug Dreams London:Karnac.Dodes LM. (1990) Addiction, helplessness and narcissistic rage. Psychoanalytic Quarterly 59:398-419.Dodes LM. (1996) Addiction and compulsion. J Am Psychoanalytic Assn. 44:815-35.Dodes L, Dodes Z. (2014) The Sober Truth Boston:Beacon Press.Freedman R. (2014) Computerization of the therapeutic task of working through. Am J Psychiatry 171:388-90.Gregory RJ, DeLucia-Deranja E, Mogle JA. (2010) Dynamic Deconstructive Psychotherapy Versus Optimized Community Care for Borderline Personality Disorder Co-Occurring With Alcohol Use Disorders: A 30 month follow up. J Nervous Mental Dis 198:192-8.Johnson B. (2001) Drug dreams: A neuropsychoanalytic hypothesis J Am Psychoanalytic Assn 49:75-96Johnson B. (2003) Psychological addiction, physical addiction, addictive character, addictive personality disorder: A new nosology of addiction. Canadian J Psychoanalysis 11:135-60.Johnson B. (2009) Widespread Zombification in the 21st Century and the Wars of the Zombie Masters Syracuse:Gegensatz Press.Johnson B. (2010) The psychoanalysis of a man with heroin dependence: Implications for neurobiological theories of attachment and drug craving. Neuropsychoanalysis 12: 207-15.Johnson B. (2013) Addiction and will. Frontiers in Human Neuroscience 7:doi: 10.3389/fnhum.2013.00545 Johnson B, Faraone SV. (2013) Outpatient Detoxification Completion and One-Month Outcomes for Opioid Dependence: A Preliminary Study of a NeuropsychoanalyticTreatment in Pain Patients and Addicted Patients. Neuropsychoanalysis 15:145-60.Johnson B et. al. (2014) Fibromyalgia, autism, and opioid addiction as natural and induced disorders of the endogenous opioid hormonal system. Discovery Medicine 18:209-20.Johnson B, Flores-Mosri D. Neuropsychoanalysis at 16, accomplishments and challenges. Submitted.Jones DS, Krotik S, Johnson B, Morrison AP. (2005) Clinical challenge: Waiting for rescue – an attorney who will not advocate for himself. Harvard Rev Psychiatry 13:344-56.Katz EC., Schwartz RP, King S, Highfield DA, O’Grady KE, Billings T, et al. (2009). Brief vs. extended buprenorphine detoxification in a community treatment program:Engagement and short-term outcomes. American Journal of Drug and Alcohol Abuse, 35: 63–67.Khantzian EJ (1997) The self-medication hypothesis of substance use disorders. A reconsideration and recent application. Harvard Review of Psychiatry 4:231-44.Koob GF, LeMoal M. (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharm 24:97-129.Okie S. (2010) A flood of opioids, a rising tide of deaths. New England Journal of Medicine 363: 1981–1985.Panksepp J. (1998) Affective Neuroscience. New York:Oxford.Proctor SL, Copeland AL, Kopak AM, Derschman PL, Polukhina N. (2014) A naturalistic comparison of the effectiveness of methadone and two sublingual formulatioins of buprenorphine on maintenance treatment outcomes: Findings from a retrospective multisite study. Exper Clin Psychopharm 22:424-33.Ramanathan S, Panksepp J, Johnson B. (2012) Is fibromyalgia an endocrine/endorphin deficit disorder?—Is low dose naltrexone a new treatment option? Psychosomatics 53: 591–594.St. Fleur D, Johnson B. (2014) “Integrating Psychotherapy and Medication for Addicted Patients” in I. R. de Olivera,, T. Schwartz, S. M. Stahl, eds. Integrating Psychotherapy and Psychopharmacology NY: Routledge Press.Streltzer J, Zigler, P, Johnson B. (2009) Cautionary guidelines for the use of opioids in chronic pain. American Journal on Addiction 18:1-4.Ziedonis DM, Amass L, Steinberg, M, Woody G, Krejci J, Annon JJ, et al. (2009) Predictors of outcome for short-term medically supervised opioid withdrawal during a randomized, multicenter trial of buprenorphine-naloxone and clonidine in the NIDA clinical trials network drug and alcohol dependence. Drug and Alcohol Dependence 99: 28–36.
I am part of a group of nearly 900 people who have gotten together to support Dr. Kim Janda's and Dr. George Koob's heroin vaccine research at The Scripps Research Institute in La Jolla, California. If education and awareness were sufficient to keep people from using drugs we would not have the increase in deaths from heroin overdoses that we are seeing. If rehab or therapy or AA were enough, we would not see the number of relapses that we do. It is clear there needs to be another tool in the arsenal of addiction treatment tools to help those that suffer from this addiction. On our own, we have raised nearly $20,000 for the vaccine research which while essentially insignificant, hopefully signals the depth of our commitment to see that this research goes forward. We hope that you will continue to support this research as you have done in the past.
I was disappointed to see that continued research on the prevention of drug abuse is no longer a NIDA strategic priority. As you know, through its leadership and funding NIDA has been a principal NIH institute in creating the field of prevention science. The evidence base identifying risk and protective factors for substance abuse disorders and the research showing the efficacy and effectiveness of individual, family, school, peer and community focused preventive interventions in reducing behavioral health problems is largely the result of work of NIDA- funded researchers. Under your leadership, substance abuse prevention has become an evidence based field with many tested and effective preventive interventions as the result of NIDA research funding.This work has laid the way for dramatic improvements in public health that would accompany widespread scaling of tested and effective preventive interventions. Recent trials indicate that effective dissemination of effective prevention systems could impact population-level public health by further reducing adolescent drug use by as much as one third.The need for effective type 2 translational research on methods for scaling effective preventive interventions and systems is underscored by the emerging trend toward legalization of marijuana. Now, more than ever, it is important to ensure that young people do not consume drugs during the key brain development years of adolescence.
There is a lack of pharmacological data for drugs of abuse especially in pregnant women . Increasingly women are receiving buprenorphine yet there are very few data on the pharmacology of this agent . Failure rates of 20% are seen when transitioning these women to buprenorphine and it is entirely possible that the dose may need to be higher . Likewise methadone dosing regimens in pregnant women are not driven by the pharmacology of the drug . Many women in the postpartum state are overdosed because the care provider doesn’t reduce the dose . Pregnant women are ignored yet it is this group of women who seek help at start of their pregnancy to try to help their baby. This is a group that should be targeted for therapy and followed up postpartum to help them stay clean.
I write on behalf of the American Association for the Treatment of Opioid Dependence, which represents over 950 Opioid Treatment Programs throughout the United States and Mexico, in addition to representing 30 state chapters. One of our state chapters is the California Opioid Maintenance Providers (COMP) and we are unified with COMP's position in opposing a portion of the California Bridge to Reform Demonstration (No. 11-W-00193/9) Amendment for Drug Medi-Cal Organized Delivery System Waiver.This waiver was submitted by the California Department of Health Care Services during November 2014. I am specifically writing with regard to the provision that concerns Medication Assisted Treatment for Opioid Addiction, including the use of the three federally approved medications to treat this disorder (methadone, buprenorphine, and Vivitrol/Naltrexone). Like our state chapter, AATOD opposes the waiver of beneficiary freedom of choice, statewideness, amount, duration, and scope and reasonable promptness as proposed in the current waiver amendment application as they relate to Medication Assisted Treatment. In our judgment, if this waiver were to be approved, it will result in limited access to medically needed opioid addiction treatment services, such as those provided in California's registered Opioid Treatment Programs and other approved opioid treatment service providers.This reduced access runs counter to federal operating authority and the interests of parity legislation and the ACA.It is not necessary to include Opioid Treatment Programs in the organized delivery system waiver in order to obtain its primary objectives. AATOD is asking CMS to advise the California Department of Health Care Services to eliminate any reference to the narcotic treatment programs from the proposed waiver.AATOD and COMP have a longstanding appreciation for what was achieved in a federal court case (Sobky vs. Smoley: 855 F. Supp. 1123, 1128/E.D. Cal. 1994). This represented a landmark court case which prevented many California counties from continuing their practice of restricting access to Medication Assisted Treatment for opioid addiction. At the time of this case, there were only 18 of 58 different California counties providing beneficiaries with access to opioid addiction treatment. Based on the evidence provided during the course of the case, the district judge, Judge David F. Levi, issued a preliminary injunction at first and then a permanent injunction against California state officials. This judgment has stood the test of time up until the present moment when the California Department of Health Care Services submitted its waiver application to CMS.There will be significant injury dealt to opioid addicted individuals in need of Medication Assisted Treatment for their disease if this waiver is approved. It will reverse the enlightened decision of the district court in the Sobky vs. Smoley case and make such opioid addicted individuals vulnerable once again to county authorities. Based on the history of California and frankly in other states as well, when the broad requirement to provide such treatment to opioid addicted individuals is withdrawn, people lose access to care. Based on fifty years of established research, once such access to care is denied, rates of co morbid infectious diseases, associated with the abuse of opioids, will rise. Such untreated opioid addicted individuals will revert to crime and occupy jail cells rather than treatment slots in medical treatment facilities.In view of the long history of county opposition by various county governments in California and inconsistent and non-evidence based policies with regard tounless the federal government denies the submitted waiver by the California Department of Health Care Services as it relates to Medication Assisted Treatment. As a reminder, the state of California is prohibited by the aforementioned federal court injunction in denying access or delaying access to Opioid Treatment Program services to Medi-Cal beneficiaries due to budgetary constraints. The submitted waiver is simply a method of returning to a very negative part of California's history with regard to restricting needed access to medical care for opioid addicted individuals . In this case, if such a waiver is approved, access to care will be restricted or denied by county authorities, increasing the suffering of the individual and their families and doing no good for the public health and well being. If CMS were to approve the submitted amendment, it will overturn the prior federal court injunction, which was based on the absolute proof of systemic violations of law, which led to incredible hardship on behalf of Medicaid beneficiaries in California. There is no need to refer to the stigma that affects opioid addicted individuals and which is used either consciously or not by various county boards of supervisors and behavioral health administrators, who are simply opposed to the use of medications to treat opioid addiction. That was the basis for the court action in Sobky vs. Smoley.I am respectfully but forcefully asking the federal government to deny the California waiver, as it relates to Medication Assisted Treatment, which will create serious impediments to the life and well being of opioid addicted individuals. It is anticipated that many counties in California will not have the resources which are necessary to administer the drug Medi-Cal program, creating delays in treatment, denial of treatment, and inevitably, death to individuals who will not be able to access care.

Basic Science, Clinical and Translational Science

NIDA should include in its strategic plan the following:Investment in somatic brain DNA variation as a cause and consequence of drug addiction.Investment in direct antagonists of cocaine action, ie, triple reuptake inhibitors and other molecules which antagonize rewarding actions of cocaine.
I respectfully submit the role of neuroinflammation in the causes and consequences of substance abuse and the potential of large molecules to provide novel treatments for substance abuse for consideration for inclusion in the NIDA strategic plan.
I think these directions could be important. Neuroinflammation and neuro-immune or neuro-glial interaction: role of TLRs, cytokines, and chemokines Circulating miRNAs as neuromodulators and biomarkersPro-resolution mediators and pathway Stem cells as drug store Testing drug effects in primary human neurons
A review of progress in scientific approaches to understanding the biological basis of substance use and substance use related disorders will reveal several overall themes that indicate expectations that the future yield from certain scientific approaches should be markedly lowered. First, the genetic architecture of substance use is considerably more complex than anticipated. It is unlikely that genetic approaches alone will lead to improvements in diagnosis. However, there is suggestive evidence that genetic information may be beneficial in guiding some forms of treatment. Second, despite their promise, there are clear limitations in existing animal models of substance use. Recent work from the Encode consortium which demonstrates relative lack of conservation of cis regulatory elements suggests that efforts to use or genetically engineer more representative animal models will face stiff challenges. Third, as highlighted in a recent publication by the ENIGMA collaboration which analyzed paired imaging and genetic data from 31,000 subjects (Nature 2015), the likelihood that structural neuroimaging approaches will contribute meaningfully to the mission of NIDA in the foreseeable future is limited.In contrast, there is reason to be optimistic about the field of epigenetics. Using only a fraction of the resources devoted to the above fields of endeavor, considerable scientific progress has been made. Using funding from NIDA, a robust DNA methylation signature of cigarette consumption at AHRR have been published by our group (Monick et al, 2012) and extensively replicated (11 consecutive times at the most recent count, see Table I). NIDA funded efforts to translate this discovery into clinical tools for clinical diagnosis and treatment are in progress. This progress in tobacco consumption is not an outlier in the field of substance use. Already, preliminary profiles exist for both cannabis and alcohol consumption. Both are pending commercial translation into usable clinical tools.Taken as a package, through their allowance more sensitive quantitation of substance use consumption, these DNA methylation tools may lead to more effective prevention and treatment for substance use. Reciprocally, they may also allow us to more effectively interrogate the early developmental processes that underlie substance use initiation and may be the only tool through which to understand the relationship between e-cigarette use and smoking.Best yet, it is quite possible that these discoveries are only the tip of the epigenetic iceberg. There is considerable reason to be optimistic that epigenetic approaches can be used to provide the “personalized medical approach” that has been so often promised, yet not delivered. Though the above methylation detection profiles are relatively robust, it has become quite apparent to those in the field that the vast majority of the epigenetic signatures found in peripheral blood are confounded by GxMeth interaction effects. What is not clear is whether by characterizing these interaction effects that we can improve our ability to predict our ability to substance use or response to medications.This is not a pie-in-the-sky possibility. To give a concrete example, in previous work Volkow and colleagues have shown that monoamine oxidase activity in the CNS is directly in activated by tobacco smoke. Conveniently, at the same time, our first work in our efforts, funded by NIDA, to understand the effects of smoke on peripheral DNA methylation was to show the profound genotype dependent demethylation of the promoter region in response to tobacco smoke. This locus is of considerable interest because the activity of this locus is critical obvious key regulatory role of monoaminergic neurotransmission and the fact that it has been targeted in previous smoking cessation attempts. Unfortunately, those clinical trials did not show significant clinical effect of MAO inhibitors on smoking cessation. Could the reason that these clinical trials did not show an impact be confounding GxMeth effects? By using information from a better understanding of these GxMeth effects, could we more likely improve treatment choice? Is this true for other smoking cessation medications such as varenicline and bupropion? These are open questions.To summarize, it is my belief that further investment in epigenetic technologies could lead to significant advances in our ability to diagnose, treat and prevent substance use. At the same time, it is important to note that advances in the field of epigenetics are closely tied to advances in the field of genetics and that no scientific discipline is an island. Finally, I thank NIDA for giving me the opportunity to conduct my studies for the past 13 years and for listening to my thoughts on improving our national efforts in combating substance use.
NIDA - Draft Strategic Priorities Basic Neuroscience: Improve our understanding of the basic science of drug use, addiction, vulnerability to addiction, and recovery Increase our knowledge of biological, behavioral, environmental, and developmental factors involved in risk and resilience for drug use and addiction Integrating animal models, behavior, genetics, epigenetics, and other molecular biomarkers for drug abuse and addiction Understand the developmental trajectory of addiction and individual heterogeneity Improve our understanding of brain circuits related to drug abuse and addiction at the cellular, circuit, and connectome levels, including:Normal development and function across the lifespan including mechanisms of reward, self-control, and conditioning Drug effects on neuroplasticity, neural structure, and circuit function across the stages of addiction Neurobiological correlates of recovery Neurobiological mechanisms that determine why some people are more susceptible to overdose than othersPulmonary, renal, hepatitic mechanisms that determine why some people are susceptivel to overdose than others.Neural-glial, -immune, and neuroendocrine interactionsBetter define the interactions between addiction and pain, including molecular, genetic, behavioral , and neural-circuit-related factors, to guide the development of alternate treatment strategies for pain patientsImprove our understanding of the interaction between addiction and co-occurring conditions Elucidate the impact of mental health, HIV, HCV, pain, etc. on addiction; Elucidate the impact of addiction on mental health, HIV, pain etc.Understand molecular mechanisms of latent HIV reservoirs in the brains of substance-abusing populationsClinical and Translational Science: Support the development of new and better interventions and treatments that incorporate the diverse needs of individuals with Substance Use Disorders (SUDs)Support the development of novel, evidence-based, targeted prevention and treatment interventions including social, behavioral, pharmacological, vaccines, and brain stimulation therapies (e.g., transcranial magnetic stimulation, direct current stimulation, etc.)Accelerate the identification of promising targets and ligands to accelerate new drug discovery and development Accelerate medications development for SUDsFocused development efforts on: Addictions without an FDA approved treatmentDetoxificationIncreasing linkage to evidence-based SUD care after detoxificationOverdose prevention or reversalPharmacological interventionsBehavioral interventionsStructural and environmental interventionsAccelerating neurobiological recoveryAddressing comorbidities (MH, HIV, HCV, pain)Integration of addiction, and other mental health and medical care in adult and pediatric settingsThe effectiveness and comparative effectiveness of treatments in the real worldThe study of health services approaches to the full spectrum of unhealthy substance use (from risky use through severe disorder)Longitudinal care approaches for ongoing substance useWays to improve the quality of care for people with or at risk for addictionDevelop techniques to measure and improve patient adherence in clinical trials (e.g., patient-developed incentives)Identify measures other than abstinence that can reliably assess SUD treatment outcomes Identify biomarkers of addiction, resilience, and recovery to enable personalized treatmentDevelop alternative smoking cessation treatment and regulatory tobacco control mechanismsPublic Health: Increase the public health impact of NIDA research and programsImprove the understanding of factors that influence the integration of evidence-based research findings into healthcare policy and practice (implementation science)Improve understanding of the social and structural determinants of substance use, and of receipt of quality services for prevention and treatment of addictionIncrease readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, changing healthcare landscape, emerging drug trends, etc.)Increase strategic partnerships with the community (academia, pharma, biotech, healthcare organizations, policy makers, criminal justice, law enforcement, etc.) to enhance the dissemination of evidence-based research findings into policy and practice Strengthen focus on bi-directional translational researchDevelopment and implementation of evidence based public health approaches to delaying substance use in adolescentsScience Infrastructure: Enhance the national research infrastructure to support advancements in scienceAccelerate the development and utilization of advanced technologies (e.g. the President’s BRAIN Initiative), data repositories (e.g. Big Data to Knowledge (BD2K) initiative, and statistical models to spur innovative research Improve training for the next generation of scientistsIncrease effective engagement and training in multidisciplinary research (informatics, engineering, computer science, chemistry, mathematics, physics, etc.)Increase the number of well-trained underrepresented scientists in the drug abuse and addiction field at all career levelsImprove mentoring of young scientistsIncrease effective collaborations in researchIncrease the ethics and transparency of research involving people with SUDIncrease effective data and resource sharing (big data, biorepositories, transgenic/optogenetic tools, data standards, etc.)Increase collaborations with other NIH Institutes and Centers (e.g. Collaborative Research on Addiction at NIH (CRAN)), Federal and State agencies, academic and industry partners, etc.Identify and implement strategies to improve the reproducibility of pre-clinical researchEnable efficiency and lower the cost of clinical trials via innovative statistical models, data standards, leveraging technology (e.g. electronic health records) and partnerships, etc.Develop and validate computational and systems-level analytics for integrating multi-dimensional data across the addiction trajectoryUnifying themes A number of unifying themes that will be addressed across each of the domains listed above include:Promoting research that considers the impact of sex and gender on drug use disorders and addictionAddressing health disparities among underrepresented populationsUnderstanding the role of development across the life spanAddressing the assessment and treatment needs of adolescents based on developmental stageAddressing the treatment needs of pregnant and post-partum women and their childrenAddressing the treatment and prevention needs related to common co-morbidities including HIV/AIDS and hepatitis C.
Because genetic variation is still expected to explain approximately 50% of the variance in addiction risk across drugs of abuse, continued investment in genetics of addiction is needed. Taking multiple approaches will be necessary. Genome-wide association studies (GWAS), begun in 2005, have made many important discoveries in the genetic determinants of human disease. For addiction, discoveries from association studies and follow-up functional studies in humans and animal models have firmly established variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 on chromosome 15q25 and CHRNB3-CHRNA6 on chromosomes 8p11 as important contributors to risk of nicotine dependence, as well as lung cancer. The variant rs16969968 in CHRNA5 has been further demonstrated to interact with some pharmacotherapies for smoking cessation in multiples studies. Unfortunately, the success with nicotine dependence as not been mirrored in addiction to other drugs. Standard GWAS with much large samples is one approach to enhancing discovery that has born fruit in other parallel phenotypes (e.g., recent substantial advances in schizophrenia). Psychiatric Genetics Consortium (PGC) Addiction group will be pursuing this, combining existing cohorts. One of the most important, low marginal cost, investments for this effort would be genotyping the many existing samples that lack funding to genotype. Beyond large-scale GWAS, integration of these data with epigenetics, brain imaging, and other biomarkers holds great promise for biologically relevant discoveries and understanding of potential mechanisms. Great strides have been made in understanding epigenetics in human brain tissue among non-addicted “normal” decedents. These data provide very import tools to understanding potential function of genes and variants specifically in tissue most relevant to addiction. Broad sharing of these data (notably BrainCloud, Brain QTL, GTEx) allow researchers to link genes and variants associated with addiction phenotypes to putative functions and set the stage for experimental follow-up of potential molecular mechanism underlying such associations. A critical gap in the epigenetics of addiction is the lack of large-scale genome-wide comparison of epigenetics between those addicted to drugs and non-using controls. To date the literature largely reports targeted expression or methylation experiments for candidate genes/variants, mostly in those of European descent. Adequately powder agnostic genome-wide tests of gene expression and methylation coupled with genome-wide genotyping among cases of addiction and non-using controls would provide data are critical to understanding differential expression and methylation specific to addiction that can not be obtained from existing resources. Additionally there is need for such data across ancestry groups, as there are substantial differences from what we know so far and a substantial under representation of groups that are not of European descent. Publically available resources of such epigenetic information would provide both the ability to “look up” results from GWAS and other genetic studies to assess potential gene function relevant for addiction, but also nominate variants for independent tests of association based on their association with differential expression or methylation. Epigenetic data will provide a view on genetics of differential brain function complementary to brain imaging studies, providing data on one set of mechanisms that could help explain observed differences in brain function between those addicted to drugs and those who are not. Another area worthy of consideration in NIDA’s strategic plan is the development of biomarkers of addiction and of recovery. New technologies such as broad-spectrum metabolomics provide novel opportunities within the field of addiction to identify biological systems perturbed by addiction or cessation of use. Metabolomic profiles that distinguish those addicted and those who are not, or treatment responders and nonresponders could provide novel insights into biological systems important to these outcomes as well as biomarkers for study of causes of individual differences in those systems. HIV acquisition and living the HIV continue to be substantial worldwide problems for which drug users have specific risks and needs. Although environmental interventions have had great success in lowering incidence rates in the U.S., acquisition among drug users continues here and much more so abroad. Based on in vitro work it is estimated that fifty percent of variability in HIV-1 susceptibility is attributable to host genetics. Indeed, mechanisms underlying the only genetic variant conclusively associated with HIV acquisition, a deletion in CCR5, gave rise to maraviroc, an antiretroviral drug. Thus identifying such genetic factors holds great promise in advancing our understanding HIV pathogenesis and providing targets drug development. Similarly, basic research across the spectrum of genomics and other omics can provide unique insights on living with HIV among drug users. Of particularly interest is the interaction between ongoing drug use and progression of HIV in the context of variability in adherence to HAART or its complete absence. Translational science needs high-risk high-reward investment to accelerate discovery and clinical application. Despite the widely held expectation that scientific discoveries will improve patient care, the yield of clinically useful discoveries from basic science remains low (5%) and the time for translation from discovery to implementation long (13-17 years). New paradigms are needed to revolutionize the science of translation: speeding discovery and implementation of evidence-based therapies by innovatively reducing, removing, or bypassing bottlenecks in therapeutic development, while evaluating them in real-world settings. In particular, it may be useful bring discovery science tools (e.g., Omics) to real world treatment settings using large numbers of patients to focus discovery on clinical outcomes specifically (e.g., treatment response), rather than beginning with the disease and then translating those discoveries, hoping the same biological mechanisms for addiction are those that are key to recovery.
Thank you for the opportunity to comment on the strategic plan that has been developed. Vermont staff from the Division of Alcohol and Drug Abuse Programs reviewed the plan and summarized feedback to you in the following paragraphs.Resilience There should be a more expansive exploration of resilience that builds upon and goes beyond existing “neuroscience” or brain circuitry explorations. We suggest including factors such as personality and temperament, parenting and/or education, social supports, cultural and anthropological notions of risk and recovery, contributing cultural and/or racial/ethnic factors, that may result in variations in resilience. These elements would be useful to enhance our knowledge of more effective preventive interventions. Systems ModelsWe support further research to identify some of latest and best advances in chronic disease management and financing, and how the growing emphasis on patient directed care and behavior shape our strategies and systems of care for addressing substance abuse issues. Furthermore, we support research that tests the application of other scientific models and methodologies, and specifically systems models, to look more holistically at this important public health challenge, e.g., operational research, microeconomics, game theory, medical anthropology, social network and market research. We see value both in understanding dynamics having impact upon an individual’s ability to get help, and those dynamics having impact upon effectiveness in delivering services and/or reducing the problem overall.

Basic Science, Clinical and Translational Science, Infrastructure

I would like to recommend the followings related to drug abuse and neurological disorder diseases within NIDA mission:(Experiments) 1. GPCRs (e.g., Cannabinoid Receptors) Structural Biology and structure based drug design (Medicinal Chemistry biology and biophysics) 2. Druggable chemical probe and ligand development of promising targets to accelerate new drug discovery and mechanism study; 3. Accelerate the identification and development of natural products to discover novel therapeutic drugs.(Big data computing): 4.“Big data” type disease specific chemical genomics (or chemogenomics) databases for system pharmacology and pharmacometrics research 5. Advancing computational technologies to manage the big data , data-mining and derive hypothesis for basic and clinic research 6. Develop Systems pharmacology and personalize medicine for treatment neuro diseases. 7. Discover and develop new therapeutic uses for existing or new lead molecules (New Therapeutic Uses or drug synergy), using big data and cloud computer prediction, computer-aided drug design technologies and chemistry modification methods;Above include research grant and training education

Basic Science, Clinical and Translational Science, Public Health

Thank you for your invitation regarding input in the NIDA research priority. I have read the list of 2015-2020 NIDA priorities in NOT-DA-15-005. All listed research priorities are very critical and of great interest. I would add 3 additional topics.1. Correlation of genomic polymorphism or variations with vulnerability to drug abuse in the population.2. Development of vaccine to prevent drug abuse that can be used in the high-risk (genetically or socially) sub-population.3. Integration of social networking behavioral pattern and communication and internet strategy for drug prevention education (like targeted and personalized marketing, high-risk individuals (identified via analyzing social networking behavior and movement data can be targeted with drug abuse prevention educational ads or text messages).
General Terrific (and ambitious) plan Consider including feeding behavior/overeating and the interactions with addictive behaviors, given the overlap in circuitry and compulsive features. The continued emphasis on basic science, including genetics, epigenetics and biomarkers, is very important. The emphasis on the integration of evidence-based research findings into healthcare policy and practice is also excellent. Additional areas that received less emphasis but which continue to be important include: -Improve understanding of the common mechanisms and trajectories underlying addictive disorders and complex health behaviors associated with addiction, including sleep problems and obesity. For example, such research could inform whether a sequential approach to treatment is more or less efficacious than changing multiple behaviors simultaneously.-Under clinical and translational science, it appears that “focused development efforts” do not include addictions for which FDA approved treatments ARE available (e.g., nicotine dependence, opioid dependence). While approved treatments may be available, there is substantial room for improvement in outcomes and development of new treatments. Perhaps this is not meant to imply that development efforts in these areas are not a priority; however, as written it implies that only addictions without FDA approved treatments will be a priority. - Integration and application of evidence to promote changes in local and federal regulation relevant to addiction. We are reaching a threshold of having sufficient data, for example, on particular tobacco products and messaging, that can and should applied to inform regulatory efforts. -Determine not only the risks, but also the potential therapeutic benefits, of changes in medical marijuana access and use. The current portfolio focuses exclusively on the risks. However to facilitate evidence-based regulation, a risk and benefit analysis would be important.-Identify efficacious methods for increasing the broad utilization of evidence based treatment in underserved populations, such as those of lower SES and those with comorbid medical or psychiatric conditions. While the current plan highlights implementation science to influence integration of findings into healthcare practice, this does not ensure that the most vulnerable individuals will avail themselves to utilize these services.
Thank you for the opportunity to provide comments on your draft 2016-2020 Strategic Plan. As someone who has spent the past 15 years working on hepatitis C and/or overdose prevention among injection drug users and in the criminal-justice involved population in public health settings, I applaud your efforts to achieve the following objectives:Basic NeuroscienceBetter define the interactions between addiction and pain, including molecular, genetic, behavioral , and neural-circuit-related factors, to guide the development of alternate treatment strategies for pain patientsImprove our understanding of the interaction between addiction and co-occurring conditions Elucidate the impact of mental health, HIV, HCV, pain, etc. on addiction; Accelerate medications development for SUDsClinical and translational scienceFocused development efforts on: Overdose prevention or reversalAccelerating neurobiological recoveryAddressing comorbidities (MH, HIV, HCV, pain)Identify measures other than abstinence that can reliably assess SUD treatment outcomes Identify biomarkers of addiction, resilience, and recovery to enable personalized treatmentThis last point is critical because a fixation on abstinence as the sole goal of drug treatment is serving as a major barrier to people with addiction and/or hepatitis C accessing housing, shelter, and life-saving hepatitis C treatment due to policy requiring abstinence even when this is not a desired or even necessarily realistic goal for many individuals. Part of the problem has been that “harm reduction” as a term is anathema to policymakers, yet no alternative framework seems to have been accepted into common usage. Public HealthImprove the understanding of factors that influence the integration of evidence-based research findings into healthcare policy and practice (implementation science)Increase readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, changing healthcare landscape, emerging drug trends, etc.)Unifying ThemesUnifying themes A number of unifying themes that will be addressed across each of the domains listed above include:Promoting research that considers the impact of sex and gender on drug abuse and addictionAddressing health disparities among underrepresented populationsUnderstanding the role of development across the life spanAddressing the treatment needs of adolescents and pregnant and post-partum womenAddressing the treatment and prevention needs related to common co-morbidities including HIV/AIDSIn collaboration with CDC and HRSA, it is critical that NIDA help establish / bolster the evidence base demonstrating the ability of persons who use drugs to adhere to medications for infectious diseases such as HIV, tuberculosis, and hepatitis C. While it would seem that some of this research does exist, many states have nonetheless implemented policies limiting access to life-saving hepatitis C treatment to those who cannot prove they have been abstinent from all illicit drugs for at least six months, despite the lack of evidence for such policies. In collaboration with CDC, it is also critical that NIDA help establish models for using multidisciplinary programs to prevent hepatitis C among young injectors, through a combination of medication assisted treatment, syringe access, antiviral treatment, and education. In collaboration with CDC (and perhaps the Bureau of Prisons), it would be great if NIDA could support a proof of concept to treat a finite group of persons with HCV, such as in a prison setting, to interrupt secondary transmission at the population level
RESPONSE TO NIDA REQUEST FOR INFORMATION-NIDA Strategic Directions SOCIETY FOR PREVENTION RESEARCH General ObservationsEach year, over six million young people receive treatment for mental, emotional, or behavioral problems. The financial costs for treatment services and lost productivity attributed to the related behavioral health problems of depression, conduct disorder, and substance abuse are estimated at $247 billion per year (O'Connell ME, Boat T, Warner, 2009; Woolf). These costs are for a system that only reaches a small portion of those in need of treatment. While treatment of existing problems remains a critical service and focus of behavioral health care, over 40 years of research shows that we can prevent substance abuse and behavioral health problems from developing in the first place (Catalano, Fagan, Gavin, Greenberg, Irwin, Ross, Shek, 2012). We must increase that focus to have substantial impact on rates of disorder and related harm. The Institute of Medicine report on prevention (O’Connell et al., 2009) documents numerous controlled trials of interventions across development that have shown prevention of substance abuse and related problems is possible. Many of these interventions exhibit effects long after intervention exposure. Most provide a significant return on investment in terms of reduced personal and societal costs (Biglan, 2015). Further, young people exposed to the highest levels of risk factors, including disproportionately low-income and/or youth of color, frequently benefit most from preventive interventions.(Hill, Bailey, Hawkins et al., 2014; Campbell, Ramey, Pungello, Sparling, Miller-Johnson, 2002; Clark, Cornelius, Kirisci, Tarter, 2005; Conduct Problems Prevention Research Group, 2014) Prevention of drug abuse, alcohol misuse and other addictions differs from most other diseases and disorders in that initiation of substance use is a socially-determined behavior. Drug use, abuse and addiction develop in a complex context of diverse psychological and behavioral precursors. Research shows that modifying one or more risk or protective factors for these problems often has additional benefits in preventing other problems such as mental health problems, aggression, and academic failure. Thus, preventive interventions can be highly efficient in addressing multiple social problems and their associated costs.NIDA funding has been essential in building the prevention science that has led these accomplishments, creating a diverse portfolio that includes basic research, methodology, efficacy trials, effectiveness research, systems research, and services research. The report on prevention from the Institute of Medicine (O’Connel, et al., 2009) highlights the contribution that NIDA has made to the progress of prevention research. Their conclusion is clear: the most effective way to halt the manifestation of substance use and allied behavioral health disorders is through prevention. Despite this, prevention intervention research remains a small portion of the NIDA portfolio, only 8% in 2012. A continued focus on and increased funding for prevention studies are imperative to improve population health. Prevention needs to play a more prominent role in the proposed 2015 NIDA strategic plan. Despite this accumulation of core prevention research, there remains much to be learned to further improve the prevention knowledge base. I suggest three broad prevention priorities be incorporated into the NIDA 2015 strategic plan: 1) prevention- related basic research to discover and specify the mechanisms of action of biopsychosocial risk and protective factors and their interaction across development; 2) prevention intervention research to develop and test new interventions that extend existing efficacy research, test emerging findings about biopsychosocial risk, specify how intervention effects are realized and for whom effects apply, and understand the salutary effects of substance abuse prevention on related problems ; and 3) research to understand how best to “scale up” (adoption, implementation, and sustainability) effective prevention intervention with reach and fidelity to achieve population-wide reductions in substance use, abuse and addiction, with related economic and health gains to individuals, families, communities, and state and federal governments. Specific suggestions are made below and denoted by a vertical line in the left margin.Basic Research: The current Strategic Priorities recognize the importance of biological science to understanding substance use, abuse and addiction. However, the priorities underemphasize the critical role of social and behavioral science in understanding and addressing these problems. I suggest that a revision is made to include both Neuroscience and Social and Behavioral research in their own subsections of Basic Research.Neuroscience: Improve our understanding of the basic science of drug use, addiction, vulnerability to addiction, and recovery Increase our knowledge of biological , behavioral, environmental, and developmental factors involved in risk and resilience for drug use and addictionIntegrating animal models, behavior, genetics, epigenetics, and other molecular biomarkers for drug abuse and addictionUnderstand the developmental trajectory of substance use, abuse, and addiction and individual heterogeneityImprove our understanding of brain circuits related to drug use, abuse and addiction at the cellular, circuit, and connectome levels, including:Normal development and function across the lifespan including mechanisms of reward, self-control, and conditioningDrug effects on neuroplasticity, neural structure, and circuit function across the stages of addictionNeurobiological correlates of recoveryNeural-glial, -immune, and neuroendocrine interactionsBetter define the interactions between substance use, abuse, and addiction and pain, including molecular, genetic, behavioral , and neural-circuit-related factors, to guide the development of alternate treatment strategies for pain patientsImprove our understanding of the interaction between substance use, abuse, and addiction and co-occurring conditions Elucidate the impact of mental health, HIV, HCV, pain, etc. on addiction; Understand molecular mechanisms of latent HIV reservoirs in the brains of substance-abusing populationsBiological processes related to substance use, abuse and addiction risk and resilience and reactivity to preventive interventionsSocial and Behavioral Research: Research suggests that despite biological predispositions, the decision to use drugs is environmentally triggered, and that socio-cultural environments (e.g., policy, peers, family, communities) play pivotal roles in the initiation, maintenance, and desistence from drug use, abuse, and dependence. Understanding the developmental and environmental influences on biological mechanisms will increase the likelihood that biological research will strengthen efforts at prevention and treatment to improve the public health.Increase our knowledge of social, environmental and developmental predictors of substance use, abuse and addiction.Increase our knowledge of interactions between biological mechanisms and social, environment and developmentally salient predictors of later substance use, abuse, and addiction.Increase understanding of neurobiological changes in response to prevention interventions and messages.Determine the mechanistic effects of programs and interventions which will provide an evidence-base to guide efforts to refine and improve program components. Explore basic, malleable conditions that promote or interfere with intervention effects.Increase understanding of interaction effects of stress and contextual factors on drug abuse risk.Expand research on the relationships between drug use, abuse, and addiction on communicable and non-communicable diseases.Clinical and Translational Science: Support the development of new and better preventive interventions and treatments. that incorporate the diverse needs of individuals at risk for the development of and those with Substance Use Disorders (SUDs) Treatment research is important but reducing the number of those who contract the disorder is also critical. In addition, treatment and prevention have some distinct operational, population assumptions, and likely mechanisms of effects that merit separate but substantial attention (Weisz, Sandler, Durlak, & Anton, 2005). I suggest separate sections on Treatment and Prevention Research.Treatment Research: Support the development of novel, evidence-based, treatment interventions including social, behavioral, cognitive, pharmacological, vaccines, and brain stimulation therapies (e.g., transcranial magnetic stimulation, direct current stimulation, etc.)Accelerate the identification of promising targets and ligands to accelerate new drug discovery and development Accelerate medications development for SUDsFocused development efforts on: Addictions without an FDA approved treatmentDetoxificationOverdose prevention or reversalAccelerating neurobiological recoveryAddressing comorbidities (MH, HIV, HCV, pain)Develop techniques to measure and improve patient compliance in clinical trialsIdentify measures other than abstinence that can reliably assess SUD treatment outcomes Identify biomarkers of addiction, resilience, and recovery to enable personalized treatmentUsing pooled data from previous evidence-based treatment trials, identify mechanisms and moderators of intervention efficacyPrevention Research Integrate discoveries from the basic biological (e.g. neurobiological), psychological (e.g. emotional, behavioral, cognitive, and developmental) and social (e.g. social learning, peer network, and communications, laws and norms) sciences to develop and test innovative preventive interventions that specifically target underlying mechanisms in drug abuse risk.Research what are critical windows during childhood to adulthood that may produce the greatest effects for specific types of preventive interventions. Increase the translation of knowledge about basic biological, genetic, and neurobiological mechanisms underlying drug use and abuse to serve as indicators of change in preventive intervention research, and/or to help determine the intervention course (psychosocial, psychopharmacological) that is most likely to be effective for an individual given underlying biological mechanisms of action.Increase research to fill critical gaps in understanding the impact of preventive intervention on vulnerable populations including low income, people of color, youth in the child welfare system.Increase research to determine the impact of preventive interventions utilizing new and emerging electronic communication technologies. In addition to efficacy of utilizing these technologies for delivery of preventive interventions, the reach (who accesses), and the usefulness of these modes of delivery for generalization and maintenance of intervention impact is needed.Increase research to identify malleable mediators and moderators of preventive intervention effects to better understand which interventions work best for whom and why, and what preventive components predict intervention effects to understand how to improve prevention effects for all.Increase research to understand what malleable underlying person or environmental conditions interfere with or promote intervention effects.Increase research to examine the impact of preventive interventions on the neural substrate level. An understanding of how an effective intervention can alter brain development and function is critical for the field.Increase research to replicate effective prevention interventions in new populations and under different conditions to understand what contributes to whether the intervention continues to be effective or is less effective. Further, research is needed on the impact of fidelity, quality, and adaptation on the effectiveness of replications.Increase research on the combination of behavioral and biomedical preventive intervention.Increase research to incorporate understanding of individual differences in response to different types of persuasion and different types of drugs in preventive intervention development. This includes further culturally-sensitive and responsive research for understanding the needs of vulnerable and high risk populations. Increase research on embedding efficacious or new prevention interventions in health care organizations to examine the impact on health costs and a range of substance related outcomes at population level. Public Health: Increase the public health impact of NIDA research and programs: A substantial research agenda is needed on the complex processes through which evidence-based interventions are adopted, implemented, and sustained at the community level, with a strong orientation toward devising empirically-driven strategies for increasing their population impact. This agenda fits with recommendations in the National Prevention Strategy including the dissemination of community-based interventions that address health inequities, especially in inner-city neighborhoods and rural areas, the development, testing, and implementation of effective strategies to engage underserved populations, and the organization of representative, multi-sector community partnerships.Improve the understanding of factors that influence the integration of evidence-based basic science, prevention and treatment research findings into healthcare policy and practice (implementation science)Increase the understanding of how organizational, leadership, and fiscal factors influence the adoption and sustainment of evidence-based practices to prevent and treat substance use and abuse in key public service sectors (mental health, health, justice, child welfare)Improve the understanding of factors that influence the integration and sustainability of evidence-based basic research, prevention and treatment research findings into state and local public health, behavioral health, education, and child welfare, and maternal health.Increase dissemination research efforts of evidence based prevention programs and policies to determine what works best, for whom and why so that programs and policies can be further refined to achieve optimal results to improve the public healthIncrease research to understand the needed elements of infrastructure development to ensure the capacity and necessary supports for large scale adoption, implementation and sustainability of evidence based preventive and treatment interventions.Increase research on training health care and other providers in prevention knowledge and practices. Increase research to understand the cost of effective preventive interventions as well as the economic benefits that follow, to facilitate uptake and support for investing in prevention by policymakers and funders.Increase readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, new populations (elderly), changing healthcare landscape, emerging drug trends, etc.)Increase strategic partnerships with the community (academia, pharma, biotech, healthcare organizations, policy makers, etc.) to enhance the dissemination of evidence-based research findings into policy and practice Strengthen focus on bi-directional translational researchScience Infrastructure: Enhance the national research infrastructure to support advancements in scienceAccelerate the development and utilization of advanced technologies (e.g. the President’s BRAIN Initiative), data repositories (e.g. Big Data to Knowledge (BD2K) initiative, new technology for intervention delivery, and statistical models to spur innovative research Develop a strategy to build a strong infrastructure (building both manpower and organizational capacity) to support the dissemination, diffusion and quality implementation of evidence-based prevention practices that range from screening and assessment of vulnerable populations and communities to the appropriate recommendations for prevention programming and monitoring.Improve training for the next generation of scientistsIncrease effective engagement and training in multidisciplinary research (informatics, engineering, computer science, chemistry, mathematics, physics, etc.)Increase the number of well-trained underrepresented scientists in the drug abuse and addiction field at all career levelsImprove mentoring of young scientistsIncrease effective collaborations in researchIncrease the transparency of researchIncrease effective data and resource sharing (big data, biorepositories, transgenic/optogenetic tools, data standards, etc.)Increase collaborations with other NIH Institutes and Centers (e.g. Collaborative Research on Addiction at NIH (CRAN)), Federal and State agencies, academic and industry partners, etc. Create opportunities for multiple federal agencies to collaborate in funding translational drug abuse prevention and treatment research; e.g., SAMSHA, ONDCP, OJJDP, CYF, MCH, etc.Increase opportunities for combining data from previous prevention and treatment trials and use innovative methods to integrate and analyze these data.Identify and implement strategies to improve the reproducibility of pre-clinical researchEnable efficiency and lower the cost of clinical trials via innovative statistical models, data standards, leveraging technology (e.g. electronic health records) and partnerships, etc.Develop and validate computational and systems-level analytics for integrating multi-dimensional data across the addiction trajectoryUnifying themes: A number of unifying themes that will be addressed across each of the domains listed above include:Promoting research that considers the impact of sex and gender on drug abuse and addictionUnderstanding the interrelation between preventive and treatment interventions affecting substance abuse and impact on other aspects of physical and mental health, social functioning, and productivityAddressing health disparities among underrepresented populationsUnderstanding the role of development across the life spanAddressing the treatment needs of adolescents and pregnant and post-partum womenAddressing the treatment and prevention needs related to common co-morbidities including HIV/AIDSAddressing the prevention needs of youth and high-risk populations.Understanding the implications of the changing drug policy environment (i.e., marijuana legalization at the state level)Understanding the developmental and contextual influences across all areas of research ReferencesBiglan, A (2015) The Nurture Effect: The Evolution of Behavioral Science, Psychology Today, 1/5/15. Campbell FA, Ramey CT, Pungello E, Sparling J, Miller-Johnson S. (2002) Early childhood education: Young adult outcomes from the Abecedarian Project. Appl Dev Sci, 6(1):42-57.Catalano, R. F., Fagan, A. A., Gavin, L. E., Greenberg, M. T., Irwin, C. E., Ross, D. A., & Shek, D. T. L. (2012). Worldwide application of the prevention science research base in adolescent health. Lancet, 379, 1653-1664.Clark DB, Cornelius JR, Kirisci L, Tarter RE. (2005) Childhood risk categories for adolescent substance involvement: A general liability typology. Drug Alcohol Depend. 77(1):13-21.Conduct Problems Prevention Research Group. (2014). Impact of early intervention on psychopathology, crime, and well-being at age 25. Am J Psychiatry..Hale DR, Fitzgerald-Yau N, Mark Viner R. (2014) A systematic review of effective interventions for reducing multiple health risk behaviors in adolescence. Am J Public Health.104(5).Hawkins JD. (2006) Science, social work, prevention: Finding the intersections. Soc Work Res. 30(3):137-152.Hill KG, Bailey JA, Hawkins JD, et al. (2014) The onset of STI diagnosis through Age 30: Results from the Seattle Social Development Project intervention. Prev Sci.;15 (Suppl 1):S19-S32.O'Connell ME, Boat T, Warner KE, editors. (2009) Preventing mental, emotional, and behavioral disorders among young people: Progress and possibilities. Washington, DC: National Academies Press.Sloboda, Z. (2012) Substance Use & Misuse, 47:1557–1568, 2012.Western B, Pettit B. (2010) Incarceration & social inequality. Daedalus. 139(3):8-19,146-147.Woolf SH. (2008) The power of prevention and what it requires. JAMA. 299(20):2437-2439.
If concerns over the rising costs of health care persist and remain important for most Americans, then support and investment for evidence-based prevention interventions is both warranted and indispensable. Unfortunately, and too often, American society’s response to major problems has been mostly reactive. Such responses have evolved out of understandable efforts to deal with problems once they have emerged. We have devised a treatment system for most of the common and costly substance use and allied psychological and behavioral disorders once these problems have developed. Some of these policies have actually increased social inequity (Western & Petit, 2010). Each year, over six million young people receive treatment for mental, emotional, or behavioral problems. The financial costs for treatment services and lost productivity attributed to the related behavioral health problems of depression, conduct disorder, and substance abuse are estimated at $247 billion per year (O'Connell ME, Boat T, Warner, 2009; Woolf). These costs are for a system that only reaches a small portion of those in need of treatment. While treatment of existing problems remains a critical service and focus of behavioral health care, there is widespread recognition and empirical evidence from over 40 years of research that we can prevent substance abuse and behavioral health problems from developing in the first place (Catalano, Fagan, Gavin, Greenberg, Irwin, Ross, Shek, 2012. We must increase that focus to have substantial impact on rates of disorder and related harm. Major advances in reducing the incidence and prevalence of addiction and behavioral health problems become possible with the continued development of prevention science and the opportunities for more integration of prevention into health care through the Affordable Care Act. The Institute of Medicine report on prevention (O’Connell et al., 2009) documents numerous controlled trials of interventions across development that have shown prevention of substance abuse and related problems is possible. Many of these interventions exhibit effects long after intervention exposure. And, most provide a significant return on investment in terms of reduced personal and societal costs. (Biglan, 2015).NIDA funding has been essential in building the prevention science that has led these accomplishments, creating a diverse portfolio that encompasses basic research, methodology, efficacy trials, effectiveness research, systems research, and services research. The report on prevention from the Institute of Medicine (O’Connell, et al., 2009) highlights the contribution that NIDA has made to the progress of prevention research. Their conclusion is clear: the most effective way to halt the manifestation of substance use and allied behavioral health disorders is through prevention. We think that the emphasis on prevention in the NIDA 2010 strategic plan reflects acknowledgement of this viewpoint, that prevention be a major emphasis. Despite this, prevention intervention research remains a small portion of the NIDA portfolio, 8% in 2012, which is less than half the proportion allotted to treatment intervention research (17%). This is a decrease of 20% of the NIDA prevention portfolio from 2011 to 2012 (Sloboda, 2012; 1564). We think that increasing, not decreasing, the percentage devoted to prevention studies is imperative to continue the quality and quantity of research to fulfill this goal in the strategic plan and for continued progress in population health. Prevention needs to play a more prominent role in the proposed 2016-2020 NIDA strategic plan.We also think increased funding is justified to support the multi-focused portfolio that has spurred the important advances in the past two decades by providing ongoing and efficient feedback from epidemiology to basic descriptive studies to intervention designs and test of efficacy, effectiveness, and readiness for to-scale implementation. This funding has contributed more robust and rapidly innovating evidence base for basic research, substance abuse prevention, as well as treatment research. Research results examining bio-behavioral- developmental interactions have underscored the importance of the inter-relation between these mechanisms and the environment. Prevention of drug abuse, alcohol misuse and other addictions differs from most other diseases and disorders in that, at the initiation stage, substance use is well-characterized as a socially-determined behavior; there is a choice to use a particular substance. The notion of choice is complex and influences and information vary by life stage. The combined portfolio approach has produced research that demonstrates that drug use, abuse and addiction develops in a complex context of diverse psychological and behavioral precursors; thus, guiding prevention that modifies one or more risk or protective factors for these problems and also showing that such prevention often has additional benefits in preventing other problems such as mental health problems, aggression, and school achievement.Prevention research has also revealed that such efforts may have biggest effects where risk is greatest and opportunity or protection scarcer. Young people exposed to the highest levels of risk factors, including disproportionately low-income and/or youth of color, frequently benefit most from preventive interventions (Hill, Bailey, Hawkins et al., 2014; Campbell, Ramey, Pungello, Sparling, Miller-Johnson, 2002; Clark, Cornelius, Kirisci, Tarter, 2005; Conduct Problems Prevention Research Group, 2014).Despite this accumulation of core prevention research, there remains much to be learned to further improve the prevention knowledge base. Below, within in the basic bullet points of the Request For Information on NIDA’s strategic plan, we have added important and poorly understood aspects of prevention that require additional rigorous research. Structurally, we strongly suggest the augmentation of the Basic Research area to include both biological and social environmental research and the augmentation of the clinical and translational research to include a prevention section in addition to the treatment section. We detail what we think are the strategic areas for research in these new sections and provide comments (in red) on the existing document.In general, we suggest three broad prevention priorities incorporated into the NIDA 2016-2020 strategic plan: 1) prevention-informed and related basic research to discover and specify the mechanisms of biopsychosocial risks and protective factors and their interaction across development; 2) prevention intervention research to develop and test new interventions that extend the comprehensiveness of existing efficacy research, test emerging findings about biopsychosocial risk, specify how intervention effects are realized and for whom effects apply, and understand the salutary effects of substance abuse prevention on related problems; and 3) research to understand how best to “scale up” (adoption, implementation, and sustainability) effective prevention intervention with reach and fidelity to achieve population-wide reductions in substance use, abuse and addiction, with related economic and health gains to individuals, families, communities, and state and federal government. This includes development and testing of efficient and effective modes of intervention delivery, as well as understanding how to integrate these effective preventive interventions into routine service delivery systems from health care and education to child welfare and mental health services. In addition, research tounderstand the role of substance use, abuse and addiction prevention as part of the Affordable Care Act and in regulatory efforts to affect substance use and other related problems is needed.Basic Research: The current Strategic Priorities recognize the importance of biological science to understanding substance use, abuse and addiction. However, the priorities underemphasize the critical role of social and behavioral science in understanding and addressing these problems. We suggest that a revision is made to include both Neuroscience and Social and Behavioral research in their own subsections of Basic Research.Neuroscience: Improve our understanding of the basic science of drug use, addiction, vulnerability to addiction, and recovery (SPR’s edits to NIDA’s draft strategic plan are highlighted in red.)Increase our knowledge of biological , behavioral, environmental, and developmentalfactors involved in risk and resilience for drug use and addictionIntegrating animal models, behavior, genetics, epigenetics, and other molecular biomarkers for drug abuse and addictionUnderstand the developmental trajectory of substance use, abuse, and addiction and individual heterogeneityImprove our understanding of brain circuits related to drug use, abuse and addiction at the cellular, circuit, and connectome levels, including:Normal development and function across the lifespan including mechanisms of reward, self-control, and conditioningDrug effects on neuroplasticity, neural structure, and circuit function across the stages of addictionNeurobiological correlates of recoveryNeural-glial, -immune, and neuroendocrine interactionsBetter define the interactions between substance use, abuse, and addiction and pain, including molecular, genetic, behavioral , and neural-circuit-related factors, to guide the development of alternate treatment strategies for pain patientsImprove our understanding of the interaction between substance use, abuse, and addiction and co-occurring conditionsElucidate the impact of mental health, HIV, HCV, pain, etc. on addiction;Understand molecular mechanisms of latent HIV reservoirs in the brains of substance- abusing populationsBiological processes related to substance use, abuse and addiction risk and resilienceand reactivity to preventive interventionsSocial and Behavioral Research: Research suggests that despite biological predispositions, the decision to use drugs is environmentally triggered, and that socio-cultural environments (e.g., policy, peers, family, communities) play pivotal roles in the initiation, maintenance, and desistence from drug use, abuse, and dependence. Further, evidence has demonstrated that the impact of preventive interventions on biological processes or predispositions is also important to study. We expect that there is an interplay of environmental and biological influences in the development of addiction. Understanding the relative contribution and mechanisms of change are critical to understanding the development of substance use, abuse, and addiction. Understanding the developmental and environmental influences on biological mechanisms will increase the likelihood that biological research will strengthen efforts at prevention and treatment to improve the public health.Increase our knowledge of social, environmental and developmental predictors of substance use, abuse and addiction.Increase our knowledge of interactions between biological mechanisms and social, environment and developmentally salient predictors of later substance use, abuse, andaddiction.Increase understanding of neurobiological changes in response to prevention interventions and messages.Determine the mechanistic effects of programs and interventions which will provide an evidence-base to guide efforts to refine and improve program components. Explorebasic, malleable conditions that promote or interfere with intervention effects.Increase understanding of interaction effects of stress and contextual factors on drug abuse risk.Expand research on the relationships between drug use, abuse, and addiction on communicable and non-communicable diseases.Clinical and Translational Science: Support the development of new and better preventive interventions and treatments. that incorporate the diverse needs of individuals at risk for the development of and those with Substance Use Disorders (SUDs) Treatment research is important but reducing the number of those who contract the disorder is also critical. In addition, treatment and prevention have some distinct operational, population assumptions, and likely mechanisms of effects that merit separate but substantial attention (Weisz, Sandler, Durlak, & Anton, 2005). We suggest separate sections on Treatment and Prevention Research.Treatment Research: Support the development of novel, evidence-based, treatment interventions including social, behavioral, cognitive, pharmacological, vaccines, and brain stimulation therapies (e.g., transcranial magnetic stimulation, direct current stimulation, etc.)Accelerate the identification of promising targets and ligands to accelerate new drug discovery and developmentAccelerate medications development for SUDsFocused development efforts on:Addictions without an FDA approved treatmentDetoxificationOverdose prevention or reversalAccelerating neurobiological recoveryAddressing comorbidities (MH, HIV, HCV, pain)Develop techniques to measure and improve patient compliance in clinical trialsIdentify measures other than abstinence that can reliably assess SUD treatment outcomes Identify biomarkers of addiction, resilience, and recovery to enable personalized treatmentUsing pooled data from previous evidence-based treatment trials, identify mechanisms and moderators of intervention efficacyPrevention ResearchIntegrate discoveries from the basic biological (e.g. neurobiological), psychological (e.g. emotional, behavioral, cognitive, and developmental) and social (e.g. social learning, peer network, and communications, laws and norms) sciences to develop and test innovative preventive interventions that specifically target underlying mechanisms in drug abuse risk.Research what are critical windows during childhood to adulthood that may produce the greatest effects for specific types of preventive interventions.Increase the translation of knowledge about basic biological, genetic, and neurobiological mechanisms underlying drug use and abuse to serve as indicators ofchange in preventive intervention research, and/or to help determine the intervention course (psychosocial, psychopharmacological) that is most likely to be effective for an individual given underlying biological mechanisms of action.Increase research to fill critical gaps in understanding the impact of preventive intervention on vulnerable populations including low income, people of color, youth in thechild welfare system.Increase research to determine the impact of preventive interventions utilizing new and emerging electronic communication technologies. In addition to efficacy of utilizing these technologies for delivery of preventive interventions, the reach (who accesses), and the usefulness of these modes of delivery for generalization and maintenance of intervention impact is needed.Increase research to identify malleable mediators and moderators of preventive intervention effects to better understand which interventions work best for whom and why, and what preventive components predict intervention effects to understand how to improve prevention effects for all.Increase research to understand what malleable underlying person or environmental conditions interfere with or promote intervention effects.Increase research to examine the impact of preventive interventions on the neural substrate level. An understanding of how an effective intervention can alter braindevelopment and function is critical for the field.Increase research to replicate effective prevention interventions in new populations and under different conditions to understand what contributes to whether the intervention continues to be effective or is less effective. Further, research is needed on the impact of fidelity, quality, and adaptation on the effectiveness of replications.Increase research on the combination of behavioral and biomedical preventive intervention.Increase research to incorporate understanding of individual differences in response to different types of persuasion and different types of drugs in preventive interventiondevelopment. This includes further culturally-sensitive and responsive research for understanding the needs of vulnerable and high risk populations.Increase research on embedding efficacious or new prevention interventions in health care organizations to examine the impact on health costs and a range of substancerelated outcomes at population level.Public Health: Increase the public health impact of NIDA research and programs: A substantial research agenda is needed on the complex processes through which evidence-based interventions are adopted, implemented, and sustained at the community level, with a strong orientation toward devising empirically-driven strategies for increasing their population impact. This agenda fits with recommendations in the National Prevention Strategy including the dissemination of community-based interventions that address health inequities, especially in inner-city neighborhoods and rural areas, the development, testing, and implementation of effective strategies to engage underserved populations, and the organization of representative, multi-sector community partnerships.Improve the understanding of factors that influence the integration of evidence-based basic science, prevention and treatment research findings into healthcare policy and practice (implementation science)Increase the understanding of how organizational, leadership, and fiscal factors influence the adoption and sustainment of evidence-based practices to prevent and treat substance use and abuse in key public service sectors (mental health, health, justice, child welfare)Improve the understanding of factors that influence the integration and sustainability of evidence-based basic research, prevention and treatment research findings into stateand local public health, behavioral health, education, and child welfare, and maternalhealth.Increase dissemination research efforts of evidence based prevention programs and policies to determine what works best, for whom and why so that programs and policies can be further refined to achieve optimal results to improve the public healthIncrease research to understand the needed elements of infrastructure development to ensure the capacity and necessary supports for large scale adoption, implementation and sustainability of evidence based preventive and treatment interventions.Increase research on training health care and other providers in prevention knowledge and practices.Increase research to understand the cost of effective preventive interventions as well asthe economic benefits that follow, to facilitate uptake and support for investing in prevention by policymakers and funders.Increase readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, new populations (elderly), changing healthcare landscape, emerging drug trends, etc.)Increase strategic partnerships with the community (academia, pharma, biotech, healthcare organizations, policy makers, etc.) to enhance the dissemination of evidence- based research findings into policy and practiceStrengthen focus on bi-directional translational researchScience Infrastructure: Enhance the national research infrastructure to support advancements in scienceAccelerate the development and utilization of advanced technologies (e.g. the President’s BRAIN Initiative), data repositories (e.g. Big Data to Knowledge (BD2K) initiative, new technology for intervention delivery, and statistical models to spur innovative researchDevelop a strategy to build a strong infrastructure (building both manpower and organizational capacity) to support the dissemination, diffusion and quality implementation of evidence-based prevention practices that range from screening and assessment of vulnerable populations and communities to the appropriate recommendations for prevention programming and monitoring.Improve training for the next generation of scientistsIncrease effective engagement and training in multidisciplinary research (informatics, engineering, computer science, chemistry, mathematics, physics, etc.)Increase the number of well-trained underrepresented scientists in the drug abuse and addiction field at all career levelsImprove mentoring of young scientistsIncrease effective collaborations in researchIncrease the transparency of research Increase effective data and resource sharing (big data, biorepositories, transgenic/optogenetic tools, data standards, etc.)Increase collaborations with other NIH Institutes and Centers (e.g. Collaborative Research on Addiction at NIH (CRAN)), Federal and State agencies, academic and industry partners, etc.Create opportunities for multiple federal agencies to collaborate in funding translational drug abuse prevention and treatment research; e.g., SAMSHA, ONDCP, OJJDP, CYF, MCH, etc.Increase opportunities for combining data from previous prevention and treatment trials and use innovative methods to integrate and analyze these data.Identify and implement strategies to improve the reproducibility of pre-clinical researchEnable efficiency and lower the cost of clinical trials via innovative statistical models, data standards, leveraging technology (e.g. electronic health records) and partnerships, etc.Develop and validate computational and systems-level analytics for integrating multi- dimensional data across the addiction trajectoryUnifying themes: A number of unifying themes that will be addressed across each of the domains listed above include:Promoting research that considers the impact of sex and gender on drug abuse and addictionUnderstanding the interrelation between preventive and treatment interventions affecting substance abuse and impact on other aspects of physical and mental health, social functioning, and productivityAddressing health disparities among underrepresented populationsUnderstanding the role of development across the life spanAddressing the treatment needs of adolescents and pregnant and post-partum womenAddressing the treatment and prevention needs related to common co-morbidities including HIV/AIDSAddressing the prevention needs of youth and high-risk populations.Understanding the implications of the changing drug policy environment (i.e., marijuana legalization at the state level)Understanding the developmental and contextual influences across all areas of research ReferencesBiglan, A (2015) The Nurture Effect: The Evolution of Behavioral Science, Psychology Today, 1/5/15.Campbell FA, Ramey CT, Pungello E, Sparling J, Miller-Johnson S. (2002) Early childhood education: Young adult outcomes from the Abecedarian Project. Appl Dev Sci, 6(1):42-57. Catalano, R. F., Fagan, A. A., Gavin, L. E., Greenberg, M. T., Irwin, C. E., Ross, D. A., & Shek,D. T. L. (2012). Worldwide application of the prevention science research base in adolescent health. Lancet, 379, 1653-1664.Clark DB, Cornelius JR, Kirisci L, Tarter RE. (2005) Childhood risk categories for adolescentsubstance involvement: A general liability typology. Drug Alcohol Depend. 77(1):13-21. Conduct Problems Prevention Research Group. (2014). Impact of early intervention on psychopathology, crime, and well-being at age 25. Am J Psychiatry..Hale DR, Fitzgerald-Yau N, Mark Viner R. (2014) A systematic review of effective interventions for reducing multiple health risk behaviors in adolescence. Am J Public Health.104(5).Hawkins JD. (2006) Science, social work, prevention: Finding the intersections. Soc Work Res. 30(3):137-152.Hill KG, Bailey JA, Hawkins JD, et al. (2014) The onset of STI diagnosis through Age 30: Results from the Seattle Social Development Project intervention. Prev Sci.;15 (Suppl 1):S19-S32.O'Connell ME, Boat T, Warner KE, editors. (2009) Preventing mental, emotional, and behavioral disorders among young people: Progress and possibilities. Washington, DC: National Academies Press.Sloboda, Z. (2012) Substance Use & Misuse, 47:1557–1568, 2012.Western B, Pettit B. (2010) Incarceration & social inequality. Daedalus. 139(3):8-19,146-147. Woolf SH. (2008) The power of prevention and what it requires. JAMA 299(20):2437-2439
Faces & Voices of Recovery is pleased to provide input on the 2016- 2020 draft strategic priorities as well as general recommendations that will sustain recent advances and accelerate discovery in addiction recovery research over the next five years. The following response reflects the views of the organization and membership as a whole.Suggested changes or additions to the list of strategic priorities, including emerging research needs and future opportunities that should be considered in the planChanges (underlined)Basic Neuroscience: Improve our understanding of the basic science of drug use, addiction, vulnerability to addiction, and the recovery process and increase our knowledge of biological, behavioral, environmental, and developmental factors involved in risk, resilience and recovery for drug use and addiction.Neurobiological correlates of recovery: Focus on the neuroplasticity properties with treatment and recovery supports that facilitate neural responses in recovery. How do environmental supports for resiliency enhance neural development in recovery?Improve our understanding of the interaction between addiction and co-occurring conditions and its impact on the recovery process. (With the shame and stigma associated with both addiction and mental health, is there a way to assess the differences in public perception, and the effect of addiction being seen more as a “choice”? Also what are the environmental andcultural differences leading to relapse, such as the right to refuse medication, over-prescribing of narcotics, beer sales, etc.)Support the development of novel, evidence-based, targeted prevention, treatment and recovery support interventions including social, behavioral, pharmacological, vaccines, and brain stimulation therapies (e.g., transcranial magnetic stimulation, direct current stimulation, etc.)Improve training for the next generation of scientists – including training on the Science of Addiction and Recovery (SOAR).Promoting research that considers the impact of sex and gender on drug abuse, addiction and the recovery process.Addressing the treatment, prevention and recovery needs related to common co-morbidities including HIV/AIDS.Identify measures other than abstinence that can reliably assess SUD treatment and recovery support services outcomes Identify biomarkers of addiction, resilience, and recovery to enable personalized treatment.AdditionsAddressing the needs of people seeking recovery in areas bereft of recovery supports (ie rural areas) such as the efficacy of online resources where there is no significant recovery community.Measure the presence, depth, and effect of stigma as a barrier to treatment and recovery, including perceived shame for relapse within the recovery community.The effect of marginalizing some types of treatment or pathways to recovery (specifically medication assisted treatment) within the recovery community.Additional research needs to be conducted to build the evidence base about the effectiveness of peer-delivered support and peer-delivered support services in both the mental health and addictions fields.More research is needed on matching individuals with the type of peer-delivered recovery support that best fits with their stage of recovery and their personal goals to improve our understanding of the most essential types of support at different stages of recovery. Factors such as age group, gender, self-identity, motivation to change, health and mental health status, and spirituality should be considered.Explore qualitatively how peer support and clinical care can complement each other.Examine people in recovery’s responses to peer support and how it influences recovery over time.Examine how integrating peer support workers contributes to aspects of the environmental context of a behavioral health program.Improve the rigor of research on the effectiveness of training programs for peer support workers, using control or comparison groups, and whenever possible randomized controlled trials.The scientific rationale for the changes or ideas proposed and the anticipated impact on advancing the science of drug abuse and addictionWhy Study Recovery?Recovery from substance use is a reality for millions of people worldwide.Addiction is a chronic disorder; addressing addiction and recovery requires that clinicians and researchers adopt a long-term approach.We know a great deal about addiction, but very little about recovery.Recovery is a lifelong process that may involve a succession of “stages” making changing demands on the individual.Most research on substance use adopts an ‘acute’ perspective to addiction, typically using short follow-up periods (e.g., 1 to 24 months).Therefore, most available data bear only on recovery initiation, a period that is short relative to the lifelong challenges of recovery.Little is known about temporal patterns of recovery over time or about predictors of long-term recovery (recovery consolidation and maintenance).Few studies provide data on outcomes beyond abstinence. Other outcomes of interest might include: housing and work status, quality of life, functioning, mental health status, and support networks.Anticipated challenges that will need to be addressed to achieve these prioritiesThe evidence base for peer-delivered recovery support services in behavioral health is growing and demonstrates that these services have a salutary effect and are an important component of the continuum of recovery support. To strengthen this evidence base, it is critical to take steps to improve the quality and methodological rigor of the research. We propose developing a national research agenda to better understand the nature, contributions, effectiveness, and cost-effectiveness of peer- delivered recovery support services.Appropriate benchmarks for gauging progress toward each recommended priorityFuture research must include greater detail and description of the peer role and peer qualifications.Future research needs to include more complete descriptions of peer-delivered services including recovery coaching, recovery community centers, telephone-based peer support; and how of the service/support elements being delivered (e.g., “one-to-one contacts to accompany peers to critical appointments,” “group sessions focused on stigma”). This includes more complete descriptions of the peers delivering services, including the demographic characteristicsof the peer support specialists/recovery coaches, their educational backgrounds, stage of recovery, and information about their experience, training, and credentials in delivering peer- delivered services.ConclusionIt is a critical time in the development of novel, evidence-based peer-based recovery support interventions. The Affordable Care Act (ACA) has afforded the opportunity for many recovery community organizations to explore funding from public and private insurers to provide peer-based recovery support services in community-based, non-clinical setting. Enhancing the scientific understanding of recovery and supporting the development and testing of interventions and services to reduce relapse and promote recovery from addiction will expand these opportunities for RCO’s. The key to this success is having the research that demonstrates positive outcomes of these interventions to meet funding eligibility requirements. This is a critical time for the field to have the evidence-base for peer support in addictions. Faces & Voices of Recovery also supports prioritizing research on cost savings and cost-effectiveness of recovery support services.Thank you for the opportunity to provide feedback on NIDA’s 2016 – 2020 Draft Strategic Plan

Basic Science, Clinical and Translational Science, Public Health, Infrastructure

NIDA Strategic Plan 2015Comments from the National Prevention Science Coalition to Improve Lives (NPSC)Translational Prevention Science SubcommitteeDr. Diana Fishbein, ChairThe question that the drug abuse prevention sciences seeks to address is “What works best (evidence-based practices premised on basic research), for who (moderation), why (mediation by malleable conditions) and under what circumstances (developmental, experiential and contextual factors). The following is geared toward this model. Basic Prevention Research to Guide Intervention Development (T1) Apply animal models to elucidate underlying mechanisms in psychopathology that portends drug abuse, transitions to drug abuse, and/or mechanisms in differential orientations to physical and social environments that influence risk. Design human laboratory or experimental studies to investigate whether neurochemical, structural and functional neuroanatomical, psychophysiological or other mechanisms observed in preclinical science can serve as important targets for the prevention of drug abuse in humans. Are neural substrates of novelty or sensation seeking, decision making, impulsivity, etc. identified in primate models amenable to change in response to psychosocial or environmental manipulations?Identify neurobiological underpinnings for differential susceptibility to environmental stressors or, conversely, differential responsivity to prevention programming.Determine the mechanistic effects of programs and interventions which will provide an evidence-base to guide efforts to refine and improve program components;Explore basic, malleable conditions that promote or interfere with intervention effects; i.e., study of moderation and mediation that accounts for changes at the neurocognitive or psychophysiological level that occur commensurate with behavioral change.Examine how neurobiological indices are related to the impact of interventions at critical or transition periods, including consideration of changing social contexts; e.g., studies of changing patterns of activation in cortical and subcortical circuits underlying emotional and cognitive processes in response to prevention messages, or recruited in the context of peer presence during decision making, etc.Conduct studies to ascribe a functional role to an epigenetic and/or genetic variant with respect to a particular aspect of drug abuse propensity. Identify epigenetic and/or genetic variant effects on behavioral responses to social inputs and interventions.If the genetic makeup sets the stage for responses to environmental input, can psychosocial interventions alter: a) genetic expression of activities in underlying substrates of risk traits and b) the behavioral phenotype? Will the outcome of this impact be sufficiently measurable in these markers?Account for the profound effects of adversity and severe and/or chronic stress on child brain development which, in turn, influences prospects for successful outcomes.Studies to understand mechanisms underlying impact of stressors and stress adaptations (physiological stress reactivity, coping, psychological status) on processes related to drug use onset, escalation and trajectories. Interaction effects of stress, genetic, and contextual factors on drug abuse risk. And does change in stress adaptations in part mediate intervention effects? If so, do interventions that effectively improve stress adaptations have potential to prevent drug abuse?Expand understanding of drug abuse to addictions, in general, and how each of these addictions might be related to each other and underlying processes.Explore interplay of implicit and explicit processes as determinants of drug misuse.Explore how deviant social networks might impact drug use decisions in real time.Explore the extent to which group identification is associated with drug abuse through reputation based collectives or actual peer group interactions. Intervention Implementation and Evaluation (T2)Integrate discoveries from the basic biological (e.g. neurobiological), psychological (e.g. emotional, behavioral, cognitive, and developmental), social (e.g. social learning, peer network, and communications), and environmental (geographical locations, access) sciences to develop and test innovative preventive interventions that specifically target underlying mechanisms in drug abuse risk. Integrated data sets account for more of the variability in intervention response than the use of one set of variables alone.How can the assessment of environmental-neurobiological relationships contribute to the design of interventions that impact at critical points in the developmental trajectory to alter risk status? Determine the types of interventions and specific program components that normalize or improve neurodevelopment in ways that lead to desirable outcomes (e.g., reductions in psychopathology, school failure, psychiatric symptoms, drug abuse, etc.).Development and/or application of new-generation designs, technologies and methodologies to identify neural substrates amenable to prevention interventions and to assess change over time.Indicate those critical windows during childhood that may produce the greatest effects for specific types curricula and program components based on developmental appropriatenessWhat are the critical developmental or transition periods for change; e.g., changing patterns of activation in the HPA axis, cortical and subcortical circuits underlying emergent emotional and neurocognitive processes in response to interventions?What are the critical stages of development during which psychosocial stress and other external influences (e.g., peer presence) differentially exert their effects?Develop and evaluate the effects of innovative educational programs targeted to various learning needs of children on neurodevelopmental markers of successful outcomes.Explore a “personalized” approach that focuses upon individual or subgroup level conditions and characteristics that influence level of liability to drug abuse. The frontier in prevention research is understanding the individual differences in liability to improve prediction and early risk identification. This tact will further lead to interventions with an appropriate level of intensity and quality that specifically target underlying mechanisms that trigger or exacerbate drug abuse liability and thereby maximize efficacies and cost/benefits. Practice-oriented Phase (T3) Research to test the degree to which efficacy and effectiveness trial outcomes can be replicated under real world settings, focused on adoption, adaptation, and disseminationStudy the characteristics of implementers, organizations, and systems that maximized adoption and maintenance of prevention and cessation programming.Study the types of adaptations that can be made without losing program impacts (e.g., through understanding “active” ingredients of programming) Scaling Up and Wide-Scale Implementation and Adaption (T4): Increase the public health impact of NIDA research and programsResearch has confirmed the limited extent to which evidence-based interventions have been broadly and effectively implemented and this indicates much progress is needed to achieve population-level impact. A substantial research agenda is needed on the complex processes through which evidence-based interventions are adopted, implemented, and sustained at the community level, with a strong orientation toward devising empirically-driven strategies for increasing their population impact. This agenda fits with recommendations in the National Prevention Strategy including the dissemination of community-based interventions that address health inequities, especially in inner-city neighborhoods and rural areas, the development, testing, and implementation of effective strategies to engage underserved populations, and the organization of representative, multi-sector community partnerships.Strengthen focus on bi-directional (back and forward across the spectrum, not just T1 to T2) translational researchScience Infrastructure: Enhance the national research infrastructure to support advancements in scienceActively pursue the Institute of Medicine strategy (IOM, 2009) on prevention, which has had a marked impact on prevention science and policy. Develop a large-scale national research program based on the input of a transdisciplinary group of basic and prevention researchers, clinicians, and practitioners. While broad, this can be achieved by assembling a core group of experts from multiple disciplines and institutions to apply a wide range of perspectives and capabilities toward understanding and reducing the drug problem.Develop a strategy to build a strong infrastructure (building both manpower and organizational capacity) to support the dissemination, diffusion and quality implementation of evidence-based prevention practices that range from screening and assessment of vulnerable populations and communities to the appropriate recommendations for prevention programming and monitoring. “Institutionalizing” evidence-based practices in school systems and communities nationwide.Exploring ways in which primary care physicians and pediatricians can assess and attend to children or families exhibiting signs of liability, without stigma or official reporting (except in the presence of imminent harm).Implement comprehensive “menus” of evidence-based programs and services in high poverty neighborhoods, as directed by the community’s assessment of needs. Programs and policies recommended by experts are well-established and evaluated and could be made available on a large-scale basis. Some of these programs and policies serve to build self-regulatory skills in individuals that increase resilience against drug-related problems, while others work more universally to shift norms in high risk areas to promote mental and physical health. On a population-wide level, this strategy would include the establishment of programs for community-level investment (e.g. parks, painting and fixing dilapidated buildings, accessible mental health and academic services, etc.) that inculcates positive work, health and skills. Ongoing research efforts to apply rigorous evaluation criteria to determine what works best, for whom and why so that programs and policies can be further refined to achieve optimal results for greater numbers. This strategy would eventually lead to the institutionalization (nationalization) of these programs and policies in communities and schools, particularly those most in need.Create a website and dynamic listserv that enable people and organizations at the state and local levels to communicate and collaborate. A website that enabled anyone to ask critical questions about prevention and to provide answers to those questions could create a large, “federation” of problem solvers who could exchange information about what is working in ways that would spread knowledge much more quickly than occurs through traditional methods. Through a new generation of media campaigns, increase public understanding of the need for and consequences of nurturing families and schools. These newly-designed campaigns should target (appeal to) areas and individual-level characteristics (e.g., sensation-seeking, impulsivity, etc.) that have been shown to be at particular risk for drug abuse. Also, these ads may disseminate information on evidence-based preventive interventions to familiarize people with new school- and community-based approaches. Rather than messages focusing centrally on drug abuse, they should demonstrate ways in which reducing conflict and coercion in these environments, reinforcing prosocial behavior, and limiting opportunities for experimentation with problem behaviors will prevent substance use and most other problem behaviors. Several decades of ads and a host of other informational campaigns were needed to eventually significantly reduce cigarette smoking; the same strategy is needed here. To move evidence-based interventions into practice, create opportunities to fund innovative methods grants in the area of implementation/translational science. Create mechanisms and concrete opportunities to translate research findings for policy-makers and the public.Support student and early career training programs in translational drug abuse prevention and intervention.Create opportunities for multiple organizations and institutions to collaboratively conduct cross-cutting, integrative research.Create opportunities for multiple federal agencies to collaborate in funding translational drug abuse prevention and treatment research; e.g., NIH, SAMSHA, ONDCP, OJJDP, etc.Require grantees to demonstrate practice and policy relevance in applications beyond just their obligatory “significance” sections.Unifying themes:Prevention – proactionDevelopmentalContextual TransdisciplinaryTranslational – from T1 to T5, leaving nothing outDisparities, adversity, inequalitySex differencesEarly intervention – starting prior to conception
Thank you for the opportunity to comment on your upcoming NIDA 2016-2020 Strategic Plan. We wish to applaud your continued efforts to remain at the cutting edge of research and practice in the field of substance use disorders and treatment. In particular, we support the following:Basic Neuroscience: Neurobiological correlates of recovery and drug effects on neuroplasticity. It is clear that repetitive behaviors and overlearning are a significant cause of the behavioral process of addiction. Consequently, there is a need to better demonstrate the behavior and cognitive practice that is needed to establish long term recovery. This is particularly relevant in the context of the recent push to expand opioid assisted treatments. This expansion leads tothe perception that medication alone is addiction treatment (for example, physician office based buprenorphine without required behavioral treatment). This is problematic in that medication cannot create the same neuroplastic changes as behavioral practice.Clinical and Translational Science: Accelerating neurobiological recovery. With the expansion of opioid replacement approaches, there would be an expected delay in the establishment of baseline neurochemistry. For example, as long as tolerance to external opioids is maintained, one would not expect to see changes in the volume of neurotransmitters or receptors. With shrinking lengths of stay it is critical to increase the rate of neurobiological recovery, so that treatment gains may be maintained.Public Health: Response to emerging health priorities. This is a critical area and should be expanded and broken into two key areas: expansion of marijuana and the opioid overdose epidemic.Marijuana: With the rapid movement to legalize marijuana, there has not been adequate time to develop research on the side effects of marijuana, proper dosage and delivery for any medicinal purposes, and development of research on medicinederivatives (Marino! etc.). Research on the effects in states where legalization has already occurred would be helpful to determine the role of legalization, if any, on the rates of addiction. This is particularly important since marijuana has a known role as a gateway drug, particularly if started in youth.Opioids: The opioid overdose epidemic requires immediate investigation to determine causes and tools needed to interrupt the cycle of addiction. The proposed solutions have disproportionately focused on administrative and medicinal solutions. This is counterintuitive to suggest that we can prescribe our way out of a prescription opiate epidemic with prescription opiates. The opioid epidemic is exacerbating at the same time the prescription opioid medications are proliferating, increasing availability via diversion and excess prescribing. Research needs to consider the role of opioid treatments in this problem and solution. Further, as psychosocial treatments have diminished over time, there has been an increase in rates of addiction and incarceration.Science Infrastructure: Increase the number of well-trained scientists in the addiction field. We agree that there is a need for increased availability of trained scientists with an interest in addictions. The availability of funding for skilled research is important in the identification of evidence based practices which will yield the best effects.We also notice that there has been a significant change in the types of goals when comparing the prior strategic plan with the current strategic plan. Specifically, the current strategic plan is almost exclusively medication and biology focused (neuroscience, medications, etc.). This is in sharp contrast to the prior strategic plan which was primarily focused on behavioral interventions (prevention services, treating comorbid disorders, matching approach to motivation, addressing relapse triggers etc.). This sharp change suggests the devaluation of psychosocial approaches in the context of a menu of treatment options. While biologically focused interventions are valuable, it should not be addressed to the exclusion of psychosocial approaches.In this light, we would like to propose the following additional areas of research:Research on Client Medication Matching: Most research has focused on how treatment may be assisted by the addition of certain medications. More research is needed on client matching criteria. Specifically, guidance is needed on who is most appropriate for methadone, buprenorphine or naltrexone, as well as who is not appropriate.Prevention Services: Additional guidance is needed on the effective prevention practices, particularly surrounding the use of fear based approaches, which have been proliferating despite research indicating that it is not effective and can increase substance use, especially in youth. As there are more overdoses, and loved ones who are motivated to help others, it is critical to have clear guidance available so that they can readily access effective evidence based approaches to prevent others from facing addictionResidential Treatment: In recent years there have been serious cuts to the funding, availability and length of stay for licensed residential treatment. Epidemiological research is needed to examine the decline of availability of licensed residential treatment services as it relates to the increase in the rates of addiction and overdose deaths. If the level of care that is designated for the most severe substance use disorders is reduced in availability or duration, it should not be surprising that there is an increase in the deaths which are associated with the most severe disorders.Implementation of Parity: Research is needed to examine the implementation of the Mental Health Parity and Addiction Equity Act. Specifically, what actions are being taken onthe state level and local levels to ensure compliance with the federal law? A compilation of tools and best practices to support implementation would be very valuable.Implementation of Medicaid Expansion: Research is needed to examine the effects of the implementation of Medicaid expansion. This would examine how states with Medicaid expansion compare with states that do not have Medicaid expansion. Specifically, it would be valuable to examine treatment availability (number of treatment beds available in each level of care) and length of stay in treatment (well known as the number one predictor of treatment outcome), as compared to overdose rates in states with or without Medicaid expansion.Screening Brief Intervention and Referral to Treatment (SBIRT): In addition to the need for trained scientists, the field is in need of proper tools for the training of physicians to screen and refer to treatment. Research on the tools, best practices and outcomes for SBIRT would help to make these skills more widely utilized and implemented. This is particularly important inlight of the increased utilization of prescription drug monitoring programs, which encourage the discussions surrounding substance use and the need for warm handoff to treatment.Workforce Development: The specialty field of substance use disorder treatment faces significant workforce challenges. Research is needed in how to attract, develop and retain a skilled workforce in the treatment of substance use disorder. This may include training materials as well as best practice guides containing the tools and procedures to expand the specialty treatment workforce.Again, we thank you for the opportunity to comment on the strategic plan and we are happy to be a part of the dialogue to continue to advance addiction science for the coming years. This work is lifesaving as well as desperately needed for the families for those whose loved ones are struggling with this disease.
This document is the Community Anti-Drug Coalitions of America's (CADCA) response to the National Institute on Drug Abuse's (NIDA) request for information regarding the 2016-2020 update oftheir Strategic Plan (RFI NOT-DA-15-005).CADCA has been successfully representing and promoting coalitions, community-based problem solving,and population-level substance abuse prevention efforts since 1992. As a member-based, not-for-profit, CADCA provides coalitions and their communities with support and services relating to all aspects of community-based substance abuse prevention. These services range from training, technical assistance, and the dissemination of best practices and research, (through its National Coalition Institute) to actively promoting and advocating for federal and state policies and practices that increase the effective use of community-based, universal prevention. CADCA currently serves over 5000 coalitions located in the United States and 18 countries around the world.The Draft Strategic Plan included in the RFI is a comprehensive and sound approach to the role thatNIDA should take in substance abuse prevention. Clearly NIDA recognizes the variety of substance abuse priorities across the Institute of Medicine's continuum of care model.CADCA's comments focus on the emphasis that Universal, Selective, and Indicated interventions should play in a comprehensive approach to prevention. CADCA's comments are organized by the Draft Strategic Priorities outlined in the RFI as follows:NIDA Priority: Basic Neuroscience: Improve our understanding of the basic science of drug use, addiction, vulnerability, to addiction, and recovery.NIDA Sub-priority: Increase our knowledge of biological, behavioral, environmental, and developmental factors involved in risk and resilience for drug use and addiction.The effectiveness of universal, selected and indicated interventions in a complete model of prevention is determined to a great extent by the science linking broad environmental conditions to large group, smaller group, and individual behaviors. A complete model of prevention requires a thorough understanding of how macro-level conditions interact with individual level processing as described inthe social-ecology model. While spending on environmentally-based approaches has been decreasing, there is a growing body of research clearly indicating that environmental approaches are highly effective. Environmentally-based approaches delay the initiation of substance use which decreases the likelihood of addiction. Focusing specifically on environmentally-based prevention also yields major economic dividends. The savings per dollar spent on substance abuse prevention can be substantial and range from $2.00 to $20.00 (Swisher, Scherer & Yin, 2004). Miller and Hendrie (2009) indicate that some prevention efforts result in cost-benefit ratios of more than 30:1. Investing in prevention yields savings and reduces economic and healthcare burdens (National Institute on Drug Abuse, 2007). NIDA and NIAAA have invested heavily in prevention science and have focused efforts to understand the factors at the school, family and community levels that make substance more or less likely for a given population. Based on both the significance of Prevention and the decreasing funds available for its implementation, CADCA recommends that a sub-priority be created that is dedicated solely to environmentally-based Prevention. This would help demonstrate and clarify NIDA's long standing commitment in this area.Recommendation: Increase our knowledge of how environmental factors relate to biological, behavioral, and developmental risk and resilience for drug use and addiction.NIDA Sub-priority: Drug effects on neuroplasticity, neural structure, and circuit function across the stages of addiction.Two behavior categories have gained increased significance over the past 5 years relating to this sub priority. The first is the growing issue of marijuana exposures. While exposures have increased and have serious consequences for all age groups, these exposures were particularly high for adolescents. According to the Rocky Mountain Poison Center and the American Association of Poison Control Centers, unwanted exposure to marijuana has increased for all age groups. However, the increase from 2006 to 2013 was 95% for adolescents between the ages of 13 and 17. For all age groups in Colorado, marijuana-related exposures increased 89%, while national marijuana-related exposure increased 32% during this same time (Rocky Mountain HIDTA, 2014). Furthermore, increased access to marijuana in certain states is strongly linked to the number of emergency admissions and illnesses. One primary areaof concern for emergency episodes involves edible marijuana. Currently there is a paucity of research on how increased medical emergencies related to marijuana correlates to addiction and how marijuana related exposure impacts biochemical and neurological functions (http://www.medicalnewstoday.com/articles/285202.php). Therefore it is important to better understand how second hand exposure as well as various drug ingestion behaviors impact the likelihood of addiction and other negative consequences.CADCA therefore recommends a research priority that specifically addresses both marijuana-related emergencies and marijuana-related exposures.Recommendation: Drug effects of both marijuana-related emergency episodes and marijuana-relatedexposures on neuroplasticity, neural structure, and circuit function across the stages of addiction.NIDA Sub-Priority: Improve our understanding of the interaction between addiction and co-occurring conditions.Another important research area under this priority involves the impact of electronic nicotine delivery systems (ENDS) on human functions through both direct exposure and indirect exposure. While use of ENDS among youth has tripled from 2011 to 2013 (Bunnell, et al.; 2014), there is little scientific data regarding the impact of its use (Callahan-Lyon, 2014), including its interaction on addiction or co occurring conditions.Due to substantial increases in exposure and use of ENDS, combined with the paucity of research in these areas, CADCA recommends that the issue of addiction to co-occurring conditions focus on both marijuana (see above) and e-cigarettes.Recommendation: Improve our understanding of the interaction between addiction and co-occurringconditions particularly relating to marijuana and e-cigarettes.NIDA Pri.ority: Clinical and Translational Science: Support the development of new and better interventions and treatments that incorporate the diverse needs of individuals with Substance Abuse Disorders (SUDS).Complex community health problems, like substance use and abuse, require comprehensive,collaborative solutions in order to achieve benefit for the entire community. "As the field of prevention has matured, it has been recognized that any single strategy is unlikely to succeed and a reinforcing set of strategies has the greatest potential to reduce use" (Johnson et al., 2007, p. 229). Substance use and abuse is influenced at multiple levels and as such interventions must be broad-based, comprehensive and seek change at multiple levels (Sorensen, Emmons, Hunt & Johnston, 1998). NIDA has long supported research on comprehensive, community-based approaches and should continue to do so. While research in the past 5 years has offered much to the field there are still two primary challenges. First, there is still a paucity of community-level, comprehensive approaches that have formally been declared as "best practices". This leads many well-meaning prevention specialists to over-rely on either post diagnosis approaches to substance abuse or indicated and selected approaches to prevention.Research support from NIDA would help solidify the scientific role that universal prevention can play in a population. In addition, research to guide practitioner use of these strategies and how to combine them in ways to achieve maximum benefit for the smallest cost are also needed. Additionally, while there is much focus on single interventions and their impact, more research is needed on the synergy thatoccurs when a comprehensive set of strategies working at multiple levels of influence are implemented. It is also important to support new and innovative approaches to universal prevention that may foster adoption of this approach. Local community members may not fully understand the intricacies of universal prevention, so they may have trouble implementing these approaches with fidelity. Implementing universal intervention strategies without fidelity is detrimental to the prevention movement because lack of fidelity decreases the potential impact of the strategies and may reflect poorly on the field.CADCA recommends that a sub-priority area focus on solidifying the scientific value of promisinguniversal approaches to prevention and increase the likelihood of successful implementation. Recommendation: Support the development of promising, evidence-based, universal prevention strategies, including practices relating to innovative implementation that enhance effectiveness.NIDA Priority: Public Health: Increase the public health impact of NIDA research and programs.Sub-priority: Increase readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, changing healthcare landscape, emerging drug trends, etc...)Research demonstrates that coalitions engaging in comprehensive, environmental strategies aresuccessful at bringing about community changes on a variety of issues (Sorensen, G., 1998; National Research Council, 2004; Hingson et al., 2005; Yang, E et al, 2012; Nargiso, J., 2013). Communities with active coalitions engaging in best practices are better prepared for changes in the substance abuse landscape. However, there are two primary challenges to a coalition's success. One is the relative paucity of research on evidence-based best practices for substance abuse prevention coalitionfunctioning. Another is the ability of coalitions to adapt existing best practices. Increasing the number of research projects on effective substance abuse prevention coalition processes would foster the development of best practices that can be integrated into everyday coalition work.Recommendation: Increase readiness to respond to emerging public health priorities by creating aseries of evidence-based best practices for coalition development and capacity. (opioid overdose epidemic, potential consequences of marijuana legalization, changing healthcare landscape, emerging drug trends, etc...)NIDA Sub-priority: Improve the understanding of factors that influence the integration of evidence based research findings into healthcare policy and practice.The relationship between substance abuse and other community health issues has long been recognized in the research. Substance abuse has been linked to child abuse, poor school performance, mental health issues, violence, a range of personal health issues, etc... While these links are generally understood by health professionals, there is a gap in practices to resolve these issues at the universal prevention level. Leveraging resources through the development of reliable and valid practices for nexus issues would enable coalitions and other groups to more effectively and efficiently manage social health issues at the community-level. There are two primary areas of research that would help coalitions manage these nexus issues. The first involves the best practices for disseminating information regardingthese nexus issues. Improving communication capacity between researchers and practitioners would greatly enhance how theory is implemented in the field. This involves at least some clarification regarding how communities should manage risk factors for nexus issues as opposed to individual issues. The next involves how to leverage resources at the community level to engage the community in developing and maintaining universal prevention for these nexus issues.Recommendation: Improve the understanding and communication of nexus-based risk factors in order to improve the ability of healthcare professionals to work with communities towards the full integration of evidence-based research findings and strategies that result in healthcare policies and practices that address multiple health issues simultaneously.NIDA Priority: Science Infrastructure: Enhance the national research infrastructure to support advancements in science.NIDA Sub-priority: Improve training for the next generation of scientistsAccording to the Bureau of Labor Statistics, the field of public health is expected to grow more than 20%, and epidemiology is expected to grow 10% over the next eight years( http://www.bls.gov/ooh/community -and-social-service/health-educators.htm#tab -1). Community based universal prevention has gained recognition as both an effective and efficient element in a complete prevention system (Yang, E et al, 2012). With this recognition is a growing need for researchers who specialize in developing community capacity to engage in universal prevention strategies.Recommendation: Improve training and mentoring opportunities for the next generation of scientists,including those who specialize in community-based, universal prevention.NIDA Sub-priority: Increase effective collaborations in research.Community-based participatory research (CBPR) is a collaborative approach to research that engages community members and researchers as equal partners in all phases of the research process (Israel, Schulz, Parker, & Becker, 1998; Foster-Fishman, 2009). CBPR more appropriately responds to the needs of communities because it engages community members in defining the problem, selecting the solutions, controlling the implementation and owning the knowledge generation process. An understanding of the community context is imperative in solving local problems and the strategies and methods selected by the community are more likely to fit the local context (Foster-Fishman, 2009; Katz, 2004). Additionally CBPR supports Type II Translational Research by making research and action more culturally competent, relevant, and useful (Foster-Fishman, 2009). This approach to research answers questions that fit practitioner needs and takes into consideration more of the factors and conditions in which interventions are implemented in real world setting; hence interventions that come out of CBPR studies are more likely to have buy-in and utility to the community.Recommendation: Increase the use of Community-based participatory research and evaluation.NIDA Sub-Priority: Increase effective data and resource sharing (big data, biorepositories, transgenic/optogenetic tools, data standards, etc...)Accurate, timely information is the cornerstone of prevention efforts at all population levels, including national, state, county, or local community. Each population level has its own unique challenges and resources and there are three primary priority areas that would greatly enhance current prevention efforts.A complete prevention model requires a variety of approaches to addiction covering the entire spectrum of behavior and motivation. This is true regardless of which holistic prevention model is being used (for example 10M, or Health Pyramid). Within each model are various types of prevention serving different populations ranging from entire populations to individuals. While there is agreement that a complete prevention model addresses the entire spectrum of audiences, there is less agreement as to the appropriate balance of prevention types that are most effective. It is therefore important to better understand how current prevention efforts attempt to find this balance. An assessment of current approaches and levels of prevention will help the field better understand how to achieve an optimal balance of strategies. A monitoring system would delineate which aspects of prevention research are being funded and which areas could use more funding. For example, while research on preventioninterventions is well funded, more monitoring would help ensure that efforts to fund translational research to support practitioner adoption of these interventions occurs.Recommendation: Develop and maintain a prevention research monitoring system in order to assessstrengths and gaps towards the development of a holistic national model for prevention.Another critical data piece for prevention is the ability of local communities to access local data on emerging trends. In fact, "readiness" described as a priority (see above) is directly related to the availability oftimely information that is presented in a useful format. Not only is local data critical as a tool for responding to emerging trends, it is also critical in tracking the effectiveness of selected strategies. Perhaps the biggest challenge to local coalitions and other local substance abuse efforts isthe availability of local data. While there is a plethora of archival data collected by various federal, state, and county agencies, all too often this data is relatively inaccessible for local communities seeking data directly addressing their smaller, local communities. There is a tendency to aggregate local data sources once it is in the data system or data reporting systems are not capable of disaggregating local data when it exists.Recommendation: Increase effective data and resource sharing applicable to all population levels,including at the local community level.It is a pleasure and honor for CADCA to offer these recommendations on behalf of more than 5,000 coalitions nationwide. NIDA has always been a powerful force in community drug prevention and CADCA is proud to continue our special relationship with your organization that helps keep communities safer and drug free. We provide the above comments as a way to strengthen our collective understanding of the factors that make substance use and abuse less likely and less severe on a population-wide level in our communities.

Clinical and Translational Science, Basic Science, Infrastructure, Public Health

The Society for Adolescent Health and Medicine (SAHM) is responding to the Request for Information (RFI) (NOT-DA-15-005) that is seeking public input on research priorities to be included in NIDA’s new Strategic Plan. SAHM is a multidisciplinary organization committed to improving the physical and psychosocial health and well-being of all adolescents through advocacy, clinical care, health promotion, health service delivery, professional development and research. We greatly appreciate the opportunity to provide our perspectives as researchers, practitioners, and advocates for the health of adolescents and young adults.The current draft strategic priorities are overall quite comprehensive and exciting. We hope that the new Strategic Plan will include a special focus on adolescent development and research on adolescents and young adults. We also have several broad suggestions for consideration:Around the need identified to “harness the latest research technologies and apply to the ever- evolving substance abuse landscape,” we would suggest clarifying that there is need for both novel research methods (using ever evolving technologies) as well as development and testing of technology-based interventions to address substance abuse. Finding innovative strategies using technology to connect with hard-to-reach populations, including youth living in vulnerable social contexts, is certainly a key priority area in adolescent health research.Many adolescent health researchers are living in states where medical and recreational marijuana use has been legalized, and we anticipate this legislation to continue to expand in the United States. We clearly need more science on marijuana pharmacology effects and risks in all of its new forms, and need the scientific community’s support to engage in this research, given the escalating availability, decreased perceived risk in adolescent populations, and new industry promoting the drug. Currently, this is only listed under public health not in the science domains.A third suggestion is to be more explicit about the need to engage more scientists and health providers to be aware of evidence based prevention methods and effects of prolonged drug use in children and adolescents more broadly such that substance use research is more integrated into basic, clinical and public health scientific inquiry. In addition to focusing on producing scientists highly trained in drug abuse research, we also need health providers and community stakeholders who can inform the science and incorporate the translation of science into evidence-based practice. While this stakeholder engagement is evident in the research priorities, it would be beneficial to include developing the capacity of health professionals and community partners as part of the training priorities.We agree that addressing health disparities is best infused in all domains. We would also suggest more specific focus on health disparities research. Currently there are no national efforts to look at why despite having a higher percentage of what are considered risk factors for drug abuse and addiction, African American youth use less drugs and alcohol than other groups. This is not explained by economics. The concern however is heightened in young adulthood when use spikes in African American young adults and reaches, and sometimes exceeds, national averages. This is at a time when other age-race groups in the US are moving toward lower risk of initiation. Understanding this epidemiology and the trajectories for youth of diverse backgrounds with careful attention to the mechanisms for these disparities should help improve strategies to prevent adolescent drug use and define what new risks emerge for this population in young adulthood that changes their trajectory.Finally, we would recommend a greater emphasis on disseminating what works and strengthening implementation and dissemination science. A model for this is the Office of Adolescent Health’s Teen Pregnancy Prevention Initiative, where great emphasis has been placed on increasing replication, adaptation, and dissemination of evidence-based interventions along with testing promising practices. While we recognize that this may step into service provision, we believe there is critically important and rigorous science needed to understand implementation and dissemination strategies. Certainly intervention proposals should be attentive to the issues of dissemination and scaling up of these interventions.We greatly appreciate the opportunity to provide our organization’s perspectives on these draft strategic priorities. Please do not hesitate to reach out to us with any further questions or clarifications as the NIDA staff and leadership develop this new Strategic Plan.

Clinical and Translational Science, Infrastructure

Big Data My lab has become increasingly involved with the challenges of “big data” through our escalating use of next generation sequencing (NGS), both RNA-seq and ChIP-seq. As can be gleaned from our initial publications (please let me know if you’d like me to send along PDFs), we have already generated interesting datasets utilizing both methods and—importantly— overlaying information on RNA expression with that of histone modifications and non-histone chromatin regulatory mechanisms. We have a substantial amount of additional data that is now in preparation or under review, which further establishes this experimental approach. In our drug abuse models alone, we have generated on the order of 100 terabytes of sequencing data with much more in the offing.To analyze this extremely large and complex dataset, we have recruited a faculty-level bioinformatician who, in turn, employs two masters-level bioinformaticians. This group of three full-time computational investigators devotes themselves virtually full-time to the NGS data generated by my lab alone, roughly half of which concerns drug abuse data (the other half is focused on depression). These individuals are very expensive. Faculty-level bioinformaticians command higher salaries than biologically-oriented faculty, and masters-level bioinformaticians command ~50% higher salaries than PhD-level biologically-trained postdoctoral fellows!It is simply impossible to provide this amount of bioinformatics support in R01 grants. It is even difficult to fully fund it from P01 or P50 grants. Thus, I am only able to deploy this amount of bioinformatics resources because much of the support comes from institutional funds, which are limited and non-recurring. And the three individuals I have are not enough. I should employ a fourth person full-time to analyze my lab’s NGS data, but I do not have the funds to do so.A small but increasing number of neuroscience graduate students and postdoctoral fellows have sufficient quantitative aptitude and interest to become partly proficient in bioinformatics. This is a positive evolution, as ultimately we’ll need a workforce of individuals who are equally comfortable in the biological and bioinformatics domains to drive this research. However, this would not take the place of true bioinformaticians, as the analytical demands of NGS data require individuals with advanced training in this area, which will not be accessible for the vast majority of biologically-oriented researchers.Proposed solutions:Two innovations are need: 1) building the workforce of appropriately trained individuals, and 2) devising schemes to enable PIs to pay for those individuals from research grants.Provide administrative supplements to R01s, P01s, P50s, etc. to support additional robust bioinformatics support. Rigorous criteria can be applied so that such funding is offered only to those labs with the infrastructure that knows how to use the funding effectively and efficiently.Provide administrative supplements, or designated F or K series grants, to biologically- trained graduate students and postdoctoral fellows to gain more experience in bioinformatics. Review criteria will need to be modified, because such grants do not do well in today’s study sections.Provide administrative supplements to offer partial support for masters- or PhD-level bioinformaticians to enable them to gain more experience in biology.Consider novel T32 or R25 grants to focus on training a mixed biological-bioinformatics workforce. However, such grants must be modified to include masters-level bioinformaticians, since this category of individual represents a large fraction of today’s bioinformatics workforce.Constitute study sections that provide appropriate review of bioinformatics-oriented grants. Today, a grant focused on sophisticated bioinformatics analysis of brain datasets related to drug abuse, for example, will be killed in biologically-oriented study sections because the members don’t understand or appreciate the value of the proposed work, while they will also be killed in bioinformatics-oriented study sections because brain data are considered too messy for hardcore bioinformaticians.Maintaining InnovationWhy do some PIs continually introduce new approaches, methodologies, and theoretical frameworks into their research, while others perseverate in using the same experimental approaches addressing the same biological questions? I think this is a basic characteristic of a PI and is not something that can be easily taught. This is not age-related: some of our oldest investigators remain the most innovative (demonstrably), while some of our youngest investigators are the least innovative. The only way that NIH can influence this process is to:Require innovation as a crucial ingredient in all grant reviews. This is already happening but should be accelerated further. This will require further changes to NIH study sections to ensure study section membership of individuals who themselves innovate. Today, too many study sections lack a critical mass of such individuals.Require innovation as a crucial ingredient in all training-related grants. Successful T32s, R25s, F series, and K series grants should demonstrate established capacity for innovation and those that don’t should be defunded. Again, this will require improvements to study sections.In addition, innovation costs money. It is more expensive to use newer methods than to rely on stale methods. As one example, it is simply far less expensive to inject a neurotransmitter agonist or antagonist into a given brain region and study locomotor sensitization than it is to inject viral vectors into a given brain region of a genetically modified mouse or rat and study drug self-administration behavior. Too many grants still do the former; this approach is flawed because an agonist or antagonist never has perfect specificity and such a locally-injected agent will affect its target in all cellular elements within the injected region (neuronal cell bodies, nerve terminals, and axons of passage as well as a host of non-neural cells). Likewise, self- administration assays, particularly those that examine long-lasting effects of drug exposure on extinction, relapse, and related measures are far better models of drug addiction but are also far more labor-intensive and expensive. As another example, it is far less expensive to analyze levels of one or a few mRNAs or proteins by use of qPCR or Western blotting than to obtain unbiased measures through NGS or proteomic approaches. While there are several reasons why labs perseverate in using stale, limited methods, the biggest is money. NIH can help by:Increasing the size of modular R01s. The $250K cap has not changed in over a decade. (Perhaps larger budgets should be specifically designated for innovative approaches.)Avoiding administrative cuts. Study sections approve budgets that are required to get the proposed research done. Administrative cuts prevent a PI from achieving this goal and, oftentimes, innovation suffers the most because PIs can make progress more easily (publish more papers) by using older methods.Rewarding innovation. Innovation should be a greater part of the review process (see above). In addition, perhaps there are ways to provide administrative supplements to labs that demonstrate success in innovation.A personal note:I think my lab innovates a lot. As just some examples, in terms of experimental approaches, we have been among the first to use viral-mediated gene transfer in brain, genetic mutant mice with inducible and cell-type specific mutations, RNA-seq and ChIP-seq on discrete brain regions, and optogenetic tools in drug abuse and depression models. Our most recent innovation is the development of a method to target a single type of histone modification to a single gene within a discrete brain region in vivo (Heller et al., Nat. Neurosci., 2014), thus revolutionizing the quality of proof to establish epigenetic mechanisms of drug abuse. In terms of biological findings, we have been among the first to demonstrate the involvement of post-receptor intracellular signaling cascades, neurotrophic mechanisms, transcription factors, and epigenetic modifications in drug-induced behavioral abnormalities. The only reason that I have been able to maintain this level of accomplishment and innovation is because: 1) I work insanely hard; 2) I receive substantial institutional support but most of which is non-recurring; and 3) I do not give up easily, so that I continue to fight for NIH funding even though every NIH grant I get buys less and less, and I have to fight against the “Occupy NIH Movement” which thinks that I have too much grant money.Improving TranslationThis is an area where the entire biomedical research enterprise has arguably failed and the neurosciences in particular. The latter is no doubt related to the fact that the brain is far more complex than any other organ system and that its diseases are far more complex as well. Still, there are ways in which NIH can help PIs translate key discoveries:Provide administrative supplements for R01s, P01s, P50s, etc. to support targeted drug screening assays and follow up medicinal chemistry to identify and optimize molecules with novel targets. (Separate grants won’t work as effectively because someone like me cannot get another grant.)The NIH’s partnership with the Broad and perhaps other screening facilities is not effective. I had a personal experience where the Molecular Libraries initiative supported a screen at the Broad, but garbage in, garbage out: the Broad went through the screen in a flawed manner that was destined not to work but didn’t care because they did the work and got paid for it.Rather than centralized screening, therefore, NIH should provide the equivalent level of funding but allow PIs to shop around and find the best screening facility that meets their needs (with NIH approval of that facility required).The generation of lead compounds (with new IP for the PI and university), and their validation in animal models, will facilitate collaborations with Pharma and Biotech, who now pretty much require novel chemical matter—already validated—to proceed.Areas to CutI believe there is still a lot of low priority science being supported by NIH. As I walk around SFN, and view the ~25,000 posters, a very large fraction focus on science that is either stale in experimental approach or biological focus or not aligned with the highest priorities of NIH which should be: 1) fundamental discovery science, 2) disease-oriented basic research, and 3) translational research to advance diagnosis and treatment of disease.A big part of the problem remains NIH study sections. I’ve used this analogy before: if I wrote a grant on the role of nose-picking in psychiatry, that grant might go to a study section including several other leaders in the field who study nose-picking in psychiatry. My grant thus might be scored extremely well because of its technical competence and the trade bias of the study section, even though we know that studying nose-picking in psychiatry is not worthy of taxpayers money.Another part of the problem is inertia and perseveration. It is hard to do new things in new ways. It is also far more expensive. But Albert Einstein once said: “If you always do what you always did, you will always get what you always got.” If we applied that rule to NIH funding, there will be a substantial amount of currently funded work that could be cut.I would be happy to be part of a panel that examined NIDA’s portfolio for areas that warrant additional investment and others that should be de-emphasized or de-funded.Tactical Suggestions on Extramural GrantsLonger-term forms of supportThe MERIT award program has been extremely helpful to me. I don’t know how it looks overall. Still, I would suggest a greater number of longer term awards (requiring administrative review only), something in the 7-10 year time frame.Larger budgets for R01sWe’ve discussed this before, but perhaps the greatest challenges I’ve faced in trying to maintain my research program is the repeated pressure on budgets via administrative cuts. I’ve been extremely fortunate to have all of my R01 grants and P01 grant competitively renewed consistently over the past 15 years, but the total dollars have barely increased at all and have, in fact, significantly decreased in real terms over this period. And this decrease in real funds doesn’t take into account the greater increase in the cost of doing state-of-the-art science. Cell-type specific manipulations of genes or microcircuits in the brain (with viral vectors, mutant mice, optogenetics, DREADDS, etc.), or genetic and epigenetic profiling of brain regions/cells in drug abuse models, have increased the cost of a typical R01’s research significantly.Facilitating the funding of younger investigatorsWe need to continue to find ways to reduce the age of first-time R01 grantees. Funding new investigators at higher (less positive) priority scores has helped a lot. I would urge continuing this policy. Another way to promote this would be to counter the phenomenon of the ever- increasing length of postdocs. NIH might consider a cap on years after training that an NIH grant can be used to support a postdoc’s salary. Expansion of K99s, and loosening some eligibility requirements, might also be considered.Continue prospective grading of grantsSome of my colleagues have proposed that PIs be judged more based on past productivity than on proposed research. However, I’m a fan of the current system where everyone must compete based on proposed research. I don’t think that established PIs need any extra favor.Abolish limits on grant numbers or dollarsLikewise, it’s not fair to establish an arbitrary limit on the number of grants or amount of grant dollars that a given PI can receive. Each grant should be judged on its own merits, with no favors but also no liabilities for PIs based on other support, seniority, etc.Fewer RFAs and Director’s awards: Implications for CSRI’m not a fan of RFAs and Director’s awards. I can see the value of RFAs for a particular public health need, but beyond that I believe those funds are better placed in the regular R01 pool of funding. I feel even more strongly about Director’s awards, whether transformational R01s, innovator awards, etc. Fewer RFAs and no Director’s awards would increase the R01 pool and help alleviate some of the bottlenecks above. Moreover, every grant should be innovative and many potentially transformational. I believe the problem lies with our study sections, some of which remain hostile to innovation although there have been significant improvements. I’d do a thorough review of all study sections and ensure that they have the right membership; too many study sections contain mediocre scientists who are jealous of innovation and success. Recruitment of more senior investigators would help. NIH should require all R01-funded PIs to serve on study sections IF ASKED. (Admittedly not all funded PIs are suitable; that’s for CSR and program officers to determine.)
Thank you for providing the opportunity to comment on the NIDA Strategic Plan for 2016-2020. It is essential that scientific agencies have strategic plans that are viable yet visionary and comprehensive enough to deal with the range of challenges facing the field. The 13 priorities and ideas for Basic Neuroscience seem well thought through. It is not clear to me whether the relatively long list of priorities reflects the planned emphasis on this topic area, and I would encourage the agency to give equal emphasis to other important areas.The 6 priorities and ideas for Clinical and Translational Science touch upon important needs for scientific research. In my view the priorities would be much better if they gave more attention to important social and behavioral approaches. A number these interventions have been developed through federal drug abuse research, and many have become mainstays of addiction treatment, including relapse prevention, case management, and behavioral reinforcement. The recent changes in federal funding of addiction treatment provide encouraging opportunities to develop, hone, and field a new set of social and behavioral interventions centering on identification of substance use, determining how to prevent problems from worsening, and how to apply behavioral principles to treat these problems more effectively. The 4 priorities and ideas for Public Health touch on important themes that need to be addressed. For the most part these seem to be general “big think” ideas that would warrant serious programmatic development at the institute.The 12 priorities and ideas for Scientific Infrastructure are vital, far-reaching, and well developed. These topics seem crucial to the future of addiction science not just in training the upcoming generations of addiction researchers, but also in providing the necessary resources, linkages, and systems to make these efforts maximally productive. The one area that seems to be missing is consideration of international outreach and collaboration, which has become so important in our developing scientific world. Each of the 5 Unifying Themes provide a kind of framework for mounting the priorities and ideas.I appreciate the opportunity to glimpse the future of NIDA and to give some input into its development
NIDA Strategic Plan for Supported Research 2016-2020In developing its strategic plan for the future, especially as it relates to addiction, there needs to be a careful reanalysis of the current situation. First, despite many efforts and strong support of research, treatment of most addictions is still very problematic, and most people are still poorly treated. Furthermore, in relation to addiction and pain (both long term pain and psychic pain) the current situation appears to have gotten worse, with many people dying from prescription drugs. Clearly, our current methods and drugs for treating addiction and prolonged pain do not work for most people.A plausible approach to solving many of these problems is to develop drugs that do not lead to the development of dependency, addiction and tolerance in the first place. We and others have some very promising novel compounds that do not lead to dependency, addiction and tolerance in various animal models of acute and prolonged pain. These compounds come from new approaches to the design of novel ligands which often are multivalent by design. To my knowledge, none of these novel ligands have been in clinical trials to see if their activities in animal models translate to man. Big pharma appears to be uninterested so it will be up to others and to NIDA to further the research and development of these novel ligands. I realize that there is a reluctance to support approaches in research and drug development that are novel and/or may fail, but unless we are willing to do so, we will continue to fail. Somehow, we have to re-establish a way to fund innovation and new approaches in drug design. I have been on many NIH Study Sections in the last 35 plus years, and though innovation has become a criteria for scoring for over a decade, in fact, my observation is that it hardly ever enters into the scoring because most innovative (new) science and new ideas are easy to criticize (it may not work – God forbid). So, we score our most innovative grants a 40 and go merrily on our way. I suspect what I have said is of little concern, because an entirely new science and review culture would have to be created, where creativity is encouraged, not punished. Nonetheless, it is pretty obvious why we are getting more and more data (results) and less and less innovation and new knowledge and understanding. We have a creativity crisis. We are not allowed to be creative anymore. (See attached).So how do we recreate this culture in science? It has to come from people (us) but apparently neither our scientific nor political leaders appear to be interested. One possible approach would be to take some small percentage of grants, say 1%, and fund them based on creativity and new ideas and mostly ignore the criticisms. I doubt if anyone has the desire or guts to do this, but someone has to point out what is happening. Our most creative students are leaving science.
We write in response to the above Request for Information, representing the Addiction Research Network (ARN) of the HMO Research Network (HMORN). The ARN of the HMORN includes 18 research centers affiliated with 18 not-for-profit health systems throughout the U.S. The ARN is a network of national reach with researchers representing the HMORN health systems. Researchers from each of the ARN sites and health systems have contributed to this response. Together these include Baylor Scott and White, Essentia Institute of Rural Health, Geisinger, Fallon/Meyers, Group Health, Harvard Pilgrim, Henry Ford, Kaiser Permanente Colorado, Kaiser Permanente Georgia, Kaiser Permanente Hawaii, Kaiser Permanente MidAtlantic, Kaiser Permanente Northern California, Kaiser Permanente Northwest, Kaiser Permanente Southern California, Marshfield Clinic, HealthPartners, and the Palo Alto Medical Foundation. The ARN is a geographically diverse network of health care systems including fully integrated systems (fully capitated, with complete overlap of health insurance and care delivery), hybrid or mixed systems (including substantial care provision by fee-for-service community providers), and multi-specialty group practices (where most care is provided via fee-for-service arrangements).Our investigators focus on addictions research in health systems. We regularly collaborate with patients, clinicians, and administrators both within our systems and more broadly to understand their priorities. The knowledge exchange guides the prevention and management of addictions in our healthcare settings. We bring this background and experience in responding to the RFI. Each of the points mentioned in the Strategic Plan are important in improving understanding of Substance Use (SU) problems and developing effective treatments. We stress that much of this research would benefit from being conducted within large networks of health systems and suggest a broadening of context to explicitly study new approaches in defined populations. 1) Basic Neuroscience: Improve our understanding of the basic science of drug use, addiction, vulnerability to addiction, and recovery.Basic research may be more impactful if it can include large, heterogeneous populations, developmental and environmental factors, and genomics as well as broad and diverse outcome measures ranging from patient reported outcomes to clinician measured health outcomes. For this, the optimal research settings would be health systems with electronic health records (EHRs) that capture comprehensive longitudinal health data on a defined population base of patients, which can be combined with neurobiological, genetic, and environmental data from research studies. At least as a start, much could be learned by using a “big data” approach to examine large numbers of individuals to identify developmental patterns of addiction and remission and thereby target potential research questions and participants. In addition, because assigning people to a potentially addictive substance within a clinical trial raises ethical concerns, it may be only initially feasible (and ethical) to use large population observational studies to understand relationships before conducting a trial.For basic research to have potential for implementation within health systems (i.e., personalized medicine), when applicable, basic research might take into account measures that allow clinicians to make personalized care decisions based on patient characteristics that are easily available directly from patients or from their health records – thus linking phenotypic data with findings from the proposed research domains. This approach supports promoting use of brief (valid/reliable) measures of SU constructs that can be implemented within routine clinical practice. New clinical approaches in healthcare, based on the comprehensive data that are accumulated in EHRs, need to develop systems whereby physicians and researchers can evaluate and compare outcomes of treatment based on targeted patient characteristics research. Another important area is the need to integrate developmental factors and environmental interactions in conceptualizing this research. As an example, the ARN of the HMORN has longitudinal health care data on large numbers of individuals with important phenotype data to merge with basic research data, as is now being done with genetics studies. This is accomplished by such systems having the facilities for, and experience with, collection of biological specimens for research, with accompanying patient surveys, patient reported data routinely collected in clinical practice, and EHR/encounter data and claims data. 2) Clinical and Translational Science: Support the development of new and better interventions and treatments that incorporate the diverse needs of individuals with Substance Use Disorders (SUDs)The research areas listed are important. We recommend the critical role of research networks be stressed. Research networks like the HMORN have developed approaches to facilitate harmonized data collection that allow use of “big data” for health services research. This enables findings to be generalizable to the range of organizations providing SU treatment in the U.S. Research networks are already developed for mental health, cancer, cardiovascular disease, diabetes mellitus, hepatitis C, drug safety, and vaccine safety and effectiveness. These networks have strengthened capacity to conduct larger and more efficient epidemiological studies, clinical and pragmatic trials, effectiveness evaluations, interventions and analyses that enable rapid responses to important health care questions. In order to capitalize on future studies to be conducted in the SU field, allowing for meta analyses that can inform patient, clinician and health system decisions, we would also reinforce previous suggestions by NIDA and the Institute of Medicine about common data elements in EHRs, reinforcing SU assessment approaches and other measures across studies. Efficient population-based or comparative effectiveness research will also benefit from innovation and consistency in measurement of SUD outcomes using EHRs. This also includes improving methods and capacity for participant recruitment. As an example, networks such as the HMORN have extensive experience with using the EHR to identify, recruit, and consent patients and providers in population-based samples, selected according to diagnosis, patient reported measures collected in clinical practice, treatments received, utilization patterns, or socio-demographic characteristics. More efficient recruitment using electronic messaging is being developed and is already used in some systems. Some outcomes of SU treatments (SU medications, psychosocial treatments) can currently be collected through existing information systems. Examples of outcomes include birth outcomes among infants exposed to maternal drug use, adverse events (e.g., injuries/poisonings after prescription drug use, mortality), emergency department and inpatient utilization and presenting problems, costs, and mortality. It is also timely in the addictions field to develop new technologies for collecting data as well as for providing interventions. For example, health systems are developing clinical decision supports for use in primary care and specialty care which can also be used for research. They are using innovative technology (video visits, web-based interventions - live or fully automated, interventions delivered via patient portals into their EHR, or tablet-based interventions) to deliver SU care in primary care as well as in specialty clinics. This is a critical area to further develop, as the field seeks to expand access and integrate SU treatment into primary care, in response to the Affordable Care Act. Examples include: (a) using the EHR for encrypted electronic messaging accessible by mobile phones, (b) using electronic tablets that interact with a patient’s EHR and record clinician- and patient-reported information at visits, (c) developing online-service delivery through patient portals, or (d) tele-health video visits and (e) use of mobile phone apps. In addition to including measures in the overall EHR, which can be a detailed process, “smart forms” and other embedded screening and monitoring tools can be efficiently added for specific studies or piloting next steps with EHRs. This is a unique and growing way to assess patient-reported outcomes.3) Public Health: Increase the public health impact of NIDA research and programsThis is a critical research priority. Health systems (and other systems, such as criminal justice) are optimal settings for conducting population-based research - important for epidemiology, for treatment development, and for implementation research. We suggest that implementation and dissemination research be emphasized in the Strategic Plan. Conducting research in such systems optimizes the potential of understanding the full population for prevention and treatment and for moving evidence-based research findings into healthcare policy and practice. Large health networks (such as the ARN) with national coverage are critical for understanding differences in state policies and other environmental characteristics, organizational complexities, population characteristics, and drug trends as they impact the understanding of SU and interventions. The national coverage, as well as up-to-date information on new types of substances used by patients who present in emergency rooms, specialty treatment and primary care allows studies that can function as “early warning systems” and identify drug use trends, which can help prepare health systems and specialty treatment programs to address them. There is a need to measure and intervene with prescription drug problems. These drugs are prescribed within health systems, thus primary prevention intervention, and treatment should also take place in those settings. We also agree that marijuana legalization is an important topic. Studies that focus on adolescents’ and adults’ marijuana use, and potential relation to health, mental health, and development of other SU problems are timely.We would suggest NIDA emphasize a range of types of clinical trials that are population-based. Pragmatic trials (including cluster randomized trials across multiple clinics) can answer broader sets of questions for both effectiveness and implementation studies, including hybrid studies. Comparative effectiveness research should also be emphasized in the Strategic Plan, taking advantage of the vast amounts of data on populations and interventions available in health systems and other systems as well. Research should include studies to improve treatment access for the population, strengthen resiliency in the community, and take into account affordability and the outcomes important to consumers and other stakeholders of healthcare.4) Science Infrastructure: Enhance the national research infrastructure to support advancements in scienceThe Strategic Plan is comprehensive and includes both development of researchers and of database, methods, and technical infrastructure. Regarding development of researchers, we would suggest that training programs include health systems for training (such as those represented in the ARN). With the advent of research using “big data”, particularly from health systems, more researchers need to be trained to understand healthcare data systems and the complex methods used, such as statistical methods in causal inference for observational data, economics analysis, clinical informatics, as well as the developing area of Natural Language Processing (NLP) to examine clinicians’ notes. Much of this work can be optimized by using EHRs and other health systems technology.In addition, computerized records can be used to identify, recruit, and consent patients and providers. These systems enhance recruitment time as well as allowing targeting of research subjects with particular characteristics (i.e. recognized addictions, addictions in remission, or specific constellations of addictions with comorbidities). Harmonized data systems are needed such as the HMORN’s Virtual Data Warehouse to make population based clinical, health services, and quality improvement research possible without the cost of maintaining registries, which is expected to lower costs in the long-run. In many studies patients can be consented online for trials, or using interactive voice recording (IVR) technology. We would suggest that the Strategic Plan also emphasize research taking advantage of the health care process. Many health systems incorporate relevant measures into their EHRs. This has been reinforced both by NIDA and the Institute of Medicine. Research is needed to assess the feasibility and effectiveness of collecting these measures, as well as research on different approaches to collecting clinical SU measures or providing interventions. The ability to conduct this kind of real-world experimentation makes this method appropriate (what the Institute of Medicine and others refer to as critical to Learning Healthcare Systems). Federal agencies, including the National Center for Research Resources and the Health IT Policy Committee, have recommended that the Department of Health and Human Services not require patient consent for the use of EHR data in research on improving the delivery of healthcare services, including when findings are widely shared. We note that numerous NIH studies are using this approach and NIDA would benefit by encouraging these new innovative approaches. In Summary, we emphasize a) broadening the context, settings, and locations of addictions research, as well as strengthening the methods and integration of the domains of research within this larger context; b) a broad range of intervention research, including comparative effectiveness studies using observational data and pragmatic trials, and cluster randomized trials – both of which would involve large population-based samples and allow for studying a wide range of population characteristics and health disparities; and c) encouraging innovative methods being used by other National Institutes of Health in studying the process of care, including Natural Language Processing in electronic health records.

Clinical and Translational Science, Infrastructure, Public Health

There is an urgent need to reduce the time lag currently observed in scientific inquiry, currently averaging 17 years from intervention development to implementation. More funding for dissemination and implementation methods and trial development would help reduce this lag and bring needed prevention and treatment services to our taxpayers who support NIDA research. As an early career researcher, I am committed to developing quality research, but am aware at the restricted funding. Early career mentored funding that allows researchers to develop their skills and thus more significantly contribute to science should be a priority, especially for under represented groups such as women and people of color. Work that supports the integration of substance abuse and mental health would benefit not only patients, but increasingly burdened service systems and budgets. It is of crucial importance that interventions for substance abuse be delivered in alternative settings that are not necessarily specific to substance abuse and mental health such as primary care, in order to accommodate individuals who have little access to such specialty services, or are hesitant to access alternative services due to stigma. There are many opportunities for such research through the changes to our health system under the implementation of the ACA
TREATMENT Investigate the effectiveness, feasibility, and patient and provider acceptability of delivering methadone treatment in office-based settingsThere has been a longstanding interest in mainstreaming addiction treatment by integrating it into primary and other health care settings.[1] Because of the relatively effective maintenance therapies available, opioid addiction is among the most promising substance use problems for such integration. In addition, with the passage of the Drug Addiction Treatment Act of 2000, it became possible for healthcare providers, who undergo special training and credentialing, to prescribe buprenorphine for the treatment of opioid addiction. While the uptake of buprenorphine has been significant for some patient populations, evidence suggests that particular patients, namely low income, non-white patients, are less likely to access buprenorphine than more affluent white patients.[2-5] In addition, although methadone maintenance is both cost-effective and effective at reducing use of other opioids, only about 12% of individuals with opioid dependence receive this treatment.[6] Additional research is needed on how to expand access to opioid treatment.Currently, with a few exceptions, methadone for the treatment of opioid dependence is only available through a highly regulated and widely stigmatized system of Opioid Treatment Programs (OTPs). Initial trials have suggested that methadone, like buprenorphine, can be effectively delivered in office-based settings[7-10] and that, with training, physicians would be willing to prescribe methadone to their patients to treat their opioid dependence.[11] Office- based methadone may help reduce the stigma associate with methadone delivered in OTPs [12] and provide a critical window of intervention to address medical and psychiatric conditions.[13] Despite this preliminary evidence, more research is needed to establish whether or not and how methadone can be effectively delivered in office-based settings, whether or not physicians would be willing to prescribe it, what ancillary supports might be needed, and what barriers exist to delivering methadone in such settings. In addition, research is needed to identify patient preferences for treatment and what factors might contribute to disparities in who does and who does not receive such office-based therapies. This research could help inform legislative changes that would be required for the delivery methadone outside of OTPs.Recommendations:NIDA should fund studies that examine the feasibility and effectiveness of office-based methadone. It should also fund studies on physician and patient preferences, barriers, and supports needed for office-based methadone to be successful. Finally, it should fund studies that examine how office-based programs and other factors might contribute to disparities in who does and who does not receive office-based treatment.ReferencesKrantz MJ, Mehler PS. Treating opioid dependence. Growing implications for primary care.Arch Intern Med, 2004,164(3):277-88.Hansen, H.B., Siegel, C.E., Case, B.G., Bertollo, D.N., DiRocco, D., & Galanter, M. Variation in use of buprenorphine and methadone treatment by racial, ethnic, and income characteristics of residential social areas in New York City. Journal of Behavioral Health Services & Research, 2013. 40(3):367-77.Knudsen, H.K., Ducharme, L.J., & Roman, P.M. Early adoption of buprenorphine in substance abuse treatment centers: data from the private and public sectors. Journal of Substance Abuse Treatment, 2006. 30(4): 363-73.Stanton, A., McLeod, C., Luckey, B., Kissin, W.B., & Sonnefeld, L.J. Expanding Treatment of Opioid Dependence: Initial Physician and Patient Experiences with the Adoption of Buprenorphine. American Society of Addiction Medicine, March 2006. Presentation. http://www.buprenorphine.samhsa.gov/ASAM_06_Final_Results.pdf. Baxter, J.D., Clark, R.E., Samnaliev, M., Leung, G.Y., & Hashemi, L. Factors associated with Medicaid patients’ access to buprenorphine treatment. Journal of Substance Abuse Treatment, 2011. 41(1):88-96.Raisch DW, Fye CL, Boardman KD, Sather MR Opioid dependence treatment, including buprenorphine/naloxone. Ann Pharmacother, 2002. Feb;36(2):312-21.King VL, Stoller KB, Hayes M, Umbricht A, Currens M, Kidorf MS, Carter JA, Schwartz R,Brooner RK. A multicenter randomized evaluation of methadone medical maintenance. Drug Alcohol Depend, 2002. 65(2):137-48.Fiellin DA, O'Connor PG, Chawarski M, Pakes JP, Pantalon MV, Schottenfeld RS. Methadone maintenance in primary care: a randomized controlled trial. JAMA, 2001. 286(14):1724-31.Krambeer LL, von McKnelly W Jr, Gabrielli WF Jr, Penick EC Methadone therapy for opioid dependence. Am Fam Physician, 2001. 63(12):2404-10.Weinrich M, Stuart M. Provision of methadone treatment in primary care medical practices: review of the Scottish experience and implications for US policy. JAMA, 2000. 283(10):1343-8.McNeely J, Drucker E, Hartel D, Tuchman E. Office-based methadone prescribing: acceptance by inner-city practitioners in New York. J Urban Health, 2000. 77(1):96-102.Salsitz EA, Joseph H, Frank B, Perez J, Richman BL, Salomon N, Kalin MF, Novick DM. Methadone medical maintenance (MMM): treating chronic opioid dependence in private medical practice--a summary report (1983-1998). Mt Sinai J Med, 2000. 67(5-6):388-97.Krambeer LL, von McKnelly W Jr, Gabrielli WF Jr, Penick EC., Methadone therapy for opioid dependence. Am Fam Physician, 2001. 63(12):2404-10.Investigate the mechanisms of “natural” recovery and treatment outcomes beyond abstinenceMost of the literature about drug cessation has focused on the role of treatment, even though the majority of those with substance use problems never seek or receive treatment.[1] Moreover, the vast majority of research on quitting substance use has been done on samples either drawn from treatment settings or among people who have been in treatment. This large body of literature that has focused on the role of treatment in cessation has obscured the prevalence of natural recovery, even though researchers who have examined “natural recovery” contend that this is not an uncommon phenomenon.[2-5]The overwhelming majority of people who use any substance do so non-problematically. [21, 22] Furthermore, what literature is available indicates that many people who are drug- dependent achieve “remission” from their dependence without any form of treatment at all. In fact, evidence suggests it is the common course of most cases of substance dependence. [23- 35] Most people who use or become dependent on substances seem to “age-out” – that is, they naturally reduce – and ultimately cease – their use as they grow older.[36]“Natural” recovery refers to changes in substance use without the aid of formal interventions.[6- 13] Until recently, the concept of “natural” recovery was considered taboo,[14] but there is potentially a great deal to be learned from those who are able to reduce or stop using drugs on their own. Because research has been biased by the large body of literature on treatment outcomes and sampling that often draws from treatment settings [15-18], little is known about the motivations or circumstances under which people reduce their drug use or quit using drugs on their own. Nor do we understand how an individual’s context or social environment influences reduction or abstinence from drugs.To date, studies of Vietnam veterans provide one of the major sources of information on natural recovery and the role of the social context.[19-20] During the war, an estimated 43% of U.S. Army male enlistees used narcotics, and 20% became dependent. Nevertheless, 8 to 12 months after returning to the US, only 5% of those who had been drug dependent in Vietnam remained so. These data demonstrate the power of environmental and social context as well as drug availability to alter drug use behaviors.A related problem is that much of the exiting research on cessation has been conducted to evaluate different treatment interventions and, thus, is mostly concerned with abstinence as the primary outcome. However, interim milestones are also important in understanding cessation and in their own right, since reductions in use (even if abstinence is not achieved) result in improved health outcomes. Studies of natural recovery could help illuminate what some of those milestones are and how people achieve them.Recommendations: NIDA should fund researchers to study the phenomena of natural recovery in the population across all substances. We recommend longitudinal cohort studies as well as qualitative studies to surface the underlying motivations and mechanisms for spontaneous remission. Samples for these studies should be drawn from non-treatment settings and include individuals who have never sought treatment. In addition, we suggest that, in all studies about cessation, NIDA also encourage investigators to consider outcomes beyond abstinence, such as reductions in drug use, improved health outcomes, employment, increases in social support, etc.ReferencesGrella CE, Stein JA. Remission from substance dependence: differences between individuals in a general population longitudinal survey who do and do not seek help. Drug Alcohol Depend. 2013 Nov 1;133(1):146-53.Graeven DB, Graeven KA. Treated and untreated addicts: Factors associated with participation in treatment and cessation of heroin use. J Drug Issues 1983; 13(2):207- 218.Klingemann HK. The motivation for change from problem alcohol and heroin use. Br J Addict 1991; 86:727-744.Price RK, Risk NK, Spitznagel EL. Remission from drug abuse over a 25-year period: patterns of remission and treatment use. Am J Public Health 2001; 91(7):1107-1113.Hubbard RL, Craddock SG, Anderson J. Overview of 5-year follow up outcomes in the drug abuse treatment outcome studies (DATOS). J Subst Abuse Treat 2003; 25(3):125- 134.Klingemann HK, Sobell LC. Introduction: natural recovery research across substance use. Subst Use Misuse 2001; 36(11):1409-1416.Preble E, Casey JJ. Taking care of business: The heroin user's life on the streets. Int J Addict 1969; 4:1-24.Chiauzzi EJ, Liljegren S. Taboo topics in addiction treatment. An empirical review of clinical folklore. J Subst Abuse Treat 1993; 10(3):303-316.Granfield R, Cloud W. Social context and "natural recovery": the role of social capital in the resolution of drug-associated problems. Subst Use Misuse 2001; 36(11):1543-1570.Rumpf HJ, Bischof G, Hapke U, Meyer C, John U. Studies on natural recovery from alcohol dependence: sample selection bias by media solicitation? Addiction 2000; 95(5):765-775.Sobell LC, Ellingstad TP, Sobell MB. Natural recovery from alcohol and drug problems: methodological review of the research with suggestions for future directions. Addiction 2000; 95(5):749-764.Edwards G. Natural recovery is the only recovery. Addiction 2000; 95(5):747.Burman S. The challenge of sobriety: natural recovery without treatment and self-help groups. J Subst Abuse 1997; 9:41-61.:41-61.Chiauzzi EJ, Liljegren S. Taboo topics in addiction treatment. An empirical review of clinical folklore. J Subst Abuse Treat 1993; 10(3):303-316.Graeven DB, Graeven KA. Treated and untreated addicts: Factors associated with participation in treatment and cessation of heroin use. J Drug Issues 1983; 13(2):207- 218.Klingemann HK. The motivation for change from problem alcohol and heroin use. Br J Addict 1991; 86:727-744.Price RK, Risk NK, Spitznagel EL. Remission from drug abuse over a 25-year period: patterns of remission and treatment use. Am J Public Health 2001; 91(7):1107-1113.Hubbard RL, Craddock SG, Anderson J. Overview of 5-year followup outcomes in the drug abuse treatment outcome studies (DATOS). J Subst Abuse Treat 2003; 25(3):125- 134.Robins LN. A Follow-up of Vietnam Drug Users. Series A, No. 1. 1973. Washington, D.C., Executive Office of the President. Special Action Office Monograph.Robins LN. The Vietnam Drug User Returns. Series A, No. 2. 1974. Washington, D.C.,U.S. Government Printing Office. Special Action Office Monograph.WHO, U., Principles of drug dependence treatment. Geneva: WHO, 2008.Esser, M.B., et al., Prevalence of Alcohol Dependence Among US Adult Drinkers, 2009- 2011. Preventing Chronic Disease, 2014. 11: p. E206.Grella, C.E. and J.A. Stein, Remission from substance dependence: differences between individuals in a general population longitudinal survey who do and do not seek help. Drug Alcohol Depend, 2013. 133(1): p. 146-53.Slutske, W.S., Why is natural recovery so common for addictive disorders? Addiction, 2010. 105(9): p. 1520-1521.Carballo, J.L., et al., Natural recovery from alcohol and drug problems: A methodological review of the literature from 1999 through 2005, in Promoting self-change from addictive behaviors. 2007, Springer. p. 87-101.Williams, C.R. and B.A. Arrigo, Drug-taking behavior, compulsory treatment, and desistance: Implications of self-organization and natural recovery for policy and practice. Journal of Offender Rehabilitation, 2007. 46(1-2): p. 57-80.Klingemann, H.K.-H., Natural recovery from alcohol problems. The essential handbook of treatment and prevention of alcohol problems, 2004: p. 161.Granfield, R. and W. Cloud, Social context and “natural recovery”: The role of social capital in the resolution of drug-associated problems. Substance use & misuse, 2001. 36(11): p. 1543-1570.Klingemann, H.K.-H. and L.C. Sobell, Introduction: natural recovery research across substance use. Substance Use & Misuse, 2001. 36(11): p. 1409-1416.Cloud, W. and R. Granfield, Natural recovery from substance dependency: Lessons for treatment providers. Journal of Social Work Practice in the Addictions, 2001. 1(1): p. 83- 104.Sobell, L.C., T.P. Ellingstad, and M.B. Sobell, Natural recovery from alcohol and drug problems: Methodological review of the research with suggestions for future directions. Addiction, 2000. 95(5): p. 749-764.Edwards, G., Editorial note: natural recovery is the only recovery. Addiction, 2000. 95(5): p. 747-747.Toneatto, T., et al., Natural recovery from cocaine dependence. Psychology of Addictive Behaviors, 1999. 13(4): p. 259.Burman, S., The challenge of sobriety: natural recovery without treatment and self-help groups. Journal of substance abuse, 1997. 9: p. 41-61.Waldorf, D. and P. Biernacki, The natural recovery from opiate addiction: Some preliminary findings. Journal of Drug Issues, 1981. 11(1): p. 61-76.Lopez-Quintero, C., et al., Probability and predictors of remission from life-time nicotine, alcohol, cannabis or cocaine dependence: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Addiction, 2011. 106(3): p. 657-69.Investigate Heroin-Assisted Treatment and Other Novel Opioid Substitution TherapiesMedication-assisted treatment models for opioid dependence using diacetylmorphine (heroin) have been safely and successfully implemented in several countries, and are now well supported in the academic literature as one tool in an effective, health-based response to problematic drug use, especially among those who have not responded to conventional treatments. Often called heroin-assisted treatment (HAT), such models have proven enormously successful and now operate in Switzerland,[1, 2] Netherlands,[3] United Kingdom,[4] Germany,[5-7] Spain,[8, 9] Denmark,[2] Belgium,[10] Canada,[11] and Luxembourg. HAT allows for the provision of pharmacological grade heroin (diacetylmorphine) to select heroin-dependent people who have not previously responded to other forms of treatment. Typically, patients receive injectable or inhalable heroin 2-3 times per day from a doctor in a clinic setting under strict controls.Peer-reviewed studies around the world have found that HAT is associated with decreased illicit drug use, crime, overdose fatalities, and risky injecting, as well as improvements in physical and mental health, employment and social relations.[1, 3-6, 8, 11-20] In contrast, few reports have appeared in the scientific literature demonstrating any harmful consequences of HAT.A Cochrane systematic review of all published studies on heroin-assisted treatment (HAT) found significant reductions in illicit drug use and crime, and improvements in health of participants. It concluded, “Each study found a superior reduction in illicit drug use in the heroin arm ratherthan in the methadone arm…the measures of effect obtained are consistently statistically significant.” [13] An important article in the New England Journal of Medicine on the success ofthe North American Opioid Medication Initiative (NAOMI) in Canada, which provided heroin byprescription to a select group of people who had not responded to other forms of treatment, reported a two-thirds (67%) reduction in illicit drug use or other illegal activity.[11] Similar reductions in illicit heroin use were reported from HAT trials in the UK (72 percent)[4] and Germany (69 percent).[5]The Canadian HAT trial involved an arm of the study that received another opioid agonist, hydromorphone, instead of heroin; these subjects showed similarly impressive results: approximately two-thirds reduction in use of illicit heroin. [21] A second randomized trial in Canada that was recently completed administered both heroin and hydromorphone.[22]Retention rates in HAT programs dwarf those of convention treatments. [5, 11, 13, 23, 24] Patients express a strong preference for HAT over methadone or other standard treatments.[25, 26] While HAT has been restricted to those who do not respond to methadone, evidence now shows it is effective even for people with no previous maintenance experience – suggesting it could be scaled up.[27] Many HAT participants freely choose to move on to another form of treatment (like methadone) or to abstinence,[28, 29] while others continue to receive HAT on a long-term basis, with lasting positive results.[23]HAT is not only more effective at reducing illegal heroin (and other drug) use than methadone, [7] but it has also proven to be more cost-effective.[30] HAT participants are much less likely to commit acquisitive crimes and other non-drug offenses. As a result, HAT programs have been shown to decrease crime in areas where they are situated – leading to additional cost savings of the HAT model.[31-35]Recommendations:Researchers, advocates and health officials have expressed interest in studying and implementing HAT in the U.S. but federal laws and policies have stood in the way of this evidence-based method of treatment. NIDA should fund a heroin-assisted treatment trial in the United States. Such a trial could also compare the safety and efficacy of injectable hydromorphone for opioid dependence. If results are favorable, NIDA should urge the U.S. Congress to amend federal law to allow these innovative opioid replacement treatments to be implemented on a pilot basis in the United States without federal interference.ReferencesUchtenhagen, A., Heroin-assisted treatment in Switzerland: a case study in policy change. Addiction, 2010. 105(1): p. 29-37.Uchtenhagen, A.A., Heroin maintenance treatment: From idea to research to practice.Drug and Alcohol Review, 2011. 30(2): p. 130-137.Blanken, P., et al., Heroin-assisted treatment in the Netherlands: History, findings, and international context. European Neuropsychopharmacology, 2010. 20: p. S105-S158.Strang, J., et al., Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. The Lancet, 2010. 375(9729): p. 1885-1895.Haasen, C., et al., Heroin-assisted treatment for opioid dependence: randomised controlled trial. Br J Psychiatry, 2007. 191: p. 55-62.Verthein, U., et al., Long-term effects of heroin-assisted treatment in Germany.Addiction, 2008. 103(6): p. 960-6; discussion 967-8.Verthein, U., C. Haasen, and J. Reimer, Switching from methadone to diamorphine: 2- year results of the german heroin-assisted treatment trial. Subst Use Misuse, 2011. 46(8): p. 980-91.Oviedo-Joekes, E., et al., The Andalusian trial on heroin-assisted treatment: a 2 year follow-up. Drug Alcohol Rev, 2010. 29(1): p. 75-80.Perea-Milla, E., et al., Efficacy of prescribed injectable diacetylmorphine in the Andalusian trial: Bayesian analysis of responders and non-responders according to amulti domain outcome index. Trials, 2009. 10: p. 70.Belgian Monitoring Centre for Drugs and Drug Addiction, 2012 National Report (2011 data) to the EMCDDA by the Reitox National Focal Point: Belgium - New Development, Trends and in-depth information on selected issues. 2013, European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): Lisbon.Oviedo-Joekes, E., et al., Diacetylmorphine versus methadone for the treatment of opioid addiction. N Engl J Med, 2009. 361(8): p. 777-86.Blanken, P., et al., Craving and illicit heroin use among patients in heroin-assisted treatment. Drug Alcohol Depend, 2012. 120(1-3): p. 74-80.Ferri, M., M. Davoli, and C.A. Perucci, Heroin maintenance for chronic heroin-dependent individuals. Cochrane Database Syst Rev, 2011(12): p. CD003410.Fischer, B., et al., Heroin-assisted Treatment (HAT) a Decade Later: A Brief Update on Science and Politics. Journal of Urban Health, 2007. 84(4): p. 552-562.Petrushevska, T., Heroin Maintenance Treatment-Are the Further Investigation Needed?Macedonian Journal of Medical Sciences, 2012. 5(4): p. 453-461.Strang, J., T. Groshkova, and N. Metrebian, New Heroin-Assisted Treatment: Recent Evidence and Current Practices of Supervised Injectable Heroin Treatment in Europe and Beyond. 2012, Lisbon: European Monitoring Centre for Drugs and Drug Addiction. 176.Killias, M., M.F. Aebi, and K. Jurist, The impact of heroin prescription on heroin markets in Switzerland. Crime Prevention Studies, 2000. 11: p. 83-100.Nordt, C. and R. Stohler, Incidence of heroin use in Zurich, Switzerland: a treatment case register analysis. The Lancet, 2006. 367(9525): p. 1830-1834.Reuter, P., Can Heroin Maintenance Help Baltimore. Baltimore, MD: Abell Foundation, 2009.Rehm, J., et al., Mortality in heroin-assisted treatment in Switzerland 1994-2000. DrugAlcohol Depend, 2005. 79(2): p. 137-43.Oviedo-Joekes, E., et al., Double-blind injectable hydromorphone versus diacetylmorphine for the treatment of opioid dependence: a pilot study. J Subst Abuse Treat, 2010. 38(4): p. 408-11.Providence Health Care. The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME). Available from: http://www.providencehealthcare.org/salome/index.html.Blanken, P., et al., Outcome of long-term heroin-assisted treatment offered to chronic, treatment-resistant heroin addicts in the Netherlands. Addiction, 2010. 105(2): p. 300-8.Nosyk, B., et al., The effect of motivational status on treatment outcome in the North American Opiate Medication Initiative (NAOMI) study. Drug Alcohol Depend, 2010. 111(1-2): p. 161-5.Bald, L.K., et al., Heroin or Conventional Opioid Maintenance? The Patients' Perspective. J Addict Med, 2013.Marchand, K.I., et al., Client satisfaction among participants in a randomized trialcomparing oral methadone and injectable diacetylmorphine for long-term opioid- dependency. BMC Health Serv Res, 2011. 11: p. 174.Haasen, C., et al., Is heroin-assisted treatment effective for patients with no previous maintenance treatment? Results from a German randomised controlled trial. Eur AddictRes, 2010. 16(3): p. 124-30.Rehm, J., et al., Feasibility, safety, and efficacy of injectable heroin prescription for refractory opioid addicts: a follow-up study. Lancet, 2001. 358(9291): p. 1417-23.Reuter, P., Can Heroin Maintenance Help Baltimore?: What Baltimore Can Learn from the Experience of Other Countries. 2009: Abell Foundation.Nosyk, B., et al., Cost-effectiveness of diacetylmorphine versus methadone for chronicopioid dependence refractory to treatment. CMAJ, 2012. 184(6): p. E317-28.van der Zanden, B.P., et al., Patterns of acquisitive crime during methadone maintenance treatment among patients eligible for heroin assisted treatment. Drug Alcohol Depend, 2007. 86(1): p. 84-90.Killias, M., et al., Effects of Drug Substitution Programs on Offending Among Drug- Addicts: A Systematic Review. 2009.Lobmann, R. and U. Verthein, Explaining the effectiveness of heroin-assisted treatment on crime reductions. Law Hum Behav, 2009. 33(1): p. 83-95.Frick, U., et al., Long-Term Follow-Up of Orally Administered Diacetylmorphine Substitution Treatment. European Addiction Research, 2010. 16(3): p. 131-138.Garcia-Portilla, M.P., et al., Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack? Br J Clin Pharmacol, 2014. 77(2): p. 272-84.DRUG SCHEDULINGInvestigate the scientific merits of the U.S. drug scheduling systemThe U.S. Controlled Substances Act (CSA) of 1970 created a five-category scheduling system for most legal and illegal drugs (although alcohol and tobacco were notably omitted). Depending on what category a drug is placed in, the drug is either subject to varying degrees of regulation and control – or, in the case of Schedule I drugs, completely prohibited and left to criminals to manufacture and distribute.The CSA divides controlled substances into five schedules originally determined by Congress. The "most dangerous" drugs are listed in Schedule I, defined as including drugs with "a high potential for abuse," "no currently accepted medical use in treatment in the United States," and "a lack of accepted safety for the use of the drug...under medical supervision." Schedule II drugs also have "a high potential for abuse" and their abuse may lead to "severe psychological or physical dependence," but they have a "currently accepted medical use." Drugs in Schedules III through V have progressively lower potential for abuse, accepted medical uses, and can only cause "limited physical dependence or psychological dependence."Under the CSA, the DEA may initiate proceedings to add, delete or change the schedule of a drug or substance, as may the Department of Health and Human Services (HHS). Additionally, interested parties, including drug manufacturers, medical or pharmacy associations, public interest groups, state or local governments, or individual citizens can petition to add, delete or change the schedule of a drug or substance. When a petition is received by the DEA, they begin their own investigation of the drug. They may begin an investigation of a drug based on information received from state or local law enforcement and regulatory agencies, laboratories or other sources. Once the DEA initiates an investigation of a drug, it collects relevant data. The DEA then requests that HHS conduct a scientific and medical evaluation and make a recommendation on whether the drug should be controlled or not and where it should be placed in the CSA schedule.HHS in turn seeks information from the Commissioner of the Food and Drug Administration (FDA) – who delegates this task to the FDA’s Controlled Substances Staff (CSS) – as well as evaluations and recommendations from the National Institute on Drug Abuse (NIDA). HHS may also seek input from the scientific and medical community at large. After consulting with FDA, NIDA, and any others, HHS submits to the DEA its medical and scientific evaluation of the drug and a recommendation on whether the drug should be controlled – and if so, in which schedule it should be placed. While HHS's medical and scientific evaluations are binding on the DEA, its scheduling recommendations are not, with one exception: If HHS recommends that a substance not be controlled, then the DEA may not control or schedule it. After receiving the scientific and medical evaluation from HHS, the DEA Administrator will evaluate all the data and make a final decision.While the CSA sets out the means and procedures for scheduling drugs in accordance with science and medicine, the DEA – a law enforcement agency – is ultimately responsible in most cases for making final decisions on how to schedule various drugs. The assignment to the DEA of this decision-making authority has produced some strange results. For instance, while methamphetamine and cocaine are Schedule II drugs making them available for medical use, marijuana is scheduled alongside PCP and heroin as a Schedule I drug, which prohibits any medical use.The DEA has consistently demonstrated that it is incapable of accurately assessing the state of medical and scientific knowledge about drugs and scheduling them appropriately.[1] Final decisions by the DEA on drug scheduling appear to be guided more by politics and the policy priorities of a law enforcement agency than science. The current system for classifying drugs is flawed.The current drug scheduling system fails to comport with scientific evidence about drug pharmacology and psychopharmacology. Schedule I is for drugs that are highly addictive and have no medical value, while the other schedules are for drugs with medical value but varying degrees of safety and dependence risks. There are no categories, however, for drugs that have no medical value but are not highly addictive either. By this measure, some substances listed under Schedule I do not belong there. Nor are there categories for drugs that have not been evaluated for medical value yet. Many emerging drugs, including synthetic cannabinoid compounds, have been placed under Schedule I without due consideration made to potential therapeutic value. [2-4] The current system for classifying drugs is also outdated and structurally cumbersome in ways that impact the ability of the government to nimbly make assessments and adjustments to the schedules that keep pace with evolutions in scientific understanding and emerging issues like synthetic drugs.[5] For instance, marijuana has remained in Schedule I since 1970 despite the emergence of study after peer-reviewed study around the world that have established the medical value of the chemicals in the marijuana plant.Experts and researchers have called for a new scheduling system based on relative harms of drugs.[6-8] For example, a report published in the esteemed Lancet Journal, researchers proposed an alternative method for drug classification in the United Kingdom, which uses a nine-category matrix to assess the harms of a range of licit and illicit drugs. The new classification system recognizes the fact that alcohol and tobacco cause far more individual and social harms than marijuana, LSD, and MDMA, which have less potential for harm relative to other legal and illegal drugs.[9, 10]Recommendations:Four decades ago, Congress created the drug scheduling system that is in place today. The current system relies too heavily on the DEA, a federal law enforcement agency, to make key decisions about how drugs should be classified according to their medical value and potential for abuse. The current system does not adequately conform to new and emerging circumstances or scientific discoveries that have a bearing on how a drug is regulated. NIDA should conduct a comprehensive evaluation of the federal drug scheduling system that examines the process for adding, changing or removing a substance from the schedules, the best way to assess the risks and benefits associated with current and emerging drugs. As part of this evaluation, NIDA should consider alternative scheduling systems based on evidence of harm and whether the current scheduling system should be reformed so that drugs are classified based on their relative risks and associated harms. NIDA should speak to the merit of overhauling the entire federal drug scheduling process to ensure that decisions on whether to criminalize a drug or not, and whether and how to regulate it, are decided by an objective, independent scientific process.ReferencesDrug Policy Alliance and Multidisciplinary Association for Psychedelic Studies, The DEA: Four Decades of Impeding and Rejecting Science. 2014, Drug Policy Alliance.Coulson, C. and J.P. Caulkins, Scheduling of newly emerging drugs: a critical review of decisions over 40 years. Addiction, 2012. 107(4): p. 766-73.Winstock, A.R. and J.D. Ramsey, Legal highs and the challenges for policy makers.Addiction, 2010. 105(10): p. 1685-1687.Kalant, H., Drug classification: science, politics, both or neither? Addiction, 2010.105(7): p. 1146-9.Nutt, D.J., L.A. King, and D.E. Nichols, Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nat Rev Neurosci, 2013.Fischer, B. and P. Kendall, Nutt et al.'s harm scales for drugs--room for improvementbut better policy based on science with limitations than no science at all. Addiction, 2011. 106(11): p. 1891-2; discussion 1896-8.Rolles, S. and F. Measham, Questioning the method and utility of ranking drugharms in drug policy. International Journal of Drug Policy, 2011. 22(4): p. 243-246.Ray, R. and A. Dhawan, DRUG SCHEDULING—SCIENCE AND CULTURAL PERSPECTIVE. Addiction, 2010. 105(7): p. 1151-1153.Nutt, D.J., L.A. King, and L.D. Phillips, Drug harms in the UK: a multicriteria decision analysis. The Lancet, 2010. 376(9752): p. 1558-1565.Nutt, D., et al., Development of a rational scale to assess the harm of drugs of potential misuse. The Lancet, 2007. 369(9566): p. 1047-1053.End the NIDA monopoly on marijuana for research purposesTwenty three states plus the District of Columbia have acknowledged the medical value of marijuana by allowing those with certain medical conditions to use the substance with the recommendation of a licensed physician. While some states, such as California, have recognized the medical value of the marijuana plant for over 15 years, at the Federal level, marijuana remains a schedule I substance. One of the requirements for a substance to be placed in schedule I, is that is has no accepted medical value. The inconsistency of the federal marijuana classification with state level use has prompted numerous petitions to the Department of Health and Human Services over the past four decades asking for an investigation into the evidence for moving marijuana out of the schedule I category. Furthermore, unlike other substances in the schedule I category, the marijuana available for research purposes can be obtained from only one source, the federal government. The federal government, therefore, is put in the position of provider of marijuana for the purposes of researching a medical benefit it denies exists.Peer-reviewed studies [1-14] around the world have established the medical value of the chemicals in the marijuana plant, including THC and CBD, for the treatment of myriad medical conditions and symptoms, including neuropathic pain,[1, 3, 4, 6, 7, 10-13] multiple sclerosis,[1, 14] seizure disorders,[15-17] glaucoma,[18-20] digestive disorders such as Crohn’sDisease,[21-23] nausea and loss of appetite.[24-28] Furthermore, preclinical and limited clinical research suggests that the chemicals in the marijuana plant may also be helpful in treating Alzheimer’s Disease,[29-31] Parkinson’s Disease,[32-36] cancer,[37-47] arthritis,[10, 48, 49] PTSD,[50-54] and severe brain injury [55, 56]. The federal government currently holds a patent on CBD, one of the active chemicals in marijuana, as a neuro-protectant. The medical use of cannabinoids has become an international hotbed of research activity. Yet most labs and research teams are limited to inferior, synthetic versions of cannabinoids, and have their research stifled at the preclinical level due to the federal monopoly on marijuana for research purposes. States that have legalized the adult use of marijuana in the United States are excited to use the revenue from their programs to fund groundbreaking medical research, but they still have to overcome the barriers to obtaining the product for their studies, even in places where marijuana is available at a corner store.In 1999, the Institute of Medicine (IOM) released a report entitled, “Marijuana and Medicine: Assessing the Science Base”.[57] While the IOM suggests that the chemical found in the marijuana plant be developed into standardized formulations apart from the raw plant, they also concluded that, “Advances in cannabinoid science over the past 16 years have given rise to a wealth of new opportunities for the development of medically useful cannabinoid-based drugs. The accumulated data suggest a variety of indications, particularly for pain relief, antiemesis, and appetite stimulation. For patients who suffer simultaneously from severe pain, nausea, and appetite loss, such as those with AIDS or who are undergoing chemotherapy, cannabinoid drugs might offer broad-spectrum relief not found in any other single medication.”[57] In order for these medications that the IOM suggests to be developed, researchers must have access to high-quality raw marijuana material. THC and CBD are only 2 of over 80 cannabinoids found in the marijuana plant.[58] Limiting access to the plant for research purposes delays the discovery and development of medications that utilize these cannabinoids and can unlock the potential treatments for a countless number of conditions for which there is currently no cure, or for which the current treatment is not effective and related to dangerous side effects.The current federal monopoly on marijuana has slowed down the process of developing cannabinoid-based medications considerably. The organization, Multidisciplinary Association for Psychedelic Studies spent 22 years on an effort to obtain marijuana from the federal government for their study of marijuana to treat symptoms of PTSD – 22 years during which thousands of veterans and others might have found relief from their PTSD symptoms had the drug development process not been hindered by the current federal policies on marijuana research.Recommendations:Ideally, the placement of marijuana in the schedule I category would be reviewed as research has shown that marijuana does not fit the definition of a schedule I substance. However, it isimmediately requested that the stipulation that marijuana used for NIH approved research mustcome from the federal supply be removed. After obtaining approval from an IRB and financial support through a research grant, researchers should be able to obtain the marijuana from a third party provider, similar to how research on other schedule I substances, such as MDMA, is conducted. The federal government should do all it can to facilitate the research and development into cannabinoid based medications, and this includes removing the barriers to access for research purposes, and seriously considering moving marijuana out of the schedule I category, as is supported by numerous public health and medical organizations, including most recently the American Academy of Pediatrics.[59]ReferencesGrant, I., et al., Medical marijuana: clearing away the smoke. Open Neurology Journal, 2012. 6: p. 18-25.Ben Amar, M., Cannabinoids in medicine: A review of their therapeutic potential. J Ethnopharmacol, 2006. 105(1-2): p. 1-25.Wilsey, B., et al., Low-dose vaporized cannabis significantly improves neuropathic pain.J Pain, 2013. 14(2): p. 136-48.Wilsey, B., et al., A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain, 2008. 9(6): p. 506-21.Abrams, D.I., et al., Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther, 2011. 90(6): p. 844-51.Abrams, D.I., et al., Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology, 2007. 68(7): p. 515-21.Fine, P.G. and M.J. Rosenfeld, Cannabinoids for Neuropathic Pain. Current pain and headache reports, 2014. 18(10): p. 1-9.Riggs, P.K., et al., A pilot study of the effects of cannabis on appetite hormones in HIV- infected adult men. Brain Res, 2012. 1431: p. 46-52.Grotenhermen, F. and K. Muller-Vahl, The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int, 2012. 109(29-30): p. 495-501.Lynch, M.E. and F. Campbell, Cannabinoids for treatment of chronic non‐cancer pain; asystematic review of randomized trials. British journal of clinical pharmacology, 2011.72(5): p. 735-744.Ware, M.A., et al., Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ, 2010. 182(14): p. E694-701.Ellis, R.J., et al., Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology, 2009. 34(3): p. 672-80.Degenhardt, L., et al., Experience of adjunctive cannabis use for chronic non-cancer pain: Findings from the Pain and Opioids IN Treatment (POINT) study. Drug Alcohol Depend, 2014.Corey-Bloom, J., et al., Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. Canadian Medical Association Journal, 2012. 184(10): p. 1143-1150.Maa, E. and P. Figi, The case for medical marijuana in epilepsy. Epilepsia, 2014.Szaflarski, J.P. and E.M. Bebin, Cannabis, cannabidiol, and epilepsy—From receptors to clinical response. Epilepsy & Behavior, 2014.Porter, B.E. and C. Jacobson, Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior, 2013. 29(3):p. 574-577.Pertwee, R.G., Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci, 2012. 367(1607): p. 3353-63.Yazulla, S., Endocannabinoids in the retina: from marijuana to neuroprotection. Prog Retin Eye Res, 2008. 27(5): p. 501-26.Kogan, N.M. and R. Mechoulam, Cannabinoids in health and disease. Dialogues Clin Neurosci, 2007. 9(4): p. 413-30.Schicho, R. and M. Storr, Cannabis finds its way into treatment of Crohn's disease.Pharmacology, 2014. 93(1-2): p. 1-3.Naftali, T., et al., Cannabis Induces a Clinical Response in Patients with Crohn’s Disease: a Prospective Placebo-Controlled Study. Clinical Gastroenterology and Hepatology, 2013. 11(10): p. 1276-1280 e1.Alhouayek, M. and G.G. Muccioli, The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends Mol Med, 2012. 18(10): p. 615-25.Sharkey, K.A., N.A. Darmani, and L.A. Parker, Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. European journal of pharmacology, 2014. 722: p. 134-146.Borgelt, L.M., et al., The pharmacologic and clinical effects of medical cannabis.Pharmacotherapy, 2013. 33(2): p. 195-209.Todaro, B., Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting. Journal of the National Comprehensive Cancer Network, 2012. 10(4): p. 487- 492.Parker, L.A., E.M. Rock, and C.L. Limebeer, Regulation of nausea and vomiting by cannabinoids. British Journal of Pharmacology, 2011. 163(7): p. 1411-1422.Izzo, A.A. and K.A. Sharkey, Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther, 2010. 126(1): p. 21-38.Cao, C., et al., The Potential Therapeutic Effects of THC on Alzheimer's Disease. J Alzheimers Dis, 2014.Martin-Moreno, A.M., et al., Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer's disease. Mol Pharmacol, 2011.79(6): p. 964-73.Mulder, J., et al., Molecular reorganization of endocannabinoid signalling in Alzheimer's disease. Brain, 2011. 134(Pt 4): p. 1041-60.Chagas, M.H., et al., Effects of cannabidiol in the treatment of patients with Parkinson's disease: An exploratory double-blind trial. J Psychopharmacol, 2014.Lotan, I., et al., Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clin Neuropharmacol, 2014. 37(2): p. 41-4.Chagas, M.H., et al., Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's diseasepatients: a case series. J Clin Pharm Ther, 2014. 39(5): p. 564-6.García, C., et al., Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson's disease. British Journal of Pharmacology, 2011. 163(7): p. 1495-1506.Zuardi, A.W., et al., Cannabidiol for the treatment of psychosis in Parkinson's disease. J Psychopharmacol, 2009. 23(8): p. 979-83.Chakravarti, B., J. Ravi, and R.K. Ganju, Cannabinoids as therapeutic agents in cancer: current status and future implications. Oncotarget, 2014. 5(15): p. 5852.Pacher, P., Towards the use of non-psychoactive cannabinoids for prostate cancer. Br J Pharmacol, 2013. 168(1): p. 76-8.Pisanti, S., et al., The endocannabinoid signaling system in cancer. Trends Pharmacol Sci, 2013. 34(5): p. 273-82.Bar-Sela, G., et al., The medical necessity for medicinal cannabis: prospective, observational study evaluating the treatment in cancer patients on supportive or palliative care. Evidence-Based Complementary and Alternative Medicine, 2013. 2013.Brown, I., et al., Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. Prog Lipid Res, 2013. 52(1): p. 80-109.Velasco, G., C. Sánchez, and M. Guzmán, Towards the use of cannabinoids as antitumour agents. Nature Reviews Cancer, 2012. 12(6): p. 436-444.Salazar, M., et al., Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. The Journal of Clinical Investigation, 2009. 119(5): p. 1359-1372.Fernández-Ruiz, J., et al., Prospects for cannabinoid therapies in basal ganglia disorders. British Journal of Pharmacology, 2011. 163(7): p. 1365-1378.Guzman, M., Cannabinoids: potential anticancer agents. Nat Rev Cancer, 2003. 3(10): p. 745-55.Singer, E., et al., Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma. Cell Death Dis, 2015. 6: p. e1601.Orellana-Serradell, O., et al., Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncol Rep, 2015.La Porta, C., et al., Involvement of the endocannabinoid system in osteoarthritis pain.European Journal of Neuroscience, 2014. 39(3): p. 485-500.McDougall, J.J., Cannabinoids and Pain Control in the Periphery. 2009. p. 325-345.Roitman, P., et al., Preliminary, Open-Label, Pilot Study of Add-On Oral Δ9- Tetrahydrocannabinol in Chronic Post-Traumatic Stress Disorder. Clinical drug investigation, 2014. 34(8): p. 587-591.Neumeister, A., et al., Elevated brain cannabinoid CB receptor availability in post- traumatic stress disorder: a positron emission tomography study. Mol Psychiatry, 2013.Neumeister, A., The endocannabinoid system provides an avenue for evidence-based treatment development for PTSD. Depress Anxiety, 2013. 30(2): p. 93-6.Passie, T., et al., Mitigation of post-traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence. Drug Testing and Analysis, 2012.4(7-8): p. 649-659.Fraser, G.A., The Use of a Synthetic Cannabinoid in the Management of Treatment- Resistant Nightmares in Posttraumatic Stress Disorder (PTSD). CNS Neuroscience & Therapeutics, 2009. 15(1): p. 84-88.Johnson, B.N., et al., Augmented Inhibition from Cannabinoid-Sensitive Interneurons Diminishes CA1 Output after Traumatic Brain Injury. Front Cell Neurosci, 2014. 8: p. 435.Zhang, J., et al., Inhibition of monoacylglycerol lipase prevents chronic traumatic encephalopathy-like neuropathology in a mouse model of repetitive mild closed headinjury. J Cereb Blood Flow Metab, 2014.Joy, J.E., S.J. Watson, and J.A. Benson, Marijuana and medicine: assessing the science base. 1999, Washington, DC: Institute of Medicine, National Academies Press.El-Alfy, A.T., et al., Antidepressant-like effect of delta9-tetrahydrocannabinol and othercannabinoids isolated from Cannabis sativa L. Pharmacol Biochem Behav, 2010. 95(4): p. 434-42.Ammerman, S., et al., The Impact of Marijuana Policies on Youth: Clinical, Research,and Legal Update. Pediatrics, 2015. HARM REDUCTIONAddress the treatment and prevention needs related to common co-morbidities including HIV/AIDS and hepatitis C by researching supervised injection facilities –Supervised injection facilities (SIFs) are controlled health care settings where people can more safely inject drugs under clinical supervision and receive health care, counseling and referrals to health and social services, including drug treatment. They have shown promise in preventing the transmission of blood-borne diseases such as HIV and hepatitis C and are also effective at reaching people who are currently out of care and linking them to treatment, both for drug dependence and for HIV and hepatitis C. SIFs can play a unique and vital role as part of a larger public health and treatment approach to drug policy. SIFs are intended to complement – not replace – existing prevention, harm reduction and treatment interventions. This intervention deserves serious consideration and research.SIFs – also called safer injection sites, drug consumption rooms and supervised injecting centers – are legally sanctioned facilities designed to reduce the health and public order issues often associated with public injection by providing a space for people to inject pre-obtained drugs in a hygienic environment with access to sterile injecting equipment and under the supervision of trained medical staff. [1, 2]There are at least 98 SIFs operating in 66 cities around the world in ten countries (Switzerland, Germany, the Netherlands, Norway, Luxembourg, Spain, Denmark, Greece, Australia and Canada) – but none in the United States. [1-5]Numerous evidence-based, peer-reviewed studies from those countries have demonstrated the positive impacts of SIFs.[1-4, 6-32]These benefits include:Increased uptake into treatment for drug dependence, especially among people who are unlikely to seek treatment on their own.[22, 23, 27]Reduced public disorder, reduced public injecting, and increased public safety.[[6, 20, 21, 31, 33]Attracting and retaining a high risk population of people who inject drugs, who are at heightened risk for infectious disease and overdose. [8, 9, 28, 29, 34-36]Reducing HIV and Hepatitis C risk behavior (i.e. syringe sharing, unsafe sex)[3, 6, 8, 9, 11, 19-21, 26, 37, 38]Reducing the prevalence and harms of bacterial infections.[2, 3, 6]Successfully managing hundreds of overdoses and reducing drug-related overdose death rates. [2, 10, 25, 39-41]Cost savings resulting from reduced disease, overdose deaths, and need for emergency medical services. [12, 13, 16, 42]Providing safer injection education, and a subsequent increase in safer injectingpractices.[21, 43]Not increasing community drug use.[2, 3, 24]Not increasing initiation into injection drug use.[18]Not increasing drug-related crime.[6]Increased delivery of medical and social services.[6, 7] [22, 44, 45]There is an extensive body of research studying Insite in Vancouver, British Columbia, with more than two dozen peer-reviewed articles now published examining its effects on a range of variables, from retention to treatment referrals to cost-effectiveness.[3, 9] These reports are in line with reviews of the Australian [4, 33, 46] and European SIFs [5], which show that these facilities have been successful in attracting at-risk populations, are associated with less risky injection behavior, fewer overdose deaths, increased client enrollment in drug dependence treatment services, and reduced nuisances associated with public injection. For example, one recent study found a 30 percent increase in the use of detoxification services among InSite clients. NIDA-funded research could review those potential outcomes in the context of US health care provision and funding.InSite has proved to be cost-effective in terms of overdose and blood borne disease prevented as well. One cost-benefit analysis of InSite estimates that the facility prevents 35 new cases of HIV each year, providing a societal benefit of more than $6 million per year after accounting for the costs of the program. A recent study published in the prestigious journal The Lancet found that the fatal overdose rate in the immediate vicinity of InSite decreased by 35 percent since it began operating in 2003, while the rest of the city experienced a much smaller reduction of 9 percent.[2, 3, 6]SIFs are worth researching and evaluating as a component of a comprehensive public health approach to reducing the harms of drug dependence, especially the co-morbidities of HIV and hepatitis C. The pilot implementation of a legal supervised injection facility staffed with medical professionals to reduce overdose deaths, increase access to health services, and further expand access to safer injection equipment to prevent the transmission of HIV and hepatitis C is worth investigating in the United States.ReferencesSchatz, E. and M. Nougier, Drug Consumption Rooms: Evidence and Practice. 2012, International Drug Policy Consortium.Semaan, S., et al., Potential role of safer injection facilities in reducing HIV and hepatitis C infections and overdose mortality in the United States. Drug Alcohol Depend, 2011.118(2-3): p. 100-10.Kerr, T., et al., Findings from the Evaluation of Vancouver’s Pilot Medically Supervised Safer Injection Facility—Insite (UHRI Report). Vancouver, BC: BC Centre for Excellence in HIV/AIDS. Addiction and Urban Health Research Initiative, 2009.Maher, L. and A. Salmon, Supervised injecting facilities: how much evidence is enough?Drug Alcohol Rev, 2007. 26(4): p. 351-3.Hedrich, D., T. Kerr, and F. Dubois-Arber, Drug consumption facilities in Europe and beyond. MONOGRAPHS, 2010: p. 305.Potier, C., et al., Supervised injection services: What has been demonstrated? A systematic literature review. Drug Alcohol Depend, 2014. 145C: p. 48-68.McNeil, R., et al., Impact of supervised drug consumption services on access to and engagement with care at a palliative and supportive care facility for people living with HIV/AIDS: a qualitative study. J Int AIDS Soc, 2014. 17: p. 18855.MacArthur, G.J., et al., Interventions to prevent HIV and Hepatitis C in people who inject drugs: A review of reviews to assess evidence of effectiveness. International Journal of Drug Policy, 2013.Boyd, N., Lessons from INSITE, Vancouver's supervised injection facility: 2003-2012.Drugs: education, prevention and policy, 2013. 20(3): p. 234-240.Christian, G., et al., Overdose deaths and Vancouver's supervised injection facility. The Lancet, 2012. 379(9811): p. 117.Pinkerton, S., How many HIV infections are prevented by Vancouver Canada's supervised injection facility? Int J Drug Policy, 2011. 22: p. 179 - 183.Pinkerton, S., Is Vancouver Canada's supervised injection facility cost-saving? Addiction, 2010. 105: p. 1429 - 1436.Andresen, M. and N. Boyd, A cost-benefit and cost-effectiveness analysis of Vancouver's supervised injection facility. Int J Drug Policy, 2010. 21: p. 70 - 76.DeBeck, K., et al., Police and public health partnerships: Evidence from the evaluation of Vancouver's supervised injection facility. Substance Abuse Treatent, Prevention and Policy, 2008. 3(1): p. 1 - 5.Wood, R., et al., Nurse-delivered safer injection education among a cohort of injection drug users: evidence from the evaluation of Vancouver's supervised injection facility. IntJ Drug Policy, 2008. 19(3): p. 183 - 188.Bayoumi, A. and G. Zaric, The cost-effectiveness of Vancouver's supervised injection facility. Can Med Ass J, 2008. 179(11): p. 1143 - 1151.Des Jarlais, D., K. Arasteh, and H. Hagan, Evaluating Vancouver's supervised injection facility: Data and dollars, symbols and ethics. Can Med Assoc J, 2008. 179(11): p. 1105- 1106.Kerr, T., et al., Circumstances of first injection among illicit drug users accessing a medically supervised safer injection facility. Am J Public Health, 2007. 97(7): p. 1228-30.McKnight, I., et al., Factors associated with public injecting among users of Vancouver's supervised injection facility. Am J Drug Alcohol Abuse, 2007. 33(2): p. 319 - 325.Petrar, S., et al., Injection drug users' perceptions regarding use of a medically supervised safer injecting facility. Addict Behav, 2007. 32: p. 1088 - 1093.Stoltz, J., et al., Changes in injecting practices associated with the use of a medically supervised injection facility. J Pub Health (Oxford), 2007. 29(1): p. 35 - 39.Wood, E., et al., Rate of detoxification service use and its impact among a cohort of supervised injection facility users. Addiction, 2007. 102: p. 916 - 919.Wood, E., et al., Service Uptake and Characteristics of Injection Drug Users Utilizing North America’s First Medically Supervised Safer Injecting Facility. American Journal of Public Health, 2006. 96(5): p. 770-773.Kerr, T., et al., Impact of a Medically Supervised Safer Injection Facility on Community Drug Use Patterns: A Before and After Study. Br Med J, 2006. 332: p. 220 - 222.Kerr, T., et al., Drug-related overdoses within a medically supervised safer injection facility. Int J Drug Policy, 2006. 17: p. 436 - 441.Tyndall, M., et al., HIV Sero-prevalence among participants at a supervised injection facility in Vancouver, Canada: implications for prevention, care and treatment. Harm Reduction Journal, 2006. 3(36): p. 1 - 5.Tyndall, M., et al., Attendance, drug use patterns, and referrals made from North America's first supervised injection facility. Drug Alcohol Depend, 2005. 83(3): p. 193 - 198.Wood, E., et al., Prevalence and correlates of hepatitis C among users of North America's first medically supervised safer injection facility. Public Health, 2005. 119(12):p. 1111 - 1115.Wood, E., et al., Do supervised injecting facilities attract higher-risk injection drug users?Am J Prev Med, 2005. 29(2): p. 126 - 130.Small, D., Mental illness, addiction and the supervised injection facility. Visions: BC's Mental Health and Addictions Journal, 2004. 2(1): p. 37 - 39.Wood, E., et al., Changes in public order after the opening of a medically supervised safer injection facility for injection drug users. Can Med Assoc J, 2004. 171(7): p. 731 -734.Fairbairn, N., et al., Women's experiences in North America's First Medically Supervised Safer Injection Facility. Soc Sci Med. 67(8): p. 817 - 823.Salmon, A.M., et al., Five years on: What are the community perceptions of drug-related public amenity following the establishment of the Sydney Medically Supervised InjectingCentre? International Journal of Drug Policy, 2007. 18(1): p. 46-53.Reddon, H., et al., Use of North America’s first medically supervised safer injecting facility among HIV-positive injection drug users. AIDS education and prevention: official publication of the International Society for AIDS Education, 2011. 23(5): p. 412.Hadland, S.E., et al., Use of a Medically Supervised Injection Facility Among Drug- Injecting Street Youth. Journal of Adolescent Health, 2014. 54(2): p. S88-S89.Wood, E., et al., Factors associated with syringe sharing among users of a medically supervised injecting facility. Am J Infect Dis, 2005. 1(1): p. 50 - 54.Kerr, T., et al., Safer injecting facility use and syringe sharing among injection drug users. Lancet, 2005. 366: p. 316 - 318.Kerr, T., et al., The role of safer injection facilities in the response to HIV/AIDS among injection drug users. Current HIV/AIDS Reports, 2007. 4(4): p. 158-164.Kerr, T., et al., A Micro-Environmental Intervention to Reduce Harms Associated with Drug-Related Overdose: Evidence from the Evaluation of Vancouver's Safer Injection Facility. Int J Drug Policy, 2007. 18: p. 37 - 45.Marshall, B.D., et al., Reduction in overdose mortality after the opening of North America's first medically supervised safer injecting facility: a retrospective population- based study. The Lancet, 2011. 377(9775): p. 1429-1437.Milloy, M.-J., et al., Non-fatal overdose among a cohort of active injection drug users recruited from a supervised injection facility. The American journal of drug and alcoholabuse, 2008. 34(4): p. 499-509.Jozaghi, E., A. Reid, and M. Andresen, A cost-benefit/cost-effectiveness analysis of proposed supervised injection facilities in Montreal, Canada. Substance Abuse Treatment, Prevention, and Policy, 2013. 8(1): p. 25.Wood, E., et al., Safer injecting education for HIV prevention within a medically supervised safer injecting facility. Int J Drug Policy, 2005. 16: p. 281 - 284.Wood, E., et al., Attendance at supervised injecting facilities and use of detoxification services. N Eng J Med, 2006. 354(23): p. 512 - 514.Wood, E., et al., Service uptake and characteristics of injection drug users utilizing North America's first medically supervised safer injection facility. Am J Public Health, 2006. 96(5): p. 770 - 773.Salmon, A.M., et al., The impact of a supervised injecting facility on ambulance call‐outsin Sydney, Australia. Addiction, 2010. 105(4): p. 676-683.Expand NIDA’s research priorities to include risk factors and harm reduction within nightlife and festival settingsA significant portion of drug use, especially among young people, takes place in nightlife and festival settings and yet the quantity of available research does not reflect that.[1-6]The majority of this drug use is non-problematic; that is, does not meet the traditional definitions of dependence or addiction.[5-17] However it can involve risky use behaviors that can lead to hospitalization and deaths.[18] Given the current popularity of large-scale festivals and events with attendance in the tens of thousands or even hundreds of thousands, we need a better understanding of the demographic makeup of these populations, as well as epidemiological data on the rate and nature of drug-related hospitalizations and deaths.Another trend that is not well understood in the US context is patterns of use and misuse of novel psychoactive substances (NPS), for which only limited prevalence data are collected. [19, 20] In contrast to many European countries, [21] which have monitored the situation for several years – having seen higher rates of intentional use of NPS (such as with the example of mephedrone) – this issue has more recently emerged in the US. [21-23] It deserves attention since as popular drugs such as cannabis, MDMA and other psychedelics remain illegal and hard to acquire, the iterative copycat versions of these drugs will keep appearing on the scene.[23-25] [26]The escalating speed with which NPS appear as well as the current popularity of large scale music events and festivals make further study of harm reduction responses crucial. This includes not only deepening evaluations of peer-based drug education efforts, for which support in the research already exists, [2-4, 27, 28] but also looking seriously at the practice of drug testing for adulterants. This practice, also known as “pill testing” or “drug checking” in the European context where it has been in place for many years, can provide a critical tool for people to identify dangerous or unexpected substances in the drugs they intend to consume. [29-33] Further research is needed to identify how this changes drug-using behavior, as well as to determine which among the technologies available are most practical and effective. Other factors that may contribute to changes in drug using behavior, like the location of drug checking services and their coordination with counseling and connection to treatment services if needed, should be explored.Recommendations:NIDA should fund research aiming to collect epidemiological data on hospitalizations and deaths related to attendance at US music festivals and other large-scale nightlife venues and events. NIDA should conduct further research on novel psychoactive substance use patterns in the US – including investigation into which substances are being by whom and in what contexts. Finally, NIDA should invest in studies on the efficacy of harm reduction interventions in nightlife environments – particularly regarding the efficacy of recreational “drug-checking” and impact of such practices on drug use behavior.ReferencesVan Havere, T., et al., Drug use and nightlife: more than just dance music. Substance abuse treatment, prevention, and policy, 2011. 6(1): p. 18.Hunt, G., M. Moloney, and K. Evans, Youth, Drugs, and Nightlife: Pleasures, Risks, and Identity. 2010: Routledge.Calafat, A., et al., Recreational nightlife: Risk and protective factors for drug misuseamong young Europeans in recreational environments. Drugs: Education, Prevention, and Policy, 2008. 15(2): p. 189-200.Bolier, L., et al., Alcohol and drug prevention in nightlife settings: a review of experimental studies. Subst Use Misuse, 2011. 46(13): p. 1569-91.Winstock, A., P. Griffiths, and D. Stewart, Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK. Drug and alcohol dependence, 2001. 64(1): p. 9-17.Winstock, A., The Global Drug Survey 2014 findings. 2014.Siliquini, R., et al., Recreational drug consumers: Who seeks treatment? European Journal of Public Health, 2005. 15(6): p. 580-586.Sanders, B., Drugs, clubs and young people: Sociological and public health perspectives. 2012: Ashgate Publishing, Ltd.Ramo, D.E., et al., Cocaine use trajectories of club drug-using young adults recruited using time-space sampling. Addict Behav, 2011. 36(12): p. 1292-300.Parks, K.A. and C.L. Kennedy, Club drugs: reasons for and consequences of use.Journal of psychoactive drugs, 2004. 36(3): p. 295-302.Miller, B.A., et al., Assessment of club patrons’ alcohol and drug use: the use of biological markers. American journal of preventive medicine, 2013. 45(5): p. 637-643.Miller, B.A., et al., Group influences on individuals' drinking and other drug use at clubs.J Stud Alcohol Drugs, 2013. 74(2): p. 280-7.Kelly, B.C., J.T. Parsons, and B.E. Wells, Prevalence and predictors of club drug use among club-going young adults in New York City. Journal of Urban Health, 2006. 83(5): p. 884-895.Järvinen, M. and S. Ravn, From recreational to regular drug use: qualitative interviews with young clubbers. Sociology of health & illness, 2011. 33(4): p. 554-569.Grov, C., B.C. Kelly, and J.T. Parsons, Polydrug use among club-going young adults recruited through time-space sampling. Substance use & misuse, 2009. 44(6): p. 848-864.Duff, C., The pleasure in context. Int J Drug Policy, 2008. 19(5): p. 384-92.Anderson, T.L., et al., Variations in clubbers' substance use by individual and scene- level factors. Adicciones, 2009. 21(4): p. 289-308.Ridpath, A., et al., Illnesses and deaths among persons attending an electronic dance- music festival-New York City, 2013. MMWR: Morbidity and mortality weekly report, 2014.63: p. 1195-1198.Substance Abuse and Mental Health Services Administration, Results from the 2013 National Survey on Drug Use and Health. 2014, Substance Abuse and Mental Health Services Administration: Rockville, MD.Johnston, L.D., et al., Monitoring the Future national survey results on drug use: 2014 Overview, Key Findings on Adolescent Drug Use. 2015, Ann Arbor: Institute for Social Research, The University of Michigan.Hughes, B. and P. Griffiths, Regulatory approaches to new psychoactive substances (NPS) in the European Union. Addiction, 2014. 109(10): p. 1591-1593.Spiller, H.A., et al., Clinical experience with and analytical confirmation of "bath salts" and "legal highs" (synthetic cathinones) in the United States. Clin Toxicol (Phila), 2011. 49(6): p. 499-505.Measham, F., et al., Tweaking, bombing, dabbing and stockpiling: the emergence of mephedrone and the perversity of prohibition. Drugs and Alcohol Today, 2010. 10(1): p.14-21.Payer, D., Novel synthetic drugs: A neuroscience perspective, in Club Health. 2013, Drug Policy Alliance: San Francisco.Winstock, A. and C. Wilkins, ‘Legal highs’ The challenge of new psychoactivesubstances. Series on Legislative Reform of Drug Policies, Number Amsterdam: Transnational Institute, 2011.Perrone, D., R.D. Helgesen, and R.G. Fischer, United States drug prohibition and legalhighs: How drug testing may lead cannabis users to Spice. Drugs: Education, Prevention, and Policy, 2012: p. 1-9.Sumnall, H., et al., A choice between fun or health? Relationships between nightlifesubstance use, happiness, and mental well-being. Journal of Substance Use, 2010.15(2): p. 89-104.Whittingham, J.R., et al., Avoiding counterproductive results: an experimental pretest of a harm reduction intervention on attitude toward party drugs among users and nonusers. Subst Use Misuse, 2009. 44(4): p. 532-47.Winstock, A.R., K. Wolff, and J. Ramsey, Ecstasy pill testing: harm minimization gone too far? Addiction, 2001. 96(8): p. 1139-1148.Hungerbuehler, I., A. Buecheli, and M. Schaub, Drug Checking: A prevention measure for a heterogeneous group with high consumption frequency and polydrug use- evaluation of zurich's drug checking services. Harm reduction journal, 2011. 8(1): p. 16.Camilleri, A.M. and D. Caldicott, Underground pill testing, down under. Forensic Science International, 2005. 151(1): p. 53-58.Murray, R.A., et al., Putting an Ecstasy test kit to the test: harm reduction or harm induction? Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2003. 23(10): p. 1238-1244.MacCoun, R.J., Testing Drugs Versus Testing for Drug Use: Private Risk Management in the Shadow of Criminal Law. DePaul L. Rev., 2006. 56: p. 507.

Clinical and Translational Science, Public Health

1. Better methods of matching the many quality interventions available to individual cases, so that treatment can be individualized for better outcomes 2. Serious investigation into motivational factors which could be harnessed to bring more people to a place where they would consider appropriate treatment
The Society for Research on Nicotine and Tobacco (SRNT) applauds the National Institute on Drug Abuse (NIDA) for revitalizing its Strategic Plan and fully supports the many of identified priorities. In addition to our overall support, SRNT would like to put forward the following general recommendations.In addition to epidemiological and clinical research, basic science research can also focus on policy-oriented items. Thus, the importance of basic science research that provides practical knowledge that can inform policy while not necessarily addressing mechanistic hypotheses should be recognized.Clearly, basic neuroscience is important and deserves major focus. However, the importance of basic science that examines behavioral mechanisms of addiction also needs full consideration.Tobacco use remains the leading cause of preventable death and illness in the United States and thus research supporting treatment development for nicotine dependence and tobacco use disorders and dissemination of findings should be a priority.In addition, greater emphasis should be placed on support for the development of novel, evidence-based targeted prevention and treatment interventions for all substance abuse disorders. SRNT recommends three additional considerations be included as sub- priorities to this goal:Development and dissemination of effective behavioral interventions using novel strategies with wide-potential population reach.Emphasis on research into the development of treatments of substance abuse disorders among high risk populations such as low-SES persons and those with comorbid physical and psychiatric conditions. Substance abuse disorders have a disproportionate impact on these populations.Research on optimizing the timing and duration of interventions for substance abuse disorders in order to improve outcomes.Changes in drug policies (e.g., legalization of marijuana use in some states) and new technologies to administer drugs (e.g., electronic delivery systems) have contributed to a void in understanding of important issues related to substance abuse disorders. Issues that warrant serious consideration include:The effects of poly drug use and additives on abuse liability.The impact of different modes of drug delivery on both drug dependence and health, with a particular emphasis on electronic drug delivery methods.The impact of exposure to one substance or one form of delivery of that substance on subsequent use of other substances or other forms of the same substance.The impact of new polices and technologies on harm reduction.

Clinical and Translational Science, Public Health, Basic Science, Unifying Themes

Here are the areas that I believe are important priorities:Not on the list:Novel delivery methods for treating brain disorders: The development of non-invasive routes of delivery of compounds or genes to the CNS should be considered a top priority. Educate the public about addiction and how it is a disease: This is very important as drug addicts do not receive the proper care or support from their families and communities. They are treated as criminals. From the list:Better define the interactions between addiction and pain, including molecular, genetic, behavioral , and neural-circuit-related factors, to guide the development of alternate treatment strategies for pain patients: There is a huge opioid epidemic in the United States and experts believe that this is due to an increase in the prescription of pain medications. Most opiate abusers start using prescription meds in order to combat pain associated with injury or surgery. Therefore it is important to understand the mechanisms involved and to better define the interactions between pain and addiction. Increase readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, changing healthcare landscape, emerging drug trends, etc.): Same as above.Promoting research that considers the impact of sex and gender on drug abuse and addiction: More studies are highlighting that there are differences between the genders. Therefore we can not use the same approach and therapies to treat males and females. There needs to be more funding focused on gender differences. Improve our understanding of the interaction between addiction and co-occurring conditions: The number of co-occurring mental health disorders together with addiction issues is very high. We need to better understand how the two are related and what leads to drug use.Support the development of novel, evidence-based, targeted prevention and treatment interventions including social, behavioral, pharmacological, vaccines, and brain stimulation therapies (e.g., transcranial magnetic stimulation, direct current stimulation, etc.)Identify measures other than abstinence that can reliably assess SUD treatment outcomes Identify biomarkers of addiction, resilience, and recovery to enable personalized treatment: Without biomarkers we will not be able to predict how a therapy is working or whether or not it is effective.

Clinical and Translational Science, Public Health, Basic Science, Unifying Themes, Infrastructure

The following is a list of priority areas that we feel represent understudied topics and/or knowledge gaps in the field:Evaluate agonist treatments for stimulant and cannabis use disorders - find ways to balance risks and benefitsRe-engineer the pipelines for med development with human laboratory studies and alternative early Phase II clinical trial designsCharacterize the use of electronic cigarettes for treating nicotine use disordersDetermine more effective ways of studying emerging drug problems ("dabbing," Spice, etc.)Examine co-abuse of substances (e.g., nicotine-marijuana, opiates-alcohol, marijuana-alcohol, opiates-benzodiazepines, cocaine-marijuana, etc.) and develop effective ways of treating co-abuseUse imaging techniques to identify treatment responseImprove the understanding of neurobiological and neuroimaging studies by incorporating drug-taking behavior and other abuse liability measures into the research where possibleStrongly support more efforts to promote research that directly examines the impact of sex and gender on drug abuse and addictionIn addition to the above, another important component for consideration is to improve how the Strategic Plan is implemented. The following are suggestions for accomplishing this:Develop procedures for communicating NIDA's interest and disinterest in certain research areas to the scientific communityDevelop a central forum at NIDA for IND's that can be accessed by granteesDevelop a more active interaction between NIDA and the DEA and FDA with regard to drug scheduling.

Clinical and Translational Science, Public Health, Infrastructure

The American Society of Addiction Medicine (ASAM) is grateful for this opportunity to comment on the National Institute on Drug Abuse’s (NIDA) 2016 Strategic Plan. ASAM is hopeful that the following comments regarding the draft 2016 research strategy strengthen what is already a thoughtful and robust agenda for future NIDA research.Clinical and Translational Science PrioritiesWhile the identification of new, evidence-based treatment interventions is necessary to address the diverse treatment needs of patients suffering with addiction, equally important is the development of practice guidelines and performance measures to encourage widespread adoption of these novel therapies. Furthermore, standardized methods for assessing quality of care, adherence to treatment and patient outcomes (e.g., urine drug testing) are needed to validate the relationship between evidence-based treatment and patient improvements in health and function.Public Health PrioritiesAddiction remains a highly stigmatized disease, despite the heightened awareness of prescription drug misuse and overdose death. NIDA, in collaboration with the Surgeon General, the Centers for Disease Control and Prevention and other federal stakeholders, could facilitate the development and dissemination of a broad public education campaign that addresses the common misperceptions, myths and fears related to addiction, treatment and recovery.Science Infrastructure PrioritiesThe vast majority of physicians do not receive any training on addiction in medical school. This results in a physician workforce with little to no knowledge about how to identify and treat patients suffering with addiction. Research that supports the integration of addiction curriculum into medical school would support efforts to both integrate addiction treatment into primary care and address shortages in the addiction provider workforce. Moreover, improved education may address the disinclination of many physicians to treat patients with addiction and, thereby, improve patient access to high-quality care.For physicians who do specialize in the treatment of addiction, the paucity of performance measures and practice-based research networks available to test the measures that do exist limits the specialists’ ability to gauge their effectiveness and the value of their medical expertise. ASAM respectfully requests that NIDA support the development of a practice-based research network of addiction physician specialists, in order to improve outcomes measurement and ongoing advancement in the field of addiction medicine.Again, ASAM is grateful for this opportunity to inform NIDA’s next strategic plan. Our members look forward to continued collaboration with NIDA, to advance the science and practice of addiction treatment.

Clinical and Translational Science, Public Health, Unifying Themes

The Association of State and Territorial Health Officials (ASTHO) appreciates the opportunity to submit comments on NIDA’s FY 2016-2020 Strategic Plan. ASTHO commends your efforts to ensure that public health is a key component of the plan and that it addresses a broad range of efforts to prevent and treat drug abuse and addiction and mitigate the impact of their consequences. We encourage you to consider an approach that assures scientific investigation that also includes recovery. Background ASTHO is a 501(c) (3) nonprofit membership association serving the state and territorial health officials and the more than 100,000 public health staff that work in the state and territorial agencies. ASTHO tracks, evaluates, and advises members on the impact and formation of health policy that may affect state or territorial health agencies, and provides guidance and technical assistance to its members on improving population health. ASTHO supports its members on a wide range of topics based on their needs, including promoting health equity, integrating public health and clinical medicine, responding to public health emergencies, reducing the harms associated with substance abuse with a focus on prescription drug misuse, abuse, and diversion and addressing the public health consequences of marijuana legalization. Prescription Drug OverdoseInappropriate prescribing practices and overutilization of opioids can result in serious adverse events and death. Deaths from drug overdose have steadily increased over the past two decades and have become the leading cause of injury and death in the United States. Among people 25- to 64-years-old, drug overdose causes more deaths than motor vehicle traffic crashes. Of the 22,134 deaths relating to prescription drug overdose in 2010, 16,651 (75%) involved opioid analgesics and 6,497 (30%) involved benzodiazepines. ASTHO supports federal, state, and community-based interventions that address prescription drug misuse, abuse, and diversion through a comprehensive framework that includes prevention, Surveillance, enforcement, and treatment and recovery. We recognize that each intervention is necessary but insufficient by itself. Additionally, ASTHO’s extensive work on this issue has generated collaboration across a range of disciplines and fields to support coordinated federal, state, and local efforts that address the prescription drug epidemic. As part of the 2014 ASTHO President’s Challenge to reduce the number of prescription drug deaths and rate of misuse and abuse 15% by 2015 (www.astho.org/rx), states pledged to address each of the areas of the comprehensive framework:· Thirty-two states focused on Prevention. Key themes addressed prescriber guidelines, education campaigns, school based programs, patient materials, Continuing Medical Education (CME) training both required and voluntary, enhanced drug disposal programs, and overdose prevention and naloxone access. Over the past two years, 25 states have enacted policies to expand access to naloxone through distribution by trained first responders or more broadly through friends and families of potential overdose victims. These laws often provide immunity from liability for those who administer naloxone in good faith. States have also enacted Good Samaritan laws, providing protections for those who seek medical assistance for individuals experiencing an overdose. States also were engaged in understanding how to provide access to care through pharmacies or in offices and utilize health reform and transformation to provide coverage for its use.· Thirty-five states pledged to support improved surveillance and monitoring. Key themes addressed increasing access and use of the Prescription Drug Monitoring Program (PDMP) for public health surveillance, supporting improved update of the usage of PDMP’s, utilizing PDMP’s to target underserved communities and areas of high need through mapping and hot-spotting, utilizing EMS electronic database that capture data on drug overdose and naloxone use by emergency professionals, and assisting in cross cutting surveillance with other drug use and alcohol use in states. States have continued to improve PDMPs by enacting policies to decrease the time that it takes for information to be reported to the database, requiring prescribers to query the database prior to prescribing, and allowing health departments to have access to the database for the purposes of conducting a population level analysis.· Twenty-two states pledged to support and collaborate with enforcement. Key themes included utilizing data for drug trafficking, continuing to support the Opiate Intervention Program within the state’s Medicaid system at the regulatory level, expanding law enforcement resources to increase availability of drug take-back programs, and increasing training for law enforcement and prosecutor groups at national and regional conferences on prescription drug abuse and diversion.· Twenty-three states pledged to support treatment and recovery efforts in their states. Key themes included promoting SBIRT protocols among hospitals and community providers; supporting the use of community health workers to link patients to services and provide support during recovery; supporting legislation for opioid treatment facilities; increased access to buprenorphine training for prescribers;, examining parity among health insurance plans for coverage; and developing systems of integrated care for individuals with co-occurring mental health and substance abuse issues.Recommendation: States are enacting policies and programs at a rapid rate to counter the prescription drug abuse epidemic. We encourage NIDA’s to support the evaluation of efforts underway in the states to address prescription opiate abuse. These evaluation efforts will assist states as they work to enact, implement and enforce evidenced-based policies to protect the health of the public.Legalization of Medical and Recreational MarijuanaPublic opinion is shifting toward favoring decriminalization or explicit legalization of marijuana. As a result, an increasing number of states and territories have enacted laws legalizing the medical and recreational use of marijuana. The recognized harms and health consequences of marijuana have seemingly been lost in the debate about the legalization. Marijuana continues to be the most commonly used illicit drug in the U.S. with patterns of use trending upward, particularly among young people. Treatment admissions for marijuana as the primary drug of abuse have tripled over the last 20 years and it is the second leading substance for which people receive drug treatment.State and territorial health agencies are often tasked with regulating their jurisdictions’ medical marijuana program. However, public health agencies also have a role to play in the prevention and mitigation of harms associated with marijuana use. ASTHO and its members appreciate NIDA’s efforts to research and disseminate findings on the implications of marijuana use, including: the risks of addiction, its role as a gateway drug, the effect on brain development, its relation to mental illness, the effect on school performance and achievement, the risk of motor-vehicle accidents, and the risk of cancer and other health effects. However, more research is needed in these and other areas.Recommendation: State-level marijuana policies are rapidly changing. Little is known about the affect these policies will have on public health outcomes. For example, we need a better understanding of the effects of second-hand cannabis smoke exposure. As the use of marijuana becomes normalized and increases, so likely will the associated harms and health consequences. We will need to be prepared to communicate the evidence of these harms, address misuse and addiction, and expand access to treatment. We encourage that NIDA’s strategic plan have a priority to research the potential consequences of marijuana legalization. Additional recommendations for your consideration · In the section ”Clinical and Translational Science” :o We strongly encourage the addition of recovery interventions to the prevention and treatment interventions you have indicated. o We support your inclusion of “Overdose prevention or reversal” with the recommended addition that this includes research on impact of “rescue drugs” accessible to first responders, family and friends and the general public. · In the section “Public Health: Increase the public health impact of NIDA research and programso We applaud this focused section in the plan and inclusion of research on the successful implementation. Additionally we recommend this include research on sustainability and replication of public health interventions.o We strongly support the section: “Increase readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, changing healthcare landscape, emerging drug trends, etc.)” Additionally, as noted above we emphasize the need for a priority focus on research of the potential consequences of marijuana legalization with a special focus on impact on youth.· In the section “Unifying themes” we strongly encourage that these themes are significantly, not just peripherally, included across all areas of the strategic plan. We encourage you to go beyond research on health disparities and include in the plan health equity with the aim to understand interventions that improve health equity. As described above, ASTHO and our members the state public health officials are engaged and actively supporting the efforts highlighted in NIDA’s strategic plan. We are pleased that public health is considered a key component of your strategy and look forward to working with you to prevent and treat drug abuse and addiction and mitigate the impact of their consequences.

Clinical and Translational Science, Unifying Themes

As research priorities move more and more in the direction of medication development and biological indicators of substance use disorders, it is critical that behavioral interventions do not get misplaced. The development of efficacious behavioral interventions is still desperately needed, particularly those tailored to extremely high-risk, vulnerable populations. Similarly, funding priorities should be increased for MSM and transgender women as these two populations experience the greatest health disparities and the most significant associations between substance use and HIV infection.

Format, Basic Science, Clinical and Translational Science, Infrastructure

Background The mission of NIDA is to lead the nation in bringing the power of science to bear on drug abuse and addiction. NIDA fulfills this mission by supporting research to prevent and treat drug abuse and addiction and mitigate the impact of their consequences, including the spread of HIV/AIDS and other infectious diseases. NIDA-supported programs span basic, clinical, and translational sciences and incorporate genetics, epigenetics, neuroimaging (functional, biochemical, structural), social neuroscience, medication and behavioral therapy development, as well as prevention and health services research.The current NIDA Strategic Plan was published in 2010. Since that time, there have been major advances in the science of drug abuse and addiction. Therefore the Institute has begun a planning process to develop a revitalized Strategic Plan for 2016–2020. NIDA seeks to harness the latest research technologies and apply them to the ever-evolving substance abuse landscape. Toward this goal, NIDA staff developed a draft set of strategic priorities and are seeking feedback to guide the development of NIDA’s Strategic Plan.Information RequestedThis RFI is intended to gather broad public input on the draft strategic priorities outlined below as well as general recommendations that will sustain recent advances and accelerate discovery in addiction research over the next five years. NIDA invites input from researchers in academia and industry, health care professionals, patient advocates and advocacy organizations, scientific or professional organizations, federal agencies, and other interested members of the public. Organizations are encouraged to submit a single response that reflects the views of their organization and membership as a whole.Please provide your perspective on the following items as they relate to the draft strategic priorities outlined below. Your comments can include, but are not limited to: Suggested changes or additions to the list of strategic priorities, including emerging research needs and future opportunities that should be considered in the plan The scientific rationale for the changes or ideas proposed and the anticipated impact on advancing the science of drug abuse and addiction Anticipated challenges that will need to be addressed to achieve these priorities Appropriate benchmarks for gauging progress toward each recommended priority Recommended measurable objectives associated with an individual priority NIDA also welcomes your general comments, including those regarding the extent to which this plan will guide and encourage participation in drug abuse research.Draft Strategic Priorities (A general comment is these objectives are almost too broad and too general to be meaningful – in an industrial setting they would be rejected as likely to unachievable no matter how many teams of researchers you “throw” at them. So I have made some track changes I hope are helpful to the NIDA team.) ed note: changes are incorporated, comments are parenthetical.Basic Neuroscience: Continue to increase the preclinical database concerning drug use, vulnerability to addiction, withdrawal, relapse and recovery. with focus on biological, behavioral, environmental, and developmental factors involved in risk for drug use and addiction and the factors influencing resilience and recovery This requires: 1)Integrating the preclinical data base across behavioral genetic, epigenetic and potential molecular biomarkers of drug use, abuse and addiction. 2) Continuing to determine the developmental trajectory of addiction (Since these studies in the preclinical setting are done in the absence of a social environment, not likely to yield directly translatable information. I might omit this particular sentence and stick to vulnerability of developing brain to addiction and determining which drug class is preferred at various developmental stages) 3) Continuing to delineate the brain circuits related to drug abuse and addiction at the cellular, circuit, and connectome levels, which includes:: Normal development and function across the lifespan including mechanisms of reward, self-control, and conditioning The effects of drugs of dependence on neuroplasticity, neural structure, and circuit function from acquisition/use to addiction/dependence, through to withdrawal and recovery. Neural-glial, -immune, and neuroendocrine interactions as applicable to the studies above. Defining the interactions between addiction and pain, including molecular, genetic, behavioral , and neural-circuit-related factors, to guide the development of alternate treatment strategies for pain patients (Is this not better served by a cross institute approach as only focusing on the interaction between addiction and pain may miss important intervention opportunities for pain in general) 3) Continuing to elucidate the significant determinants of addiction in those with comorbid conditions (eg.psychiatric, HIV, HCV, pain). And the converse to determine the impact of addiction on the underlying diseases such as whether the molecular mechanisms of latent HIV reservoirs in the brains of SUDindividuals differ from those without SUD Clinical and Translational Science: Support (Support is a weak term – how about Direct resources toward the development?) the development of new and better interventions including preventative and treatments for SUDs. To fulfil this objective resources will be allocated as follows: Support the development of novel, evidence-based (If they are novel it is hard to have a clinical evidence base yet – just using buzz words?), targeted prevention and treatment interventions including social, behavioral, pharmacological, vaccines, and brain stimulation therapies (e.g., transcranial magnetic stimulation, direct current stimulation, etc.) Target the introduction of novel prevention and treatment interventions that may be social, behavioral, pharmacologic (including vaccines)or devices (transcranial magnetic stimulation as an example)Identify the most promising targets and or ligands to assiste in new drug discovery and developmentCollaborate in the effort to accelerate medications development for SUDFocus this development on SUD with no known pharmacologic treatment for either dependence, toxicity, withdrawal or agents to hasten neurobiologic recoveryTarget treatments for SUD plus comorbidities (HIV,pain as examples) Develop techniques to measure and improve patient compliance in clinical trials (This should be a cross agency endeavor if limited to addiction may result in tailored but not generalizable data/techniques – I would develop the techniques broadly then apply to SUD)2) Describe and quantify measurable outcomes beyond abstinence that can be used in clinical trials/clinical assessment of SUD. These outcomes could include biomarkers of addiction, withdrawal, relapse risk or sustained relapse. Public Health: Increase the public health impact of NIDA research and programsImprove the understanding of factors that influence the integration of evidence-based research findings into healthcare policy and practice (implementation science) Increase readiness to respond to emerging public health priorities (opioid overdose epidemic, potential consequences of marijuana legalization, changing healthcare landscape, emerging drug trends, etc.) Increase strategic partnerships with the community (academia, PhRMA or pharmaceutical companies, biotechnology companies, healthcare organizations, policy makers, etc.) to enhance the dissemination of evidence-based research findings into policy and practice Strengthen the focus on bi-directional translational research Science Infrastructure: Enhance the national research infrastructure to support advancements in science 1) Accelerate the development and utilization of advanced technologies (e.g. the President’s BRAIN Initiative), data repositories (e.g. Big Data to Knowledge (BD2K) initiative, and statistical models to spur innovative research 2) Improve training for the next generation of scientists 3) Increase effective engagement and training in multidisciplinary research (informatics, engineering, computer science, chemistry, mathematics, physics, etc.) 4) Increase the number of well-trained underrepresented scientists in the drug abuse and addiction field at all career levels because this ensures diversity in scientific discovery and the inclusion of the needs of diverse populations 5)Improve mentoring of young scientists and junior faculty 6) Increase effective collaborations in research (All research or specific to SUD?/mission) 7)Increase the transparency of research performed by grantees and within NIDA 8) Increase effective data and resource sharing (big data (More buzzwords of the moment – but big data means: mining data from insurers, large care providing institutions and available data from pharmaceutical companies??), biorepositories, transgenic/optogenetic tools (Sharing resources developed by grantees, such as optogenetic tools), data standards, etc.) 9) Increase collaborations with other NIH Institutes and Centers (e.g. Collaborative Research on Addiction at NIH (CRAN)), Federal and State agencies, academic and industry partners, etc.( We try to avoid etc in industry – people interested in how their money is spent don’t like it much) 10) Identify and implement strategies to improve the reproducibility of pre-clinical research(This is probably the most important statement in the document but belongs with transparency and should be the highlighted rationale for transparency – you can even comment on it under drug development) 11)Enable efficiency and lower the cost of clinical trials via innovative statisticalmethods such as adapative design, helping to establish SUD data collection and reporting standards, leveraging technology (e.g. electronic health records) and developing partnerships 12)Develop and validate computational and systems-level analytics for integrating multi-dimensional data across the addiction trajectory(And in reality this means?) Unifying themes: A number of unifying themes that will be addressed across each of the domains listed above include: Promoting research that considers the impact of sex and gender on drug abuse and addiction Addressing health disparities among underrepresented populations Understanding the role of development across the life span Addressing the treatment needs of adolescents and pregnant and post-partum women (For what it is worth first time mentioned in whole document) Addressing the treatment and prevention needs related to common co-morbidities including HIV/AIDS

Format, Basic Science, Public Health, Clinical and Translational Science, Unifying Themes, Infrastructure

On behalf of the American Psychiatric Association (APA), the medical specialty association representing 36,000 psychiatrists and their patients and families, I am pleased to share APA’s comments on the National Institute on Drug Abuse’s draft strategic plan. We would like to commend NIDA on developing a well-organized draft that is thoughtful, comprehensive, impactful and wide-reaching in its scope. Our feedback on the draft strategic priorities reflects our great concern about the impact of substance use disorders on people in the U.S. and great hope for improvement in the realm of research going forward.APA strongly supports NIDA's mission. Abuse of and addiction to alcohol, nicotine, and illicit and prescription drugs cost Americans more than $700 billion a year in increased health care costs, crime, and lost productivity.1-3 Each year, illicit and prescription drugs and alcohol contribute to the death of more than 90,000 Americans, while tobacco is linked to an estimated 480,000 deaths per year.4-5 These disorders are diagnosable and treatable, and when not treated are associated with suffering, premature death and diminished quality of life. The presence ofsubstance use disorders can also exacerbate the severity of other medical illnesses, inhibit appropriate medical management, and is associated with increased general medical costs.We particularly appreciate several aspects of NIDA’s current work and its draft strategic plan including in the basic neuroscience domain. Efforts to gain greater knowledge about the multiplicity of factors for risk and resilience in drug use and addiction and understanding the developmental pathways of addiction and individual heterogeneity are extremely important. NIDA’s awareness of the need to focus on drug use and co- occurring conditions including HIV/AIDs is to be applauded. This priority is consonant with NIDA’s excellent work on comorbidities in relation to mental health, HIV, and the Hepatitis C virus.NIDA’s draft strategic priority centered on the development of novel, evidence-based, targeted prevention and treatment interventions in a variety of domains is essential. In particular, focused development efforts on overdose prevention and reversal hold great promise in the face of the recent epidemic levels of opiate use disorders and mortality due to overdose. The APA agrees with and praises NIDA on its attention to the public health domain and its prioritization of the identification of factors that facilitate the integration of evidence-based research findings into healthcare policy and practice. In addition, the APA concurs with NIDA about the importance of increasing partnership with a wide variety of stakeholders to advance the dissemination of evidence-based research findings into policy and practice.APA appreciates NIDA drawing attention to the need for acceleration of development and utilization of advanced technologies. In addition, we commend NIDA’s focus on generating higher levels of transparency and reproducibility of research.We wish to acknowledge that NIDA has proposed appropriately that the domains of its draft priorities on drug use be regarded through the multiple lenses of gender, age spectrum and life course, underrepresented and underserved populations, and common comorbidities.NIDA’s draft has stimulated several additional suggestions and recommendations which we respectfully offer for NIDA’s consideration. The highlights of these suggestions span the full range of areas covered in the draft and are summarized as follows:Basic Neuroscience: Encourage research on neurobiological correlates of vulnerability to addictions and the study of treatment targets as a consideration of neurobiological correlates of recovery.Clinical and Translational Science: Support bidirectional research involving translation of bench findings to clinical research in humans as well as research on strengthening bedside to bench. Ensure that functional measures are included along with biomarkers of addiction, resilience and recovery to enable personalized treatment. Support dissemination of research so that evidence-based practices are applied in the community. Develop evidence-based approaches to substance use disorder interventions in integrated care settings. Increase efforts to develop more efficacious medications for treating addictions. Foster collaborative research involving psychiatry and general medicine given the high morbidity and mortality associated with comorbidity of substance use disorders and medical illnesses. Expand focused development efforts to study population-based strategies for treatment adherence in patients living with substance-related disorders, HIV, and the hepatitis C virus.Public Health: Conduct research on cost analysis and economic feasibility of treatments. Engage in greater dissemination of NIDA progress, initiatives, research and education to outlets with strong public health impact including the health media. Undertake initiatives to improve training of clinicians at the front lines of public health, equipping them with tools for clinical implementation to decrease the research-practice gap. Consider pursuing efforts to improve the understanding of how interventions should be tailored to meet the needs of diverse populations: gender, race/ethnicity, sexual orientation, gender identity and limited English proficiency. There is also a need for greater attention to the interrelationship between substance use disorders and trauma, given that sexual assault and abuse frequently trigger substantial rates of substance use disorders.Science Infrastructure: Encourage collaborative efforts with: federal agencies including the Department of Veterans Affairs and SAMHSA; cross Institute and academic centers with brain banks and genetic material depositories; and professional organizations such as APA, American Association of Addiction Psychiatry, American Society of Addiction Medicine, and others. Develop and mentor well-trained female and underrepresented scientists in the drug abuse and addiction field at all levels. Establish a partnership between the APA and NIDA modeled after the highly successful Program for Minority Research Training in Psychiatry (PMRTP), which was funded by NIMH, to lead young researchers into the field.Unifying Themes: Consider bringing this section to the front of the draft to assist readers in placing specific strategic priorities in context. In order to ensure that NIDA’s work addresses the full breadth of the U.S. population, include factors such as age, race, ethnicity, gender, sexual orientation, gender identity and social determinants of health.The following paragraphs delineate our detailed response to each area of NIDA’s draft strategic priorities:Basic NeuroscienceAPA proposes additions to the draft priorities in this area.Neurobiological CorrelatesWith regard to the improvement of understanding of brain circuits related to drug abuseand addiction at the cellular, circuit, and connectome levels, neurobiological correlates of vulnerability to addiction should also be included. Another area in the category of basic neuroscience that deserves attention is treatment targets, which should be a consideration of the neurobiological correlates of recovery.Comorbidity of Substance Use Disorders and Chronic DiseasesAPA requests NIDA bolsters its attention to the comorbidity of substance use disorders and medical illnesses. Thanks to previous NIDA research, it is well recognized thatsubstance use disorders are a significant contributor to the severity, morbidity, and mortality from many illnesses, including cardiovascular disease, gastrointestinaldisorders, HIV/AIDS, and pain disorders. APA recommends that NIDA expand its support for collaborative research between psychiatry and general medicine to furtheraddress these comorbidities and develop an array of effective interventions.4DiversityDrawing on one of the aforementioned unifying themes of diversity, it also is importantto consider the role of race as a determinant in the prevalence of co-occurring disorders. This issue is particularly relevant among racially diverse, vulnerable populations experiencing what has been referred to as “the triple whammy” of mental illness, addiction, and chronic disease, particularly HIV.Clinical and Translational ScienceAPA would like to suggest augmentation to NIDA’s vision in this area.Bidirectional Research, Functional Measures, Animal Models and Complex AddictionsWe recommend that NIDA consider supporting the translation of bench findings to clinical research in humans, as well as research on strengthening bedside to benchapplications (bidirectional research). With regard to clinical and translational scientific approaches, we recommend the inclusion of functional measures along with biomarkersof addiction, resilience, and recovery to enable personalized treatment. Clinical and translational research could also be used to assess the applicability of animal models or addiction mechanisms identified from animal models for human addiction vulnerability and treatment. APA encourages NIDA to support efforts on the treatment of complex addiction involving multiple substances.Age and Developmental ConsiderationsWhile addressing clinical and translational research domains, it is essential to concentrateon populations of study for focused developmental efforts including adolescents, young adults, and geriatric populations. One example of this is the need for research on addiction to prescription and pain/benzodiazepine medications and interventions for withdrawal in older adult populations.Dissemination of ResearchAPA strongly supports NIDA's dissemination of research and implementation of science so that evidence-based practices are dispersed to the community. NIDA's Clinical TrialNetwork (CTN) is an outstanding example of this important public health concept.Substance Use Disorder Treatment in Integrated SettingsChoosing where and how to invest finite resources is critically important. APA supportsNIDA's strong emphasis on the identification and evaluation of high-quality, cost- effective models for substance use disorder treatment services in integrated care settings. However, APA recommends this work build on the current excellent NIDA efforts (e.g., the development of screening tools for primary care and other healthcare professionals to assess patients or clients for tobacco, alcohol, and other drug use) to begin to focus on development of evidence-based approaches to substance use disorder interventions in these settings, such as the primary care opiate dependence intervention program.6 Theseactivities highlight the importance of integrating primary care with behavioral health components.There is a robust and growing research base documenting the ability of integrated care models to improve health outcomes. More research is needed on the dissemination and implementation of these models in a wide range of real-world practice settings, as well ason increasing our understanding of the economic impact of integrated care. APA enthusiastically supports research on the responsible integration of technology into all levels of the health care system, in the service of enhancing clinical interventions, and improving patient outcomes.Similarly, mental health services are benefiting from a growing interest in the development of collaborative care programs. Indeed, there is clear evidence of the role for integrated care in managing mental illness and reducing the disease burden of comorbid chronic conditions, such as hypertension and diabetes. Furthermore, the work of Jürgen Unützer, M.D., has identified that racial/ethnic minority women may have a more robust response to collaborative care programs than White (non-Latino) counterparts from similar socio-economic backgrounds. However, there is still a need for more research identifying effective models for the integration of substance use disorder treatment into primary care clinics. This is an additional area where NIDA can make a significant contribution.Medications for Addiction TreatmentAPA is appreciative of the development efforts on treating addictions that are currentlywithout FDA-approved medications. APA suggests these efforts include the treatment of addictions both with and without FDA-approved medications. Currently, FDA-approved medications for addictions do not lead to completely satisfactory outcomes. For example, both bupropion and varenicline (FDA-approved medications to assist with tobacco smoking) have a 1-year abstinence rate of approximately 10%, which is only double the success rate of people trying to quit without medication. Clearly, there is a great need for medications with better efficacy. A recent study showed that varenicline combined with nicotine replacement therapy was more effective than varenicline alone in achieving abstinence from tobacco but further study is needed to assess long term efficacy andsafety. 7Comorbidities of Substance Use Disorder, HIV/AIDS and Hepatitis CAPA asks that NIDA consider expanding its focused development efforts in its strategic plan to researching population-based strategies for treatment adherence in patients livingwith substance-related disorders, HIV, and the hepatitis C virus. Translational science such as this will be critical to ensuring that clinicians, substance abuse counselors, andothers have effective tools to curb the HIV epidemic. As research continues to show promising HIV-prevention interventions in drug abuse treatment settings, a cascadecontinues to exist in which the rates of treatment adherence declines for persons living with HIV and substance-related disorders who were previously linked to care.8 APA believes that continued research in treatment adherence strategies is a key to preventing the spread of HIV/AIDS and improving the vitality of patients living with HIV and asubstance-related disorder.Furthermore, the medical field has concluded that those currently most at risk for HIV are black men who have sex with men (MSM), yet there are still unmet HIV-related service delivery needs among black MSM.9 Additionally, recent evidence has shown that social determinants such as incarceration, stigma, discrimination, social isolation, mental health disparities, or social networks play a significant role in the elevated incidence rates of HIV.10 APA asks that NIDA further consider including investments in research of preventative biopsychosocial interventions that aim to meet the needs of dual-minority populations, such as the black MSM community, into their strategic plan.Public HealthEffective progress in the prevention, reduction, and recovery from substance usedisorders is a complex undertaking. Of note, prevention of substance use disorders is not thoroughly delineated in the current draft strategic priorities. In the realm of public health and the need to increase the public health impact of NIDA research and programs, APA has a number of suggestions to expand upon prevention priorities in the draft strategic plan.Cost AnalysisConducting research on costs associated with drug abuse and the economic feasibility oftreatments would be helpful to the field.Publicizing NIDA ProgressGreater dissemination of NIDA progress, initiatives, research, and education to outletswith strong public health impacts would be useful, including the health media. In particular, support for studying the efficacy of NIDA’s and other organizations’ public health messages, especially to vulnerable groups, such as adolescents, is crucial.Training of Clinicians in Public Health SettingsImplementing public health strategies for substance use disorders necessitatesimprovement in the training of clinicians at the front lines of public health, including developing and arming them with tools for clinical implementation to decrease the research-practice gap. A critical component of developing well-trained clinicians at the forefront of public health is mentorship of trainees interested in public health leadership to help address workforce shortages, an area for which NIDA is urged to consider continuing its robust support.Diverse PopulationsAPA requests that NIDA further improve the public health sector's understanding of how interventions should be tailored to meet the needs of diverse populations (e.g., gender,race/ethnicity, sexual orientation, gender identity and limited English proficiency). A specific example related to this is the recent decriminalization of non-medical cannabisuse in Washington State and Colorado. There has been an emergence of sales outlets located in communities of color. The APA suggests that NIDA consider assessingpatterns of legal sales, drug use, and disparities in impact, for example, co-location of drug oases in food deserts.Connection between Substance Use Disorders and TraumaAPA strongly encourages NIDA to focus attention on the interrelationship between substance use disorders and trauma. The field of psychosomatic medicine offers a uniquevantage point to see a powerful interplay between trauma, mental illness, stigma, addiction, and the costly medical consequences of unrecognized/untreated conditions.Data reveal that sexual assault/abuse frequently results in substantial rates of substance use disorders, and substance use disorder treatment may precipitate re-emergence ofPTSD symptoms. NIDA is uniquely positioned to advance this research through its Clinical Trial Network.Science InfrastructureEnhancing the national Science Infrastructure is required to support advancements in science. APA appreciates the suggested areas of focus in NIDA’s draft strategic plan andoffers additional input.Fostering CollaborationAPA recommends that NIDA further strengthen its collaboration with the Department ofVeterans Affairs (VA) and the Substance Abuse and Mental Health Services Administration (SAMHSA). NIDA's cooperation with the Department of Defense and the VA is critically important to advance the development of non-opioid pain management medication. Cross-institute/academic center collaborations with brain banks and other biological material depositories (such as genetics) will lead to important partnerships and advances in the field; this will require concerted efforts across the NIH Institutions. APA offers its assistance to increase collaborative efforts between NIDA and professional organizations including the APA, American Academy of Addiction Psychiatry (AAAP), American Osteopathic Academy of Addiction Medicine (AOAAM), and the American Society of Addiction Medicine (ASAM).Increase Diversity in the Scientific WorkforceWith regard to the development of human resources to augment the science infrastructure, APA requests NIDA's further efforts to cultivate well-trained female andunderrepresented scientists in the drug abuse and addiction field at all career levels. Training should include health disparities and cultural competence. Relatedly, more emphasis on the mentoring of young scientists, particularly women and under- represented minorities would be helpful to the field and would have a positive impact on patient care. APA has had great success in the past partnering with NIMH in the development of such a program, the Program for Minority Research Training in Psychiatry. This program was extremely successful, leading to the development of over 500 psychiatrist researchers from underserved and underrepresented populations whohave achieved at the highest levels of science.11 Such a program focused on women and minorities could easily be duplicated involving a partnership between the APA andNIDA.Increasing the Pipeline of Scientific ResearchersAPA recognizes the federal funding environment has impacted all of NIH. Difficultdecisions have been made at every Institute to adapt to flat research financing. Nevertheless, APA is concerned that the mechanisms to fund training and mentorship are declining and request NIDA re-examine these tools which are a critical area to develop researchers. Of particular concern to the APA is the declining number of physician- scientists and the significant delay in funding RO1 grants for young researchers. The struggle for young researchers to be funded has had an adverse effect on building the scientific workforce. Current fiscal pressures have negatively impacted research program grants (P30, P50, P60) which are utilized to develop local hubs with strategic scientific focus that can support training. NIDA recently limited Centers to two periods of funding. APA requests NIDA revisit this funding policy to more efficiently develop sustained research programs and further develop scientific researchers on critical topics.Unifying ThemesAPA suggests that the section on unifying themes is better suited for placement at thebeginning of the plan so that each point can be considered as readers review the specific strategic priorities. Further, APA recommends this section be expanded to include a number of the following important issues.Integration of Behavioral ProcessesThe integration of behavioral processes that underlie drug abuse and addiction is a criticaland overarching issue that APA suggests NIDA give prime consideration in drug abuse research.Chronic Pain SyndromesTaking into account the treatment and prevention needs related to comorbid chronic pain syndromes and other psychiatric disorders is another example of challenges facing ournation that can guide NIDA's unifying themes going forward.DiversityIn order to ensure that NIDA’s work addresses the full breadth of the U.S. population, the impact of factors such as age, culture and ethnicity, and social determinants are areas thatAPA suggests that NIDA explore. APA applauds NIDA's dedication to studying the developing brain. The differential effects of substance use and substance use disorders onthe brains of individuals vary at different stages of development, including late childhood, early adolescence, middle and late adolescence, young adulthood, and latelife. NIDA may wish to consider expanding its research on cannabis use (medical or recreational) in the older adult population. APA supports NIDA's research on the impact of race/ethnicity, sexual phenotype, gender identity, sexual orientation, and social determinants on drug abuse. This includes research focusing on culturally- and linguistically-appropriate services among groups experiencing health disparities, such as women and underrepresented and underserved minority populations.APA appreciates the opportunity to comment on the NIDA draft strategic plan. I look forward to further discussions and continued collaborative initiatives.

February 11, 2015