RFI Comments - Unifying Themes

Unifying Themes

• Thank you for inviting responses. I suggest explicit mention of the justice population since they are over represented with regard to addiction and HIV/Hep C risk.
• I would suggest adding to the Unifying Themes: “addressing the treatment and prevention needs of older adults (people age 65 and older)”.   There is considerable literature and research revealing that substance abuse among seniors is a hidden and ignored problem for the most part in the substance abuse treatment and prevention spheres.  Very few seniors with struggling with substance abuse problems are identified for treatment although the percentage of this age group needing treatment is the same as for other adults and very little prevention resources are devoted to this age group although there is evidence that the level of misuse of substances is greater for this age group than for other adults.  It is time, especially because this is the fastest growing age group in our country, that some special attention is paid to seniors who abuse and misuse substances.
• Overall, the NIDA strategic plan is excellent but there is one VERY MAJOR flaw.  NIDA and the field of Addiction Medicine promote addiction as a family problem/family disease as well as a brain-disease for the affected individual.   However, there are only a few funded projects that address any issues pertinent to families, children of parents with a substance use disorder (SUD), and parents or other family members affected by an adolescent or adult’s SUD.  For example, many parents are devastated by a child’s SUD, yet research and clinical services tend to ignore this important area or give it minimal attention.   The Strategic Plan mentions “family” on a number of occasions but the reader never gets the sense that this area is a priority.  In fact, the “Treatment Objectives (p5 and p21)” do not mention the word family; the “Cross-Cutting Priorities (p6, p44) state one of the priority is “to educate a variety of audiences” but does not include families in the list of audiences.  And, not a single one of the 30 references mentions the word “family” in the title.  Only one reference (#8, p50) mentions anything relevant to family “. . . offspring of mothers who smoked during pregnancy.”  It is much easier to find information on NIDA’s comprehensive website about a specific drug (stimulants, hallucinogens) or treatment for individuals with a problem to a specific drug than it is to find information about the impact of a SUD on children or parents, or what can be done to help these individuals.   There is a paucity of information available on interventions to help families and members (including parents and children) deal with the many emotional, health, financial and other burdens associated with SUDs.  NIDA generally does a superb job in disseminating information to professionals and others on numerous topics related to SUDs, treatment and recovery.  This has lead to many programs increasing their use of evidenced-based treatments.  However, I really believe that NIDA is doing a great disservice to the field of clinical care if it continues to put minimal resources towards research interventions aimed at screening families and members for the impact of SUDs, and finding more effective ways of reducing this burden and improving the quality of the lives of family members affected by a loved one’s SUD.
• The Council on Compulsive Gambling of New Jersey (CCGNJ) has had an opportunity to review the draft goals formulated by NIDA for its 2016-2020 Strategic Plan. The 2010 NIDA Strategic plan had no mention of the term gambling, and none of the new goals and objectives seem to consider gambling addiction. It is our contention that gambling disorders are related to the behavioral health of this country and in many cases directly to drug abuse or addiction.  Ignoring them threatens to weaken the entire plan.Gambling disorders were re-classified in DSM 5 under “Addiction and Related Disorders” in 2013. This is a recognition by the American Psychiatric Association that gambling fits the addiction model more so than the Impulse Control Disorder classification that had been used since 1980. This change was based on scientific literature on brain rewards that reflected commonalities between gambling and substance disorders based on cravings, hereditary nature, similar forms of treatment (12 step, CBT), tolerance and withdrawal.  Other similarities noted were clinical presentation, co-morbidity with other disorders, association with personality factors and neurotransmitter involvement. It is important to note that “gambling disorder” became the first “process addiction” (no ingestion of substance) to be classified as an addictive disorder.NIDA acknowledges a public health perspective and impact for its work. The public health model speaks of increasing readiness to address emerging public health priorities. We believe that gambling disorders have reached a high priority problem level and need to be addressed. A goal of the public health perspective should be to insure that all Americans enjoy a high quality, self-directed, satisfying life in a community of their choice. We believe gambling disorders have a toll similar to substance abuse on individuals, families and communities.  Studies have consistently shown that gambling disorders can lead to increased levels of divorce, bankruptcy, and domestic violence. These results certainly interfere with a self-directed life. This would certainly warrant the inclusion of gambling disorders as a research priority.Over the past 3 decades, NIDA has provided consistent leadership for the nation in furthering the understanding of addiction. The Council strongly believes that inclusion of problem gambling within NIDA’S efforts to provide a framework for research over the next five years is strongly indicated.   We have noted several sections where this disorder might fit in.Section II, Objective 2 addresses the issue of comorbidity and how that might affect treatment for addiction.   The Council suggests that gambling disorder is one such co-occurring disorder, although it is not specifically listed among the conditions of interest.   It cannot be taken for granted that treatments and therapies (pharmacological or behavioral) used for drug addiction will be equally effective for addicts who also have a gambling disorder.  There may well be differences in medication effects or adverse effects, and there are often diagnostic challenges. Section IV is focused on Cross-Cutting Priorities.  This could be an ideal place to include gambling addiction.   Goal 1 under this section specifically references “Compulsive Behavior Disorders” but then restricts the focus to OCDs and Eating Disorders.   We urge that NIDA consider investigating whether the common etiologies under study might also apply to gambling disorders.Addiction concerns are by nature holistic; they incorporate all parts of an individual’s life.  Our Council is concerned that many individuals stop drugging or drinking and turn to gambling as a “substitution of addiction”.  We also are concerned about gambling as a relapse trigger for drugs and alcohol.  In summary, we believe that the Federal research into both drug and alcohol addiction needs to include problem gambling within its primary concerns, and we urge NIDA to make necessary amendments if at all possible.Thank you for giving us the opportunity to share our comments.   
• On behalf of the Society for Women’s Health Research (SWHR®), we are writing in response to the request for input on the National Institute on Drug Abuse (NIDA) Strategic Plan (NOT-DA-15- 005). SWHR has consistently worked to make sure all of Institutes at the National Institutes of Health (NIH) are aware of the impact of biological sex and gender differences in the research work they support.SWHR is a non-profit organization, based in Washington D.C. that is widely considered to be a thought leader in promoting research on biological differences in disease. We are dedicated to transforming women’s health through science, advocacy, and education and bring attention to the growing list of diseases and conditions that uniquely affect women. Due to SWHR’s past efforts, women are now routinely included in most major medical research studies and scientists are considering biological sex as a fundamental variable in their research.We were pleased to see that the NIDA draft strategic plan priorities highlighted and put appropriate emphasis on the promotion of research that considers the impact of sex and gender on drug abuse and addiction and the need to increase knowledge of biological, behavioral, environmental, and developmental factors that increase the risk in and resilience for drug  abuse and addiction. For years, NIDA has been a leader in furthering the study of sex and gender differences research and urging the translation of that research into clinical practice. We hope that by NIDAs emphasis on increasing the inclusion of sex and gender differences as crucial biological variables in all of their research portfolios, the adoption of these issues among other Institutes and researchers will be expedited.We are also pleased to see that NIDA is expanding its focus to look at the role of addiction and drug abuse across the lifespan and in underrepresented populations. SWHR would suggest that NIDA require in its grants and publications, analysis by demographic subgroups (sex, gender, race, age, and ethnicity) as appropriate, to be able to determine appropriate treatments for all individuals at various stages of the lifespan. Additionally, SWHR supports a reinvigorated focus on increasing the public health impact of NIDA’s research and programs. SWHR has a unique outreach to a wide variety of stakeholders from all aspects of the medical research and healthcare community. We stand ready to serve as a strategic partner with the Institute in any way to increase NIDA’s priority initiatives and facilitate the translation and dissemination of this important research into practice.Thank you for providing this opportunity to provide input to NIDA as it drafts its strategic plan. We hope that you will take our comments into consideration as you work towards producing a final plan.
• The National Council on Problem Gambling (NCPG) is pleased to provide comments on the NIDA 2016-2020 Strategic Plan.  NCPG’s vision is to improve health and wellness by reducing the personal, social and economic costs of problem gambling. Our purpose is to serve as the national advocate for programs and services to assist problem gamblers and their families.  Our mission is to lead state and national stakeholders in the development of comprehensive policy and programs for all those affected by problem gambling.Gambling addiction is a significant public health concern characterized by increasing preoccupation with gambling, a need to bet more money more frequently, restlessness or irritability when attempting to stop, "chasing" losses, and loss of control manifested by continuation of the gambling behavior in spite of mounting, serious, negative consequences. The American Psychiatric Association defines gambling disorder as: “Persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress” that meets at least four of nine criteria.1The past-year prevalence rate of problem gambling in adults in the US is 2.2%.2 In addition to those presenting with the disorder, millions of individuals representing spouses, children, parents, family members, employers, neighbors and the general community are negatively impacted by this disorder.Strategic Priority: Basic NeuroscienceIn order to increase knowledge of factors involved in risk and resilience of addiction gambling addition should be included in NIDA research. The new DSM 5 Substance-Related and Addictive Disorders category includes gambling addiction, "reflecting evidence that gambling behaviors activate reward systems similar to those activated by drugs of abuse and produce some behavioral symptoms that appear comparable to those produced by the substance abuse disorders." It is likely that the prevention of gambling addiction will reduce costs and consequences of other disorders, as "at a minimum, the rate of problem gambling among people with substance use disorders is four to five times thatfound in the general population."3American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.Washington, DC: American Psychiatric Association (2013).Williams, R. and Volberg, R. Population Prevalence of Problem Gambling, Ontario Problem Gambling Research Center (2012).Problem Gambling Toolkit for Substance Abuse Professionals. SAMHSA (2009).Several of the high risk populations identified in the current NIDA Strategic Plan have been found to be at higher risk for gambling problems.  Adolescents are one such group, as 2.1% of youth are classified as past-year problem gamblers, and another 6.5% meet two to four criteria for pathological gambling and are therefore considered at-risk for a gambling problem.4  Adolescents with gambling problems are twice as likely to binge drink and to use illegal drugs.  In addition, student behavior surveys have consistently shown that gambling participation is correlated to elevations in all known risk factors, and decreases in all known protective factors, for youth as they relate to substance use and anti-social behaviors.5Other high-risk groups include males (prevalence of problem gambling in men has been found to be 2 to 3 times higher than in women) and racial/ethnic minorities; individuals with a family history of gambling (elevated rates of problem and pathological gambling have been found in twins of males with gambling problems); veterans and individuals with disabilities. 6Strategic Priority: Clinical and Translational Science.There are no FDA approved medications for gambling addiction, though there are promising clinical trials.7  In addition, dopamine agonist medications were much more likely to be associated with reports of impulsive behaviors compared to other drugs reported in the FDA database, and gambling was the most frequent behavior.8Strategic Priority: Public HealthGambling addiction is an emerging public health priority given the unprecedented amount of existing and expanding gambling.  Legalized gambling is now available in 48 states and 80% of adults gambled at least once in the year; 15% at least weekly.  The estimated six million adult problem gamblers are five times more likely to have co-occurring alcohol dependence, four times more likely to abuse drugs, three times more likely to be depressed.9As problem gambling is integrated into health systems, treatment for gambling problems will reduce social costs generated by untreated problem and pathological gamblers and may provide cost savings for states through improved recovery rates and decreased demand on traditional public sector substanceWelte, J, Barnes, G, et al. The Prevalence of Problem Gambling Among US Adolescents and Young Adults: Results from a National Survey. J Gambl Stud (2008) 24:119-133.2008 Youth Survey, Arizona Criminal Justice Commission (2008).Advancing Health Through System Reform-Problem Gambling. NCPG (2009).Hodgins, D., Stea, J., Grant, J. Gambling Disorders. Lancet (2011).Moore TJ, Glenmullen J, Mattison DR (2014) Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Internal Medicine. Publishedonline October 20, 2014Advancing Health Through System Reform-Problem Gambling. NCPG (2009)abuse and mental health systems.  Individuals with gambling problems report committing crimes to finance their gambling at extremely high rates, and studies of arrestees find rates of gambling problems 3 to 5 times higher than the general population.10  Undetected and untreated gambling problems may exacerbate relapse and recidivism.  By providing recovery and therapeutic approaches that are appropriate for problem gamblers and their families, it is hypothesized that recovery rates will increase for a wide variety of health and substance abuse disorders.
• Thank you for the opportunity ?to review the NIDA Strategic Plan that was posted for public comment. First, I want to tell you that not only is it a very forward thinking plan, it is an excellent resource for those of us looking for state of the science information about a wide range of topics on addiction. I especially like your focus on effective treatment as that is a critical need -- identifying the most effective and science based treatments for our loved ones with this disease.  However, there is one topic that needs more attention in your plan.  I ask you to give more attention to  the health of the families living with substance use disorders.  Your plan does mention that this disease disrupts families,  and that family therapy can help the victim with the disorder, but there is nothing specific in the strategic plan that addresses how to improve the health of a family living with addiction.   Again, thank  you for the opportunity to provide feedback on your plan.  I am copying the other members of the United We C.A.N (Change Addiction Now) Advisory Board on this feedback to you.  The mission of our non-profit is to Embrace, Educate and Empower families and communities living with addiction.  We understand the challenge of helping these families return to health during the traumatic events that accompany addiction, and we are aware of the need for science based information for treatment of the family as well as the family member with the disease.

Basic Science, Public Health, Infrastructure, Unifying Themes

• On behalf of the Prevention Science Institute at the University of Oregon, we have some additional comments for consideration in the FY 2016-2020 Strategic Plan for the National Institute on Drug Abuse. Specifically, although we agree with the strategic plans as currently drafted, we advocate for a separate and specific focus on prevention (in addition to the focus on intervention and treatment). In addition,  to fully support NIH’s proposed strategic plan to invest in evidence-based health care prevention interventions, the directors and researchers at the University of Oregon’s Prevention Science Institute recommend the addition of the following priorities:Improve the understanding of biological processes related to substance use, abuse and addiction risk and resilience and reactivity to preventive interventions.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. Develop a strategy to build a strong infrastructure 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.Create opportunities for multiple federal agencies to collaborate in funding translational drug abuse prevention and treatment research;Increase opportunities for combining data from previous prevention and treatment trials and use innovative methods to integrate and analyze these data.Address the prevention needs of youth and high-risk populations (in addition to continuing a focus on treatment).Understand the implications of the changing drug policy environment (i.e., marijuana legalization at the state level). Understand the developmental and contextual influences across all areas of research. Thank you for consideration of this input.

Basic Science, Unifying Themes

• RE: NIDA Strategic Priorities – 2016-2020The strategic priorities that I believe will have the greatest impact on NIDA’s goal of reducing drug abuse are: Increase our knowledge of biological, behavioral, environmental, and developmental factors involved in risk and resilience for drug use and addictionUnderstand the developmental trajectory of addiction and individual heterogeneityNormal development/function across the lifespan including mechanisms of reward, self-control, and conditioningImprove our understanding of the interaction between addiction and co-occurring conditionsAlthough research over the past 5-10 years has clearly shown that environmental enrichment and exercise can significantly alter the reinforcing effects of drugs, relatively little is known about how the types of foods and chemicals we consume on a daily basis (e.g., fats, sugars, caffeine, etc.) impact one’s vulnerability to abuse drugs. Preliminary data from our laboratory and others has provided compelling evidence that feeding animals high amounts of fat, or allowing them to consume caffeinated water can dramatically increase their sensitivity to behavioral effects of cocaine. Moreover, the impact of these nutritional manipulations appears to be greatest when the consumption occurs during adolescence, a period of development that is already associated with increased risk for developing a substance abuse disorder. While many think of the consumption of fat and/or caffeine as benign, if not unavoidable in modern western society, the fact of the matter is that the past 10 years has seen unprecedented levels of childhood obesity, driven in large part by the fact that western diets tend to be high in fat and sugar, and skyrocketing numbers of highly caffeinated “energy drinks”, which are primarily marketed towards adolescents and young adults. To address these issues, I think it is imperative that we invest in basic scientific research aimed at identifying and understanding how environmental, nutritional, and pharmacologic history impacts (1) the likelihood of initiating drug use during adolescence, (2) the rate at which drug use transitions to drug abuse/addiction, and (3) individual vulnerability to resume drug taking after a period of abstinence. In addition to improving our basic understanding of how the choices we make for ourselves, and our children, can impacts drug effects, the results of such studies would have practical implications that are “relatively” easy to implement. For instance, with only slight modifications to the types, amounts and/or timing of meals and snacks that we feed our children, we could substantially reduce their sensitivity to drugs of abuse. Another area that I would like to see emphasis placed is on dose and drug selection. In reading the drug abuse literature, I am consistently struck by how many studies include a single dose of a single drug, often cocaine. As a pharmacologist I believe that the only way to accurately assess how a condition (e.g., candidate medication, behavioral intervention, etc.) impacts the abuse-related effects of a drug is to evaluate the full dose-response curve. While there are situations in which a single dose might be advisable, I would like to see NIDA push their investigators to employ a more rigorous approach, particularly in basic drug abuse research.  A third area that would benefit from additional emphasis is the intersection of injury/pain and vulnerability to drug abuse. In particular, given the more than decade’s long War in the Middle East, as well as the increased awareness of concussions resulting from contact sports, it is vitally important that we gain a better understanding of how traumatic brain injury, chronic pain and post-traumatic stress disorder impact individual vulnerability to drug abuse.Lastly, although there are currently many great animal models of drug abuse, I think the field would benefit from the development, and adoption of more sophisticated behavioral assays. For instance, while the use of the food-drug choice procedure has proven to be a powerful tool for evaluating candidate medications, relatively little work has been done using self-administration procedures in which multiple drugs are concurrently available. In addition to allowing for studies of commonly co-abused drugs (e.g., caffeine and nicotine, alcohol and THC, benzodiazepines and opioids, etc.), such poly-drug abuse procedures would strengthen our ability to accurately model the human condition in which drug abusers commonly use more than one substance. In addition, while traditional reinstatement procedures have been instrumental in identifying the neurobiology of relapse, implementing more sophisticated procedures (e.g., progressive ratio, choice, etc.) to study the strength relapse-related behaviors would greatly improve not only our understanding of the factors that contribute to abstinence and relapse, but also our ability to accurately assess the effectiveness of candidate medications to maintain abstinence/prevent relapse.

Basic Science, Infrastructure, Unifying Themes

• The goal of the Psychiatric Genomics Consortium (PGC) is to conduct mega-analyses of genome-wide genetic data for psychiatric disorders. In existence since 2007, the group, the largest consortium of mental health researchers to date, has contributed substantially to advancing our scientific understanding of the genetic contributions to psychiatric disorders. PGC Addictions was established in 2012. The goal of our group is to study the role of common and rare genetic variants in the etiology of addiction, ranging from diagnostic indices, quantitative indices of use, treatment and relapse and to integrate these findings with emerging results from other efforts targeting substance use, mental health and neuroimaging outcomes. As a group, we propose the following avenues for NIDA’s strategic plan.Continued support for genotyping and sequencing of large repositories of well-characterized samples for the identification of common and rare variants for addictions.Large scale studies of schizophrenia (PMC4112379) have shown that increasing sample sizes can result in a substantial boost in power to detect common variation associated with complex behavioral and psychiatric traits, and most recently brain volumetric assessments. The PGC has already collated a majority of the addiction samples with GWAS data of which we’re aware, however, current numbers of cases  and controls (N=12397/28080 for the most common disorder, alcohol dependence, and many fewer for illicit drugs) are modest. Experience with other disorders indicates that a much larger number of samples will be required.  Continued support for genotyping utilizing modern cost-efficient arrays will substantially improve our ability to identify variants affecting risk for addictions. We stress also the need for samples to be well-characterized for substance use disorders (SUD). With the sustained push for personalized medicine, sequencing of samples with refined assessments of addictions is necessary (e.g. by SSAGA or SSADDA; or from the PhenX toolkit). When combined with GWAS and exome data, sequence information allows for study across the spectrum of allele frequencies and effect sizes for genes affecting risk/protection. In particular, family based data (including dense pedigrees, family trio and affected sibling pair studies) can provide a powerful platform for the study of rarer alleles and their mode of transmission. Support for collection and careful characterization of new samples related to addictions is essential. Also, we encourage additional phenotyping of existing collections when recontact is possible; this includes support for longitudinal studies, particularly during key periods of exposure and risk (e.g. adolescence).Recent studies (e.g. PMC3865158; PMC4233207) show that careful characterization of outcome measures (e.g. symptom counts, quantitative indices during periods of heavy use, such as maxdrinks for alcohol, information on route of administration, exposure opportunity in control population) can impact resolution of genetic signals. While studies of tobacco smoking have seen significant success with the use of ad hoc measures, such as cigarettes per day, there are known challenges associated with such measures when they are applied to illicit substance use behaviors. Future data collection efforts aimed at assembling samples with detailed phenotypic assessments of addiction are needed.Support for genotyping and phenotyping of existing and new longitudinal studies, including studies of high risk families and high risk neighborhoods, can provide unparalleled insights into the evolution of addictive behaviors, from exposure opportunity to remission/relapse. This also necessitates the detailed measurement of both self-report and the built environment (e.g. GIS) and the interplay between environmental vulnerability and genetic liability.Another potential area for substantial growth is developing repositories of genotyped treatment samples (e.g. methadone, buprenorphine) that would allow for the assessment of genetic moderators of treatment outcomes.Extending studies to under-represented groupsA majority of previous genomic efforts have relied on data from participants of European-American (or Native American) descent. Given the vast socio-cultural and linkage disequilibrium/haplotypic differences between Caucasians and other ancestries, developing cohorts of African-American, Mexican-American, Native American and Asian descent will be essential. This should include genotyping and sequencing of well-characterized collections already available, if consent can be obtained, as well as new collections. Consistent with the current literature, it is quite likely that many risk alleles will be population-specific. To obtain findings relevant for further treatment in a population, it may be necessary to study adequately powered samples in that population. Such an effort should be accompanied by international collaborations that leverage data from population isolates, indigenous groups etc.NIH interagency collaboration that would result in targeted studies of the genetic contributions to the comorbidity between addiction and other mental health outcomes.Despite substantial clinical and epidemiological evidence that rates of substance use disorders are considerably elevated in individuals with other psychiatric illness, and support from twin studies that these phenotypes share partially overlapping genetic etiologies, systematic genomic studies of this comorbidity are limited (e.g. PMID24957864).  Large samples ascertained for other psychopathology, such as in the PGC, are likely to include substantial numbers of subjects with detailed clinical assessments of addiction. Support for additional characterizations of substance use/abuse/dependence in other samples, contributions to additional genotyping or sequencing if needed, and for data analysis should be prioritized. Similar efforts at integrating results from recent neuroimaging efforts (e.g. ENIGMA, NCANDA) with emerging GWAS findings and the development of targeted neurogenetic studies can facilitate gene-brain-behavior studies.Support for secondary analysis of existing large repositories of unmined addiction data and for development and implementation of methodological tools for genomic studiesThe past 2 years have witnessed an explosion in polygenic methods, including genetic risk scores, pathway and network analyses, detection of genomewide loci influencing cross-trait covariance, heritability estimation from genomewide data. Such efforts require larger samples that are currently available but require sustained funding support.With emerging GWAS and sequencing findings, there is a strong need for further development of methodological tools that can be used to (a) annotate results, including integration of epigenetic, expression/eQTL data; (b) model complex gene-gene and gene-environment interplay; (c) implement other sophisticated approaches (e.g. graph theory).The development of user/consumer-friendly web utilities that allow for the integration of genomic results for addiction across multiple NIDA-funded consortia and from other analytic platforms (e.g. recent ENIGMA meta; brain functional studies, EEG/ERP) should be a priority. Such utilities should also allow for easy visualization of findings, annotation and download of summary statistics.

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, 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, 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.

Format, Basic Science, Unifying Themes

• Suggested changes or additions to the list of strategic priorities, including emerging research needs and future opportunities that should be considered in the plan:We believe the future priorities of NIDA should take into account the increased level of legalization of cannabis, the continued abuse of prescription medications, and the potential problems associated with e-cigarettes in teenagers.An emerging research topic that is not stressed enough in the current outline is the role of the neuro immune system in the development of substance use disorders. The majority of the literature concerning neuroinflammation in drug addiction has appeared after the last strategic plan was published by NIDA. Contemplated in the past plan of strategic priorities, but we didn’t see in the present outline, is the study of specific populations, specifically, military personnel, where there is an increased abuse of prescription drugs compared to the civilian population. An example of this type of research could be the study of how post-traumatic stress disorder influence the development of drug addiction. Also, NIDA should promote research that consider the incarcerated population. In the prison system, a 65% of prisoners meet the medical criteria for substance abuse addiction, but the study of this population is not mentioned in the current outline. Lastly, behavior and environment are big components of the susceptibility and vulnerability to drug addiction. NIDA should prioritize studies that address the interaction between psychiatric diseases like major depressive disorder, anxiety disorder and the development of drug abuse.Anticipated challenges that will need to be addressed to achieve these priorities. A first step towards elucidating the pathophysiology of psychiatric disorders in addiction should include a deep knowledge of the participating neuronal circuits, the cell types, and the molecules in each neuronal population involved, and how these structures are interacting and influencing each other.

Format, Infrastructure, Unifying Themes

• Dear Colleagues -Thank you for the opportunity to comment on the drafted Strategic Plan elements for NIDA for 2016-2022.I am writing about three items needing attention.  One item is a general language issue.  Second are two gaps I noticed in a priority. And the final one is a priority item that I think needs expansion.  I submit these considerations as an individual and not on behalf of any group or entity.  My titles and professional information are provided only to verify that these come from me in my professional capacity as an researcher, educator, licensed clinician, mentor, and advocate.FEEDBACK ON NIDA 2016-2022 STRATEGIC GOALS1. First I will address the general language issue needing attention.  The document needs to strike the word abuse from it in its entirety, excepting where there may be some historical reference to this antiquated and stigmatizing term.  Use of the word abuse is out of step with current diagnostic nosology, pejorative, and reinforces stigma.  SUGGESTED CHANGE:  I urge the removal of the term "abuse" and substitution of the word "use" and/or the phrase "use disorders" as appropriate.  RATIONALE:  This will not only remove inappropriate, outdated language, but will keep the focus across the entire range of problems we see related to substance use -- from exposure, to experimentation, to use, to problematic use, and use involving addiction.   2.  Second, I aim to address the gaps of concern to me, both of which were on science infrastructure.  On the element: Science Infrastructure: Enhance the national research infrastructure to support advancements in science, you note "improve training for the next generation of scientists."  Problem A:  What strikes me about this is that it does not explicitly address a need for work on educational technologies (we do use science in making good education, and this increasingly uses technology) and a broader focus on education of professionals.Problem B:  Additionally, it does not address the need for improving training for the next generation of clinicians, clinician-scientists, and academics - who are not necessarily scientists.  With all this talk about translation - beyond implementation in the field with those already trained - we need a focus on training that is broader and connected to basic educational matters for all professionals involved at this level of the game.So the gaps that you are talking about re: scientific infrastructure should really highlight education more generally and include educational methods and technology, not just "training."  Additionally, it needs to go beyond "scientists" to all those engaged in learning science at that level more advanced (e.g., higher level clinicians and clinician scientists and other scholars (e.g., scholars, practitioners, and scholar-practitioners).NOTE:  Conceptualization of training for these other groups really is not limited to public health matters (another element of your plan), or simply implementation science.  Instead, we are talking about, just as with researchers, part of their scientific education and training that clinicians, clinician-scientists, and scholars in this area receive, just like that received by researchers while in school, apprenticeship, fellowship, etc.  Supporting educational innovations and training of these groups is imperative as all groups receive training in science related to addictions and substance use behavior, beyond what is covered in your current expression of "improving training for the next generation of scientists." This also is not covered elsewhere adequately in your goals.   SUGGESTED CHANGE:   I suggest this noted element be amended as:  "improve education and training for the next generation of scientists, clinician-scientists, scholars, and clinicians" or "improve education and training for the next generation of professionals working in substance use and addiction science, practice, scholarship, and their interfaces." ADDITIONAL RATIONALE:  It is harder to train people after they have left their programs than while they are in them.  Let us equip the educators and trainers with the technology and funding they need do get things right while new trainees are going out the door. And let us be inclusive of the entire "symphony" of players involved - not just focusing on the scientists.  If we are truly moving into integrative, and collaborative efforts, then let us start this early, in the classrooms of all involved with the best technologies we can use.3.  Third, I aim to address the minor change and expansion of Unifying Theme priorities:  Promoting research that considers the impact of sex and gender on drug abuse and addictionAddressing health disparities among underrepresented populations PROBLEM A:  I was most pleased to see both of these items included.  However, I was somewhat taken aback to see the issue be framed with an absence of the general contribution of culture, race, and ethnicity and their contribution to use and addiction.  Our literature is deficient in these areas.  it is not just with underrepresented groups that these issues need attention.  These issues need attention on their own for their unique contributions.PROBLEM B:  These issues (sex, gender, race, ethnicity, culture) may interact with each other and/or the status of being in an underrepresented group.  Our literature remains fairly ignorant on these matters, particularly with regard to developmental issues.  Therefore age is also relevant as a universal theme, as is how these items may interact.PROBLEM C:  Socioeconomic status is a relevant demographic that needs to be teased out sensitively around all of these previously mentioned descriptors. This is because it may interact with any one or number of them to affect risk, or be its own unique risk factor.  It also may be confused with one or another of these for its impact and so should be included.SUGGESTED CHANGE:  I suggest amendment of the first bullet to fix language, address these much needed concepts (e.g., race, ethnicity, culture, age, socioeconomic status) on their own merits and not simply as a function of lumping them in to "underrepresented populations."  I also suggest amendment that accounts for how these issues may interact.  A continued focus on health disparities among underrepresented populations is not disputed, so can stand on its own.  However, the phrase "underrepresented" is inadequate to address these other very important demographic concepts and should not be used as some sort of a proxy in a strategic plan. Promoting research that considers the impact of age, sex, gender, race, ethnicity, culture, and socioeconomic status, including their interactions, on substance use and addictionAddressing health disparities among underrepresented populations RATIONALE:  Our population in the US is constantly changing.  Underrepresented status may, in and of itself, transition and be a risk factor but function in different ways for different populations.  Additionally, with our changing demographics, varied descriptors may combine to create unique risk factor patterns (for example, gendered racism) that demands study of the interaction of demographic factors such as age, race, ethnicity, and culture with sex and gender.  We also need to be careful not to confuse variables such as socioeconomic status and its impact with these other demographic issues. As such, these all need continued study for their unique and potentially interactive impact to substance use and addiction.Thank you for your consideration of these thoughts.  Again, they are submitted on my behalf as an individual, not as representing any group or entity with which I may be affiliated.

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

• I am writing on behalf of the College on Problems of Drug Dependence, Inc. (CPDD), in response to the Request for Information regarding the FY 2016–2020 Strategic Plan for the National Institute on Drug Abuse, National Institutes of Health (NOT-DA-15-005). CPDD is the longest standing scholarly society in the United States that devotes its focus to the issues of drug addiction and other drug use disorders. The College has over 1000 members, and serves as an interface among governmental, industrial and academic communities maintaining  liaisons with regulatory and research agencies as well as educational, treatment, and prevention facilities in the drug abuse field. We appreciate the opportunity to provide comments regarding the NIDA draft strategic priorities, which clearly represents considerable thought and discussion regarding the topics of critical relevance to our field. We had the following comments after our review of the proposed plan. Several of these are referenced in the plan, but are so important that they should be more clearly stated to ensure that they be given full consideration in the Plan.NIDA should work with other government and private agencies such as The Liaison Committee for Medical Education (LCME) to increase the education of medical students, residents (especially pediatricians) and other health care providers to enhance their ability to recognize the behavioral signs in  children that have been shown to be predictors of drug abuse in adolescence. This will be helpful in addressing treatment NIDA should develop mechanisms to work with industry, both big pharma and the biotechnology industry, as well as with academia, to enhance the development of medications to treat diseases of drug addiction.  Special financial incentives and new approaches may be necessary.Research with pediatric populations that looks at the role of other mental diseases on drug abuse and dependency is necessary. While we realize and appreciate the “ABCD” study is related to this topic, other work in this area is needed.In addition to work in children and adolescents, there is a need for increasing focus on drug use in older populations – especially in the context of the growing number of older baby boomers. There is opportunity to characterize this phenomenon (e.g., prevalence), and to also examine biologic underpinnings that may be helpful in understanding broader issues of drug use (such as factors that contribute to continued use for some persons).Work that examines the similarities and differences among drug dependencies to various abused substances (e.g., opioids, cocaine, cannabis, alcohol) is needed. This has the potential to better elucidate common vulnerabilities to drug use (both biologic and environmental), and will help in the development of better treatment and prevention methodologies.There is a need for a concentration on studies investigating the relationship of co-morbidity of mental disease and drug dependency. One population where this work is essential is veterans with PTSD and their families, but it also has applicability to other populations with substance use disorders.There is a need to continue support of basic science research that has downstream potential to help understand the etiology, proclivities, and sustaining factors associated with drug use. This should include an increase in knowledge of the genetic factors that predict drug abuse and dependency.There should continue to be an emphasis on support of young investigators in the field. The loss of a future generation of scientists would be a catastrophe!We would encourage that work conducted by the intramural research community be effectively leveraged for work by the extramural community. This can be accomplished by supporting travel and presentations by intramural scholars at national scholarly meetingsThe College continues to be a strong advocate for the work of NIDA, and we greatly appreciate the opportunity to address this Plan.

Public Health, Unifying Themes, Infrastructure

• Below are suggestions to assist the Substance Use Disorder field to follow the NIDA 2016-2020 strategic plan priorities. The suggestions apply equally to all four priorities of Prevention, Interventions, Treatment and Recovery Support Services. Suggested research topics for Prevention, Interventions, Treatment and Recovery Support Services are as follows: a) emerging issues, such as opiates and the changing marijuana environment; b) workforce development; c) research for specific populations including, youth through older adults, ethnic and sexual minority populations, high risk populations, such as pregnant and parenting women, geographic differences in providing services between urban and frontier communities.  Understanding which interventions are most likely to be successful with which population is important and NIDA can lead the way. Continuing to learn and grow in the four areas listed above may help to achieve the NIDA 2016-2020 strategic plan. Our division credits NIDA’s previous work and continued supportive commitment to increase Medication Assisted Treatments, therapies for those with co-occurring conditions, and continue to prioritize identifying innovation strategies to address our nation’s most significant drug issues (not including alcohol); marijuana and opiates. In closing it is critical that NIDA work in collaboration with NIAAA on Alcohol Issues, and CDC on nicotine therapies.

Unifying Themes, Infrastructure

• Thanks for this opportunity to contribute thoughts on your strategic plan.  I think that NIDA could contribute more to the genetic, epigenetic, hormonal, and other biological mechanisms around eating disorders, weight gain, and obesity, in that many of these are shared pathways with those involved with substance addiction.  Knowing what is similar and different between eating behaviors and substance addiction behaviors and the underlying biological mechanisms would help a large proportion of the public.  NIDA and its investigators have deep expertise in this arena and could contribute substantially if NIDA could add this topic area to its portfolio, rather than leaving it to NHLBI or NIDDK.Also, NIDA’s R25 programs in statistical genetics have been useful for recruiting quantitative researchers into statistical genetics of addiction but because those who are on visas are not eligible for K awards, some of our trainees may struggle in launching b/c they have to compete directly for R awards.  The bridging support of K awards are very helpful for the transition into independence with a safety net for those who are eligible.