Five Areas Where “More Research” Isn’t Needed to Curb the Overdose Crisis

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“…but more research is needed.” That’s often the refrain in science, and it includes addiction research. As the addiction and overdose crises continue to claim an unprecedented number of lives and fray communities, science is an essential part of the solution.

In the science-to-medicine pipeline, there is a point when a body of evidence is so well-established that to not put the science into action would be an abdication of responsibility. When it comes to the current crisis, there are at least five things that science has shown conclusively to be effective, where communities and healthcare providers can apply what we already know works.

We don’t need to keep asking if these things work. Instead, we must find ways to help providers, people, and communities overcome the barriers to implementing these valuable interventions.

1. Naloxone saves lives.

Opioids now claim 188 lives in the U.S. every day. Among their other effects, they attach to cells in the brainstem that control respiration, slowing down breathing to sometimes deadly levels. This is an overdose. Naloxone is a medication that can quickly reverse an opioid overdose by kicking opioid agonist drugs like fentanyl off opioid receptors and blocking them, which quickly restores breathing. It must be used promptly, and it requires another person to be nearby to administer it.

All over the country, putting naloxone in the hands of first responders has saved countless lives. And because it is such a safe drug, it can be put directly in the hands of people who use opioids, their loved ones and friends, and anybody else who may find themselves in a position to save the life of someone overdosing on an opioid.

Yet despite the safety and lifesaving value of this drug, there are impediments to widespread use. Naloxone is not available over the counter, which could ease access. Doctors don’t always prescribe it to patients who need it, pharmacies don’t always stock it, the price may be prohibitive when they do stock it. While many states now have standing orders allowing anyone to get it from the pharmacist without a prescription, people often do not know that. People who offer harm reduction in communities are also affected by costs and product shortages.

NIDA is supporting research to overcome regulatory and attitudinal barriers to wider use of naloxone and educating about its use. Opioid overdose education and distribution (OEND) programs have been implemented in some areas, with dazzling effectiveness at saving lives. Despite concerns of critics, having a naloxone kit has not been shown to increase a person’s opioid use. New methods of reversing overdoses with novel molecules and delivery techniques are also in the research pipeline.

2. Medications for opioid use disorder can work.

Decades of research has shown beyond doubt the overwhelming benefit of medication for opioid use disorder (or MOUD). The full opioid agonist methadone (in use for half a century) and the partial agonist buprenorphine (first approved two decades ago) have proven to be life-savers, keeping patients from illicitly using opioids, enabling them to live healthy and successful lives, and facilitating recovery. Naltrexone, an antagonist that prevents opioids from having an effect, is also effective for patients who do not want to use agonist medications and are able to undergo initial detoxification under medical supervision.

The efficacy of MOUD has been supported in clinical trial after clinical trial, and MOUD is now considered the standard of care in treatment of opioid use disorder, whether or not it is accompanied by some form of behavioral therapy. Yet even now, only half of addiction treatment facilities offer any FDA-approved medications, and only a tiny fraction offer all three. And while recovery supports like 12-step groups can be a useful adjunct to treatment, many continue to discourage participants from taking medication—a legacy of decades of misconception that medication substitutes one addiction for another.

Science is no longer needed to show that these medications are effective. Where we are directing efforts and dollars is toward research aimed at overcoming attitudinal barriers and, again, increasing the implementation of these effective treatments. Research is also needed for strategies to improve retention in MOUD treatment, since discontinuation of medication is high. Also, because the available medications are not right for everybody, we support research to determine which of these medications work best for whom and to develop additional treatments for opioid use disorder and other drug use disorders, including addiction to stimulants and addiction to multiple drugs (polysubstance use disorders).

3. Contingency management is an effective treatment for stimulant use disorders.

We don’t have an FDA-approved medication to treat stimulant use disorders. Although opioids, especially fentanyl, still cause the majority of overdose deaths, stimulants like methamphetamine and cocaine are increasingly showing up as contributors to overdose, in many cases in combination with opioids. Even without an FDA-approved drug to treat stimulant use disorders, there is an effective behavioral treatment available: Contingency management. But regulatory barriers—and unclarity about the regulations—have thus far limited its reach.

Addiction is a disorder that profoundly affects motivation: Through repeated use, seeking the drug prevails over other goals (social connection, career, school) in part by reorienting the brain’s reward system. Even when people want to quit, they have a hard time finding the motivation to pursue a life free of the drug, since they don’t have alternative reinforcing stimuli to motivate them. Contingency management provides such reinforcement, encouraging positive behavior change with small prizes—usually, the opportunity to win a small gift card, movie pass, or similar small monetary gift—for negative drug tests, adhering to medications regimens, and other healthy behaviors.

It sounds strange that small rewards would help keep people experiencing addiction from using drugs, but when they want to quit, these token prizes can boost their incentive enough that they can do it and experience the growing benefits of a life without drugs. Contingency management has been shown in trial after trial to be especially effective for people with addiction to stimulants (including people with both stimulant and opioid use disorders), outperforming other behavioral approaches.

However, too-stringent interpretation of regulations put in place to prevent medical fraud (coercive inducements or kickbacks) have limited the dollar value of rewards to trivial amounts that often are not very effective. And providers unsure about the legality of contingency management often do not provide it at all.

We don’t need more science to show the effectiveness of contingency management. We need more treatment centers to implement it. For this to happen, there needs to be greater clarity from regulators that it is a legitimate medical treatment, not an inducement with potential legal penalties. And raising the dollar caps will greatly enhance the treatment’s effectiveness. 

4. Syringe services programs (SSPs) greatly mitigate harms of opioid use.

Syringe services programs or SSPs are another harm-reduction approach backed by massive scientific research showing their effectiveness at reducing the transmission of infectious diseases like HIV and hepatitis C among people who inject opioids and other drugs.

SSPs also have a range of additional benefits, including linking clients to SUD treatment and other needed healthcare that they may be reluctant seeking elsewhere. Staff at SSPs, who are often in recovery themselves, treat clients with dignity, a positive experience of healthcare engagement when they may experience stigma from most others.

Critics have worried that dispensing sterile injection equipment implicitly sanctions or encourages drug use, and it has led to their limited utilization. But studies show SSPs do not increase drug use or negatively impact surrounding neighborhoods. They are a win for communities and a good investment. History has shown that disease outbreaks can result when communities fail to implement SSPs. For instance, a 2018 modeling study suggested that an earlier public health response including timely implementation of an SSP might have blunted or prevented the 2014-2015 HIV outbreak in Scott County, Indiana.

SSPs are among the most-studied of harm-reduction techniques, and now we need to write the next chapter: build the evidence base to see what other harm-reduction approaches could help in the current crisis and how they can be adapted to diverse communities.

5. Prevention interventions can have broad and lasting impact.

With the current addiction and overdose crisis, our country has been playing catch-up, ramping up treatment and harm-reduction services to staunch the tide of deaths and devastated lives. What is also needed is prevention, and this is another area where research shows us the way to go.

Decades of research on periods of developmental vulnerability and the kinds of social-environmental factors that raise the risk of early drug experimentation and addiction have led to the development of numerous evidence-based prevention interventions that mitigate the risk factors as well as strengthen protective factors. These interventions, ranging from nurse-home visitation of low-income first-time parents (such as Nurse-Family Partnership) to family-based pre-teen/teen programs (Strengthening Families Program: For Parents and Youth 10-14) or school-based interventions to strengthen self-control skills (such as Life Skills Training) show multiple benefits including, in some cases, reduced or delayed drug experimentation in adolescence and young adulthood.

Some of these interventions show benefits in reduced drug use decades out—even across generations. Children of parents who received an elementary-school intervention called Raising Healthy Children showed improved outcomes too. And since many of the risk factors for substance use are shared with other mental illnesses, prevention interventions reap a wide range of mental-health benefits. Best of all, benefit-cost analyses show prevention to be an extremely good investment for communities, averting many direct and indirect costs of substance use and other related problems.

Yet such interventions are seldom adopted. Short-term thinking, unwillingness to invest in long-term solutions, plays some role. But there are real challenges in scaling up interventions that work in small trials and effectively implementing them in the real world, adapting them to the specific characteristics and needs of unique communities. It’s an area where NIDA is investing in research to find ways to bring effective evidence-based prevention interventions to scale.

A year ago in this blog, I called for radical change to solve the opioid crisis. It remains true. But radical measures are really not that radical: If we are guided by science, they are actually conservative and commonsensical, undoubted wins in any kind of benefit-cost calculus. We just need the collective will to put the science into action, and research to find ways to do it most effectively in the real world.

Video: What Radical Change Means