How People with Substance Use Disorders (SUDs) Can Lend a Needed Hand in Addiction Research

FROM THE MONTHLY BLOG OF DR. LORA VOLKOW
April 22, 2019

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One of the major challenges in health science today is that not enough patients participate in clinical trials and similar studies. Without volunteers willing and able to participate in studies testing new treatments or therapeutic approaches for cancer or Alzheimer’s, for example, researchers cannot test their effectiveness. There are many reasons for the lack of participation in medical research: Patients often are not aware of studies, or they don’t see any direct benefit from participating. Many clinical trials for new cancer treatments, for example, have been delayed or even cancelled altogether because of the difficulty of recruiting participants.

Drug Lab Research

In research testing new medications or behavioral treatments for substance use disorders, the obstacles to recruiting study volunteers are even more daunting. Just finding participants can be a challenge, since they may not intersect with the healthcare system for their addiction, the same way someone with cancer or Alzheimer’s would. Only a fraction of people with substance use disorders receive care from physicians who may be in a position to know about or link them to research studies being planned. Most recruitment for clinical trials related to opioid addiction medications, for instance, is done via ads placed at large opioid treatment centers where patients on methadone receive their daily doses. 

People with substance use disorders already face stigma and the fear of further social or legal consequences of their addiction, and this deters potential volunteers from signing up to participate in research. Some distrust the medical profession altogether. Many people with addiction do not want or believe they need treatment at all. Additionally, because many people with addictions who might otherwise want to participate in a trial are unemployed, poor, or homeless (perhaps as a result of their substance use), they may lack the resources or access to transportation necessary to visit a hospital or research center regularly. Often as many as half or even more than half of participants recruited for a trial are not able to complete it.

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Scientists studying new treatment approaches for addiction must always be thinking about how they can make their research studies more practical and feasible in the real world. They must make study participation easy and appealing and the studies accessible—including access at odd hours or weekends for those whose jobs or school prevent participation during regular work hours. Also, people with addictions often use multiple substances, and this commonly excludes them from studies testing treatments for a single substance, due to strict criteria on who can be included in a trial. Yet the reality is that addiction is complex, and often involves not only use of multiple drugs but also co-occurring mental and physical illnesses. Designing more inclusive studies and clinical trials that can take this complexity into account will be necessary for scientific advancement in treating and preventing addiction.

An all-hands-on-deck approach is needed in order to confront America’s current drug crisis, and the needed hands must include families and individuals directly affected by substance use disorders. By increasing participation in research by those who most stand to benefit, we can find solutions to the complex addiction issues facing our nation today. It is also an opportunity for individuals suffering from addiction to participate in clinical research, just as people with other medical conditions do.

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For more information on the benefits of participating in a clinical trial—for addiction or any other disease—please feel free to visit https://www.nih.gov/health-information/nih-clinical-research-trials-you. Are you a provider? You can learn about trials to recommend to your patients here: https://www.nih.gov/health-information/nih-clinical-research-trials-you/finding-clinical-trial.

FIND HELP NEAR YOU

The following website can help you find substance abuse or other mental health services in your area: www.samhsa.gov/Treatment. If you are in an emergency situation, people at this toll-free, 24-hour hotline can help you get through this difficult time: 1-800-273-TALK. Or click on: www.suicidepreventionlifeline.org. In addition, you can find contact information in your phone book or online for Alcoholics Anonymous, Narcotics Anonymous, Celebrate Recovery, or other 12-step programs.

 

 

Scientific Findings and Achievements in Drug Abuse Research for 2018

From the Blog of Dr. Nora Volkow, Director
National Institute on Drug Abuse
January 7, 2019

Dr. Volkow noted, “As we enter 2019, it is a good time to take stock of what NIDA accomplished over the past year. As always when I look back at the research being done by NIDA grantees and partners, I am amazed at the wealth of knowledge being created from our investments. Here I want to highlight just a few of the many outstanding developments in basic science, new therapeutics, and epidemiology and prevention research from the year that just ended.”

Basic Science Advances

Recent years have seen major advances in the understanding of receptor functioning. In March 2018, a team of researchers at NIDA’s Intramural Research Program (IRP) reported in Nature Communications on an advance in understanding G protein-coupled receptors (GCPRs), a large family of receptors that play an important role in the brain’s response to drugs. These receptors often assemble into larger complexes, but it has been unknown whether those complexes are merely the product of random collision between signaling molecules as they move across the membrane or whether they pre-form into complexes that serve specific functions.

The IRP team found that two common GCPRs in the reward pathway, adenosine A2A and dopamine D2 receptors (along with their G proteins and target enzyme), assemble into preformed macromolecular complexes that act as computation devices processing incoming information and enabling the cell to change its function based on that information. This knowledge could facilitate the development of more precise medication targets.

In June 2018, a team of NIDA-funded researchers at the University of California–San Francisco, along with colleagues in Belgium and Canada, reported in Neuron magazine that they had developed a genetically-encoded biosensor that can detect activation of opioid receptors and map the differences in activation within living cells produced by different opioids. The fact that opioids bind to receptors on structures within the cell—and not just on the cell membrane—was itself a novel finding, but the team also discovered striking differences in how endogenous versus synthetic opioids interact with these structures.

While endogenous peptides activated receptors on membrane-bound compartments within the cell called endosomes, synthetic opioid drugs activated receptor sites on a separate structure called the Golgi apparatus (which acts as a hub for routing proteins to various destinations in the cell). These very different patterns of activation within the cell may lead to greater understanding of why non-peptide opioid drugs produce tolerance as well as the behavioral distortions seen with opioid misuse and addiction whereas the body’s endogenous opioid peptides do not.

The same month, a team led by neuroscientists at UCLA studying narcolepsy reported research in Science Translational Medicine based on their discovery that postmortem brains from individuals who had been addicted to heroin show greatly increased numbers of neurons producing the neuropeptide hypocretin. Hypocretin helps regulate wakefulness and appetite, and a diminished number of cells in the brain producing it is associated with narcolepsy. The researchers went on to conduct a study administering morphine to mice, which as observed in the postmortem study produced increased numbers of hypocretin neurons. The results suggest that increases in these cells and in brain hypocretin could underlie the complaints of sleep problems in patients with an opioid use disorder (OUD). Since insomnia is a factor that contributes to drug taking in OUD and other addictions, strategies to counteract hypocretin signaling might have therapeutic benefits.

Prevention and Treatment

Last year, NIDA-funded research resulted in new therapeutics and apps for opioid use disorder. In May, the FDA approved lofexidine, the first medication approved to treat physical symptoms of opioid withdrawal. In December, the FDA cleared the first mobile health app intended to help retain patients with OUD in treatment, called reSET-O. It uses interactive lessons to deliver a community reinforcement approach therapy and enables users to report cravings and triggers to their health care provider between office visits, along with whether or not they have used Suboxone. NIDA funded the clinical trial that led to this app’s approval. A version called reSET was approved in 2017 to help with behavioral treatment of several non-opioid substance use disorders.

NIDA-funded research in epidemiology and prevention also added greatly to the knowledge of new drug trends in 2018. Last month’s striking findings on monitoringthefuture.org alerted us to escalating use of vaping devices among adolescents. Although most adolescents in 2017 claimed they used vaping devices only to vape flavors, this year most reported they used them to vape nicotine. Alarmingly, there was also an increase in vaping of cannabis.

Several other studies published in 2018 increased our understanding of factors that may lead youth to experiment with vaping. For example, a longitudinal cohort study by researchers at Yale and reported in Addictive Behavior found that exposure to ads for e-cigarettes on social media sites like Facebook significantly increased the likelihood of subsequent e-cigarette use among middle and high school students in Connecticut. In another study published in Preventive Medicine, the researchers also found that higher socioeconomic status was associated with greater exposure to e-cigarette advertising (which in turn was associated with increased likelihood of use)—important data that can help with targeting prevention efforts. Other work by UCSF researchers and published in Pediatrics found that e-cigarette use in adolescents was positively associated with being a smoker of conventional cigarettes, lending further support to the view that these devices are not diverting youth from smoking cigarettes but may be having the opposite effect in some users.

Looking To The Future

This year the Adolescent Brain Cognitive Development (ABCD) Study successfully completed recruitment of 11,874 participants, ages 9-10, who will be followed for 10 years, through young adulthood. The study, which is being conducted at 21 research sites around the country, is using neuroimaging to assess each individual’s brain development while also tracking cognitive, behavioral, social, and environmental factors (including exposure to social media) that may affect brain development and other health outcomes. The first release of anonymized data was made available so that both ABCD and non-ABCD researchers can take advantage of this rich source of information to help answer novel questions and pursue their own research interests.  Last year alone, the data resulted in more than 20 publications.