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.

 

Ambitious Research Plan to Help Solve the Opioid Crisis

From the blog of Dr. Lora Volkow, National Institute on Drug Abuse Posted June 12, 2018

NIDA Banner Science of Abuse and Addiction

In spring 2018 Congress added an additional $500 million to the NIH budget to invest in the search for solutions to the opioid crisis. The Helping to End Addiction Long-term (HEAL) initiative is being kicked off June 12th with the announcement of several bold projects across NIH focusing on two main areas: improving opioid addiction treatments and enhancing pain management to prevent addiction and overdose. The funding NIDA is receiving will go toward the goal of addressing addiction in new ways, and creating better delivery systems for addictions counseling for those in need.

NIH will be developing new addiction treatments and overdose-reversal tools. Three medications are currently FDA-approved to treat opioid addiction. Lofexidine—a drug initially developed to treat high blood pressure—has just been approved to treat physical symptoms of opioid withdrawal. Narcan (naloxone) is available in injectable and intranasal formulations to reverse overdose. Regardless, more options are needed. One area of need involves new formulations of existing drugs, such as longer-acting formulations of opioid agonists and longer-acting naloxone formulations more suitable for reversing fentanyl overdoses. Compounds are also needed that target different receptor systems or immunotherapies for treating symptoms of withdrawal and craving in addition to the progression of opioid use disorders.

Much research already points to the benefits of increasing the availability of treatment options for Opioid Use Disorder (“OUD”), especially among populations currently embroiled in the justice system. Justice Community Opioid Innovation Network is working to create a network of researchers who can rapidly conduct studies aimed at improving access to high-quality, evidence-based addiction treatment in justice settings. It will involve implementing a national survey of addiction treatment delivery services in local and state justice systems; studying the effectiveness and adoption of medications, interventions, and technologies in those settings; and finding ways to use existing data sources as well as developing new research methods to ensure that interventions have the maximum impact.

The National Drug Abuse Treatment Clinical Trials Network (“CTN”) facilitates collaboration between NIDA, research scientists at universities, and a myriad of treatment providers in the community, with the aim of developing, testing, and implementing addiction treatments. As part of the HEAL initiative, the CTN Opioid Research Enhancement Project will greatly expand the CTN’s capacity to conduct trials by adding new sites and new investigators. The funds will also enable the expansion of existing studies and facilitate developing and implementing new studies to improve identification of opioid misuse and OUD. Further, it will enhance engagement and retention of patients in treatment in a variety of general medical settings, including primary care, emergency departments, ob/gyn, and pediatrics.

Opioid Epidemic in America.jpg

A great tragedy of the opioid crisis is that there are a number of effective tools not being deployed effectively in communities in need. Only a fraction of people with OUD receive any treatment, and of those less than half receive medications that are universally acknowledged to be the standard of care. Moreover, patients often receive medications for too short a duration. As part of its HEAL efforts, NIDA will launch a multi-site implementation research study called the HEALing Communities Study in partnership with the Substance Abuse and Mental Health Services Administration (SAMHSA). The HEALing Communities Study will support research in up to three communities highly affected by the opioid crisis, which should help evaluate how the implementation of an integrated set of evidence-based interventions within healthcare, behavioral health, justice systems, and community organizations can work to decrease opioid overdoses and prevent and treat OUD. Lessons learned from this study will yield best practices that can then be applied to other communities across the nation.

The HEAL Initiative is a tremendous opportunity to focus taxpayer dollars effectively where they are needed the most: in applying science to find solutions to the worst drug crisis our country has ever seen.

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. We also have step by step guides on what to do to help yourself, a friend or a family member on our Treatment page.