Reviewing NIDA’s 2019 Achievements and Looking to the Future

As NIDA sets its sights on new goals and objectives for 2020 and beyond, I like to reflect on how far we have come in our research efforts, especially as they concern the opioid crisis, one of the biggest public health issues of our era. Although deaths from synthetic opioids like fentanyl continue to rise, glimmers of hope are starting to appear. Provisional numbers show that overall overdose deaths have held steady rather than increasing since 2018, and a massive federal investment toward finding scientific solutions to the crisis promises to further turn the tide against opioid and other drug use disorders.

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Image of year 2019 being replaced with 2020
©iStock/Oakozhan

The biggest news of the past year is the grant awards in the Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM. In Fiscal Year 2019, 375 grants, contracts, supplements, and cooperative agreements totaling $945 million were awarded in 41 states. As part of this aggressive, trans-agency effort, NIDA is funding research on prevention and treatment of opioid use disorder, including developing new treatments and expanding access to those that already exist.

The HEALing Communities Study led by NIDA in close partnership with the Substance Abuse and Mental Health Services Administration is testing the implementation of an integrated array of evidence-based practices in various healthcare, behavioral health, justice, and community settings in 67 hard-hit communities across four states. Objectives of the study include increasing the number of people with OUD receiving medications for their disorder, increasing naloxone distribution to help reverse opioid overdoses, and reducing high-risk opioid prescribing, with the goal of reducing opioid overdose deaths by 40 percent in those communities over of the next three years. Effective strategies learned from this project can then be exported to other communities.

Other HEAL projects are aimed at finding ways to address the prevention and treatment needs of the most at-risk populations. Grants to 12 institutions as part of the Justice Community Opioid Innovation Network (JCOIN) will create a network of researchers in 15 states and Puerto Rico to study ways to scale up and disseminate evidence-based interventions in a population with extremely high rates of OUD and overdoses, including evaluating the use of the different medications for OUD in jails and prisons as well as in parolees suffering from OUD. In a separate set of projects, NIDA is funding research aimed at preventing the transition from opioid use to OUD in young adults, including projects targeting rural and American/Indian communities.

NIH HEAL money has also allowed NIDA to greatly expand our Clinical Trials Network and, in partnership with other Institutes, is additionally partially supporting pilot studies in preparation for a large-scale study of brain health and development across the first decade of life. The HEALthy Brain and Child Development (hBCD) study, along with the already-underway Adolescent Brain and Cognitive Development (ABCD) study (not funded through HEAL), will contribute in innumerable ways to our understanding of brain development and the many factors influencing risk and resilience for substance use during childhood and adolescence.

Basic Science Highlights

In 2019, researchers at NIDA-funded Yale University made significant strides toward understanding biological predictors of addiction and relapse. Using functional magnetic resonance imaging and machine learning, Sarah W. Yip and colleagues found that functional connectivity among a number of brain regions predicted chances of achieving abstinence in patients receiving treatment for cocaine use disorder. Their results, published in the American Journal of Psychiatry last February, could lead to new approaches to treating cocaine addiction by intervening directly in those pathways.

Genetic approaches are also yielding important insights in this area. An analysis of genome-wide association studies (GWAS) published in Nature Genetics last January identified hundreds of gene loci associated with tobacco and alcohol use and related health conditions. Genes involved in dopaminergic, nicotinic, and glutamatergic signaling were among those identified. Another partially NIDA-supported GWAS study published in Nature Neuroscience in July identified an association between expression of the gene for the cholinergic receptor nicotinic α2 subunit with cannabis use disorder in brain tissue from a large Icelandic sample.

NIDA-supported basic science is also shedding important light on opioids and the brain’s opioid signaling systems. Research published in June in ACS Central Science provided new insights while raising new questions about the drug kratom. Its active ingredient mitragynine acts as a weak partial agonist at the mu-opioid receptor (MOR), but new findings by a team that included researchers at Columbia and Memorial Sloan-Kettering found that the drug’s analgesic properties are significantly mediated by a metabolite produced when mitragynine is consumed orally, called 7-hydroxymitragynine. In mice, at least, this compound seems to provide analgesia but with fewer respiratory-depressing and reward-associated side effects than other opioids such as morphine. These findings point toward the potential of this drug in pain research as well as the need for further research on the pharmacology of kratom’s constituents, their toxicity and potential value in the treatment of OUD.

Although the MOR system is most commonly associated with pain and pain relief, other receptors are also involved.  One important dimension of pain is the negative affect commonly associated with it, and NIDA-supported research published in Neuron in March found that the kappa-opioid signaling system, specifically in cells located in the shell of the nucleus accumbens, are involved in processing pain-associated negative affect. This discovery could perhaps provide new targets for treating the emotional distress associated with many pain-associated syndromes.

Other

Translating addiction science into new treatments and treatment tools is another area where NIDA is having an impact. For example, in the past few years, NIDA has been extremely successful in winning interest for biotechnology investment in devices and other products to address the opioid crisis and addiction more generally. Historically, addiction is a market that has scared away pharmaceutical companies and investors, who viewed it as small and risky and one that would not lead to recovery of investment. However,  NIDA’s medication development program expansion along with NIDA’s Office of Translational Initiatives and Program Innovations (OTIPI) are turning this around. OTIPI, which I highlighted previously on this blog, uses a wide array of funding mechanisms to support startups in developing or adapting devices, apps, and other technologies in ways that can better deliver treatment to people with substance use disorders and related conditions.

NIDA science continues to contribute knowledge to help guide policy. One example is from our annual Monitoring the Future (MTF) survey, which in 2019 showed steep increases in the use of vaping devices both for nicotine and for marijuana among teenagers.  The survey also revealed that a large proportion of teens vaped because they liked the taste. When these vaping data (along with those of the National Youth Tobacco Survey) were released last November, it prompted the makers of the popular Juul devices to pull their mint flavored products from the shelves, and it prompted the FDA to finalize their enforcement policy on flavored vaping (e-cigarette) products.

The new scientific knowledge and innovations generated by our Institute in 2019 and the unprecedented investment in large-scale, coordinated studies through HEAL leave us poised to make considerable scientific progress in 2020 toward effective strategies for addiction prevention and treatment. As the ABCD study has already begun to, these new research programs will generate vast troves of data that promise new opportunities for collaboration and an accelerated pace of discovery.

Dr. Nora Volkow, Director

Here I highlight important work being done at NIDA and other news related to the science of drug use and addiction.

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Comments

 accomplishments

Fact is, with all the millions of dollars that NIDA has received, very little in the way of impacting the drug abuse problem in this country has taken place. Most alarming is the lack of foresight and ability to impact the methamphetamine problem in this country. as well, effective prevention efforts seem non existent as the problem continues to get worse. Totally lack of focus on these issues is apparent. Much, much work to be done.

 Addiction is a complex

Addiction is a complex disorder having many causes—not only biological but also social and economic. Consequently many forces are needed to address it, both within and outside of healthcare. NIDA’s portfolio includes research to develop and deliver effective prevention and treatment interventions as well as better integrate the many systems that must work together to end the opioid crisis and the stimulant crises (cocaine, methamphetamine) that are developing in its wake.

 Treatments

I lived with this disease for a long time. I changed my life around. I have been clean 5 yrs.Yet, I take suboxone. When I found out I was pregnant I had to stop using heroin & transition to suboxone. I'm THE 1ST PERSON TO TELL YOU I DEFINITELY DO NOT FEEL CLEAN! I'm miserable, my brain receptors feel foggy. I'm missing out on things I did for joy & happiness. Playing with my children, looking forward to events or vacations & most of all: MY FEELINGS & EMOTIONS! I CANT FEEL! AT TIMES I THINK I MIGHT AS WELL JUST GET HIGH! I JUST KEEP HOLDING ON & RECHECKING ALL OF THESE WEBSITES.In HOPES THAT THEY CAME OUT WITH SOMETHING NEW! I BEG OF YOU. PLEASE FIND SOMETHING. THIS IS MISERY!And, addicts don't have patients to even be researching! I CAN TELL YOU IT MAKES ME SO SAD, ANGRY & FRUSTRATED TO SEE SOME OF these places that have "rapid detox, technology for the ears, students spending millions of dollars to come up with a drink to detox painlessly, or keeping you under sedation for a few days".... AND YET STILL THERE ARE PEOPLE DYING AND OVERDOSING RIGHT THIS EXACT SECOND. PLACES CLAIM THEY HAVE THE BEST RESOURCES and YET YOU NEED CASH, OR THEY DON'T EXCEPT INSURANCE. They have testimonials of patients successfully completing and still clean. SHAME ON YOU. ALL OF YOU. YOU HAVE FOUND A WONDERFUL WAY TO HELP.BUT YOU DON'T. ITS ALL ABOUT THE $$$

 meds

you people seem to forget about the ones that need the medds to have any type of quality of life.I am a 60 year old female with spinal cord injury and sever back problems. ive had 3 knee replacements ,]shoulder surgery; 2 neck surgerys and 3 back surgerys. i am a chronicpain patient i have been on heavyu pain meds for the past 14 yeatrs. but they made me mobile i have to wa;k with a walker because i have no balance due to spinal cord injury,.I have sever nerve damage. my dr quit 1 1/2 months ago. io have been forced to do my own detox due to the drug laws,. sto[p putting peo[ple in one catagory. some preo[le need the meds to live. the sudden dsto[p of meds has caused heart trouble and bed bound. until tyhis hzAppens to you you have no idea what its like/. stop trying to get rid of the meds that help some people and start figuring out how to change the way thje drugs are administered. if they can put a hormone pelet under your skin that slow releases for 2 months thjey can do tjhe sam with pain meds. get real and try helping instead of blocking

 How much damage?

Speaking of the future, a wishful future anyway, a local radio talk show host recently asked me rhetorically what would happen if all US illegal, recreational drug use ended tomorrow. A simple enough question, right?

Actually not, so I was hoping NIDA could take a stab. I would like to know how many lives are being lost because of addiction related suicide and overdoses, driving while high auto accidents, and the drug warfare among the gangs, drug dealers and cartels? Would the sum total of drug related deaths in the US and Mexico be around a hundred-fifty thousand/year or so?

Then I'd like to know the total financial/economic burden we have from dollars and guns flowing south, drug law enforcement, interdiction, jails and prisons, how much addiction treatment is costing us, how much lost productivity there is from addiction and/or drug habits, how much burden this poses because of violence added to the inner cities, and whatever else you can think of. My wild guess is the economic burden costs us around a trillion dollars a year, perhaps?

Plus, what percentage of the total demand for illegal drugs is purely because of addiction? Perhaps the remaining percentage of unaddicted drug users supply the essential 'seed' money that keeps the gangs and cartels in business?

Basically, in the liberalized aftermath of the Sixties 'counter-revolution', a substantial number of Americans viewed illegal drugs favorably. They said "Yes" to drugs, and now we must endure a staggering burden of problems, imo. Unfortunately.

Thanks!

 PREVENTION is key to any long term solution to the crisis

I think that until there is an effective way to keep people from ever entering the addiction pipeline, we will never turn off the faucet, and continue to mop up the floor. We need more a more effective risk and objective assessment prior to taking oral opioids. In as little as 3 days, someone can be headed down the path to OUD. We should assess risk and encourage joint decision making between patient and provider. Patients must have a more informed and active role in their pain management strategy pre and post-op. #powerofprediction

 Thanks for the thoughtful

Thanks for the thoughtful comment.  We just want to clarify the distinction between dependence and addiction—especially following 3 days of exposure.  Most people do not start to develop an OUD that quickly; however many may experience dependence (including tolerance and signs of withdrawal), which is not addiction. Dependence happens with many drugs that are not addictive, for example antidepressants, and requires the person to slowly taper off their medication when it is no longer needed.  Addiction and dependence should not be conflated, and fear of addiction should not cause someone who is appropriately prescribed an opioid to stop abruptly.  Patients should talk to their physician or other health care provider about their concerns when starting and stopping the use of opioid medications.

 Question about what Nora Volkow said at Congressional Briefing

I attended a Congressional Briefing where she was on the panel, in Oct of 2019.

She spoke about the fact that withholding pain medication from patients in severe pain can actually increase addiction because the hunt for effective treatment for their pain can lead to having pain relief at times and other times not, which can trigger the reward center of their brains. Not sure if I said it correctly, but I am hoping that I made enough sense that someone could help me find the research that she is referring to.

Due to time constraints on the room we were in, I was only able to have a very brief conversation with her, but would love to have the chance to follow up. My main concern was finding the research that led her to that statement. I believe she is on the right track and can even add more context to back up her statement with what I have learned in my own studies and travels even since that briefing a few months ago.

I would greatly appreciate any help to find this information.

Thank you for all you. And THANK YOU for your comment above separating addiction & dependence; that confusion being allowed at every level in America is killing patients daily.

TameraLynn Stewart

 Relief of pain is rewarding

Relief of pain is rewarding in itself, and it may be that that reward and its reinforcing effects may be greater when the desire for relief is prolonged due to inadequate pain management. The neural circuits underlying the rewarding properties of pain relief are discussed in this article.

 Accomplishments? REALLY?

I agree with the first comment.
Congratulations on using drug abuse to access more HUNDREDS OF MILLIONS OF DOLLARS.
Great accomplishment.

What accomplishments could actually HELP? I didn’t see anything about HARM REDUCTION.
Harm reduction would be the easiest and cheapest way to STOP THE HARM being done by drug abuse!

Only NOW, in 2020, you’re looking at the benefits of KRATOM?
When the DEA learned that KRATOM was being used to help Americans quit abusing opioids what was their reaction?
THEY TRIED TO BAN THE PLANT! (In 2016).

Literally TENS OF THOUSANDS of Americans commented on a government website which, thankfully, which put an end to the DEA attempt to make KRATOM unavailable to Americans.

READ THE COMMENTS.
While antidotal it is overwhelming proof that the plant COULD BE used as an alternative to opioids.
What is the NIDA doing to advocate for KRATOM? Very little.

What about Ibogaine? Another plant that NIDA did clinical trials on in the 90’s, which successfully helped patients quit opioid abuse. Why did the NIDA BURY the research instead of use it to help reduce deaths?

Why doesn’t NIDA look at countries like Holland, where heroin is legal and free, given by medical professionals using sterile syringes?

HARM REDUCTION, EASY ACCESS TO BUPRENORPHINE, PLANT THERAPY, these are ways to help this crisis at a very small cost.
THAT’S the problem.
You’re in this for the MONEY, not for what’s best for our nation.