This article reviews scientific advances in the prevention and treatment of substance-use disorder and related developments in public policy. In the past two decades, research has increasingly supported the view that addiction is a disease of the brain. Although the brain disease model of addiction has yielded effective preventive measures, treatment interventions, and public health policies to address substance-use disorders, the underlying concept of substance abuse as a brain disease continues to be questioned, perhaps because the aberrant, impulsive, and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology. Here we review recent advances in the neurobiology of addiction to clarify the link between addiction and brain function and to broaden the understanding of addiction as a brain disease. We review findings on the desensitization of reward circuits, which dampens the ability to feel pleasure and the motivation to pursue everyday activities; the increasing strength of conditioned responses and stress reactivity, which results in increased cravings for alcohol and other drugs and negative emotions when these cravings are not sated; and the weakening of the brain regions involved in executive functions such as decision making, inhibitory control, and self-regulation that leads to repeated relapse. We also review the ways in which social environments, developmental stages, and genetics are intimately linked to and influence vulnerability and recovery. We conclude that neuroscience continues to support the brain disease model of addiction. Neuroscience research in this area not only offers new opportunities for the prevention and treatment of substance addictions and related behavioral addictions (e.g., to food, sex, and gambling) but may also improve our understanding of the fundamental biologic processes involved in voluntary behavioral control. In the United States, 8 to 10% of people 12 years of age or older, or 20 to 22 million people, are addicted to alcohol or other drugs. 1 The abuse of tobacco, alcohol, and illicit drugs in the United States exacts more than $700 billion annually in costs related to crime, lost work productivity, and health care. 2-4 After centuries of efforts to reduce addiction and its related costs by punishing addictive behaviors failed to produce adequate results, recent basic and clinical research has provided clear evidence that addiction might be better considered and treated as an acquired disease of the brain (see Box 1 for definitions of substance-use disorder and addiction). Research guided by the brain disease model of addiction has led to the development of more effective methods of prevention and treatment and to more informed public health policies. Notable examples include the Mental Health Parity and Addiction Equity Act of 2008, which requires medical insurance plans to provide the same coverage for substance-use disorders and other mental illnesses that is provided for other illnesses, 5 and the proposed bipartisan Senate legislation that From the National Institute on Drug Abuse (N.D.V.) and the National Institute of Alcohol Abuse and Alcoholism (G.F.K.) — both in Bethesda, MD; and the Treatment Research Institute, Philadelphia (A.T.M.). Address reprint requests to Dr. Volkow at the National Institute on Drug Abuse, 6001 Executive Bld., Rm. 5274, Bethesda, MD 20892, or at nvolkow@ nida . nih . gov.

Review Article: Neurobiologic Advances from the Brain Disease Model of Addiction

The opioid crisis in the United States has come about because of excessive use of these drugs for both legal and illicit purposes and unprecedented levels of consequent opioid use disorder (OUD). More than 2 million people in the United States are estimated to have OUD, which is caused by prolonged use of prescription opioids, heroin, or other illicit opioids. OUD is a life-threatening condition associated with a 20-fold greater risk of early death due to overdose, infectious diseases, trauma, and suicide. Mortality related to OUD continues to escalate as this public health crisis gathers momentum across the country, with opioid overdoses killing more than 47,000 people in 2017 in the United States. Efforts to date have made no real headway in stemming this crisis, in large part because tools that already exist—like evidence-based medications—are not being deployed to maximum impact. To support the dissemination of accurate patient-focused information about treatments for addiction, and to help provide scientific solutions to the current opioid crisis, this report studies the evidence base on medication assisted treatment (MAT) for OUD. It examines available evidence on the range of parameters and circumstances in which MAT can be effectively delivered and identifies additional research needed.

Medications for Opioid Use Disorder Save Lives

Alexander Tsai and co-authors discuss the role of stigma in responses to the US opioid crisis.

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Stigma as a fundamental hindrance to the United States opioid overdose crisis response.

Crowdsourcing, the use of the Internet to outsource work to a large number of people, has witnessed a dramatic growth over the past decade. One popular crowdsourcing option, Amazon Mechanical Turk (MTurk), is now commonly used to sample participants for psychological research. Addiction science is positioned to benefit greatly from crowdsourced sampling due to the ability to efficiently and effectively tap into populations with specific behavioral and health histories. The primary objective of this review is to describe the utility of crowdsourcing, broadly, and MTurk, specifically, for conducting research relevant to substance use and misuse. Studies in psychological and other health science have supported the reliability and validity of data gathered using crowdsourced samples. Promising research relevant to addiction science has also been conducted, including studies using cross-sectional designs and those for measure development purposes. Preliminary work using longitudinal methods and for interventions development has also revealed the potential of MTurk for studying alcohol and other drug use through these designs. Additional studies are needed to better understand the benefits, as well as the limits and constraints, of research conducted through crowdsourced online platforms. Crowdsourcing, such as on MTurk, can ultimately provide an important complement to existing methods used in human laboratory, clinical trial, community intervention, and epidemiological research. The combinations of these methodological approaches could help improve the rigor, reproducibility, and overall scope of research conducted in addiction science. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The use of crowdsourcing in addiction science research: Amazon Mechanical Turk.

Introduction: The opioid epidemic has become an immense problem in North America, and despite decades of research on the most effective means to treat opioid use disorder (OUD), overdose d...

Emerging Evidence for Cannabis' Role in Opioid Use Disorder

Why aren't physicians prescribing more buprenorphine?

Evidence of anhedonia and differential reward processing in prefrontal cortex among post-withdrawal patients with prescription opiate dependence

A hidden aspect of the U.S. opioid crisis: Rise in first-time treatment admissions for older adults with opioid use disorder.

Background and objectives In order to address the current opioid crisis, research on treatment outcomes for persons with opioid use disorder (OUD) should account for biological factors that could influence individual treatment response. Women and men might have clinically meaningful differences in their experience in OUD treatment and might also have unique challenges in achieving successful, long-term recovery. This review summarizes and synthesizes the current literature on sex-based differences in OUD treatment outcomes. Methods Relevant literature was identified via automated and manual searches using the terms "opioid treatment outcome sex [or gender] differences" and "opiate treatment outcome sex [or gender] differences." Search methodology was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and were conducted within the PubMed electronic database during March and April of 2018. Results The initial PubMed search yielded 241 manuscripts and 31 original research articles that met inclusion/exclusion criteria were synthesized in this review. Several important trends emerged, including findings that women are more likely than men to present to treatment with co-occurring mental health conditions such as depression, and that women might respond particularly well to buprenorphine maintenance. Discussion and conclusions While much of the literature on this topic is subject to potential cohort effects, interventions that address co-occurring mental health conditions and psychosocial stress might improve treatment outcomes for women with OUD. Scientific significance Funding agencies and researchers should focus attention toward human laboratory studies and clinical trials that are prospectively designed to assess sex-based differences in OUD recovery. (Am J Addict 2019;28:246-261).

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Review: Sex-Based Differences in Treatment Outcomes for Persons With Opioid Use Disorder.

Background and objectives Individuals exposed to fentanyl are at risk of precipitated withdrawal using typical buprenorphine/naloxone induction procedures Methods This case series describes buprenorphine/naloxone inductions of four individuals who tested positive for fentanyl Results Buprenorphine-precipitated withdrawal was observed in two individuals who completed a conventional buprenorphine/naloxone induction strategy Two more individuals completed a revised buprenorphine/naloxone induction strategy that did not precipitate withdrawal Discussion and conclusion Using multiple 2 mg doses of buprenorphine/naloxone in patients already in mild/moderate withdrawal improved outcomes Scientific significance Persons who use illicit fentanyl might be less likely to experience precipitated withdrawal from this revised buprenorphine/naloxone induction strategy (Am J Addict 2021;30:83-87)

Andrew S. Huhn

Papers

Why aren't physicians prescribing more buprenorphine?

Evidence of anhedonia and differential reward processing in prefrontal cortex among post-withdrawal patients with prescription opiate dependence

A hidden aspect of the U.S. opioid crisis: Rise in first-time treatment admissions for older adults with opioid use disorder.

Review: Sex-Based Differences in Treatment Outcomes for Persons With Opioid Use Disorder.

Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone.