10 Startling Studies that Shifted the Way We Think About Addiction

The following first appeared on Substance.com:

Over the past decade, addiction has come out of the shadows and into popular culture as never before. This is a time when the very definition of addiction is hotly contested, and we appear to be a tipping point where the “spiritual” framing of addiction is fast yielding to the “scientific” one. Some of us wonder what has taken so long.

Science rarely progresses in a straight line, and the science of addiction is no exception. Since the mid-1960s, when the approach to substance use disorder began to shake off the dark cloak of moral stigma, the fields of medicine, psychology, neuroscience, sociology and advocacy have, at times, competed and, at other times, collaborated to advance our understanding of the nature, causes, course and, most important, treatment of addiction. As moralism gave way to medicine, so abstinence expanded to include controlled drinking and spontaneous remission. No sooner does one model gain ascendance than cracks appear in its certitudes and it is forced to make room or make way for new thinking.

We may still be living in the age of the disease model of addiction, but a factors like the environment, stress, brain chemistry and genes have all complicated and enriched our understanding, leading to a growing array of evidence-based treatments, including individual and group psychotherapy, cognitive-behavioral treatment (CBT), motivational interviewing (MI), relapse prevention, methadone and other medication, and the harm reduction movement itself.

The following 10 studies, surveys, lab research, and other empirical and theoretical work have blazed trails—often sparking dramatic controversy and even hostility—and in doing so have proved to be the defining texts of addiction science. But check back in another 50 years to see if they still withstand the test of time.

1. “Heroin Addiction: A Metabolic Disease” (1967)

Why It Matters: This study led to the recognition of addiction as a treatable disease, not a result of character flaws or bad morals.

Methadone is an opioid agonist that both reduces cravings and lessens withdrawal if taken instead of heroin or another opioid drug. Multiple large-scale public health agencies agree that Methadone Maintenance Therapy (MMT) is the most effective treatment for opiate addiction. However, this wasn’t always the case—and controversy remains over whether MMT simply perpetuates opioid addiction.

MMT was initially developed in the 1960s, and a landmark study to come out of that program was a paper by Rockefeller University’s Dr. Vincent Dole and Dr. Marie Nyswander examining the use of MMT as part of a multimodal treatment program. Of 304 patients admitted, more than 90% completed the program—an exceptionally high rate—and almost 75% were “socially productive and living as normal citizens in the community after only six months of treatment.”

Over the 50 years since this pioneering work, MMT has been proven to reduce heroin use, reduce death and crime rates associated with use, and allow patients to improve their health and social productivity. In 2001, oversight of MMT programs went from the FDA to the SAMHSA—with standards for accreditation being guided by “best practices.” In 2004, WHO/UNAIDS/UNODC published a consensus review on the effectiveness of methadone and other replacement medications like buprenorphine, concluding that substitution maintenance therapy is one of the most effective treatments for opioid dependence and designating it an “essential medicine” that should be available worldwide to all patients who need it.

2. “Individualized Behavior Therapy for Alcoholics” (1973)

Why It Matters: This was the first study that showed that controlled drinking—instead of abstinence—was possible for recovering alcoholics.

Experiments psychologists Mark Sobell and Linda Sobell provided powerful momentum to the anti-abstinence movement in addiction studies in the 1970s by showing that controlled drinking was not only possible but demonstrated success in recovery.

The Sobells performed a study and two follow-up reports that found that among 70 severe alcoholics at a Southern California hospital, those who were trained to drink in moderation had better outcomes at two and three years’ follow-up than those who followed abstinence-based recovery methods. Their work sparked controversy, with attacks on its methodology and its conclusions, including outright accusations of fraud. The Sobells were later cleared of misconduct.

Their work has led the way for legitimizing moderation-based approaches to treating alcoholism, including Moderation Management and harm reduction techniques.

3. “The Vietnam Drug User Returns” (1974)

Why It Matters: This study demonstrated that most people do not become addicted for life to heroin, and that those who have an addiction can recover spontaneously, without treatment.

Prior to this study, it was believed that heroin addiction was fast and lasting—and that people addicted to heroin needed treatment to remain abstinent. In her study, which made use of a “highly exposed normal population” of Vietnam veterans returning in 1971 from the war, Dr. Lee Robins, a Washington University sociologist, interviewed 617 men over three years after they came home on their experience using heroin and/or opium. She found “surprisingly low levels of re-addiction” and much more polysubstance drug abuse as opposed to being addicted to heroin alone.

Her work exploded fundamental assumptions of addiction professionals and anti-drug advocates, who responded to it with skepticism and even derision. In 1993, giving the prestigious sixth-annual Thomas James Okey Memorial Lecture 1993, Robins gave an equally heralded paper, “Vietnam Veterans’ Rapid Recovery From Heroin Addiction: A Fluke or Normal Expectation?” offering further support for the findings and examining the institutional resistance to this proof of spontaneous remission.

Robins’ seminal work withstood attacks and has helped pave the way for new treatment modalities involving harm reduction, MMT and non-abstinence-based recovery models. Yet to this day there remains controversy surrounding why abstinence-based recovery models such as 12-step programs are so prevalent in light of scientific evidence that abstinence is not necessarily required to prevent re-addiction.

4. “The Effect of Housing and Gender on Morphine Self-Administration in Rats” (1978)

Why It Matters: This study poked holes in the strict disease model of addiction, showing that addiction may be a consequence of stressful circumstances and not of drug use itself.

Rat Park, as it came to be known, grew out of Canadian psychologist Bruce Alexander’s doubts about the disease model of addiction, which gained popularity in the 1970s as a growing number of animal studies traced addiction to the exclusive effect of the use of a drug on brain processes.

Alexander hypothesized that in lab rats, it was stressful living conditions rather than drug consumption that created the conditions for addiction. In Rat Park, he created two different living situations for his lab rats: solitary confinement in a cage vs. social grouping in a large box. After a period of forced consumption of morphine followed by a period of abstinence, he discovered that the isolated rats drank more morphine solution than the social rats, and that the females drank more than the males.

While the study remains controversial decades after its publication because of the limitations of extrapolating rats’ drug-taking behavior to that of humans, Rat Pack increased attention to the idea that factors such as environment and stress play a significant role in the development of addiction.

Alexander collaborated with addiction specialist (and Substance.com columnist) Dr. Stanton Peele in writing several chapters of Peele’s 1985 book The Meaning of Addiction: Compulsive Experience and Its Interpretation, which popularized the anti-disease model theory.

5. “Neuroleptics and Operant Behavior: The Anhedonia Hypothesis” (1982)

Why It Matters: This study laid the groundwork for the reigning dopamine hypothesis of addiction.

Much of what we understand as the dopamine hypothesis of addiction—that the motivation for using drugs comes from their effect of increasing mesolimbic dopamine levels in the brain—comes from groundbreaking studies performed in the 1970s andearly 1980s by behavioral neuroscientist Roy Wise. In these studies, Wise determined that by using neuroleptics—drugs that block the dopamine pathways in the brain—he could reduce reward-seeking behavior in rats. Whether it’s food, water, intravenous opiates, stimulants or barbiturates, Wise came to conclude that neuroleptics acted to gradually reduce motivation in rats seeking rewards, and that this motivation is essential for behavior directed toward the goal of pleasure.

Years of research later, it is commonly known that dopamine surges precede and encourage drug use—and that after getting sober, many people experience the effect of a chronic lack of dopamine as anhedonia, or the inability to experience pleasure in everyday rewards or life events.

6. “Inpatient alcoholism treatment. Who benefits?” (1986)

Why It Matters: This study found that the then-prevalent treatment—residential, longer and more intensive—was no more effective than shorter outpatient programs, effectively setting the stage for personalized treatment for alcohol use disorders.

Alcoholism has had a long history of being stigmatized—isolating patients to institutions or directing them to institutionalized recovery programs. Two clinical psychologists at the University of New Mexico, Dr. William Miller and Dr. Reid Hester, did game-changing research that reviewed findings from 26 controlled studies, showing there to be no overall advantage for residential over nonresidential settings, for longer over shorter programs or for more intensive over less intensive interventions in treating alcohol misuse. In other words, the content of treatment turned out to matter more than the setting. The authors recommended that third-party reimbursement policy favor cost-effective, research-supported alternatives to intensive residential models for problematic alcohol use.

Miller’s subsequent meta-analysis of treatment methodologies, which he published in a leading treatment manual called the Handbook of Alcoholism Treatment Approaches: Effective Alternatives, found that the most effective treatments were active and empathic, while the least effective were passive or confrontational. He went on to lay the groundwork that led to the development of Motivational Enhancement Therapy—now recommended by NIDA as a core behavioral treatment for alcohol, marijuana and nicotine dependence/addiction. MET aims to help patients develop a motivation to stop using alcohol or drugs in order to discover an authentic sense of purpose in life.

7. “The Neural Basis of Drug Craving: An Incentive-Sensitization Theory of Addiction” (1993)

Why It Matters: This paper defined the incentive-sensitization theory of addiction.

The research of Dr. Kent Berridge, a professor of psychology and neuroscience at the University of Michigan, into the nature of compulsive substance use—which is best represented in a paper he co-wrote in 1993 with fellow psychologist Dr. Terry Robinson—helped develop the dopamine hypothesis of addiction by delineating the difference between wanting and liking, or reward-seeking and pleasure. Berridge essentially recast dopamine from the “pleasure” molecule to the “reward” neurotransmitter. Specifically, dopamine acts to mediate reward, or give “incentive salience to reward-associated stimuli.” Berridge also helped describe how this incentive salience leads to drug sensitization—that is, only feeling motivated for that drug, by that drug.

His work has helped scientists further define the neuroanatomy of reward-seeking and pleasure centers of the brain, and how addiction influences and is influenced by memory, learning and higher decision-making. Dr. Eric Nestler, the chair of Mount Sinai Medical Center’s Department of Neuroscience, has done pioneering work linking dysfunction in dopamine circuits to depression, and new clinical trials are investigating how cravings can be lessened by tweaking memories—essentially, dampening down the emotional salience of cravings.

8. “Drug Dependence, a Chronic Medical Illness: Implications for Treatment, Insurance, and Outcomes Evaluation” (2000)

For most of its history, addiction has been considered a social rather a medical problem. In a milestone paper, psychologist Dr. A. Thomas McLellan, head of the Treatment Research Institute in Philadelphia, reviewed literature to compare the diagnoses, heritability, genetic and environmental factors, pathophysiology and treatment response of drug addiction and common diseases such as type 2 diabetes, hypertension and asthma. He found that genetics, choice and environmental factors are involved in similar ways in the course of all these diseases. He also suggested that addiction should be not only treated like a medical condition but also continually monitored as a chronic disease.

One of the biggest changes to come in the near 15 years since McLellan’s work was the passing of the Mental Health Parity Act (MHPA) in 1996 and the Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008: If insurers offer mental health and substance abuse care, they have to offer the same coverage and reimbursement as for other medical illnesses. The Affordable Care Act, passed in 2010, took parity one step further by requiring insurers to offer mental health and substance abuse treatment.

9. “Clinical Guidelines for Implementing Relapse Prevention Therapy” (2002)

In this paper, the University of Washington’s Dr. G. Alan Marlatt identified cognitive-behavioral therapy as an effective approach to preventing relapse in people with substance use disorders. In understanding how to cope with cravings or triggers, recovering addicts can learn to stop associating using drugs with the experience of pleasure (or lack of pain) and thereby build healthier behavior in response to their negative thoughts and feelings.

As a pioneering researcher of harm reduction and relapse prevention, Marlatt helped pave the way for the current explosion of mindfulness-based research and its therapeutic applications. In Mindfulness-Based Relapse Prevention—which is partly drawn from Vipassana meditation—recovering addicts learn to examine their thoughts and feelings without judgment as a way to disengage from the compulsion to act on cravings. Marlatt turned the prevailing concept of relapse as an endpoint—or termination of abstinence—into simply one part of the ongoing recovery process. In doing so, he helped bring credibility to cognitive-behavioral relapse prevention techniques.

10. “National Epidemiologic Survey on Alcohol and Related Conditions” (2006)

Why It Matters: This is the largest-ever epidemiological study of alcohol use disorders and co-morbid psychiatric diseases among the US general population.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) conducted the largest and most ambitious study to date looking into the prevalence and expression of alcohol use and other substance use disorders—as well as comorbid psychiatric conditions—during two waves, in 2001 and then from 2004 to 2005. Because the study delved into patterns of both substance use and psychiatric disorders such as major depression, anxiety disorders and personality disorders, its epidemiological approach furthered the growing move toward tracking drug use (and mental illness) trends using hard, statistical evidence.

Over the past decade, the study has had far-ranging effects, including more large-scale epidemiological studies, refining the definitions of “dependence” and “abuse,” as well as improved treatment methods specific to, for example, ethnicity or co-morbid disease status. The study offered both researchers and treatment providers a much broader idea of the variation in substance use disorders across a population, and how they are influenced by myriad factors.