June 19, 2025 by Alex Brewer, PharmD, MBA
TL;DR
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Psychedelics have been studied as treatments for addiction since the 1930s, with early reports showing promise in alcohol and heroin dependence.
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After decades of prohibition, modern studies and real-world evidence are reigniting interest—especially in LSD, ketamine, psilocybin, ibogaine, and MDMA.
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Today’s clinical trials aim to validate past findings with more rigorous methods and explore how psychedelics interact with brain function and behavior change.
Today, we’re discussing a review article published by a team of researchers primarily based at Imperial College London. This article reviews the role of psychedelics in treating addiction, including substance use disorders.
As a review article, the authors aren’t publishing their own original research. Instead, they look back at the past to summarize data from clinical studies as far back as 1934, before looking at the current research landscape. They use this data, plus their expertise in the field, to try and predict the type of research we may see in the near future regarding psychedelic treatment for substance misuse and abuse.
I’ve decided to split our discussion into two articles. Today’s discussion focuses on past data and the present state of research. My next article will focus on the article’s points regarding future research.
Addiction 101
First, let’s define addiction and clear up some misconceptions. According to the NHS, “Addiction is defined as not having control over doing, taking or using something to the point where it could be harmful to you.” This “something” could be drugs (including alcohol or tobacco), gambling, work, sex, shopping – just about anything can be addicting.
Addiction is not a personal or moral failure. There are a variety of factors – genetic and environmental – attributed to the pathology of addiction, and just like anything pertaining to the human brain, there’s still so much more to uncover that we don’t understand. Which makes treating addiction difficult.
A 2018 Lancet article estimates 164 million persons globally are affected by addiction, and I would surmise to say this has increased following the COVID-19 pandemic. While much attention has been paid to overdose deaths related to opioid use and misuse in the U.S., opioid overdose is a global issue – WHO estimates around 125,000 deaths globally in 2019 due to opioid overdose. Beyond the avoidable loss of life, addiction incurs a $442 billion annual bill in economic burden, “impacting employment, productivity, public health and the judicial-legal system.”
Current best practice, evidence-based treatment for addiction is a psychosocial intervention (such as cognitive-behavioral therapy, or CBT) combined with pharmacologic treatment (medications, such as methadone for opioid use disorder). Unfortunately, our current best practice leaves room for improvement. Regarding substance use disorder, one estimate from a Cambridge study posits “over 20% of individuals will relapse within 1 month and a further 40% within 6 months” despite usual treatment.
Given the 1) high prevalence and harm, and 2) lack of effective treatment options, scientists and healthcare professionals continue searching for effective approaches to handling substance use disorder.
Since this is a psychedelic newsletter, it should come as no surprise that this is the point in the article where we start talking about psychedelics and their role in treating addiction.
Past Psychedelic Studies
The year is 1934. Bill Wilson, future co-founder of Alcoholics Anonymous, has made numerous (failed) attempts at treating his alcohol use disorder. Now on his fourth attempt, he tries a henbane + belladonna mixture, two plants which can elicit psychedelic-like effects. Experiencing a “bright white light” and “a feeling of great peace”, Bill had himself a good ol’ spiritual awakening and apparently never consumed alcohol again. His story is one of the first documented accounts in Western medicine for use of psychedelic substances as a treatment for addiction.
In total, the Imperial College London research team found over 10,000 scientific papers published in the mid-to-late 1900s describing use of psychedelics to treat a psychiatric condition – including addiction. Let’s look at a few psychedelic agents in particular:
LSD
Bill Wilson’s firsthand account for the effectiveness of psychedelics, including lysergic acid diethylamide (LSD, which Bill also dabbled in at least once) spurred further interest on its potential for treating addiction. Some examples include:
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“Treatment of Chronic Alcoholism with Lysergic Acid Diethylamide” (Jensen, S.E., and Ramsay, R., 1963)
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“Psychedelic Therapy Utilizing LSD in the Treatment of the Alcoholic Patient: A Preliminary Report” (Kurland, A.A., et al., 1967)
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“A Controlled Comparison of Lysergic Acid Diethylamide (LSD) and Dextroamphetamine in Alcoholics” (Hollister, L.E., Shelton, J., and Krieger, G., 1969)
LSD research in the 1970s also examined its use for treating heroin addiction. One study (C. Savage, O.L. McCabe, 1973) randomized 78 correctional institution inmates randomized to either one dose of LSD (300 – 350 micrograms) plus psychotherapy or weekly group psychotherapy (the “control” group). At 12 months, 33% of the LSD maintained heroin abstinence, compared to just 5% of the control group. One research participant, Leonard, described his experience:
“The two experiences of heroin and LSD are like night and day. Heroin is night, a time to sleep and with sleep, nothing comes but a dream. But with LSD, it is like dawn, a new awakening, it expands your mind, it gives you a brand-new outlook on life.”
Ibogaine
Used in traditional African practices for centuries, ibogaine has received less attention in Western research compared to LSD or psilocybin. Today’s review article only mentions one “complete” study: an open label, 33-patient case series involving treatment for opioid addiction between 1962 and 1993. Ibogaine was found to resolve opioid withdrawal symptoms in 25 of the participants within the 72-hour observation time frame.
The US National Institute of Drug Abuse (NIDA) funded a study in the 1990s to further evaluate ibogain’s potential for treating opioid withdrawal, but it was halted due to concerns regarding heart health. However, participants who had already completed the study and received ibogaine showed no signs of opioid withdrawal.
Ketamine
The review article only notes one ketamine study – “Krupitsky, EM, and Grinenko, AY. Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. J Psychoactive Drugs. (1997)”. Evaluating ketamine for alcohol addiction, this study was not randomized – participants could choose between receiving ketamine-psychedelic therapy (KPT) or conventional treatment.
The ketamine group showed superiority in achieving and maintaining abstinence from alcohol, but the study design makes it very difficult to make any sort of conclusions beyond “hey, this may be worth investigating further”. (Spoiler alert – there’s a reason I mention this study despite the major flaws. Keep reading!)
Psilocybin
We talk about psilocybin a lot here. But today’s review article makes no mention of studies for addiction using psilocybin from the “past” lookback period (1933 – 2000).
But we will discuss it in the next section, as we move into analyzing “current” studies from 2000 up until today.
Current Psychedelic Studies
The asinine, authoritarian “War on Drugs” froze clinical and institutional research on psychedelics. However, prohibition did not stop the collection of what we call “real-world evidence”. I like real-world evidence (RWE) for a variety of reasons, but especially because it’s easy to define. I don’t have to explain it because it’s exactly what it sounds like.
While randomized clinical trials (RCTs) are considered the “gold standard” in clinical research, RWE plays an important role as it shows us real-world results. RCTs allow us to narrow and isolate variables to better determine cause-and-effect relationships, but the “real world” does not operate in this manner.
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For example – we can use a RCT to compare medication A with medication B to see which has a stronger effect at lowering blood pressure.
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However, this RCT likely won’t offer insight into how medication A will “behave” in a patient taking other medications for other medical conditions and oh by the way they also drink a glass of wine with dinner each night and recreationally use cannabis most weekends and typically forget to take a dose of medication A at least once per week.
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We can use RWE to fill in gaps left answered due to the nature of a RCT.
For example, a retrospective study “looks back” at existing events and data to try and find connections. One such study by Pisana et al. evaluated 44,000 individuals with past opioid misuse habits. They found a 27% reduction in risk for opioid dependence amongst those who admitted to psychedelic use. There are similar studies which evaluated real-world evidence around ibogaine:
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One observational study evaluated 32 individuals with opioid dependence and found ibogaine caused a significant reduction in opioid withdrawal symptoms
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An open-label case series involving 89 persons with cocaine use disorder found a significant reduction in cocaine cravings after ibogaine use, which was sustained at 1-month follow up
Again, we cannot use this data to state “psychedelics treat addiction!” But it does provide enough fuel to fire up a stronger clinical trial to further evaluate the claim.
Speaking of – there are now a plethora of clinical trials involving psychedelics, thanks to the “psychedelic renaissance” and the work of dedicated scientists and healthcare professionals driven by a desire to help others.
Psilocybin
Psilocybin is under investigation for potential in treating numerous conditions related to addiction, including:
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Alcohol dependence: a phase II, double-blind randomized RCT published in 2022 involving 93 participants found a 14% difference in “heavy drinking days” between the group that received psilocybin (10%) compared to the group that received diphenhydramine (24%). The psilocybin group also reported a significantly lower average number of alcoholic drinks consumed per day.
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Tobacco dependence: a 15-participant study found that 80% of participants remained abstinent from tobacco at 6-month follow up after undergoing two to three psilocybin doses plus cognitive behavioral therapy (CBT). In comparison, pharmacological treatment (such as using nicotine replacement therapy or medications such as varenicline or bupropion) typically shows less than 35% abstinence rates after 6 months.
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Cocaine and methamphetamine use disorders: a study evaluating psilocybin for cocaine use disorder was recently completed at the University of Alabama at Birmingham (UAB). And the Portland VA is running a trialevaluating psilocybin for treating methamphetamine misuse.
Ketamine
Spurred by research (including the Krupitsky, EM, and Grinenko, AY article discussed earlier), ketamine has received an influx of attention for treating a variety of conditions, including addiction.
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A 2020 study conducted by a team of U.S.-based researchers found, when combined with motivational therapy, ketamine more effective than the benzodiazepine midazolam for producing abstinence from heavy drinking in 40 outpatients with alcohol use disorder (AUD)
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A 2022 study by a research team based in the U.K. found ketamine + therapy more effective than placebo + therapy at producing abstinence days in 96 adults with AUD. This suggests a possible synergistic effect when ketamine is combined with psychotherapy.
MDMA
A proof-of-concept study published in 2021 by a team of U.K.-based researchers established safety of using MDMA in adults with AUD. 14 adults with AUD received two dosing sessions with MDMA (187.5 mg) which included psychological support, along with 8-week recovery therapy and a community alcohol detoxification program.
No serious adverse effects were reported, and participants also noted a drastic drop in alcohol consumption – 18.7 units per week after the treatment, compared to 130.6 units per week before the detox.
The biotechnology company AWAKN Life Sciences is conducting further testing for utilizing MDMA for treating AUD.
Ibogaine
There are several recently completed and still-in-progress studies evaluating ibogaine for substance use disorders:
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A recently completed study from a team of researchers based in Spain evaluates the safety and potential effectiveness of ibogaine for methadone detoxification. (Methadone is an opioid with a proven track record for treating opioid addiction and dependence – but it can also create its own addiction issues, since it’s, you know, also an opioid.)
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A recent Phase I/2a study evaluated ibogaine for opioid withdrawal, and noted potentially significant safety concerns. Specifically, ibogaine showed potential to cause a side effect called QT prolongation. However, a study using noribogaine (an active metabolite of ibogaine) for AUD was recently completed and results are pending.
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Researchers at the University of California developed an ibogaine analog, Tabernanthalog (TBG), which is undergoing studies to evaluate its safety and efficacy for treating AUD and heroin dependency.
Conclusion: Looking Towards the Future
That’s a wrap for part 1 reviewing this study. We’ve reviewed their review of past psychedelic studies, as well as the state of current research.
Next time, we’ll pick up evaluating the authors’ thoughts on the future of psychedelic research – including some very cool advances in medical technology that allow us to “see” into the brain and uncover how psychedelics work.