Psychedelics and Addiction

Addiction is the compulsive and chronic need for a habit-forming substance, behavior, or activity. Addiction consists of both physiological and psychological aspects. In all too many cases, addiction leads to harm to the addicted individual and their loved ones and others. Our best current estimate is 164 million addicted people worldwide1. Between countries, this ranges from a few percent to more than 5%. That is 1 in 20 people addicted in the United States.

Psychedelics show that a single high-dose experience, usually surrounded by therapy, can break someone free from addiction. Some of the earliest experiments with LSD were done to treat alcoholism. Some of the participants haven't touched a drop since. Other psychedelics such as ibogaine have a long history of treating addiction and getting people back to their former selves.

Psychedelics for addiction is still in the early phases of being proven effective. What is the best therapeutic framework? What drugs work for whom and at what dose? Are there dangers to using these substances, both for the body and the mind? These and more questions will be passed and partially answered. Many researchers and companies are working to develop psychedelics for addiction, and we're looking forward to the day some of them can be tools to help people thrive again.

Addiction covers an extensive range of unwanted behaviors, and this article won't cover them all. We will focus on alcohol addiction (or alcohol use disorder, AUD), addiction to a variety of drugs (substance use disorder, SUD), and finally, adddiction in other categories such as opioids (pain killers), gambling, and more.

The Psychedelics And Addiction report is currently in development. For now, you can find all the papers.

Research Papers Compared Measured Researchers Gaps Companies


These are all the papers that cover addiction and psychedelics. Browse the meta, review, commentary articles for an overview. Check out the individual studies for specific experiments and observations.

Classic psychedelics in the treatment of substance use disorder: Potential synergies with twelve-step programs

2021 | Berghella, A. P., Garcia-Romeu, A., Hendricks, P. S., Johnson, M. W., Regier, P. S., Yaden, D. B.

This paper proposes that there are synergies to be found between psychedelics for substance use disorders and the twelve-step facilitation (TSF) program, specifically Alcoholics Anonymous (AA). Although controversial, as total abstinence is often promoted, the founder of AA (Bill Wilson) did have positive experiences with psychedelics.

Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders

2017 | Lastra, D., Malcolm, B., Thomas, K.

This 2017 review examines studies on psilocybin-assisted therapy to treat psychiatric disorders related to depression, anxiety, and substance abuse. In contrast to conventional paradigms, psilocybin-assisted therapy consists of only a few six-hour medication therapy sessions that may significantly improve symptoms and help patients achieve response or remission within weeks with support from integrative psychotherapy sessions.

Psychedelic Psychiatry’s Brave New World

2020 | Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J.

This popular commentary article (2020) describes the current resurrection of research into psychedelics (both neuroscience and therapeutic applications). It describes the evidence for the serotonin receptor (5-HT2a) agonism (psychedelics binding to that receptor) and the possible mechanisms through which long-lasting therapeutic effects can be found.

The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens

2016 | Cabral, J., Canal, C. E., Murnane, K. S.

This review (2016) investigates and proposes a model how psychedelics work in the brain, specifically with regards to the 5-HT (serotonin) 2C receptor. The authors also explain how this mechanism may work to treat addiction.

A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics

2017 | Cruz, A. P. M., Domingos, S., Gallardo, E., Martinho, A.

This review (2016) examines the psychoactive properties and therapeutic potential of Salvinorin A, a kappa-opioid receptor agonist that is the bioactive constituent of the indigenous plant Salvia divinorum. Next to highly potent psychoactive properties as a dissociative hallucinogen, preliminary scientific evidence also indicates it may have broad-range therapeutic applications for treating addiction, inflammation, pain, and depression.

Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress

2018 | Ross, S.

This systematic review (2018) investigated studies that used psychedelics for the treatment of psychological distress related to cancer. It found 10 studies (n=445) that qualified of which four (n=104) were randomized controlled trials. Overall studies showed improvements in anxiety, depression, and fear of death.

Psychedelic-Assisted Group Therapy: A Systematic Review

2019 | Anderson, B. T., Glick, G., Hooker, A. R., Stauffer, C., Trope, A., Woolley, J. D.

This review (2019) investigates what research has been done with psychedelic-assisted group therapy. It identifies 12 studies, mostly with LSD (2 with psilocybin), and ranging from surveys to randomized controlled trials.

Registered clinical studies investigating psychedelic drugs for psychiatric disorders

2021 | Gill, H., Lipsitz, O., Lui, L. M. W., McIntyre, R. S., Rosenblat, J. D., Siegel, A. N., Teopiz, K. M.

This review (2021) summarizes the study characteristics of all ongoing registered clinical trials investigating psychedelic drugs for psychiatric disorders and identifies that their majority focuses on investigating MDMA and psilocybin for treating depression or PTSD, while only 30% of their results are published.

The antiaddictive effects of ibogaine: A systematic literature review of human studies

2016 | Bouso, J. C., Dos Santos, R. G., Hallak, J. E.

This systematic review (2017) examined the antiaddictive effects of ibogaine (420 - 2030mg/70kg) in humans and identified seven open-label studies that indicated that ibogaine/noribogaine significantly reduced opiate/opioid withdrawal symptoms and that many subjects remained drug-free for several days after treatment. However, these results were largely heterogeneous and the only additional clinical trial performed failed to find significant reductions in opiate/opioid withdrawal symptoms in response to noribogaine.

Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review

2018 | Back, S. E., Brady, K. T., Jones, J. L., Malcolm, R. J., Mateus, C. F.

This systematic review (2018) examines the efficacy of ketamine treatment for substance use disorder and summarizes evidence which suggests that ketamine may improve the ability to establish and maintain abstinence.

Production Options for Psilocybin: Making of the Magic

2018 | Blei, F., Fricke, J., Hoffmeister, D., Lenz, C., Wick, J.

This historic review (2019) examines the biosynthesis and pharmacology of psilocybin, and summarizes the biotechnological routes of its synthesis.

Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use

2017 | Lawn, W., McAndrew, A., Morgan, C. J. A., Nutt, D. J., Stevens, T.

This review (2017) looks at the (preliminary) evidence that we have of psychedelics in the treatment of addictions (AUD, SUD). Trials with psilocybin, ibogaine, ayahuasca, ketamine (etc) are showing positive results, but randomized controlled trials (RCTs) are badly needed.

Psychedelics as an emerging novel intervention in the treatment of substance use disorder: a review

2020 | DiVito, A. J., Leger, R. F.

This article (2020) reviews the current evidence regarding the psychopharmacology of psychedelics and their promise as treatments for a variety of forms of addictions or substance use disorder (SUD).

Ibogaine: a review

2004 | Alper, K.

This book chapter (2001) reviews the topics of the First International Conference on Ibogaine, and reviews the chemical structure of ibogaine, its biological mechanisms of action, effects in humans and animal models, pharmacokinetics, and safety profile, etc. Case reports in humans and effects in preclinical models of drug dependence suggest the iboga alkaloids may have efficacy in addiction on the basis of mechanisms that are not yet known and which can possibly be dissociated from toxic effects and may present significant promise as a paradigm for the study and development of pharmacotherapy for addiction.

The Use of Salvia divinorum from a Mazatec Perspective

2018 | Maqueda, A. E.

This book chapter (2018) investigates the use of salvia divinorum by the Mazatec people. Applications discussed include headaches (pain), inflammation, addiction, and depression. Next to medicinal and psychotherapeutic applications, the inner exploration (recreational) purposes are also discussed.

The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation

2015 | Hilber, K., Koenig, X.

This review (2015) examines how the anti-addictive drug ibogaine affects the heart and the cardiovascular system and outlines a sequence of deleterious events that lower heart rate and selectively block cardiac ion channels which pave the way for life-threatening arrhythmias. Due to the longevity of noribogaine—ibogaine’s active metabolite—in human plasma, cardiac adverse events may also occur several days after, which highlights the need for developing less toxic variants of ibogaine such as 18-MC.

Why MDMA therapy for alcohol use disorder? And why now?

2017 | Sessa, B.

This commentary (2017) proposes that MDMA can be used as a safe and effective adjunct for psychotherapy in the treatment of alcohol use disorder. Given that alcoholism is often associated with early traumatic experiences, it is argued that MDMA therapy may be applied efficaciously to a wider range of mental disorders beyond that of only PTSD.

Therapeutic potential of ketamine for alcohol use disorder

2021 | Gould, T. J., Worrell, S. D.

This review (2021) investigates the potential of ketamine for alcohol use disorder (AUD). This is partly motivated by the concurrent depression and PTSD that those with AUD suffer from, for which more evidence of ketamine's effectiveness is known.

Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine

2017 | Chiamulera, C., Fattore, L., Fumagalli, G., Piva, A., Zanda, M. T.

This study (2017) reviews the clinical and preclinical data concerning cannabinoids and ketamine as they relate to possible reconsolidation processes of maladaptive memories.

Effects of ayahuasca and its alkaloids on substance use disorders: an updated (2016-2020) systematic review of preclinical and human studies

2021 | Bouso, J. C., Dos Santos, R. G., Hallak, J. E., Osório, F. L., Rocha, J. M., Rodrigues, L. S., Rossi, G. N.

This review (2021; s=9) of ayahuasca for substance use disorders (SUDs; e.g. alcoholism) found improvements in both rodents and humans who were suffering from SUDs (also on scores of anxiety and depression). The human studies were observational (vs RCTs) thus lacking the power to (confidently) infer causality.

Do Hallucinogens Have a Role in the Treatment of Addictions? A Review of the Current Literature

2021 | Nigam, K. B., Pandurangi, A. K.

This paper (2021) reviews the current literature regarding LSD, psilocybin, ketamine, ibogaine, and ayahuasca as potential treatments for addiction. The authors conclude that the available evidence is promising, but that more robust research is needed.

Ibogaine for treating drug dependence. What is a safe dose?

2016 | Galea, S., Newcombe, D., Schep, L. J., Slaughter, R. J.

This review (2016) argues that the current doses of ibogaine administered as a treatment for drug dependence are too high and should be reconsidered to avoid toxicity and fatalities.

Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

2016 | de Araujo, D. B., Tófoli, L.F.

This book chapter (2016) reviews the evidence regarding the effects of psychedelics on the brain and their potential as treatments for psychiatric and addictive disorders.

Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: a systematic review

2021 | Benyamina, A., Hermand, M., Karila, L., Pétillion, A., Romeo, B.

This systematic review (2021) of studies from 1990 to 2020 aimed to determine factors that can predict successful response to psychedelic treatment. In a variety of disorders, the authors found that the intensity of the experience was the best such predictor.

How toxic is ibogaine?

2016 | Brunt, T. M., Litjens, R. P. W.

This systematic review (2016) investigated the pharmacological properties of ibogaine with special attention to its potential toxicity for human subjects. The authors found that evidence of toxicity exists, and suggest that certain factors like pre-existing cardiac conditions and concurrent medications may pose an additional risk.

Lysergic acid diethylamide: a drug of ‘use’?

2016 | Barnwal, P., Das, S., Mondal, S., Ramasamy, A., Sen, S.

This review (2016) provides a chronologic history of LSD and examines its safety profile, the potential for abuse, its therapeutic potential to treat alcoholism or terminally ill patients. It also summarizes insights about its receptor pharmacology, mechanism of action, and (adverse) effects, while highlighting some of its potential clinical applications such as an antianxiety agent, a creativity enhancer, a suggestibility enhancer, or a performance enhancer.

Ketamine abuse potential and use disorder

2016 | Lin, D., Liu, Y., Wu, B., Zhou, W.

This review (2016) contrasts the therapeutic potential of ketamine as a fast-acting antidepressant to its potential for substance abuse. It specifically examines the social harms, the psycho-physiological and neurochemical effects, reinforcement mechanisms, and the treatment of ketamine abuse. It concludes that ketamine elicits significant reinforcing and toxic effects, which must be weighed against its antidepressant potential, which needs to be investigated in greater depth.

Ketamine Users Have High Rates of Psychosis and/or Depression

2015 | Chan, F., Liang, H. J., Tang, K. L., Tang, W. K., Ungvari, G. S.

This meta-analysis (n=129) evaluated the relation between long-term treatment with ketamine and the frequency of psychotic and mood disorders, amongst patients located in Hong Kong, China. According to standardized diagnostic criteria, psychosis and/or depression were very common amongst these patients, which raises the issue of safety when considering ketamine for long-term treatment of depression.

Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

2020 | Feduccia, A. A., Garel, N., Greenway, K. T., Jerome, L.

This meta-review (2020) examines the therapeutic frameworks surrounding contemporary practices of psychedelic-assisted psychotherapy, with regard to the historic development of therapeutic models and contemporary insights into extra-pharmacological factors and underlying mechanisms. They highlight that these therapies entail greater environmental sensitivity from the patient's perspective, which requires more meticulous attention for the preparation of the set and setting, a considerably resource-intensive endeavor.

Ketamine for the treatment of addiction: Evidence and potential mechanisms

2018 | Ezquerra-Romano, I. I., Krupitsky, E. M., Lawn, W., Morgan, C. J. A.

This review (2018) looks at the studies done with ketamine for the treatment of addiction. The results are promising and various mechanisms underlie these effects. Both effects at the neurological (neurogenesis, neuroplasticity, and more) and psychological (mystical experience, reconsolidation of drug-related memories) are discussed.

A Review of Lysergic Acid Diethylamide (LSD) in the Treatment of Addictions: Historical Perspectives and Future Prospects

2014 | Liester, M. B.

This review (2014) examines the historic transformation of LSD, from a psychoactive drug that exhibited great promise for the treatment of addiction, to an illicit substance affiliated with counterculture without a medical purpose. This review outlines aspects of its psychopharmacology that are still relevant for the treatment of addiction, which may warrant a renewed interest to continue research in this domain.

Treatment of alcoholism using psychedelic drugs: a review of the program of research

2011 | Mangini, M.

This review (2011) looks at the history of LSD as a possible treatment for alcoholism. It highlights the research that had been done and how psychedelics were subsequently relabelled as drugs of abuse.

From Hofmann to the Haight Ashbury, and into the Future: The Past and Potential of Lysergic Acid Diethlyamide

2014 | Dickerson Davidson, L., Raswyck, G. E., Smith, D. E.

This review (2014) summarises the history of LSD research and outlines the potential applications in the future.

Can psychedelic compounds play a part in drug dependence therapy?

2015 | Johnson, M. W., Sessa, B.

This editorial (2015) discusses the potential of and obstacles to psychedelic therapies for substance dependence.

Harm potential of magic mushroom use: A review

2011 | Opperhuizen, A., van Amsterdam, J., van den Brink, W.

This review (2011) summarizes the literature on physical or psychological dependence, acute and chronic toxicity, the risk for public health, and criminal aspects related to the consumption of magic mushrooms. The authors conclude that the use of magic mushrooms is relatively safe as only few and relatively mild adverse effects have been reported.

Can MDMA Play a Role in the Treatment of Substance Abuse?

2013 | Jerome, L., Schuster, S., Yazar-Klosinski, B.

This review (2013) evaluates the potential of MDMA to treat substance abuse and dependence. The authors provide evidence that MDMA may have potential as a treatment for these morbidities, but also highlight that classical psychedelics have a better risk:benefit ratio.

Potential Therapeutic Effects of Psilocybin

2017 | Griffiths, R. R., Johnson, M. W.

This review (2017) evaluates the therapeutic research into psilocybin as a treatment for addiction, treatment-resistant depression, and mood and anxiety disorders. The authors also analyse the safety data from these clinical trials.

Psychedelics and Psychedelic-Assisted Psychotherapy

2020 | Carpenter, L. L., Kalin, N. H., McDonald, W., Nemeroff, C. B., Reiff, C. M., Richman, E. E., Rodriguez, C. I., Widge, A. S.

This review (2020) finds that randomized clinical trials (RCTs) support the efficacy of various psychedelic-assisted therapies for mental health disorders.

Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin

2013 | Bogenschutz, M. P.

This review (2013) summarizes preclinical evidence to support the therapeutic efficacy of psychedelics in the treatment of alcoholism and makes suggestions for future paradigms to assess their clinical efficacy, bearing in mind the issues of blinding and expectancies that are addressed within double-blind placebo-controlled study designs.

Classical Psychedelics as Therapeutics in Psychiatry - Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

2021 | Mertens, L. J., Preller, K. H.

This review (2021) investigates the studies with psychedelics (psilocybin, LSD, ayahuasca) since 2011 for substance use disorders (SUD) and mood disorders (e.g. depression). More (rigorous) studies (RCTs) are needed.

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research

1997 | Grinenko, A. Y., Krupitsky, E. M.

This review (1997) suggests that ketamine psychedelic therapy (KPT) could be an effective tool in treating alcoholism. Total abstinence at one year compared favourably (65.8% to 24%) to a group receiving conventional treatment.

‘Hitting highs at rock bottom’: LSD treatment for alcoholism, 1950–1970

2006 | Dyck, E.

This commentary paper (2006) traces the history of LSD as a treatment for alcoholism from 1950-1970.

Classic hallucinogens in the treatment of addictions

2016 | Bogenschutz, M. P., Johnson, M. W.

This review (2016) describes the historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, and other relevant research concerning hallucinogens, before suggesting directions for future research.

Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, peyote, ibogaine and ayahuasca

2014 | Winkelman, M. J.

This review (2014) evaluates the use of LSD, peyote, ibogaine, and ayahuasca in the treatment of dependencies and the possible mechanisms underlying these treatments, including the notable “after-glow” effect that in part reflects their action on the serotonin neurotransmitter system.

A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses

2020 | Chi, T., Gold, J. A.

This review (2020) presents modern human studies into psychedelic drugs, including psilocybin, LSD, MDMA, and ayahuasca in the treatment of various psychiatric illnesses, including treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. Safety and efficacy data are also presented, from both human and animal studies.

Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies

2020 | Andersen, K. A. A., Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J.

This systematic review (2020) looked at 10 modern studies (n=188) on psychedelics (psilocybin, ayahuasca, LSD) for the treatment of a variety of mental health disorders. The review found the studies to provide evidence for efficacy (up to months later) and safety.

Classical hallucinogens and neuroimaging: A systematic review of human studies: hallucinogens and neuroimaging

2016 | Crippa, J. A., Dos Santos, R. G., Hallak, J. E., Osório, F. L.

A systematic review (2016) found that psychedelics (serotonergic 'hallucinogens') have a distinct influence on brain structures that have anxiolytic (anxiety-relieving), antidepressant, and antiaddictive properties.

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

2012 | Johansen, P. Ø., Krebs, T. S.

This very stringent meta-analysis (including 6 trials, n=536) concludes that a single session/dose of LSD treatment has short-term (<6 months) effects on alcoholism (less misuse, more abstinence) but no positive long-term outcomes (>12 months).

Self-reported PTSD is associated with increased use of MDMA in adolescents with substance use disorders

2021| Basedow, L. A., Golub, Y., Kuitunen-Paul, S., Roessner, V., Wiedmann, M. F.

This survey study (n=121) explored the co-occurrence of PTSD in patients with a substance use disorder (SUD). It was found that SUD patients with PTSD were more likely to use MDMA than those without PTSD and MDMA use was associated with avoidance symptoms. The authors conclude that MDMA use might reflect an attempt to self-medicate to deal with avoidance symptoms however, it may also be the case that MDMA use led to more severe avoidance symptoms.

"This Is Something That Changed My Life": A Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders

2021| Ashbullby, K. J., Grabski, M., Keeler, J., Ketzitzidou-Argyri, E., Mollaahmetoglu, O. M., Morgan, C. J. A.

This qualitative study (n=12) conducted within a Phase II double-blind randomized controlled trial, examines participant experiences of ketamine infusions (56mg/70kg) and how these relate to therapeutic mechanisms in a clinical trial setting. Subjective feelings of dissociation and detachment from one's sense of self and physical body were accompanied by seemingly paradoxical feelings of connectedness with the universe and of decreased self-importance and self-absorption, which led to a transformation of the patients' self-reported relationship to alcohol.

Ayahuasca, a psychedelic beverage, modulates neuroplasticity induced by ethanol in mice

2021| Almeida, C. A. F., Bruno, V., Camarini, R., Ceron, C. S., Costa, K. C. M., Garcia, R. C. T., Marcourakis, T., Pereira, B. P., Pereira Junior, A. A., Rangel, J. G., Silveira, G. O., Torres, L. H., Yonamine, M.

This animal study investigated the effects of ayahuasca (35.2 µg DMT) on alcohol withdrawal in mice and found that it exerted an anxiolytic effect and attenuated the behavioral sensitization to alcohol. Furthermore, it prevented alcohol-induced changes on 5-HT1a receptor and prodynorphin levels in the hippocampus and reduced ethanol effects in the dynorphin/prodynorphin in the striatum.

Ibogaine Blocks Cue- and Drug-Induced Reinstatement of Conditioned Place Preference to Ethanol in Male Mice

2021| Anjos-Santos, A., Barbosa, P., Barros-Santos, T., Berro, L. F., Bertagna, N. B., Cruz, F. C., Favoretto, C. A., Henriques, G. M., Libarino-Santos, M., Marinho, E. A. V., Moraes, C. R., Nascimento-Rocha, V., Oliveira-Lima, A. J., Reis, H. S., Rodrigues, I. R., Yokoyama, T. S.

This study explored the effects of ibogaine (10 or 30 mg/kg) on ethanol-induced conditioned place preference (CPP) mice. The study found that ibogaine blocked ethanol-induced CPP during a drug priming reinstatement test and during a drug-free test, after mice had been re-exposed to ethanol. These findings suggest ibogaine may be useful for treating alcohol use disorder.

Spiritual experiences in psychedelic-assisted psychotherapy: Case reports of communion with the divine, the departed, and saints in research using psilocybin for the treatment of alcohol dependence

2021| Bogenschutz, M. P., Duane, J. H., Malone, T. C., Mennenga, S. E., Owens, L. T., Podrebarac, S. K.

This paper (n=3) presents case studies of experiences with the divine in an ongoing clinical trial at NYU exploring the effects of psilocybin on alcohol dependence.

Associations between ayahuasca consumption in naturalistic settings and current alcohol and drug use: Results of a large international cross-sectional survey

2021| Bouso, J. C., Galvão-Coelho, N. L., Opaleye, E. S., Perkins, D., Sarris, J., Schubert, V., Simonová, H., Tófoli, L.F.

This cross-sectional survey study (n=8269) investigates associations between ayahuasca consumption in naturalistic settings and the use of alcohol and other drugs across 40 different countries. Ayahuasca use was both strongly and consistently associated with very low (or even abstinence from) drug or alcohol use, with and without prior substance use disorders.

A Nationwide Study Comparing Mental Health Professionals' Willingness to Try Hallucinogenic Drugs in Basic Research or Clinical Practice

2021| Ben-Sheetrit, J., Lev-Ran, S., Madjar, N., Shoval, G., Weizman, A.

This survey study (n=347) examined Israeli mental health professionals' attitudes toward recreational drug users and willingness to use five hallucinogens (LSD, MDMA, ketamine, cannabis, psilocybin) in research or clinical practice. Compared to nurses and paramedics, psychiatrists were more familiar with the potential therapeutic role of psychedelics and had a higher willingness to conduct research or use such substances for clinical purposes. However, psychiatrists were also the most susceptible to personal bias, as evidenced by cases wherein negative attitudes toward recreational users impeded their support for psychedelic within the context of clinical treatments or research.

Novel Class of Psychedelic Iboga Alkaloids Disrupts Opioid Addiction States

2021| Abi-Gerges, N., Ansonoff, M., Bechand, B., Havel, V., Hemby, S. E., Hodges, A., Hunkele, A., Hwu, C., Javitch, J. A., Katritch, V., Kruegel, A. C., Majumdar, S., McIntosh, S., Nelson, M., Pintar, J. E., Sames, D., Stallings, L., Wulf, M. G., Yang, M., Zaidi, S. A.

This preprint (2021) animal in vivo and human in vitro study examines a new class of oxa-iboga alkaloids (10 & 40 mg/kg) with respect to their effects on opioid addiction in rats and their cardiotoxic effects on human heart cells. In contrast to noribogaine, oxa-iboga analogs exhibited no risk of inducing arrhythmia in adult human primary cardiomyocytes, and oxa-noribogaine induced acute and long-lasting suppression of morphine self-administration in rats in response to both single and repeated dosing regimes.

Lysergide Treatment of Schizophrenic and Nonschizophrenic Alcoholics; A Controlled Evaluation

1970| Edwards, R. V., Tomsovic, M.

This historic study (1970; n=75) used LSD (500μg) in the treatment of alcoholics and found that those without schizophrenia (about 2/3 of patients) responded better.

A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial

2019| Basaraba, C. N., Choi, J., Dakwar, E., Hart, C. L., Levin, F. R., Nunes, E. V., Pavlicova, M.

This randomized, double-blind, active placebo-controlled pilot study (n=40) examined the effects of ketamine (49.7mg/70kg, n=17) or the active control midazolam (1.75mg/70kg, n=23) combined with motivational enhancement therapy to treat patients with alcohol use disorder. The preliminary data showed that a single ketamine infusion in combination with motivational enhancement therapy improves measures of drinking in patients with alcohol use disorder.

Psilocybin and LSD Have No Long-Lasting Effects in an Animal Model of Alcohol Relapse

2020| Güngör, C., Meinhardt, M. W., Mertens, L. J., Skorodumov, I., Spanagel, R.

This rodent study (n=81) investigates the efficacy of psilocybin and LSD (microdose, sub-chronic dose, high-dose) to mitigate relapse behavior in an alcohol-deprived rat model of addiction. Contrary to the previous hypothesis, psilocybin and LSD had no long-lasting effects on relapse after alcohol deprivation, but the subchronic dose exerted a short-lasting effect.

Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey

2020| Davis, A. K., Erowid, E., Erowid, F., Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W.

This cross-sectional survey study (n=444) analyzed self-reported cases of reduced substance abuse disorder after using psychedelics and found that that the number of responders who fulfilled the criteria for their disorder dropped by 59% thereafter. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in drug consumption, and most respondents claimed lasting improvements for over 1 year after using a psychedelic.

Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics

2018| Kuypers, K. P. C., Mason, N. L.

The observational survey study (n=1,967) investigated the frequency and efficacy of self-medication practices amongst psychedelic users and found that the prevalence of lifetime psychopathologies amongst psychedelic users was higher than in the general population. Although psychedelics were seldom used for self-medication, those who did use psychedelics in this manner reported it to be more effective than the current lines of treatment for mental illness.

A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder

2018| Barsuglia, J. P., Calvey, T., Kelmendi, B., Malcolm, R. J., Palmer, R., Polanco, M.

This case report SPECT imaging study explored the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder (AUD). It reported that the patient felt improvement in mood, cessation of alcohol use, and decreased cravings at 5 days post-treatment, but the patient returned partially to mild alcohol use at 2 months. Also, higher perfusion in multiple brain regions broadly associated with AUD and known pharmacology of both compounds was reported.

Ayahuasca and Its DMT- and β-carbolines – Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment

2018| Barbosa, P., Barros-Santos, T., Berro, L. F., Cata-Preta, E. G., Costa, J. L., Kisaki, N. D., Laukkonen, R., Libarino-Santos, M., Marinho, E. A. V., Moreira-Junior, E. D., Oliveira-Lima, A. J., Reis, H. S., Santos, L. C., Serra, Y. A., Silva, R. R. R.

This animal study finds that a moderate (not high or low) dose of ayahuasca can help with alcohol use disorder (AUD). This was done using the conditioned place preference (CPP) paradigm in male mice.

Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes

2018| Allen-Ferdinand, K., Duque, L., Mash, D. C., Page, B.

The clinical study reviewed open-label case series (n=191) of human volunteers to review in-patient ibogaine (0.5-0.8g) detoxification using multi-dimensional craving questionnaires. It was found that Ibogaine therapy in a "safe dose range" decreases opioid withdrawal symptoms and drug cravings. The study proposed the development of a single oral dose of ibogaine to treat opioid withdrawal during medically monitored detoxification to help drug-dependent individuals in abstinence.

Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report

2017| Aixalá, M., Alcázar-Córcoles, M. A., Bouso, J. C., Cura, P., Dos Santos, R. G., Hallak, J. E., Moreno, E., Solá, J., Wilkins, C.

This case report (2017) explores using low, repeated, and increasing doses of ibogaine for someone who is heroin-dependent and is currently undergoing methadone maintenance treatments (MMT). It found that every administration of ibogaine reduced the withdrawal symptoms for several hours, and attenuated the tolerance to methadone until all withdrawal symptoms vanished with no serious adverse effects at the end of the treatment. This is the first such case report on ibogaine treatment using low and cumulative doses for MMT.

Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada

2019| Argento, E., Capler, R., Lucas, P., Thomas, G., Tupper, K. W.

This interview study (n=11) examines the possibilities of ayahuasca‐assisted therapy for addiction by undertaking a qualitative analysis among an Indigenous community in Canada. The study indicated that retreats helped participants recognize negative thought patterns and barriers related to their addiction that differed significantly from conventional therapies. All subjects reported a decrease in substance use and cravings, eight (72%) participants fully ceased using one substance afterward.

Ayahuasca and Public Health: Health Status, Psychosocial Well-Being, Lifestyle, and Coping Strategies in a Large Sample of Ritual Ayahuasca Users

2018| Alcázar-Córcoles, M. A., Bouso, J. C., Dos Santos, R. G., Gomariz, A., Hallak, J. E., Jiménez-Garrido, D. F., Kohek, M., Massaguer, T., Ona, G.

This study (n=380) focuses on psycho-social well-being, lifestyle, and coping strategies in a large sample of long-term ayahuasca users. The participants in this study associated long-term ayahuasca use with a higher positive perception of health or with a healthy lifestyle, among others. The study offers insight into the long-term effects of ayahuasca on public health and proposes incorporating a "communitarian approach" into society to benefit public health to ensure a respectful and controlled use of hallucinogenic/psychedelic drugs.

Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration

2016| Aarde, S. M., Taffe, M. A.

This book chapter (2016) investigates animal models of drug abuse potential (addiction) of psychedelics. It finds that MDMA is self-administered (by mice) but less frequently than (meth)amphetamine or two novel psychedelic compounds (4MMC, methylone).

Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

2018| Belgers, M., Knuijver, T., Markus, W., Schellekens, A., van Oosteren, T., Verkes, R. J.

This case study (n=1) describes one participant who took ibogaine in a study to treat their opioid use disorder (SUD) and subsequently suffered from hallucinogen persisting perception disorder (HPPD).

Metabolite Profiling of Antiaddictive Alkaloids from Four Mexican Tabernaemontana Species and the Entheogenic African Shrub Tabernanthe iboga (Apocynaceae)

2019| Chevalier, Q., Dickinson, J., Herrera, S. J., Krengel, F., Reyes, C. R.

This metabolite profiling study examined antiaddictive alkaloids from alternative plant sources and identified four structurally related iboga type alkaloids – coronaridine, ibogamine, voacangine, and ibogaine – as the predominant chemical feature of four Mexican Tabernaemontana species – T. alba, T. amygdalifolia, T. arborea, and T. donnell-smithii – and the African shrub Tabernanthe iboga.

Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder

2019| Krystal, J. H., Petrakis, I. L., Yoon, G.

This open-label pilot study (n=5) investigated the use of naltrexone pretreatment (380 mg) with ketamine infusions (35mg/70kg, 4 infusions over 4 weeks) for depression and found that it does not interfere with ketamine's antidepressant effects. On the contrary, the study found that it might help in treating co-morbid alcohol use disorder and called for pre-clinical research to further understand these results, also in light of earlier conflicting research.

Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits.

2019| Carrera, I., Cassina, P., González, B., Martínez-Palma, L., Marton, S., Miquel, E., Pazos, M., Prieto, J. P., Rodríguez, P., Rodríguez-Bottero, S., Sames, D., Scorza, C., Seoane, G.

This animal study (n=36) investigated the effects of ibogaine (0, 20, 40 mg/kg) in rats and found that higher doses promoted the expression of Glial cell Derived Neurotrophic Factor (GDNF) and that both doses promoted proBDNF expression in the Nucleus Accumbens, which may be underlying mediators of its long-lasting effect on reducing drug dependence.

A Mixed-Method Analysis of Persisting Effects Associated with Positive Outcomes Following Ibogaine Detoxification

2018| Barsuglia, J. P., Davis, A. K., Polanco, M., Renn, E., Windham-Herman, A-M.

This qualitative and quantitative retrospective survey study (n=73) investigated the effects of ibogaine (1050mg/70kg) on opioid withdrawal, with the aim of identifying differences related to whether the patients respond to treatment. Patients who were able to decrease or quit using opioids successfully experienced the greatest degree of changes in gratitude, authenticity, and sense of meaning in life, in response to ibogaine treatment.

Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

2018| Barsuglia, J. P., Malcolm, B., Polanco, M.

This retrospective cohort study (n=50) investigated the efficacy of ibogaine (1.26 – 1.4g/70kg) to treat withdrawal symptoms amongst patients with opioid use disorder and found that ibogaine reduced effectively facilitated opioid detoxification, reduced cravings, and reduced withdrawal.

Ceremonial ‘Plant Medicine’ use and its relationship to recreational drug use: an exploratory study

2018| Dorsen, C., Palamar, J., Shedlin, M. G.

This qualitative interview study (n=15) investigated how plant medicine facilitators differentiate the use of hallucinogenic drugs such as psilocybin and ayahuasca from recreational drug use and found that they define their practice through a “higher purpose” such as the healing of childhood traumas or treating of addiction that lays particular emphasis on ritual and integration as essential to this process.

Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment: The Case of Takiwasi Center

2021| García, S., Loewinger, G., Loizaga-Velder, A., Marcus, O., Mendive, F., Rush, B., Spitalier, A.

This methodological paper (2021) describes a study protocol designed for the purpose of investigating ayahuasca-assisted treatment for substance use disorders via various types of longitudinal measures that are sensitive to contextual factors to evaluate the therapeutic outcomes of an established intervention within a naturalistic setting.

Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues

2014| Ewald, A. W., Groer, C. E., Kivell, B. M., Prisinzano, T. E., Riley, A. P., Young, D.

This animal study (n=12) synthesized several different furan-substituted salvinorin A analogs and identified three potent variants which reduced drug-induced reinstatement of cocaine-seeking behavior, without producing the sedation observed with other κ-opioid agonists.

Inhibitory effects of ibogaine on cocaine self-administration in rats

1993| Cappendijk, S. L. T., Dzoljic, M. R.

This animal study (n=56) examined the effects of single and repeated injections of ibogaine (40 mg/kg) on the cocaine self-administration model in rats and found that it inhibited addictive behaviors for 1-2 days or longer with additional weekly injections, even when ibogaine levels in the body were undetectable.

Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic

2018| Hasíková, L., Hobden, P., Horák, M., Verter, N.

This qualitative interview study (n=46) examined the self-reported therapeutic potential of ayahuasca and found that while many users apply it as a 'cure-for-all' others report it to be most applicable to treat addiction. The intensity of subjective effects was not proportional to therapeutic effects, which often entailed the re-activation of forgotten or suppressed memories.

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities

2015| Barker, S., Elices, M., Feilding, A., Franquesa, A., Friedlander, P., Pascual, J. C., Riba, J., Soler, J.

This observational study (n=25) found that ayahuasca intake led to significant increases in mindfulness comparable to those obtained after extensive mindfulness practice. The authors argue that this effect may be the mediating factor responsible for ayahuasca's observed therapeutic potential.

Psychological and cognitive effects of long-term peyote use among Native Americans

2005| Halpern, J. H., Hudson, J. I., Pope Jr, H. G., Sherwood, A. R., Yurgelun-Todd, D.

This correlational study (n=176) investigated the long-term residual psychological and cognitive effects of peyote use amongst native American Church members, compared between regular users (n=61), minimal users (n=79), and members with a history of alcohol dependence (n=36). Only members with prior alcohol dependence showed neuropsychological deficits, but there was no link between psychological or cognitive deficits linked to peyote use.

Treatment of a Complex Personality Disorder Using Repeated Doses of LSD-A Case Report on Significant Improvements in the Absence of Acute Drug Effects

2020| Borgwardt, S., Holze, F., Lang, U. E., Liechti, M. E., Mueller, F., Mühlhauser, M., Walter, M.

This case study of a patient with mental health problems, found no acute effects of LSD (50 to 200 µg) and persistent (7 days) positive effects (dose-dependent) on depression (TRD) and suicidal ideation scores.

Assessment of Alcohol and Tobacco Use Disorders Among Religious Users of Ayahuasca

2018| Areco, K., Barbosa, P., Berro, L. F., Bogenschutz, M. P., Hoy, R., Marinho, E. A. V., Tófoli, L.F., Winkelman, M. J.

This survey study (n=1947) indicates an association between reduced current tobacco and alcohol use and attendance of religious ayahuasca ceremonies. Lifetime use of these substances, however, was higher in the ceremony-attending group in most age groups.

Report on psychoactive drug use among adolescents using ayahuasca within a religious context

2005| Alonso, J. N., da Silveira, D. X., Dobkin de Rios, M., Doering-Silveira, E., Grob, C. S., Lopez, E., Tacla, C.

This study (n=86) compared the substance consumption of adolescents within a Brazilian ayahuasca sect with adolescents who never drank ayahuasca. The authors found that the ayahuasca group was not at a higher risk of drug misuse, and that the non-ayahuasca group contained a higher proportion of alcohol users. Lifetime substance consumption, however, did not differ between the two groups.

A Qualitative Study of Intention and Impact of Ayahuasca Use by Westerners

2021| Bathje, G. J., Fenton, J., Hill, L. C., Pillersdorf, D.

This qualitative interview study (n=41) found that ayahuasca use by Westerners (in group settings), led to many sustained positive outcomes. These related to mental health, substance use, interpersonal relationships, and also creativity, physical health, connection to nature. Two participants indicated problematic experiences (sexual assault, enduring psychotic symptoms).

Treating drug dependence with the aid of ibogaine: A retrospective study

2014| Chaves, T. V., da Silveira, D. X., de Castro Comis, M. A., Schenberg, E. E.

This retrospective analysis (n=75) found no serious adverse events and 61% abstinence when ibogaine was used as an underground treatment for a variety of drug (e.g. alcohol, cocaine) addictions.

A single ketamine infusion combined with mindfulness-based behavioral modification to treat cocaine dependence: a randomized clinical trial

2019| Basaraba, C. N., Carpenter, K. M., Choi, C. J. J., Dakwar, E., Foltin, R. W., Hart, C. L., Levin, F. R., Mathew, S. J., Nunes, E. V., Pavlicova, M.

This double-blind, placebo-controlled study (n=55) investigated the use of ketamine (35mg/70kg) versus midazolam (an anesthetic), plus mindfulness-based therapy (5-week program) for cocaine dependence. The ketamine group scored significantly better and were 53% less likely to relapse.

Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes

2017| Alper, K., Brown, T. K.

This observational field study (n=30) investigated the effects of ibogaine on opioid detoxification amongst individuals who sought addiction treatment at a private clinic and found that the treatment had a substantiative effect of reducing drug use up to 1 month, or even up to 12 months amongst select individuals.

Serotonin antagonists fail to alter MDMA self-administration in rats

2016| Aronsen, D., Bukholt, N., Foote, J., Highgate, Q., Schenk, S., Van de Wetering, R., Webster, J.

This vehicle-controlled rat study (n=23) investigated the role of serotonergic agonists in preventing relapse into drug-seeking behavior, in response to re-exposure to a single dose of MDMA or cocaine (10.0 mg/kg), or a conditioned light-cue associated with their drug-intake prior to extinction. Results indicate that 5-HT1A and 5-HT2A agonists prevent relapse into cocaine self-administration, but neither of the 5-HT1A, 5-HT1B, or 5-HT2A agonists could alter the maintenance of MDMA self-administration. However, the 5-HT1A agonists prevented relapse into drug-seeking behavior elicited by exposure to cues that had been associated with self-administered MDMA.

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans

2016| Dos Santos, R. G., Nunes, A. A., Osório, F. L., Sanches, R. F.

This systematic literature review (2016) examined the effects of ayahuasca across animal and human studies which investigated behaviors and symptoms associated with drug-related disorders. Results suggest that ayahuasca and its alkaloids which include harmine and harmaline may have antiaddictive properties that can alleviate substance dependence by means of modulating dopaminergic neurotransmission. The lack of clinically controlled studies, however, makes it difficult to determine if observed health improvements are related to drug effects, to the religious environment and culture, or the combination of both factors.

The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization

2016| Bokor, P., Frecska, E., Winkelman, M. J.

This review (2016) examines the therapeutic potential of ayahuasca based on a summary of its neurobiological, neuroregenerative, and psychophysiological mechanisms and effects on vegetative states and the central nervous system. It emphasizes highlights the therapeutic utility of ayahuasca on a biological level as an anti-inflammatory agonist of the Sigma-1 receptor while incorporating its effects on higher-order psychotherapeutic effects within a bio-psycho-socio-spiritual model.

Ascending single-dose, double-blind, placebo-controlled safety study of noribogaine in opioid-dependent patients

2016| Cape, G., Crockett, R. S., Darpo, B., Devane, J., Friedhoff, L., Glue, P., Harland, S., Howes, J. F., Hung, N., Hung, C. T., Lam, F., Lockhart, M., Tunnicliff, D., Weis, H., Zhou, M.

This randomized, double-blind, placebo-controlled study (n=27) evaluated the safety, tolerability, and pharmacokinetics of noribogaine (60, 120, or 180mg/70kg) administered to opioid-dependent patients withdrawing from methadone. Noribogaine was well tolerated across the entire dose range and a statistically nonsignificant trend toward decreased total score in opioid withdrawal ratings. The ascending noribogaine dose was correlated to prolongation of heart contractions (longer QT intervals) to a degree that would be concerning in a clinical setting, which indicates the need for ECG monitoring to enable dose adjustment or discontinuation to mitigate cardiovascular risk in future studies.

Treatment of acute opioid withdrawal with ibogaine

2009| Alper, K. R., Bastiaans, J., Frenken, G. M. N., Lotsof, H. S., Luciano, D. J.

This series of open-label case studies (n=33) investigated the efficacy of ibogaine (0.42 to 2,03g/70kg) to treat acute withdrawal in patients with opioid dependence. Based on the diagnostic observations of two principal investigators, seventy-six percent of the patients in this series were reportedly free of opioid withdrawal signs and symptoms at 24 hours and did not seek drugs over the period of observation of 72 hours. Observations warrant future investigations to assess the efficacy of ibogaine to treat opioid withdrawal more reliably in controlled clinical studies.

DPT as an adjunct in psychotherapy of alcoholics

1973| Grof, S., Kurland, A. A., Richards, W. A., Soskin, R. A.

This early study (1973; n=51) investigated the use of DPT (tryptamine psychedelics) in combination with therapy for the treatment of alcoholism (AUD). At the six-month follow-up, 38% of participants stayed completely abstinent, about 50% were classified as rehabilitated.

Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents

2016| Ameer, B., Howes, J. F., Maillet, E. L., Mash, D. C., Prou, D.

This vehicle-controlled rodent study (n=54) investigated the dose-dependent effects of noribogaine (10, 30, or 100mg/kg) on the uptake and anti-withdrawal symptoms of morphine. Results demonstrate the efficacy of noribogaine to reduce the somatic signs of morphine withdrawal up to 88% in mice two hours after oral administration and attenuates the negative signs of morphine withdrawal within substance-dependent mice, in a dose-dependent manner.

The association of psychedelic use and opioid use disorders among illicit users in the United States

2017| Franciotti, K. J., Halpern, J. H., Holden, S. C., Kramer, H. M., Pisano, V. D., Putnam, N. P.

This survey study (2017; n=44,000) found that the use of psychedelics and cannabis was associated (but as always, this doesn't imply causation) with a lower risk of opioid dependence and abuse in a large national survey.

Development of a Psychotherapeutic Model for Psilocybin-Assisted Treatment of Alcoholism

2016| Bogenschutz, M. P., Forcehimes, A. A.

This review (2016) summarizes the scientific rationale behind the development of the therapeutic model that is being used within a clinical trial of psilocybin-assisted treatment of alcoholism. Participants receive both alcohol-specific treatment within the cognitive-behavioral approach of 'Motivational Enhancement and Taking Action' which addresses their problematic alcohol use more directly, as well as hallucinogen- specific treatments to prepare for, and integrate their experiences under the influence of psilocybin, ranging from 25 mg/70 kg to 40 mg/70 kg.

Psilocybin for treating substance use disorders?

2016| de Veen, B. T. H., Homberg, J. R., Schellekens, A., Verheij, M. M.

This study (2017) reviews the human evidence regarding psilocybin as a potential treatment for substance use disorders (SUD). The authors conclude that the evidence thus far seems promising, but will need to be confirmed in future studies.

Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes

2021| Agin-Liebes, G. I., Davis, A. K., Lancelotta, R., Ramaekers, J. G., Uthaug, M. V.

This survey study (n=452) found that the use of mescaline led to improvements in scores on clinical conditions for those suffering from clinical conditions (anxiety 80%, depression 86%, PTSD & AUD 76%). Those who scored higher on acute mystical experience (MEQ30), ego dissolution, and psychological insight had larger improvement than those who scored lower.

The Heffter Research Institute: Past and Hopeful Future

2014| Nichols, D. E.

This essay describes the history and the development of the Heffter Research Institute, in their ongoing efforts to supply psilocybin for the purposes of fundamental and applied clinical research, with a prospective outlook that psilocybin will one day be recognized to have legitimate medical value and integrated within a specialized therapeutic practice.

Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist ketamine: a randomized, crossover trial

2016| Dakwar, E., Foltin, R. W., Hart, C. L., Levin, F. R., Nunes, E. V.

This active placebo-controlled, randomized, crossover, within-subjects study (n=20) investigated the effects of ketamine (49.7mg/70kg) on cocaine self-administration amongst medically healthy, non-treatment-seeking cocaine-dependent individuals. Faced with the choice to using cocaine (25mg) or receiving money ($11) after a single ketamine infusion, participants decreased cocaine self-administration by 67% and some of them maintained abstinence for at least 2 weeks after.

Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use

2016| Hendricks, P. S., Kosson, D. S., Lucas, P., Smith, S., Swogger, M. T., Thiessen, M. S., Walsh, Z.

This prospective survey study (n=302) investigated whether prior hallucinogen use among incarcerated men with substance use disorders would predict a reduced likelihood of intimate partner violence after their release. Results indicated substantial differences across individuals who reported lifelong hallucinogen use, who were less than two-thirds as likely to be arrested for intimate partner violence, as those who did not report having used hallucinogens. This suggests that hallucinogenic substances may have the potential to protect against behaviors associated with externalizing psychopathology.

Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study

2021| Belgers, M., Donders, R., Knuijver, T., Kramers, C., Schellekens, A., van Oosteren, T., Verkes, R. J.

This open-label observational study (n=14) investigated the safety profile of ibogaine (700mg/70kg) for patients with opioid use disorder who were undergoing acute opioid withdrawal. Although patients experienced mild withdrawal symptoms and transient well-tolerated psychomimetic effects, they exhibited abnormal patterns in heart rhythm that constituted an adverse level of cardiovascular risk. This study indicates that even a low-dose administration of ibogaine requires strict cardiac monitoring, and should be restricted to well-controlled settings.

Mania following use of ibogaine: A case series

2015| Koek, R. J., Kopelowicz, A., Marta, C. J., Ryan, W. C.

This case report (n=3) examines patients who developed manic symptoms and diagnosed with Bipolar-I disorder in response to ibogaine use. None of the patients had a prior diagnosis or family history of bipolar disorder, but all of them were poly-drug users or recovering from addiction. Manic symptoms which often included grand delusions that lasted up to two weeks after using ibogaine.

First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants

2019| Nutt, D. J., Sakal, C., Sessa, B.

This paper presents data on the first four of 14 participants in the open-label trial on the safety and tolerability of MDMA-assisted psychotherapy for alcohol use disorder.

First study of safety and tolerability of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in patients with alcohol use disorder

2021| Brew-Girard, E., Burrows, S., Durant, C., Higbed, L., Rickard, J. A., Rose-Morris, A., Sakal, C., Sessa, B., Titheradge, D., Williams, T. M., Wilson, S., Wiseman, C.

This open-label study (n=14) with MDMA-assisted psychotherapy (2 sessions;187.5mg) found it to be well-tolerated and safe to use. The average consumption of alcohol at 9 months later was 18.7 units, versus 130.6 units before the detox (start of study).

Cessation and reduction in alcohol consumption and misuse after psychedelic use

2019| Davis, A. K., Erowid, E., Erowid, F., Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W.

This survey study (n=343) suggests that naturalistic psychedelic use may be associated with reduced problematic alcohol consumption. This complements clinical studies that found similar results with smaller sample sizes.

Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up

2002| Burakov, A. M., Dunaevsky, I. V., Grinenko, A. Y., Krupitsky, E. M., Romanova, T. N., Strassman, R. J.

This randomized double-blind clinical trial (2002, n=70) found that existential psychotherapy in combination with psychedelic doses of intramuscular (im) ketamine (140mg/70kg) achieved larger results in the treatment of heroin addiction than sub-hallucinogenic doses (14mg/70kg).

Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions

2012| Liester, M. B., Prickett, J. I.

This hypothesis paper (2012) proposes four unique but interrelated mechanisms in the domains of biochemical, physiological, and psychological pathways and transcendent experiences, through which ayahuasca may exert anti-addictive effects.

Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short-and long-term outcomes and current psychological functioning

2017| Barsuglia, J. P., Davis, A. K., Lynch, M., Polanco, M., Windham-Herman, A-M.

This survey study (n=88) found that ibogaine can be an effective treatment against opioid addiction.

A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment

2017| Alexandre, J. F. M., Chaves, B. D. R., da Silveira, D. X., de Castro Comis, M. A., Schenberg, E. E., Tófoli, L.F.

This interview study (n=22) analyzed the subjective experiences associated with ibogaine treatment for substance dependence, and found both similarities and differences to effects reported for classic psychedelics.

Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence

2011| Burakov, A. M., Dunaevsky, I. V., Grinenko, A. Y., Krupitsky, E. M., Romanova, T. N., Slavina, T. Y.

This open-label longitudinal study (n=59) investigated the efficacy of a single versus three-sessions of ketamine-assisted psychotherapy (140mg/70kg/session) for people with heroin dependence and found that the three-session program is more than twice as effective (abstinence 50% vs. 22.2%) one year after treatment.

Ayahuasca-assisted therapy for addiction: results from a preliminary observational study in Canada

2013| Capler, R., Lucas, P., Martin, G., Thomas, G., Tupper, K. W.

This observational study (n=12) investigated the impact of ayahuasca-assisted group therapy within the context of a retreat ceremony, on self-reported and qualitative measures of mental health and addiction. Participants exhibited improved mindfulness, personal empowerment, and hopefulness, and reported less frequent use of cocaine, alcohol, and tobacco up to 4 weeks after the ceremony. Their intake of cannabis, sedatives, and opiates (e.g. methadone) did not change, however, these were not identified as the substances of primary concern by the majority of participants.

User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study

2010| Carhart-Harris, R. L., Nutt, D. J.

This survey study (n=626) investigated user perceptions of the benefits and harms of using LSD, psilocybin, MDMA, cannabis, ketamine, and alcohol. Overall, LSD and psilocybin were regarded as having the most positive impact on wellbeing, and the least harms in terms of physical and mental health.

Within-treatment changes in a novel addiction treatment program using traditional Amazonian medicine

2021| Berlowitz, I., O’Shaughnessy, D. M., Quirk, F., Rodd, R., Sarnyai, Z.

This open-label study (n=36) found that ayahuasca led to significant (and clinically relevant) changes in addiction scores (e.g. ASI) and cognitive function. There was significant drop-out (39%), and the open-label character makes it difficult to draw causative conclusion. Still, this research provides another data point for ayahuasca for substance use disorder (SUD) treatment.

A clinical study of LSD treatment in alcoholism

1971| Lazar, R., Levine, J., Ludwig, A., Stark, L.

This randomized study (1969, n=176) found no long-lasting (up to 12 months later) positive effects of LSD-assisted therapy (210μg/70kg) versus no therapy, an effect that was found in other studies from this time.

Treating drug dependence with the aid of ibogaine: a qualitative study

2016| Alexandre, J. F. M., Chaves, B. D. R., da Silveira, D. X., de Castro Comis, M. A., Schenberg, E. E., Tófoli, L.F.

This open-label qualitative study (n=22) investigated the therapeutic efficacy of ibogaine (840/1050mg) in combination with cognitive behavior therapy (CBT) and relapse prevention to treat drug-dependent patients. Patients reported decreases in craving and improvements in personal relationships, quality of life, and self-efficacy.

Mechanisms of antiaddictive actions of ibogaine

2006| Glick, S. D., Maisonneuve, I. M.

This placebo-controlled animal study found that ibogaine (9.6 mg) reduces drug self-administration (cocaine, morphine) in rats. Authors discuss the potential mechanism of reducing drug abuse, whereby (nor)ibogaine acts as a kappa opioid agonist, an NDMA antagonist, and a nicotinic antagonist to dampen the response of the mesolimbic reward system.

Drugs as instruments: A new framework for non-addictive psychoactive drug use

2011| Müller, C. P., Schumann, G.

This paper (2011) provides a neurobiological framework for non-addictive forms of drug-use that elicit alterations in the users' mental state and proposes a new classification system of different memory subtypes (episodic, semantic, conditioned) that aims to identify how learning mechanisms operate within the gradient transition between addictive and non-addictive behavior.

Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament

2008| Blackwell, K. C., Halpern, J. H., Passie, T., Ruttenber, A. J., Sherwood, A. R.

This qualitative interview study (n=32) analyzed the self-report of interviewees, recruited from the community of the Santo Daime Church, who use ayahuasca as a religious sacrament. Interviewees attributed psychological and physical benefits to their ayahuasca use and reported the remission of psychiatric disorders and drug abuse.

A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: results from a randomized, controlled laboratory study

2018| Dakwar, E., Foltin, R. W., Hart, C. L., Hu, M. C., Levin, F. R., Nunes, E. V.

This study (n=20) found that the mystical experience elicited by ketamine (but not dissociation or near-death-like experiences) may play an important role in ketamine's therapeutic potential for cocaine addiction.

Therapeutic effects of ritual ayahuasca use in the treatment of substance dependence: qualitative results

2014| Loizaga-Velder, A., Verres, R.

This interview study (n=29) provides qualitative evidence for the efficacy of ritualized ayahuasca use in the treatment of substance dependence. It also discusses several factors that can influence therapeutic outcome.

A phenomenological investigation into the lived experience of ibogaine and its potential to treat opioid use disorders

2018| Barsuglia, J. P., Bucky, S. F., Camlin, T. J., Eulert, D., Horvath, A. T., Polanco, M.

This interview study (n=10) suggests that ibogaine has the potential to attenuate opioid abuse and discusses common subjective themes reported by recipients of ibogaine therapy.

Classic Psychedelics as a Psychotherapeutic Aid in the Treatment of Stimulant Use Disorder: a Case Report

2020| Black, Q. C., Johnson, S.

This case study (2020) describes a 22-year-old male with a history of mood disorder and polysubstance use who decided to seek out psychotherapy for the first time following consumption of 3.5 grams of psilocybin-containing mushrooms. As treatment progressed, the patient reported being better able to consolidate his therapeutic gains through the integration of insights obtained through his use of classic psychedelics, ultimately remaining abstinent from all stimulant drugs.

Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction

2014| Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W.

This follow-up study (n=15) to an open-label pilot-study of psilocybin-facilitated smoking addiction treatment found that the mystical experience (MEQ) but not the intensity of the experience was predictive of smoking abstinence (80% at 6-month follow-up).

An online survey of tobacco smoking cessation associated with naturalistic psychedelic use

2017| Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W., Johnson, P. S.

This retrospective cross-sectional anonymous online survey (n=358) characterized individuals who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting more than 1 year ago. Of the 358 participants, 38% reported continuous smoking cessation, 28% reported a persisting reduction, and 34% reported a temporary reduction before returning to baseline smoking levels.

The psychedelic debriefing in alcohol dependence treatment: illustrating key change phenomena through qualitative content analysis of clinical sessions

2018| Bogenschutz, M. P., Forcehimes, A. A., May, D. G., Nielson, E. M.

This open-label pilot study (n=10) of psilocybin-assisted treatment of alcohol dependence (21mg/70kg) presents a qualitative content analysis of the 17 debriefing sessions conducted in the pilot study, which occurred the day after corresponding psilocybin medication sessions. Participants articulated a series of key phenomena related to change in drinking outcomes and acute subjective effects of psilocybin.

Pharmacokinetics of Hoasca alkaloids in healthy humans

1999| Andrade, E. N., Andrade, E. O., Brito, G. S., Callaway, J. C., Grob, C. S., Mash, D. C., McKenna, D., Poland, R. E., Raymon, L. P.

This open-label field study (n=15) investigated the pharmacokinetics, subjective, neuroendocrine, autonomic, and cardiovascular effects of ayahuasca (35.5 mg DMT, 158.5 mg THH, 29.7 mg Harmaline, 252.3 mg Harmine), providing a time-course of these parameters in a 24-hour period in the context of a religious ceremony.

Therapeutic infusions of ketamine: do the psychoactive effects matter?

2014| Anerella, C., Dakwar, E., Hart, C. L., Levin, F. R., Mathew, S. J., Nunes, E. V.

This double-blind, randomized, inpatient study (n=8) evaluates the mystical and dissociative effects of ketamine in the treatment of cocaine dependant individuals. Ketamine led to significantly greater acute mystical-type effects than the active control, and mediated motivation to quit cocaine 24h post-infusion.

Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder

2018| Amegadzie, S. S., Bogenschutz, M. P., Duane, J. H., Malone, T. C., Mennenga, S. E., Owens, L. T., Podrebarac, S. K., Ross, S.

This study describes the treatment trajectories of (n=3) participants administered with psilocybin (25-40mg/70kg) in a double-blind placebo-controlled clinical trial investigating the treatment of Alcohol Use Disorder. These participants experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol. Increased mindfulness, and control over choices, were also reported following the treatment.

Assessment of addiction severity among ritual users of ayahuasca

2010| Alcázar, M. A., Barbanoj, M. J., Barbosa, P., Bouso, J. C., Cutchet, M., Fernández, X., Fondevila, S., Fábregas, J. M., González, D., Riba, J.

This paper reports the results of two survey-based studies (n=242), comparing the addiction severity among rural Ayahuasca users with those in urban areas. Overall, the authors report that ritual Ayahuasca use does not appear to be associated with deleterious psychosocial effects typically associated with other drugs of abuse.

Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials

2020| Elices, M., Farré, M., Fonseca, F., Fuentes, J. J., Torrens, M.

This review (2020) presents the results of 11 randomized-controlled clinical trials (n=567) involving the therapeutic administration of LSD (20-800 μg). Multiple variables regarding LSD treatment, therapeutic approach, and quality of experience were revealed and related to therapeutic outcomes. The authors find the strongest evidence to be for the use of LSD in the treatment of alcoholism, but highlight the lack of double-blind studies.

DARK Classics in Chemical Neuroscience: Ibogaine

2018| Surratt, C. K., Wasko, M. J., Witt-Enderby, P. A.

This literature review (2018) of the history of ibogaine looks back at the early use, pharmacological studies, and subsequent clinical trials that investigate this compound for the treatment of mental health disorders.

Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial

2020| Azhari, N., Dakwar, E., Haug, N. A., Rothberg, R. L.

This further analysis of a randomized, double-blind, active-placebo controlled study (n=40) of ketamine (50mg/70kg) found that the mystical-type experiences (not dissociation) mediated the effect of ketamine on drinking behavior.

Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers

2015| Bosch, O. G., Kraehenmann, R., Pokorny, T., Preller, K. H., Scheidegger, M., Seifritz, E., Vollenweider, F. X.

This double-blind, placebo-controlled, fMRI study (n=25) found that a moderate dose of psilocybin (11.2mg/70kg) lowered amygdala (which is hyperactive in those with major depression) reactivity to negative and neutral (visual) stimuli. The decrease in emotional processing was correlated with an increase in positive mood.

Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy

2020| Garcia-Romeu, A., Johnson, M. W., Strickland, J. C.

This further analysis of an open-label, counter-balanced study (n=10) with psilocybin (20-30mg/70kg) found that overtone-based music (e.g. gongs) was more effective than classical music.

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study

2015| Barbosa, P., Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Strassman, R. J., Wilcox, C. E.

This open-label study (n=10) combined therapy with two psilocybin (21-28mg) sessions and showed a significant reduction in (heavy) drinking days up to 36 weeks later.

Ayahuasca’s entwined efficacy: an ethnographic study of ritual healing from ‘addiction’

2017| Sanabria, E., Talin, P.

This interview (ethnographic) study finds that the caregiving context of ritual ayahuasca use plays a key role in the treatment of addiction. This offers an contrasting narrative to the more 'standard' or 'medical' model in which addiction is often framed.

Hallucinogen use predicts reduced recidivism among substance-involved offenders under community corrections supervision

2017| Clark, C. B., Cropsey, K. L., Fontaine, K. R., Hendricks, P. S., Johnson, M. W.

This survey study (n=25.622) found that hallucinogen use predicted reduced recidivism.

Long-term follow-up of psilocybin-facilitated smoking cessation

2017| Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W.

This follow-up study (n=15) found that at 12-months 67% of participants didn't return to smoking (biologically confirmed). This was 60% at an average of 30-months follow-up. This study is a first (very positive) step in seeing of psilocybin-assisted psychotherapy may be a viable way for people to quit smoking.

Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

2014| Cosimano, M. P., Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W.

This is the first study (and still one of the few) to use psilocybin and cognitive behavioral therapy (CBT) in concert for smoking cessation. 80% of participants, in the open-label study, were smoking-free after 6 months.

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts

2018| Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W., Noorani, T. N., Swift, T. C.

This long-term, qualitative follow-up study dissects the factors that lead to long-term smoking cessation. Vivid insights, rapport with the study team, good preparation, were some of the factors that led to this effect.

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