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.

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.

Psychedelics and Health Behavior Change

2021 |

This review (2021) explores the prospects of psychedelic substances as facilitators of behavioral change that promote a healthy lifestyle concerning diet, exercise, and substance abuse, through psychological mechanisms such as the relaxation of prior beliefs. The authors emphasize that self-determination, confidence, and interconnectedness as useful concepts to understand how individuals derive positive perspectives and internal motivation from a well-integrated psychedelic experience. It is noted that psychedelic substances should not replace, but augment, prior commitments, as they highlight their integration within the context of therapeutic models, such as Cognitive Behavioral Therapy or Acceptance and Commitment Therapy.

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 |

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).

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., Wilson, S., Williams, T. M., 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, F., Erowid, E., 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


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., Fábregas, J. M., Fernández, X., Fondevila, S., 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.

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

1970| 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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