Alcohol Use Disorder (AUD)Tobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Psilocybin

Classic hallucinogens in the treatment of addictions

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.

Ask Blossom about this paper

Authors

  • Matthew Johnson
  • Michael Bogenschutz

Published

Progress in Neuro-Psychopharmacology and Biological Psychiatry
meta Study

Abstract

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction.

Unlocked with Blossom Pro

Research Summary of 'Classic hallucinogens in the treatment of addictions'

Editorial

βBlossom's Take

This review is useful because it reassembles the addiction-treatment thread across the old LSD literature and the modern psilocybin pilots into one account. It shows why the question stayed alive, the controlled alcoholism studies, the later positive smoking and alcohol reports, and the recurring role of meaningful experience, but also where the evidence is still too thin for broad clinical claims.

Study Details

Cited By (79)

Papers in Blossom that reference this study

Psilocybin or Nicotine Patch for Smoking Cessation A Pilot Randomized Clinical Trial

Johnson, M. W., Naudé, G. P., Hendricks, P. S. et al. · JAMA Network Open (2026)

3 cited
Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder

Meshkat, S., Kaczmarek, E., Doyle, Z. et al. · Psychedelic Medicine (2025)

7 cited
Processing of self-related thoughts in experienced users of classic psychedelics and non-users: a source localisation EEG study

Ruban, A., Magnuski, M., Hobot, J. et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2025)

1 cited
The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

Tap, S. C. · Addiction Biology (2024)

11 cited
Naturalistic use of psychedelics does not modulate processing of self-related stimuli (but it might modulate attentional mechanisms): An event-related potentials study

Orłowski, P., Hobot, J., Ruban, A. et al. · Psychophysiology (2024)

5 cited
Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin

Rosenblat, J. D., Meshkat, S., Doyle, Z. et al. · Med (2024)

89 cited
Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study

Borkel, L. F., Rojas-Hernández, J., Henríquez-Hernández, L. A. et al. · Expert Review of Clinical Pharmacology (2023)

37 cited
Effect of LSD and music on the time-varying brain dynamics

Adamska, I., Finc, K. · Psychopharmacology (2023)

8 cited
A neurophenomenological approach to non-ordinary states of consciousness: hypnosis, meditation, and psychedelics

Timmermann, C., Vollenweider, F. X. · Trends in Cognitive Sciences (2023)

142 cited
The association between naturalistic use of psychedelics and co-occurring substance use disorders

Rabinowitz, J., Lev-Ran, S., Gross, R. · Frontiers in Psychiatry (2023)

14 cited
Show all 79 papers
Reactivations after 5-methoxy-N,N-dimethyltryptamine use in naturalistic settings: An initial exploratory analysis of the phenomenon’s predictors and its emotional valence

Ortiz Bernal, A. M., Raison, C. L., Lancelotta, R. et al. · Frontiers in Psychiatry (2022)

26 cited
Mescaline: The forgotten psychedelic

Narine, K., Campbell, I., Dyck, J. et al. · Neuropharmacology (2022)

98 cited
Self-Entropic Broadening Theory: Toward a New Understanding of Self and Behavior Change Informed by Psychedelics and Psychosis

Dourron, H. M., Strauss, C., Hendricks, P. S. · Pharmacological Reviews (2022)

34 cited
A systematic literature review of clinical trials and therapeutic applications of ibogaine

Köck, P., Frölich, K., Walter, M. et al. · Journal of Substance Abuse Treatment (2022)

61 cited
Associations between classic psychedelics and nicotine dependence in a nationally representative sample

Jones, G. M., Lipson, J., Nock, M. K. · Scientific Reports (2022)

31 cited
New insights into the clinical and nonclinical effects of psychedelic substances: An integrative review.

Forstmann, M., Sagioglou, C. · European Psychologist (2022)

6 cited
Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample

Jones, G. M., Ricard, J. A., Lipson, J. et al. · Scientific Reports (2022)

53 cited
Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression

Murphy, R., Murphy-Beiner, A., Kettner, H. et al. · Frontiers in Pharmacology (2022)

222 cited
Exploring protective associations between the use of classic psychedelics and cocaine use disorder: a population-based survey study

Jones, G. M., Nock, M. K. · Scientific Reports (2022)

42 cited
Psychedelic use is associated with reduced daily opioid use among people who use illicit drugs in a Canadian setting

Argento, E., Socias, M. E., Hayashi, K. et al. · International Journal of Drug Policy (2022)

32 cited
MDMA/ecstasy use and psilocybin use are associated with lowered odds of psychological distress and suicidal thoughts in a sample of US adults

Jones, G. M., Nock, M. K. · Journal of Psychopharmacology (2022)

60 cited
Toward a positive psychology of psychoactive drug use

Arnaud, K. O. S. · Drugs Education Prevention and Policy (2021)

4 cited
Serotonergic Psychedelics in Neural Plasticity

Torregrossa, M. M., Lu, J., Lukasiewicz, K. et al. · Frontiers in Molecular Neuroscience (2021)

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

Henriques, G. M., Anjos-Santos, A., Rodrigues, I. R. et al. · Frontiers in Pharmacology (2021)

10 cited
LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1

Rodriguiz, R. M., Nadkarni, V., Means, C. R. et al. · Scientific Reports (2021)

88 cited
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

Podrebarac, S. K., O'donnell, K. C., Mennenga, S. E. et al. · Spirituality in Clinical Practice (2021)

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

Mollaahmetoglu, O. M., Keeler, J., Ashbullby, K. J. et al. · Frontiers in Psychiatry (2021)

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

Perkins, D., Opaleye, E. S., Simonová, H. et al. · Drug and Alcohol Review (2021)

53 cited
Trips and Neurotransmitters: Discovering Principled Patterns across 6,850 Hallucinogenic Experiences

Ballentine, G., Friedman, S. F., Bzdok, D. · Science Advances (2021)

44 cited
Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis

Vizeli, P., Straumann, I., Holze, F. et al. · Scientific Reports (2021)

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

Rush, B., Marcus, O., García, S. et al. · Frontiers in Pharmacology (2021)

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

O'shaughnessy, D. M., Berlowitz, I., Rodd, R. et al. · Therapeutic Advances in Psychopharmacology (2021)

29 cited
Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants

Galvão-Coelho, N. L., Marx, W., Sinclair, J. et al. · Psychopharmacology (2021)

143 cited
Discriminative Stimulus Effects of Substituted Tryptamines in Rats

Gatch, M. B., Hoch, A., Carbonaro, T. M. · ACS Pharmacology and Translational Science (2020)

12 cited
Virtual Reality and Psychedelics for the Treatment of Psychiatric Disease: A Systematic Literature Review

Ortiz, M. I., Gómez-Busto, F. J. · Clinical Neuropsychiatry (2020)

12 cited
A non-hallucinogenic psychedelic analogue with therapeutic potential

Cameron, L. P., Tombari, R. J., Lu, J. et al. · Nature (2020)

460 cited
The potential synergistic effects between psychedelic administration and nature contact for the improvement of mental health

Gandy, S., Forstmann, M., Carhart-Harris, R. L. et al. · Health Psychology Open (2020)

63 cited
Pivotal Mental States

Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)

145 cited
Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin

Varker, T., Watson, L., Gibson, K. et al. · Journal of Psychoactive Drugs (2020)

56 cited
Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans

Davis, A. K., Averill, L. A., Sepeda, N. D. et al. · Chronic Stress (2020)

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

Chi, T., Gold, J. A. · Journal of the Neurological Sciences (2020)

94 cited
Natural Psychoplastogens As Antidepressant Agents

Benko, J., Vranková, S. · Molecules (2020)

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

Garcia-Romeu, A., Davis, A. K., Griffiths, R. R. et al. · Frontiers in Psychiatry (2020)

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

Fuentes, J. J., Fonseca, F., Elices, M. et al. · Frontiers in Psychiatry (2020)

172 cited
Transformative experience and social connectedness mediate the mood-enhancing effects of psychedelic use in naturalistic settings

Forstmann, M., Yudkin, D. A., Prosser, A. M. B. et al. · PNAS (2020)

184 cited
Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats

Sakloth, F., Leggett, E., Moerke, M. J. et al. · Experimental and Clinical Psychopharmacology (2019)

42 cited
Metabolism of lysergic acid diethylamide (LSD): an update

Libânio Osório Marta, R. F. · Drug Metabolism Reviews (2019)

51 cited
Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

Richards, W. A., Garcia-Romeu, A. · International Review of Psychiatry (2018)

Predicting responses to psychedelics: a prospective study

Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)

418 cited
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression

Roseman, L., Demetriou, L., Wall, M. B. et al. · Neuropharmacology (2018)

237 cited
LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm

Timmermann, C., Spriggs, M. J., Kaelen, M. et al. · Neuropharmacology (2018)

83 cited
Psychedelics and music: neuroscience and therapeutic implications

Barrett, F. S., Preller, K. H., Kaelen, M. · International Review of Psychiatry (2018)

83 cited
DMT models the near-death experience

Timmermann, C., Roseman, L., Williams, L. et al. · Frontiers in Psychology (2018)

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

Davis, A. K., Renn, E., Windham-Herman, A. M. et al. · Journal of Psychoactive Drugs (2018)

34 cited
Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts

Noorani, T., Garcia-Romeu, A., Swift, T. C. et al. · Journal of Psychopharmacology (2018)

283 cited
The entropic brain - revisited

Carhart-Harris, R. L. · Neuropharmacology (2018)

539 cited
Unifying theories of psychedelic drug effects

Swanson, L. R. · Frontiers in Pharmacology (2018)

184 cited
Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

Reiche, S., Hermle, L., Gutwinski, S. et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2018)

124 cited
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

Barsuglia, J. P., Polanco, M., Palmer, R. et al. · Progress in Brain Research (2018)

37 cited
Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD

Atasoy, S., Leor, R., Kaelen, M. et al. · Scientific Reports (2017)

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

Davis, A. K., Barsuglia, J. P., Windham-Herman, A. M. et al. · Journal of Psychedelic Studies (2017)

58 cited
Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

Argento, E., Strathdee, S. A., Tupper, K. et al. · BMJ Open (2017)

60 cited
Serotonin and brain function: a tale of two receptors

Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)

727 cited
Developing Guidelines and Competencies for the Training of Psychedelic Therapists

Phelps, J. · Journal of Humanistic Psychology (2017)

211 cited
Patients’ accounts of increased “Connectedness” and “Acceptance” after psilocybin for treatment-resistant depression

Watts, R., Day, C. M., Krzanowski, J. et al. · Journal of Humanistic Psychology (2017)

568 cited
The psychological and human brain effects of music in combination with psychedelic drugs

Kaelen, M. · Imperial College London (2017)

10 cited
5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Bryson, A., Carter, O., Norman, T. et al. · International Journal of Neuropsychopharmacology (2017)

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

Morgan, C. J. A., McAndrew, A., Stevens, T. et al. · Current Opinion in Behavioral Sciences (2017)

39 cited
Crystal Structure of an LSD-Bound Human Serotonin Receptor

Wacker, D., Wang, S., Mccorvy, J. D. et al. · Cell (2017)

464 cited
Phenomenology, Structure, and Dynamic of Psychedelic States

Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

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

Canal, C. E., Murnane, K. S. · Journal of Psychopharmacology (2016)

66 cited
The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving

Sweat, N. W., Bates, L. W., Hendricks, P. S. · Journal of Psychoactive Drugs (2016)

48 cited
Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

Tófoli, L. F., De Araujo, D. B. · International Review of Neurobiology (2016)

25 cited
The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging

Dos Santos, R. G., Balthazar, F. M., Bouso, J. C. et al. · Journal of Psychopharmacology (2016)

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

Walsh, Z., Hendricks, P. S., Smith, S. et al. · Journal of Psychopharmacology (2016)

62 cited
Lysergic acid diethylamide: a drug of ‘use’?

Das, S., Barnwal, P., Ramasamy, A. et al. · Therapeutic Advances in Psychopharmacology (2016)

51 cited
New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

McKenna, D., Riba, J. · Current Topics in Behavioral Neurosciences (2016)

67 cited
Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

118 cited
Psychedelic medicine: a re-emerging therapeutic paradigm

Tupper, K. W., Wood, E., Yensen, R. et al. · Canadian Medical Association Journal (2015)

184 cited