Psychedelic therapy in the treatment of addiction: the past, present and future
This review (2023) charts the resurgence of interest in psychedelic therapy for treating addiction, beginning with historical studies from the mid-late 1900s, then examining real-world evidence from naturalistic, observational, and survey-based studies, and contemporary clinical trials ranging from first-in-human to Phase II. It also explores translational human neuropsychopharmacology techniques like fMRI and PET to understand the therapeutic mechanisms of psychedelics.
Authors
- David Nutt
- Leor Roseman
- David Erritzoe
Published
Abstract
Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction. In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes.
Research Summary of 'Psychedelic therapy in the treatment of addiction: the past, present and future'
Introduction
Zafar and colleagues frame addiction as a chronic, relapsing condition with large and growing global prevalence, substantial mortality and a major socioeconomic burden. They note current treatments—primarily psychosocial interventions with limited pharmacological adjuncts—have low reach and modest effectiveness (for example, high relapse rates within months and few licensed medications for alcohol use disorder). The introduction highlights renewed scientific interest in psychedelic therapies, both ‘‘classic’’ serotonergic agents (LSD, psilocybin, DMT/ayahuasca, 5-MeO-DMT, mescaline) and ‘‘non-classic’’ compounds (ketamine, MDMA, ibogaine), and indicates that modern work ranges from observational, naturalistic studies through to contemporary randomized controlled trials and mechanistic neuroimaging studies. This review sets out to summarise the historical and contemporary clinical evidence for psychedelic therapies in addiction, to synthesise real-world and trial data from the mid‑20th century to the present, and to outline translational human neuropsychopharmacology techniques (fMRI, PET, SPECT, EEG and molecular imaging) that could illuminate mechanisms of action. The authors emphasise that a mechanistic, biomarker-driven understanding could help optimise drug development and personalise treatment for people with substance use and behavioural addictions.
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Zafar, R., Siegel, M., Harding, R., Barba, T., Agnorelli, C., Suseelan, S., Roseman, L., Wall, M., Nutt, D. J., & Erritzoe, D. (2023). Psychedelic therapy in the treatment of addiction: the past, present and future. Frontiers in Psychiatry, 14. https://doi.org/10.3389/fpsyt.2023.1183740
References (55)
Papers cited by this study that are also in Blossom
Passie, T., Halpern, J. H., Stichtenoth, D. O. et al. · CNS Neuroscience and Therapeutics (2008)
Fuentes, J. J., Fonseca, F., Elices, M. et al. · Frontiers in Psychiatry (2020)
Dyck, E. · Social History of Medicine (2006)
Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)
Ezquerra-Romano, I. I., Lawn, W., Krupitsky, E. M. et al. · Neuropharmacology (2018)
Krupitsky, E. M., Grinenko, A. Y. · Journal of Psychoactive Drugs (1997)
Lason, W., Carnicella, S., Mash, D. C. et al. · Frontiers in Pharmacology (2019)
Alper, K. R., Lotsof, H. S., Frenken, G. M. N. et al. · The American Journal on Addictions (2010)
Carhart-Harris, R. L., Wagner, A. C., Agrawal, M. et al. · Journal of Psychopharmacology (2021)
Pisano, V. D., Putnam, N. P., Kramer, H. M. et al. · Journal of Psychopharmacology (2017)
Show all 55 referencesShow fewer
Johnson, M. W., Garcia-Romeu, A., Johnson, P. S. et al. · Journal of Psychopharmacology (2017)
Garcia-Romeu, A., Davis, A. K., Fire Erowid et al. · Journal of Psychopharmacology (2019)
Garcia-Romeu, A., Davis, A. K., Griffiths, R. R. et al. · Frontiers in Psychiatry (2020)
Jones, G. M., Nock, M. K. · Scientific Reports (2022)
Argento, E., Socias, M. E., Hayashi, K. et al. · International Journal of Drug Policy (2022)
Calleja-Conde, J., Morales-García, J. A., Echeverry-Alzate, V. et al. · Addiction Biology (2022)
Ermakova, A. O., Dunbar, F., Rucker, J. et al. · Journal of Psychopharmacology (2021)
Davis, A. K., Barsuglia, J. P., Lancelotta, R. et al. · Journal of Psychopharmacology (2018)
Nunes, A. A., Dos Santos, R. G., Osório, F. L. et al. · Journal of Psychoactive Drugs (2016)
Fábregas, J. M., González, D., Fondevila, S. et al. · Drug and Alcohol Dependence (2010)
Barbosa, P., Tófoli, L.F., Bogenschutz, M. P. et al. · Frontiers in Psychiatry (2018)
Narine, K., Campbell, I., Dyck, J. et al. · Neuropharmacology (2022)
Agin-Liebes, G. I., Lancelotta, R., Uthaug, M. V. et al. · ACS Pharmacology and Translational Science (2021)
Frampton, C. M., Yazar-Klosinski, B., Nollar, G. E. · The American Journal of Drug and Alcohol Abuse (2017)
Brown, T. K. · Current Drug Abuse Reviews (2013)
Malcolm, B., Polanco, M., Barsuglia, J. P. · Journal of Psychoactive Drugs (2018)
Logrip, M. L., Mash, D. C., Duque, L. et al. · Frontiers in Pharmacology (2018)
Barsuglia, J. P., Polanco, M., Palmer, R. et al. · Progress in Brain Research (2018)
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Sessa, B., Higbed, L., Durant, C. et al. · Journal of Psychopharmacology (2021)
Bogenschutz, M. P., Ross, S., Bhatt, S. R. et al. · JAMA Psychiatry (2022)
Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)
Johnson, M. W., Garcia-Romeu, A., Griffiths, R. R. · The American Journal of Drug and Alcohol Abuse (2016)
Dakwar, E., Levin, F. R., Hart, C. L. et al. · American Journal of Psychiatry (2020)
Grabski, M., McAndrew, A., Lawn, W. et al. · American Journal of Psychiatry (2022)
Wagner, A. C. · Frontiers in Psychology (2021)
Mitchell, J., Bogenschutz, M. P., Lilienstein, A. et al. · Nature Medicine (2021)
Mithoefer, M. C., Feduccia, A. A., Jerome, L. et al. · Psychopharmacology (2019)
Cameron, L. P., Tombari, R. J., Lu, J. et al. · Nature (2020)
Glazer', J., Murray, C. H., Nusslock', R. et al. · Neuropsychopharmacology (2022)
Grimm, O., Kraehenmann, R., Preller, K. H. et al. · European Neuropsychopharmacology (2018)
Dolder, P. C., Schmid, Y., Müller, F. et al. · Neuropsychopharmacology (2016)
Pokorny, T., Preller, K. H., Kometer, M. et al. · International Journal of Neuropsychopharmacology (2017)
Mertens, L. J., Wall, M. B., Roseman, L. et al. · Journal of Psychopharmacology (2020)
Wall, M., Nutt, D. J., Kaelen, M. et al. · Journal of Psychopharmacology (2022)
Doss, M. K., Považan, M., Rosenberg, M. D. et al. · Translational Psychiatry (2021)
Gattuso, J. J., Perkins, D., Ruffell, S. G. D. et al. · International Journal of Neuropsychopharmacology (2022)
McCulloch, D. E-W., Knudsen, G. M., Barrett, F. S. et al. · Neuroscience and Biobehavioral Reviews (2022)
Vollenweider, F. X., Leenders, K. L., Maguire, P. et al. · Neuropsychopharmacology (1997)
Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Psychopharmacology (2011)
Carhart-Harris, R. L., Leech, R., Erritzoe, D. et al. · Schizophrenia Bulletin (2012)
Daws, R. E., Timmermann, C., Giribaldi, B. et al. · Nature Medicine (2022)
Barroso Flores, J., Hoffmann, R., Wagner, K. et al. · Science Advances (2021)
Calder, A. E., Hasler, G. · Neuropsychopharmacology (2022)
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Ertl, N., Ashraf, I., Azizi, L. et al. · Biorxiv (2025)
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