A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy
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Abstract
After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4-methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a significant mean between-groups effect size of 1.21 (Hedges g), which is larger than the typical effect size found in trials of psychopharmacological or psychotherapy interventions. For the three studies that maintained a placebo control through a follow-up assessment, effects were generally maintained at follow-up. Overall, analyses support the efficacy of psychedelic-assisted therapy across four mental health conditions—post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. While study quality was high, we identify several areas for improvement regarding the conduct and reporting of trials. Larger trials with more diverse samples are needed to examine possible moderators and mediators of effects, and to establish whether effects are maintained over time.
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Third-wave/mindfulness-based therapies and classic psychedelic therapies have produced moderate-to-large improvements relative to control conditions.
“These interventions have shown particular promise in enhancing outcomes with moderate-to-large effect sizes compared to control conditions (Luoma et al., 2020; Öst, 2008).”
From Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca (2022) · cites this paper as Luoma et al., 2020
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- Authors
- Luoma, J. B., Chwyl, C., Bathje, G. J., Davis, A. K., & Lancelotta, R.
- Affiliations
- Portland Psychotherapy Clinic, Research, & Training Center, Portland, OR, USA
- Adler University (US)
- Johns Hopkins University (US)
- Innate Path Psychotherapy Clinic, Lakewood, CO, USA
- Corresponding author
- Luoma, Jason B.
- Venue
- Journal of Psychoactive Drugs
- Publisher
- Informa UK Limited
- Published
- 2020-06-12
- Volume
- 52
- Issue
- 4
- Pages
- 289-299
- ISSN
- 0279-1072 (ISSN-L)
- 2159-9777
- PMC
- PMC7736164
- OpenAlex
- W3035643259
- Cited by
- 212
- References
- 26
- Citations by year
- 2026: 22 · 2025: 47 · 2024: 38 · 2023: 28 · 2022: 44 · 2021: 30 · 2020: 3
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- Journal of Psychoactive Drugs (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PsyArXiv (OSF Preprints) (submittedVersion, cc-by)
- PsyArXiv (OSF Preprints) (submittedVersion)
- Funders
- National Institute on Drug Abuse (DA07209)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- psychedelic therapy, psilocybin, LSD, ayahuasca, MDMA, mental health, post-traumatic stress disorder, major depressive disorder, treatment effect size, long-term treatment outcomes, trial reporting quality
- MeSH terms
- Adult, Hallucinogens, Humans, Lysergic Acid Diethylamide, Psilocybin, N-Methyl-3,4-methylenedioxyamphetamine, Banisteriopsis
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