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Abstract
Objectives
Critique the available systematic review and de novo assessment of the role of psychedelics in the treatment of alcohol use disorder.
Methods
A systematic literature search of PubMed was completed from 1960 to 9/9/2023. We pooled randomized controlled trials comparing psychedelics to control therapy for the treatment of alcohol use disorder.
Results
At the first recorded follow-up, LSD [n = 3, Odds Ratio (OR) 1.99 (95% Confidence interval (CI): 1.10 to 3.61)] and any psychedelic [n = 4, OR 2.16 (95%CI: 1.26 to 3.69)] enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol versus placebo in randomized, double-blind, placebo-controlled trials. When the inclusion criteria were relaxed to include controlled trials without double-blinding or placebo control, LSD [n = 5, OR 1.79 (95%CI: 1.36 to 2.34)] and any psychedelic therapy [n = 6, OR 1.89 (95%CI: 1.42 to 2.50)] still enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol. Four of 6 trials had high risk of bias and other methodological issues. One trial found an instance of suicidal ideation as well as transient increases in blood pressure that requires further exploration before the balance of benefits to harms can be determined.
Conclusions
The use of psychedelics to treat alcohol use disorder is promising, but the weaknesses in the literature base preclude making definitive statements about its value. Future trials with greater methodological rigor are needed.
PLAIN LANGUAGE SUMMARY
Lysergic acid diethylamine (LSD) and psilocybin (hallucinogenic mushrooms) are psychedelics that have been studied in patients with alcohol use disorder (chronic issue with heavy or problem drinking). When all the studies are pooled together in a meta-analysis, the odds of being able to refrain from drinking alcohol or to substantially reduce the amount of alcohol consumed was enhanced by 89%. This is a promising finding that if bore out in additional studies, especially those with higher study quality, would be a major advance in patients with alcohol use disorder. We cannot make more definitive conclusions because all the LSD studies were published between 1966 and 1970 which may not reflect contemporary practice and most of the studies had methodological weaknesses that reduce confidence in the studies to prove the benefits. It is heartening that the single psilocybin trial from 2022 was of higher methodological quality, reflected contemporary practice, and still showed positive effects.
Transparency
Declaration of funding
This is an unfunded study.
Declaration of financial/other relationships
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. A reviewer on this manuscript declared that they work in the psychedelics research field and has received commercial and government funding to conduct this work. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.
Author contributions
Conception and design (C. Michael White, Adrian Hernandez), analysis and interpretation of the data (Dakota Sicignano, Benjamin Schiff, Nawal Elmahy, Adrian Hernandez, C. Michael White), drafting of the paper (C. Michael White, Adrian Hernandez) or revising it critically for intellectual content (Dakota Sicignano), and the final approval of the version to be published (C, Michael White). All authors agree to be accountable for all aspects of the work.
Acknowledgements
None.