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Assessing the risk–benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research

David A Bender, David J Hellerstein

Psychopharmacology January 13, 2022 DOI: 10.1007/s00213-021-06049-6 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Topics LSD Psilocybin
Keywords Blinding Clinical trial Hallucinogen Adverse effect Clinical psychology Pharmacology
Citations 82
Key findings Small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation to symptoms of multiple psychiatric conditions, with no serious adverse events reported.

Abstract

RationaleA broad reassessment of the potential benefits of psychedelic drugs has led to the initiation of multiple major clinical trials in an effort to advance their status to become FDA-approved medications, as well as local legislative efforts to legalize or decriminalize their use.ObjectivesTo use recently published data to assess potential risks and benefits of psychedelic drugs as therapeutics, as well as to synthesize what is currently known in order to generate fruitful future research directions.MethodsA review of studies conducted since 1991 identified 14 clinical trials of classical psychedelics, including 11 of psilocybin (N = 257 participants), 1 of lysergic acid diethylamide (N = 12 participants), and 2 of ayahuasca (N = 46 participants). Other published studies (e.g., of healthy volunteers, survey studies, case reports, neuroimaging) were also considered for review.ResultsPublished studies since 1991 largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation to symptoms of multiple psychiatric conditions. No serious adverse events attributed to psychedelic therapy have been reported. Existing studies have several limitations, including small sample sizes, inherent difficulty in blinding, relatively limited follow-up, and highly screened treatment populations.ConclusionsSubstantial data have been gathered in the past 30 years suggesting that psychedelics are a potent treatment for a variety of common psychiatric conditions, though the ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial. Unique factors related to study design are vital for clinical researchers in the field to address.

Comparable studies

Other systematic reviews and meta-analyses on LSD, most cited first.

Study Year Design Participants
Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials Participants in randomized controlled trials of LSD for alcoholism 2012 Meta-analysis n = 536
Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Patients from included clinical trials 2016 Systematic review
Default Mode Network Modulation by Psychedelics: A Systematic Review Participants from included studies 2022 Systematic review
Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews Patients with mood, anxiety, or substance-use disorders, including cancer patients and... 2018 Systematic review of systematic reviews
Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials Patients with psychiatric disorders, primarily alcoholism 2020 Systematic review n = 567

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