Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis

Nov 4, 2020Psychological medicine

Long-term psychological effects of traditional serotonin-based psychedelics: a combined review and analysis

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Abstract

A total of 34 studies involving 549 participants indicate significant psychological effects of classical psychedelics, such as psilocybin, ayahuasca, and LSD, measured at least 24 hours after administration.

Classical psychedelics demonstrated significant improvements in various psychological outcomes, including psychiatric symptoms and affect-related measures.
Large between-group effects were observed, with effect sizes ranging from 0.84 to 1.08.
Effects on personality traits and mindfulness were noted to be weak.
Some effects appeared to be larger in clinical samples compared to non-clinical samples.
No post-acute adverse effects were reported across the studies reviewed.

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BACKGROUND: Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias.

METHODS: We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain.

RESULTS: A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects.

CONCLUSIONS: High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

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Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis

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