Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants

This meta-analytic review (2021, n=257) found that psychedelics provide improvements in mood for patients with mood disorders (and healthy subjects), both short (3h to 1d) and long-term (up to 60d).


Rationale: Major depressive disorder is one of the leading global causes of disability, for which the classic serotonergic psychedelics have recently reemerged as a potential therapeutic treatment option.

Objective: We present the first meta-analytic review evaluating the clinical effects of classic serotonergic psychedelics vs placebo for mood state and symptoms of depression in both healthy and clinical populations (separately).

Results: Our search revealed 12 eligible studies (n = 257; 124 healthy participants, and 133 patients with mood disorders), with data from randomized controlled trials involving psilocybin (n = 8), lysergic acid diethylamide ([LSD]; n = 3), and ayahuasca (n = 1). The meta-analyses of acute mood outcomes (3 h to 1 day after treatment) for healthy volunteers and patients revealed improvements with moderate significant effect sizes in favor of psychedelics, as well as for the longer-term (16 to 60 days after treatments) mood state of patients. For patients with mood disorder, significant effect sizes were detected on the acute, medium (2-7 days after treatment), and longer-term outcomes favoring psychedelics on the reduction of depressive symptoms.

Conclusion: Despite the concerns over unblinding and expectancy, the strength of the effect sizes, fast onset, and enduring therapeutic effects of these psychotherapeutic agents encourage further double-blind, placebo-controlled clinical trials assessing them for management of negative mood and depressive symptoms.”

Authors: Nicole L. Galvão-Coelho, Wolfgang Marx, Maria Gonzalez, Justin Sinclair, Michael de Manincor, Daniel Perkins & Jerome Sarris


All studies included were randomized, placebo-controlled, and double-blind trials, which had either a cross-over or parallel design, with outcomes between 3 h and 60 days after dosing session.”

The 12 studies that were included are the following (see table 2 in the paper for an overview):

“We observed a significant moderate effect size for reduction of acute negative mood outcomes in healthy volunteers, compared to placebo, as well as significant moderate effects sizes for acute and long-term reductions of negative mood state in patients with mood disorders. For depressive symptoms, a significant large effect size was detected from a medium-term assessment, and a moderate effect size for both acute and long-term outcomes was observed for patients, compared to placebo.”

The review ends with a reflection on the methodology of the studies. It presents a fair critique regarding the difficulty in blinding participants, no apparent publication bias, and possible issues of the methodology by using different measures and timescales.

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