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Classic Serotonergic Psychedelics for Mood and Depressive Symptoms: a Meta-analysis of Mood Disorder Patients and Healthy Participants

Overview
Specialty Pharmacology
Date 2021 Jan 11
PMID 33427944
Citations 43
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Abstract

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.

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References
1.
Akil H, Gordon J, Hen R, Javitch J, Mayberg H, McEwen B . Treatment resistant depression: A multi-scale, systems biology approach. Neurosci Biobehav Rev. 2017; 84:272-288. PMC: 5729118. DOI: 10.1016/j.neubiorev.2017.08.019. View

2.
Araujo A, Carvalho F, Bastos M, Guedes de Pinho P, Carvalho M . The hallucinogenic world of tryptamines: an updated review. Arch Toxicol. 2015; 89(8):1151-73. DOI: 10.1007/s00204-015-1513-x. View

3.
Baumeister D, Barnes G, Giaroli G, Tracy D . Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Ther Adv Psychopharmacol. 2014; 4(4):156-69. PMC: 4104707. DOI: 10.1177/2045125314527985. View

4.
BERLIN L, Guthrie T, WEIDER A, GOODELL H, Wolff H . Studies in human cerebral function: the effects of mescaline and lysergic acid on cerebral processes pertinent to creative activity. J Nerv Ment Dis. 1955; 122(5):487-91. View

5.
Bershad A, Schepers S, Bremmer M, Lee R, de Wit H . Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers. Biol Psychiatry. 2019; 86(10):792-800. PMC: 6814527. DOI: 10.1016/j.biopsych.2019.05.019. View