Nicole L Galvão-Coelho1,2,3,4,5, Wolfgang Marx6, Maria Gonzalez7, Justin Sinclair7, Michael de Manincor7, Daniel Perkins8, Jerome Sarris7,9. 1. Laboratory of Hormone Measurement, Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil. nicolelgalvaocoelho@gmail.com. 2. Postgraduate Program in Psychobiology and Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil. nicolelgalvaocoelho@gmail.com. 3. National Institute of Science and Technology in Translational Medicine, São Paulo, Brazil. nicolelgalvaocoelho@gmail.com. 4. NICM Health Research Institute, Western Sydney University, Westmead, Australia. nicolelgalvaocoelho@gmail.com. 5. Departamento de Fisiologia e Comportamento, Universidade Federal do Rio Grande do Norte, Caixa Postal, 1511, CEP: 59078-970, Natal, RN, Brasil. nicolelgalvaocoelho@gmail.com. 6. IMPACT Research Institute, School of Medicine, Deakin University, Geelong, Australia. 7. NICM Health Research Institute, Western Sydney University, Westmead, Australia. 8. School of Social and Political Science, University of Melbourne, Melbourne, Australia. 9. Professorial Unit, The Melbourne Clinic, Department of Psychiatry, University of Melbourne, Melbourne, Australia.
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.
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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