Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants
Open accessAbstract
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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Recent quantitative findings suggest that moderate-to-high doses of psychedelics-if administered in safe and supportive contexts-may impact outcomes related to leadership, including psychological health, creative thinking, and interpersonal attitudes and behaviors.
“recent quantitative findings suggest that moderate-to-high doses of psychedelics—if administered in safe and supportive contexts—may also impact outcomes related to leadership (see also Schlag et al., 2022 for potential risks), including psychological health (Galvão-Coelho et al., 2021), creative thinking (Prochazkova et al., 2018; Wießner et al., 2022), and interpersonal attitudes and behaviors (”
From Altered states of leadership: mindfulness meditation, psychedelic use, and leadership development (2023) · cites this paper as Galvão-Coelho et al., 2021
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“Eligible diagnoses include post-traumatic stress disorder (Mitchell et al., 2023), major depressive disorder (Galvao-Coelho et al., 2021), anxiety disorders (Holze et al., 2023b), substance use disorders (Bogenschutz et al., 2022), obsessive-compulsive disorder (Moreno et al., 2006), eating…”
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- Authors
- Galvão-Coelho, N. L., Marx, W., Gonzalez, M., Sinclair, J., de Manincor, M., Perkins, D., & Sarris, J.
- Affiliations
- Deakin University (AU)
- Western Sydney University (AU)
- The University of Melbourne (AU)
- ORCID
- Venue
- Psychopharmacology
- Published
- 2021-01-11
- Volume
- 238
- Issue
- 2
- Pages
- 341-354
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC7826317
- OpenAlex
- W3120778817
- Cited by
- 137
- References
- 31
- Citations by year
- 2026: 6 · 2025: 23 · 2024: 26 · 2023: 35 · 2022: 28 · 2021: 19
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Psychopharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- La Trobe University (cc-by)
- Funders
- Multiple Sclerosis Australia
- Deakin University
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance Code 001)., 88887, /2019‐00, 88887.466701/2019-00, APP1125000)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (465458/2014-9, #2014/50891-1, /2014-9)
- Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (#465458/2014–9, 2014/50891‐1)
- National Health and Medical Research Council (88887.466701/2019-00, 1125000)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- psilocybin, lysergic acid diethylamide, ayahuasca, major depressive disorder, depressive symptoms, mood states, placebo comparison, mood disorders
- MeSH terms
- Affect, Depression, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Hallucinogens, Humans, Lysergic Acid Diethylamide, Psilocybin, Randomized Controlled Trials as Topic, Treatment Outcome, Serotonin Receptor Agonists, Mood Disorders, Banisteriopsis, Healthy Volunteers
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