Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use
Abstract
Background Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggest that psilocybin's effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period. Aims To learn the extent to which antidepressants may diminish the effects of psilocybin-containing mushrooms both concurrently and after discontinuation of antidepressants. Methods Online retrospective survey of individuals with use of psilocybin mushrooms (1) with an antidepressant and/or (2) within 2 years of discontinuing an antidepressant. Participants who took mushrooms with an antidepressant and either took the same dose pre-antidepressant or took the same dose with other people not on antidepressant reported the strength of drug effects relative to their expectation. Participants who took mushrooms following discontinuation of an antidepressant also reported the presence of weakened effects. Results In reports ( n = 611) of taking mushrooms with an antidepressant, probabilities [95% CI] of weaker than expected drug effects were 0.47 [0.41-0.54] (selective serotonergic reuptake inhibitors, SSRIs), 0.55 [0.44-0.67] (serotonin norepinephrine reuptake inhibitors, SNRIs) and 0.29 [0.2-0.39] (bupropion). Following SSRI/SNRI discontinuation ( n = 1,542 reports), the probability of reduced drug effects was not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3…
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A recent retrospective online survey found that psilocybin's effect was attenuated up to 3 months after discontinuing SSRIs or SNRIs.
“Conversely, a recent retrospective online survey found that psilocybin ' s effect was attenuated up to 3 months after discontinuing SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs). 92”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [92]
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“Longer tapering periods may also be considered, as they would allow for sufficient time for serotonin receptor density to adjust (Horowitz and Taylor, 2019).”
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Scala, M., Fabbri, C., Fusar-Poli, P., Di Lorenzo, G., Ferrara, M., Amerio, A., Fusar-Poli, L., Pichiecchio, A., Asteggiano, C., Menchetti, M., et al. (2024) · CNS Spectrums · doi:10.1017/s1092852924002268 · Cited by 9 · see citing works
Serotonergic psychedelics for depression: A comprehensive overview
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- Authors
- Gukasyan, N., Griffiths, R. R., Yaden, D. B., Antoine, D. G., & Nayak, S. M.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Gukasyan, Natalie
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2023-06-08
- Volume
- 37
- Issue
- 7
- Pages
- 707-716
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W4379967727
- Cited by
- 67
- References
- 10
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 14 · 2023: 6
- FWCI
- 19.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Philanthropic contributions from Tim Ferriss, Matt Mullenweg, Blake Mycoskie, and Craig Nerenberg
- Steven and Alexandra Cohen Foundation (Center for Psychedelic and Consciousness Research)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- psilocybin, antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, drug interactions, antidepressant discontinuation, depression, psychedelics, fluoxetine, drug washout
- MeSH terms
- Serotonin and Noradrenaline Reuptake Inhibitors, Agaricales, Antidepressive Agents, Humans, Psilocybin, Retrospective Studies, Selective Serotonin Reuptake Inhibitors
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