Serotonin syndrome, also called serotonin toxicity, is described in a 2019 review as a potentially life-threatening drug-induced toxidrome marked by neuromuscular abnormalities, autonomic hyperactivity and changes in mental state (Scotton et al., 2019). The same review says severe cases usually follow starting two or more serotonergic drugs together, and that combining an MAO inhibitor with serotonergic drugs is especially dangerous (Scotton et al., 2019).
For psilocybin the picture is uncertain. A 2025 scoping review of 18 studies found no increased serotonin-syndrome risk when classic psychedelics, particularly psilocybin, were used with antidepressants, but most of its evidence was case reports, surveys and open-label studies (Tap et al., 2025). In 443 Reddit posts about SSRIs and mushrooms, 13 posts may have reflected serotonin toxicity (Sakai et al., 2024).
Ayahuasca is a different case: researchers warned in 1998 that its MAO-inhibiting harmala alkaloids combined with SSRIs may induce serotonin syndrome (Callaway and Grob, 1998). Nobody can say any such combination is safe. This is not medical advice.
General information, not medical advice. In an emergency in Canada, call 911. For a mental-health crisis, call or text 9-8-8.
Sources
- Scotton et al. (2019), Serotonin syndrome: pathophysiology, clinical features, management
- Tap et al. (2025), Concomitant use of antidepressants and classic psychedelics
- Callaway and Grob (1998), Ayahuasca preparations and serotonin reuptake inhibitors
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