If you're on SSRIs or SNRIs, serotonin agonists and serotonin releasing agents will probably either provide less of an experience than you expect or none at all, though they may still have a significant antidepressant effect. Serotonin agonists are primarily psychedelics: tryptamines (shrooms, DMT), lysergamides (LSD), and others. Serotonin releasing agents are primarily entactogens: phenethylamines (MDMA, the 2Cs) and others. This is likely because SxRIs cause downregulation of 5-HT2A receptors, which all these classes of compound act upon.
Serotonin syndrome is a condition caused by an excess of serotonin in the brain, mostly seen in people with MDMA overdoses. Severe cases require immediate medical attention. There is "little to no risk" of serotonin syndrome from combining normal doses of these with SxRIs, according to a literature review. The magnitude of risk may be slightly higher for SRAs but if you're on MAOIs, SRAs and 5-MeO-DMT (toad venom) can kill you. SxRIs are contraindicated with MAOIs, and ayahuasca contains a MAOI in the vine stems, so doing actual ayahuasca on SxRIs can also kill you. (Combining actual ayahuasca with MDMA can also kill you but I suspect anyone doing that is operating on a level that makes them immune to physical harm, psychic attack, etc.)
There is a washout period (weeks to months) of blunted effect while your brain's 5-HT2A receptors recover to normal levels, even after complete SSRI dose stepdown and discontinuation; you can't make them work better by briefly pausing your treatment, and stopping cold turkey is very likely to give you extremely nasty withdrawal because suddenly: no serotonin. Hopefully your doctor told you that last part, but they don't always do that.
more information:
literature review on serotonin syndrome when combining antidepressants and psychedelics/entactogens (sci-hub link):
Malcolm, B., Thomas, K. Serotonin toxicity of serotonergic psychedelics. Psychopharmacology 239, 1881–1891 (2022). doi: 10.1007/s00213-021-05876-x
paper on reduced subjective experience but maintained antidepressant effect of psychedelics (open access)
Barbut Siva J, Barba T, Kettner H, et al. Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study. Journal of Psychopharmacology. 2024;0(0). doi:10.1177/02698811231224217
paper on post-discontinuation effect of SSRIs on MDMA effectiveness (open access)
Feduccia AA, Jerome L, Mithoefer MC, Holland J. Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. Psychopharmacology (Berl). 2021 Feb;238(2):581-588. doi: 10.1007/s00213-020-05710-w. Epub 2020 Nov 21. PMID: 33221932; PMCID: PMC7826309.
paper on pre- and post-discontinuation effects of SSRIs on psychedelic experience (not on sci-hub, only results available)
Gukasyan N, Griffiths RR, Yaden DB, Antoine DG 2nd, Nayak SM. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. J Psychopharmacol. 2023 Jul;37(7):707-716. doi: 10.1177/02698811231179910.
