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Board Certified Psychiatric Pharmacists (BCPP) Dr.’s Ben Malcolm and Kelan Thomas recently published a review article to characterize serotonergic psychedelics and the risk of serotonin toxicity when taken alone or in combination with other psychiatric medications. In this article, the authors offer a short summary of their main findings.
Introduction
As interest increases in using serotonergic psychedelics to treat mental illness, it will be important to evaluate the risk of serotonin toxicity if they are combined with current treatment options.
Serotonergic psychedelics, such as 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and the monoamine oxidase inhibitor (MAOI)-containing decoction ayahuasca have preliminary positive evidence for effectively treating mental illness. The first-line psychiatric medications currently used to treat depression, anxiety, and posttraumatic stress disorder (PTSD) are antidepressants that block serotonin reuptake, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). As interest increases in using serotonergic psychedelics to treat mental illness, it will be important to evaluate the risk of serotonin toxicity if they are combined with current treatment options.
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Methods
The review article summarized the published journal articles about combinations of psychiatric medications with serotonergic psychedelics and provided details regarding management strategies for the rare, but serious, serotonin toxicity cases that may become life-threatening.
Results
While MDMA and SSRIs both independently increase serotonin in the synapse, their use in combination actually decreased the subjective and physical effects of MDMA in clinical trials, so the risks of serotonin toxicity in these controlled clinical settings appears to be relatively low.
Combinations involving serotonin releasing agents (MDMA) or serotonin reuptake inhibitor agents (SSRIs or SNRIs) in combination with MAOIs carry the highest risks of serotonin toxicity and should not be combined. While MDMA and SSRIs both independently increase serotonin in the synapse, their use in combination actually decreased the subjective and physical effects of MDMA in clinical trials, so the risks of serotonin toxicity in these controlled clinical settings appears to be relatively low. Classic psychedelic serotonin agonists (LSD, DMT and psilocybin) appear to be the safest in combination with other psychiatric medications and seem to have a negligible risk of serotonin toxicity.
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Conclusions
The main takeaway from the review is that classic psychedelic serotonin agonists are the least likely to have serotonin toxicity in combination with antidepressants. Serotonin-releasing agents like MDMA had a low risk of serotonin toxicity when combined with SSRIs or SNRIs in a few small clinical trials, while combinations of MAOIs (including ayahuasca) with other antidepressants should be avoided due to a substantially increased risk of serotonin toxicity.
References
Malcolm, B., & Thomas, K. (2021). Serotonin toxicity of serotonergic psychedelics. Psychopharmacology, 10.1007/s00213-021-05876-x. Advance online publication. https://doi.org/10.1007/s00213-021-05876-x
Art by Trey Brasher.
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