Serotonin toxicity of serotonergic psychedelics.

Abstract

In recent years, psychedelic substances with serotonergic mechanisms have accumulated substantial evidence that they may provide therapeutic benefits forpeople suffering with psychiatric symptoms. Psychiatric disorders targeted by these psychedelic-assisted therapies are managed with serotonergic drugs likeselective serotonin reuptake inhibitors (SSRIs) as the current standard of care, so it is important to evaluate the potential risks of drug-drug interactions andserotonin toxicity (ST) between these agents. A critical evaluation of the scientific literature is necessary to delineate the risks of ST when combining psychedelics with available serotonergicpharmacotherapy options. This review article describes signs and symptoms of ST, characterizes mechanisms of ST risk, summarizes what is known aboutserotonergic psychedelic drug interactions, and outlines potential management strategies. True ST typically occurs with a serotonergic drug overdose or in combinations in which a drug that can increase intrasynaptic serotonin is combined with amonoamine oxidase inhibitor (MAOI). Serotonergic psychotropics that do not contain MAOIs are low risk in combination with psychedelics that also do notcontain MAOIs. Signs and symptoms warranting immediate medical attention include myoclonus, extreme and fluctuating vital signs, agitation or comatosemental state, muscle rigidity, pronounced hyperthermia (fever), and/or seizure activity. Serotonin-related adverse reactions exist along a spectrum with serotonin syndrome being the most severe manifestations of ST. Due to varyingserotonergic mechanisms of psychedelics and psychotropics, with varying propensities to increase intrasynaptic serotonin, some combinations may present asignificant risk for serotonin toxicity (ST) while others are likely benign.