The risk of chronic psychedelic and MDMA microdosing for valvular heart disease

Taking very low, repeated doses of psychedelics like LSD, psilocybin, mescaline, DMT, or MDMA may pose a risk of valvular heart disease because these substances activate the serotonin 5-HT2B receptor, which is linked to heart valve damage. All five compounds and some of their metabolites bind to this receptor with potency equal to or greater than their binding to the 5-HT2A receptor. Safety margins based on typical microdose blood levels are higher than those of known valvulopathogens, but risk is not absent. No animal or clinical studies properly designed to assess this risk exist for the psychedelics, though chronic full-dose MDMA use is associated with valvular heart disease. Further research is needed.

Study at a glance

Abstract

Psychedelic microdosing is the practice of taking very low doses of psychedelic substances, typically over a longer period of time. The long-term safety of chronic microdosing is relatively uncharacterized, but valvular heart disease (VHD) has been proposed as a potential risk due to activation of the serotonin 5-HT 2B receptor. However, this risk has not yet been comprehensively assessed. This analysis searched for all relevant in vitro, animal, and clinical studies related to the VHD risk of lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT), and the non-psychedelic 3,4-methylenedioxymethamphetamine (MDMA). All five compounds and some metabolites could bind to the 5-HT 2B receptor with potency equal to or greater than that of the 5-HT 2A receptor, the primary target of psychedelics. All compounds were partial agonists at the 5-HT 2B receptor with the exception of mescaline, which could not be adequately assessed due to low potency. Safety margins relative to the maximum plasma concentrations from typical microdoses were greater than known valvulopathogens, but not without potential risk. No animal or clinical studies appropriately designed to evaluate VHD risk were found for the four psychedelics. However, there is some clinical evidence that chronic ingestion of full doses of MDMA is associated with VHD. We conclude that VHD is a potential risk with chronic psychedelic microdosing, but further studies are necessary to better define this risk.