The risk of chronic psychedelic and MDMA microdosing for valvular heart disease
Journal of Psychopharmacology – August 12, 2023
Source: OpenAlex
Summary
Chronic microdosing of psychedelics like Lysergic acid diethylamide and Psilocybin may pose a heart valve risk. Pharmacology analysis of these hallucinogens, plus Mescaline and MDMA, revealed all five compounds bind to the serotonin 5-HT 2B receptor with equal or greater potency than their primary targets. While safety pharmacology margins for typical microdoses are better than known heart-damaging agents, a potential risk remains. Forensic Toxicology and Drug Analysis show MDMA's link to valvular heart disease at full doses. This insight into neurotransmitter receptor influence on behavior informs future drug studies and medicine.
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.