Cardiac Consequences Associated with Psychedelic Use: A Systematic Review of Lysergic Acid Diethylamide, 3,4-Methylenedioxymethamphetamine, and 5-Hydroxytryptamine 2B-Mediated Valvular Heart Disease.
Pharmacopsychiatry February 5, 2026 Tianyi Xu, Sabrina Wong, Gia Han Le et al.
Lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine activate the 5-hydroxytryptamine 2B receptor, a pathway known to cause drug-induced valvular heart disease. This systematic review of 17 studies found no research on psilocybin, dimethyltryptamine, or mescaline. Both lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine show high or moderate affinity for this receptor and promote signaling linked to fibrotic changes in heart valve tissue. In vivo studies confirm serotonin-induced valvulopathy, and chronic 3,4-methylenedioxymethamphetamine use has been associated with valve abnormalities in humans. No clinical cases of lysergic acid diethylamide-induced valvulopathy have been reported, but preclinical data suggest potential for fibrotic signaling under sustained exposure. Preliminary evidence supports the need for cardiac safety monitoring in psychedelic research.