Association Between Lifetime Hallucinogen Use and Valvular Heart Disease: Findings from the All of Us Research Program

Recent literature suggests potential associations between hallucinogen use and valvular heart disease (VHD) due to prolonged activation of serotonin 5-HT2B receptors, which may lead to valvular fibrosis – a condition also linked to drugs including fenfluramine and pergolide. Despite these concerns, epidemiological studies exploring this association are lacking. This exploratory analysis investigated associations between lifetime hallucinogen use and VHD using cross-sectional data from US adults with linked electronic health record data in the NIH All of Us Research Program who completed the Lifestyle survey. This survey included questions about lifetime hallucinogen use (lysergic acid diethylamide [LSD], mushrooms/psilocybin, 3,4-Methylenedioxymethamphetamine [MDMA]/ecstasy, ketamine, phencyclidine [PCP]). Multivariable logistic regression models examined the association between hallucinogen use and VHD, adjusting for sociodemographic factors and other confounding health conditions. Our sample comprised 286,842 adults (mean age 50.8 [SD 16.7], 61.4% female, 60.6% White). Among them, 13.2% reported lifetime hallucinogen use. Individuals with lifetime hallucinogen use had lower unadjusted VHD prevalence compared to those without lifetime hallucinogen use (3.6% vs. 4.7%, p < .001). However, after adjusting for confounders, models revealed modestly increased VHD odds (aOR = 1.08, 95% CI: 1.01–1.55, p = .017). This exploratory study found that hallucinogen use was associated with modestly increased VHD odds after adjustment, requiring confirmation through longitudinal research.