Association Between Lifetime Hallucinogen Use and Valvular Heart Disease: Findings from the All of Us Research Program
This study addressed a major safety question in psychedelic medicine: whether lifetime use of hallucinogens is associated with an increased risk of valvular heart disease (VHD), a concern because some serotonergic drugs can activate the 5-HT₂B receptor, which has been linked to heart valve damage.
The researchers analyzed data from the large U.S. All of Us Research Program cohort.
Lifetime hallucinogen use was associated with a small increase in the odds of valvular heart disease after statistical adjustment, but the effect was weak, observational, and based on a highly heterogeneous exposure measure.
It is also worth highlighting that “Hallucinogen use" was a single pooled category
LSD
Psilocybin/mushrooms
MDMA/ecstasy
Ketamine
PCP
were all grouped together. The study cannot tell which substance, if any, was driving the association. No dose or frequency information available. It was cross-sectional design—the study cannot establish causation and it cannot determine whether hallucinogen use preceded the heart valve diagnosis
The effect size was very small - An adjusted odds ratio of ~1.08 is close to null and vulnerable to residual confounding.
Abstract
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.
Kevin H. Yang, Miranda Rasmussen, et al. (2026). Association Between Lifetime Hallucinogen Use and Valvular Heart Disease: Findings from the All of Us Research Program. Journal of Psychoactive Drugs. Published online May 18, 2026. Read Paper
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