Associations between lifetime classic psychedelic use and cardiometabolic diseases

Cardiometabolic diseases such as heart disease and diabetes are major contributors to global morbidity and mortality. While traditional approaches—pharmacological treatments and intensive lifestyle programmes—can modify risk, long-term effects of classic psychedelics on cardiometabolic health have not been examined. Classic psychedelics are defined here as substances acting primarily as agonists at serotonin 2A receptors and include tryptamines (for example DMT, ayahuasca, psilocybin), the lysergamide LSD, and phenethylamines (for example mescaline and mescaline-containing cacti). Prior work has established a favourable safety profile for these compounds in psychiatric contexts and has suggested links to improved physical-health markers, including lower odds of overweight/obesity and hypertension; several mechanistic pathways are plausible, including facilitation of healthful lifestyle change, improvements in comorbid mental health, anti-inflammatory and immunomodulatory effects, and activity at serotonin receptor subtypes implicated in cardiometabolic regulation. Simonsson and colleagues set out to test whether lifetime use of classic psychedelics is associated with lower odds of two cardiometabolic outcomes: medically diagnosed heart disease in the past year and medically diagnosed diabetes in the past year. Using pooled data from the National Survey on Drug Use and Health (NSDUH) for 2005–2014, the investigators hypothesised that people reporting ever having used a classic psychedelic would show lower odds of both heart disease and diabetes within the prior 12 months.

This cross-sectional study used pooled public-use data from the NSDUH survey years 2005–2014, chosen because these were the years containing items on heart disease and diabetes in the past year. The dataset is an annual, nationally representative survey of substance use and selected health measures in the United States. The extracted text does not clearly report the overall sample size in the Methods section, but later text reports 376,207 observations for the heart disease item and 376,167 observations for the diabetes item. The dependent variables were binary indicators derived from the question asking which conditions a doctor or medical professional had told respondents they had in the past 12 months: (1) heart disease and (2) diabetes. The primary independent variable was lifetime classic psychedelic use, coded positive if respondents reported ever having used any of the following: DMT, ayahuasca, LSD, mescaline, peyote, San Pedro, or psilocybin. The investigators also considered subcategories of lifetime use by class: tryptamines (DMT, ayahuasca, psilocybin), LSD, and phenethylamines (mescaline and cactus sources). Control variables included demographic and socioeconomic covariates (age grouped 18–25, 26–34, 35–49, 50–64, 65+; sex; marital status; ethnoracial identity categories; annual household income bands; and detailed educational attainment categories), self-reported engagement in risky behaviour, and lifetime use of other substances (cocaine, marijuana, MDMA/ecstasy, PCP). Missing or non-informative responses such as "Bad Data", "Don't Know", "Refused", and blank were coded as missing. Analyses applied NSDUH-provided weights and were performed in Stata version 17. Descriptive zero-order comparisons were reported, followed by multivariable logistic regression to estimate adjusted odds ratios with 95% confidence intervals for the associations between lifetime classic psychedelic use (and subcategories) and the two cardiometabolic outcomes. Because this was a secondary analysis of public data, the study was exempt from ethical review by the Department of Sociology Research Ethics Committee at the University of Oxford.

Descriptive comparisons indicated substantially lower prevalence of both outcomes among respondents who reported lifetime classic psychedelic use. The prevalence of heart disease and diabetes in the past year among lifetime classic psychedelic users was roughly 51% and 52%, respectively, of the prevalence observed among respondents who had never used a classic psychedelic. The subgroup of respondents who had ever used a tryptamine exhibited even lower relative prevalences: heart disease and diabetes prevalences were about 45% and 41%, respectively, of the prevalences among non-tryptamine users. The paper notes these descriptive relationships do not adjust for potential confounders. Multivariable logistic regression adjusting for the listed demographic, socioeconomic, risk-behaviour, and other lifetime substance-use covariates found that lifetime classic psychedelic use was independently associated with lower odds of both cardiometabolic outcomes. Specifically, lifetime classic psychedelic use was associated with a 23% lower odds of heart disease in the past year and a 12% lower odds of diabetes in the past year, after adjustment. When the three main classes of classic psychedelics (tryptamines, LSD, phenethylamines) were entered simultaneously into the regression models, none of the classes showed a unique statistically significant association with heart disease or diabetes; the association between lifetime tryptamine use and diabetes approached conventional levels of statistical significance. The extracted text does not provide full regression tables in prose, but reports the adjusted percentage reductions described above and the numbers of observations for the two outcomes (heart disease: 376,207 observations; diabetes: 376,167 observations).

The investigators interpret their findings as evidence that lifetime classic psychedelic use is associated with lower odds of medically diagnosed heart disease and diabetes in the past year, suggesting a potential beneficial relationship between classic psychedelic exposure and cardiometabolic health. They situate the results as novel, extending an emerging literature that has linked lifetime classic psychedelic use with more favourable markers of physical health such as lower prevalence of overweight/obesity and hypertension. However, the authors emphasise several important limitations. Chief among these is the cross-sectional design, which precludes causal inference; although regression models adjusted for numerous covariates, unmeasured or latent confounding remains possible (for example, a predisposing factor that both increases likelihood of psychedelic use and promotes salutary lifestyle behaviours). The dataset lacked key details on context of use, dose, and frequency, so the analysis could not explore whether associations vary by these features. Outcome measurement was also limited by broad question wording: the term "heart disease" encompasses many conditions and "diabetes" can denote type 1 or type 2 diabetes or other metabolic disorders, so associations might differ across specific subtypes. Finally, the authors call for further research to investigate potential causal mechanisms, including lifestyle change facilitation, mental-health improvements, anti-inflammatory and immunomodulatory effects, and interactions with serotonin receptor subtypes implicated in cardiometabolic regulation. Overall, the discussion frames the results as hypothesis-generating and advocates for additional research—ideally designs that can address temporality, dose/context effects, and biological mediators—to clarify whether classic psychedelics exert causal effects on cardiometabolic health and, if so, by what pathways.