Association Between Lifetime Classic Psychedelic Use and Hypertension in the Past Year

Hypertension is increasing globally and arises from complex interacting factors, including lifestyle risks (smoking, diet, physical inactivity, alcohol) and psychosocial contributors such as chronic stress and internalising disorders. Emerging evidence implicates low-grade inflammation and alterations of the serotonin system in hypertension pathophysiology. Classic psychedelics, serotonin 2A receptor agonists that have been the subject of renewed clinical research for mental health, are thought to produce durable changes in behaviour and mood that could plausibly influence cardiovascular risk factors, yet their long-term effects on blood pressure have not been established. Simonsson and colleagues set out to examine whether lifetime use of classic psychedelics is associated with lower odds of having hypertension in the past year. The investigation used pooled US population survey data to test two hypotheses: that lifetime classic psychedelic use (ever vs never) would be associated with reduced odds of past-year hypertension, and that among major psychedelic classes (tryptamines, lysergamides [LSD], and phenethylamines) lifetime tryptamine use would show the strongest association.

The study analysed pooled data from the National Survey on Drug Use and Health (NSDUH) for the years 2005–2014, a nationally representative annual survey of the civilian non-institutionalised US population. The extracted text reports an unweighted total sample of 381,682 adults aged 18 years or older; a later fragment in the extraction references 375,362 unweighted observations for some analyses, and the text does not clearly reconcile this discrepancy. Survey weights provided by NSDUH were used so results are presented as population-representative estimates. The primary dependent variable was self-reported hypertension in the past 12 months, derived from the question asking which conditions a doctor or medical professional told the respondent they had in the past year. The main independent variable was lifetime classic psychedelic use, coded positive if the respondent reported ever using any of the following even once: N,N-dimethyltryptamine (DMT), ayahuasca, LSD, mescaline, peyote, San Pedro, or psilocybin. The authors also examined lifetime use by psychedelic class: tryptamines (DMT, ayahuasca, psilocybin), lysergamide (LSD), and phenethylamines (mescaline, peyote, San Pedro). Covariates included demographic factors (age, sex, ethnoracial identity, educational attainment, annual household income, marital status), self-reported engagement in risky behaviour, lifetime use of multiple other substances (cocaine, other stimulants, sedatives, tranquilizers, heroin, pain relievers, marijuana, phencyclidine, MDMA/ecstasy, inhalants), several forms of tobacco use (smokeless, pipe, cigar, daily cigarettes), and age at first alcohol use. Mental health history (lifetime depression and anxiety) was included in robustness checks and additional models. Analyses consisted of weighted descriptive statistics and multivariable logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals for the association between lifetime psychedelic use and past-year hypertension. Two regression specifications are described: model 1 for any lifetime classic psychedelic use, and model 2 for lifetime use by psychedelic class. The authors report using Stata version 16 and note that no adjustment for multiple comparisons was made, although exact P values are reported.

Descriptive results indicated that lifetime classic psychedelic use was more common among middle-aged adults, men, non-Hispanic White and non-Hispanic Native American/Alaska Native respondents, people with higher education and income, those who had never married or were divorced/separated, respondents reporting greater engagement in risky behaviour, and those reporting lifetime use of a range of other illicit substances and tobacco types. Lifetime psychedelic users were also more likely to report first alcohol use before age 20 and to have a history of depression or anxiety. Prevalence estimates in the extracted text show that the prevalence of past-year hypertension among respondents who had ever used a classic psychedelic was approximately 67% of the prevalence among respondents who had never used one; for lifetime tryptamine users the prevalence was approximately 56% of that among non-tryptamine users. In multivariable logistic regression adjusted for the covariates listed above, lifetime classic psychedelic use was associated with lower odds of past-year hypertension (adjusted odds ratio 0.86, 95% CI 0.81–0.91; P<0.0001), corresponding to a 14% lower odds. When examining psychedelic classes, only lifetime tryptamine use showed a statistically significant association with past-year hypertension (adjusted odds ratio 0.80, 95% CI 0.73–0.89; P=0.0001), corresponding to a 20% lower odds. Lifetime LSD use and lifetime phenethylamine use were not significantly associated with past-year hypertension in the adjusted models. Robustness checks reported in the extraction indicated that the association between lifetime classic psychedelic use and past-year hypertension was broadly similar among respondents with and without histories of depression or anxiety, and including mental health history as covariates did not materially change the main findings. The NSDUH only provided recency of use for LSD, and analyses found no significant association between recency of LSD use and past-year hypertension; including recency of LSD use in models did not alter the principal results.

The authors interpret the findings as novel population-level associations between lifetime classic psychedelic use and lower odds of past-year hypertension, with the signal concentrated in lifetime tryptamine users. They suggest several possible explanations for these associations: psychedelic-induced changes in health-related behaviour (for example, improvements in diet, exercise, and reductions in alcohol use reported in prior qualitative and clinical research), improvements in mental health and reductions in chronic stress, anti-inflammatory and immunomodulatory effects attributed to classic psychedelics, and pharmacological actions at serotonin receptors (noting serotonin 2A affinity generally and serotonin 1A activity for some tryptamines) that might plausibly influence blood pressure. The discussion emphasises caution about causal inference. The cross-sectional design prevents establishing temporality or causality, and unmeasured confounding is possible (for example, factors that predispose individuals both to healthier lifestyles and to psychedelic use). The authors also note limitations of the NSDUH data: absence of detail on set and setting, dose, frequency, intentions or psychological support for psychedelic use, and reliance on self-report of a medical professional's diagnosis for the hypertension outcome rather than clinical blood pressure measurements. The authors recommend future research using rigorous randomised controlled trials and studies with objective blood pressure measures to clarify causality and underlying mechanisms, as well as investigations of whether effects vary across different populations and psychedelic classes.

Simonsson and colleagues conclude that lifetime classic psychedelic use was associated with lower odds of past-year hypertension in this large, US population-representative survey, and that lifetime tryptamine use showed the strongest association among psychedelic classes. They argue these findings are preliminary and primarily hypothesis-generating, underscoring the need for rigorous randomised trials and clinical studies to investigate potential causal pathways and to assess clinical blood pressure outcomes.