Association between Lifetime Classic Psychedelic Use and Sick Leave in a Population-Based Sample

Hypertension prevalence and associated costs are increasing globally, driven by multiple modifiable risk factors such as smoking, poor diet, physical inactivity and alcohol use, together with psychosocial contributors including chronic stress, depression and anxiety. Recent work has also implicated low-grade inflammation and serotonergic system alterations in the pathophysiology of hypertension. Although classic psychedelics (serotonin 2A receptor agonists) have been studied primarily for mental health outcomes over the past two decades, emerging evidence suggests these compounds can produce persistent changes in behaviour and mental state that may indirectly affect cardiovascular risk factors, and they may also have immunomodulatory or anti-inflammatory effects relevant to blood pressure regulation. Simonsson and colleagues set out to examine whether lifetime use of classic psychedelics is associated with lower odds of having been told by a medical professional that one had hypertension in the past 12 months. Building on prior population findings that therapeutic associations may differ across psychedelic classes, the investigators also tested whether associations varied by the three main classes of classic psychedelics — tryptamines (DMT, ayahuasca, psilocybin), lysergamides (LSD), and phenethylamines (mescaline, peyote, San Pedro). The authors hypothesised that lifetime classic psychedelic use would be associated with lower odds of recent hypertension, and that tryptamine use would show the strongest association.

The study used pooled cross-sectional data from the US National Survey on Drug Use and Health (NSDUH) for survey years 2005–2014. The analysed sample comprised 381,682 adults aged 18 years or older (unweighted); the data were weighted to be representative of the civilian non‑institutionalised US adult population. The extracted text also contains a secondary unweighted count of 375,362 for some analyses, but it is not clear which specific models, if any, used that smaller number. The primary exposure was lifetime classic psychedelic use, coded positive if a respondent reported ever having used any of the following even once: DMT, ayahuasca, LSD, mescaline, peyote, San Pedro or psilocybin. In secondary analyses the authors evaluated lifetime use of the three main classes separately (tryptamines, LSD, phenethylamines). The dependent variable was a dichotomous indicator of hypertension in the past year, derived from the survey question asking which conditions a doctor or other medical professional had told the respondent they had in the past 12 months. Covariates included age, sex, ethnoracial identity, educational attainment, annual household income, marital status, self‑reported engagement in risky behaviour, lifetime use of a range of other substances (cocaine, other stimulants, sedatives, tranquilizers, heroin, pain relievers, marijuana, PCP, MDMA/ecstasy, inhalants), multiple tobacco use variables (smokeless tobacco, pipe tobacco, cigar use, cigarettes daily) and age of first alcohol use. Lifetime depression and anxiety were included in robustness checks. Analyses used the NSDUH sampling weights and were performed in Stata version 16. The primary analytic approach was weighted logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals. The authors did not apply a correction for multiple comparisons, but reported exact P values to four decimal places.

Weighted descriptive statistics showed that lifetime classic psychedelic use was more common among middle‑aged adults, men, non‑Hispanic White and non‑Hispanic Native American/Alaska Native respondents, individuals with higher education and income, those who were never married or divorced/separated, people reporting higher engagement in risky behaviour, and respondents with lifetime use of other illicit substances and earlier initiation of alcohol use. Lifetime depression and anxiety were also more common among classic psychedelic users. Prevalence estimates indicated that the proportion reporting hypertension in the past year among respondents who had ever used any classic psychedelic was approximately 67% of the prevalence among respondents who had never used a classic psychedelic. For respondents who had ever used a tryptamine (DMT, ayahuasca or psilocybin) the prevalence of past‑year hypertension was about 56% of that among non‑tryptamine users. In adjusted logistic regression (model 1), lifetime classic psychedelic use was associated with lower odds of hypertension in the past year: a 14% reduction in odds (aOR 0.86, 95% CI 0.81–0.91; P<0.0001). In model 2, which evaluated the three psychedelic classes separately, only lifetime tryptamine use showed a significant association with hypertension (aOR 0.80, 95% CI 0.73–0.89; P=0.0001), corresponding to a 20% lower odds; associations for LSD and phenethylamines were not significant in the extracted text. Robustness checks reported 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 that including lifetime depression and anxiety as covariates did not materially change the main findings. The NSDUH only provided recency of use for LSD, and analyses did not find significant associations between recency of LSD use and past‑year hypertension; including LSD recency in models did not substantively alter the main results.

The investigators interpreted their findings as a novel population‑level association between lifetime classic psychedelic use and lower odds of hypertension in the past year, driven primarily by lifetime tryptamine use. They proposed several non‑mutually exclusive mechanisms that could help explain the observed associations: long‑term health behaviour changes following psychedelic experiences (for example improved diet, increased exercise, reduced alcohol use), improvements in mental health and reductions in chronic stress, immunomodulatory and anti‑inflammatory effects of classic psychedelics, and pharmacological actions at serotonergic receptors (notably 5‑HT2A and, for tryptamines, 5‑HT1A) that might influence blood pressure. The authors emphasised that causal inference is limited by the study's cross‑sectional design and self‑reported outcome. They acknowledged the possibility of unmeasured confounding, such as shared factors that predispose individuals both to healthier behaviours and to trying psychedelics. Important data were not available in NSDUH, including contextual details of use (set and setting), dose, frequency, intentions, and psychological support, which precluded analyses of how these factors might relate to blood pressure. The hypertension measure was based on respondents reporting a clinician's diagnosis in the past year rather than clinical blood pressure measurements, which could introduce measurement bias. Given these limitations, the authors framed the results as hypothesis‑generating and called for rigorous randomised controlled trials and prospective studies with clinical blood pressure assessments to test causal pathways and to determine whether effects vary across populations and psychedelic classes.

The study found an association between lifetime classic psychedelic use and 14% lower odds of being told by a medical professional that one had hypertension in the past year, with lifetime tryptamine use showing the strongest association (20% lower odds). The authors conclude that these novel population‑level findings warrant further rigorous research, including randomised trials and clinical measurements, to investigate potential causal effects of classic psychedelics on blood pressure.