Past-Year Hallucinogen Use in Relation to Psychological Distress, Depression, and Suicidality among US Adults

Depressive disorders are common in the United States, affecting over 10% of adults annually and representing a major source of disability, psychological distress, and economic burden. Depression is a strong risk factor for suicidal behaviour, and both depression and suicidality are closely associated with use of psychoactive substances such as alcohol, cannabis, and opioids. In recent years there has been renewed clinical interest in hallucinogens (for example LSD, MDMA, ketamine, and DMT) for treating psychiatric conditions, yet the relationship between non‑medical hallucinogen use and mental health outcomes at the population level remains unclear. Yang and colleagues note that prior epidemiological studies have produced mixed findings, in part because many have considered lifetime use or grouped different hallucinogens together rather than examining recent use of specific substances. To address this gap, the study uses nationally representative US survey data to evaluate how past‑year use of individual hallucinogens is associated with past‑year serious psychological distress (SPD), major depressive episode (MDE), and suicidality in adults aged 18 and older.

The investigators pooled data from the 2015–2020 National Survey on Drug Use and Health (NSDUH), a nationally representative, annual cross‑sectional survey of non‑institutionalised US residents. The analytic sample comprised adults aged 18 and older, with a pooled sample size of N=241,675. Sampling employed a multistage area probability design covering all 50 states and the District of Columbia. Substance use measures included self‑reported lifetime and recency items for several hallucinogens: LSD, salvia divinorum, ecstasy/MDMA, ketamine, and a combined item for DMT/AMT/Foxy. Respondents who reported last using a substance within the past 30 days or within the past 12 months were coded as past‑year users. The authors were unable to assess past‑year use of psilocybin, peyote, or mescaline because NSDUH only asked about lifetime use for those substances. Past‑year use of other drugs (cannabis, cocaine, methamphetamine, heroin) and misuse of prescription tranquilizers/sedatives, stimulants, and opioids were also assessed; misuse was defined as any non‑medical use (for example, without a prescription or in greater amounts than prescribed). Mental health outcomes were derived from NSDUH instruments: serious psychological distress (SPD) was measured using the Kessler‑6 (K6) scale with SPD defined as a K6 score >13; MDE in the past year was coded when participants endorsed at least five of the nine DSM‑IV criteria for a major depressive episode; suicidality was assessed by asking about past‑year suicidal ideation, with follow‑up items on planning and attempts. For analyses, the authors first estimated prevalences and conducted bivariable comparisons using Rao‑Scott chi‑square tests. They then fitted generalised linear models with a Poisson distribution and log link to estimate adjusted prevalence ratios (aPRs) for each outcome. Adjusted models controlled for survey year, sex, age, race/ethnicity, annual household income, education, marital status, and past‑year use of cannabis, cocaine, methamphetamine, heroin, and misuse of prescription tranquilizers/sedatives, stimulants, and opioids.

The pooled sample size was N=241,675 from NSDUH years 2015–2020. In bivariable analyses, the authors report that past‑year use of all examined hallucinogens was associated with increased prevalence of SPD, MDE, and suicidality; however, many of these associations did not persist after covariate adjustment. In multivariable models, several substance‑specific associations remained statistically significant. Past‑year LSD use was associated with higher prevalence of past‑year major depressive episode (aPR=1.23, 95% CI: 1.10–1.37) and suicidal thinking (aPR=1.21, 95% CI: 1.09–1.34). Use of salvia divinorum in the past year was associated with increased likelihood of suicidal thinking (aPR=1.41, 95% CI: 1.00–1.98). The combined DMT/AMT/Foxy category was associated with greater likelihood of suicidal planning (aPR=1.81, 95% CI: 1.17–2.81). By contrast, past‑year ecstasy/MDMA use was associated with lower prevalence of several outcomes: serious psychological distress (aPR=0.83, 95% CI: 0.77–0.89), MDE (aPR=0.91, 95% CI: 0.83–0.99), and suicidal thinking (aPR=0.86, 95% CI: 0.75–0.99). Ketamine showed positive associations in bivariable models, but no statistically significant associations with SPD, MDE, or suicidality were observed in the adjusted multivariable analyses. The models therefore indicate heterogeneity across specific hallucinogens in their population‑level associations with depression and suicidality. The extracted text does not provide full tabulated prevalence estimates or model coefficients beyond those reported above.

Yang and colleagues interpret their findings as evidence that hallucinogens differ in their associations with depression and suicidality when examined individually and using past‑year use measures. The authors note that while bivariable analyses suggested higher risk across all examined hallucinogens, adjustment for sociodemographic and other substance‑use covariates attenuated many associations, leaving substance‑specific patterns: positive associations for LSD, salvia divinorum, and DMT/AMT/Foxy with depression and/or suicidality, and inverse associations for ecstasy/MDMA with several outcomes. Several possible explanations are offered for these patterns. One is a potential direct causal relationship in which particular substances may precipitate adverse psychological or behavioural consequences; the authors point to case reports linking LSD to depression and suicidality and evidence that salvia divinorum and some tryptamines can precipitate psychosis in susceptible users. Hallucinogen persisting perception disorder (HPPD), impaired cognition, and impulsivity are discussed as additional mechanisms that could increase suicide risk for some users. An alternative explanation is self‑medication: adults experiencing depressive symptoms might seek out hallucinogens for perceived therapeutic effects, with media coverage and changing attitudes possibly influencing non‑medical use. Regarding the negative associations for ecstasy/MDMA, the authors suggest these could reflect potential short‑term beneficial effects, or differences in the user population or contexts of use (for example party use), while noting that chronic MDMA use has been linked to depression at the individual level. The investigators acknowledge several limitations. NSDUH data are cross‑sectional and self‑reported, so recall and social desirability bias may affect reporting and no causal or temporal ordering can be established. The survey did not distinguish medical from non‑medical use, excluded institutionalised populations, and did not query past‑year use for some hallucinogens (psilocybin, peyote, mescaline) or the frequency/intensity and reasons for use. The authors contend that a major strength is the large, nationally representative sample allowing investigation of low‑prevalence substances, and they call for future cross‑sectional and longitudinal studies with detailed assessments of frequency, intensity, and motivations for use to better understand the observed associations and potential risk factors for hallucinogen use among adults with psychiatric symptoms.