Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

Argento and colleagues frame suicide as a persistent global public health problem, with particular severity among marginalised populations such as street-involved and drug-using women who exchange sex. Earlier research has highlighted elevated rates of depression, post-traumatic stress disorder and suicidality in these groups, and has linked suicidality to a complex interplay of biological, interpersonal and sociostructural drivers including childhood trauma, violence, social exclusion and criminalisation. The literature on effective prevention and treatment is limited by heterogeneity, publication bias and ethical constraints on suicide research, leaving a need for innovative approaches tailored to vulnerable populations. Against this background, the study investigates whether lifetime use of psychedelic drugs is associated with a reduced incidence of suicidality (defined as suicidal ideation or attempts) in a community-based prospective cohort of marginalised women in Metro Vancouver, Canada. The authors hypothesised that psychedelic drug use would have an independent protective effect over the observation period, and positioned the work amid renewed clinical and observational interest in psychedelic substances for mood, trauma and addiction-related conditions.

The analysis used data from AESHA, a large community-based prospective cohort of women sex workers established in 2010. Eligibility for AESHA included cisgender or transgender women aged 14 years or older who had exchanged sex for money in the previous 30 days. Participants completed interviewer-administered questionnaires and serological testing for HIV/STI/HCV at enrolment and then biannually; outreach and peer-experiential staff supported recruitment and retention. For this study, analyses were restricted to participants who reported no lifetime suicidal ideation or attempts at baseline and who completed at least one follow-up visit between January 2010 and August 2014. The primary outcome was a first episode of suicidality during follow-up, measured by a self-report question on thinking about or attempting suicide in the preceding 6 months. Key exposures included lifetime use of psychedelics (specified to include LSD, psilocybin and MDMA/ecstasy) and a range of other time-fixed and time-updated covariates: sociodemographics (age, gender/sexual minority status, indigenous ancestry, immigrant/migrant status, education), childhood physical and/or sexual abuse, recent homelessness, recent client-perpetrated violence, police harassment/arrest, solicitation venue and various injection and non-injection drug use variables. Statistical analysis employed extended Cox proportional hazards regression, which allows inclusion of time-updated covariates, to estimate unadjusted and adjusted hazard ratios (HR; a time-to-event measure). Psychedelic use was specified a priori as an exposure of interest. Variables associated with the outcome at p<0.10 in bivariate testing, together with psychedelic use, were entered into multivariable models; backward selection using the Akaike information criterion identified the final model. The study used a complete case approach, excluding observations with missing data, and right-censored participants lost to follow-up. Analyses were conducted in SAS v9.4; two-sided p values are reported.

From 766 women who completed the baseline questionnaire, 355 (46%) reported lifetime suicidality and were excluded. The analytic sample comprised 290 women without baseline suicidality who had at least one follow-up visit; participants contributed a total of 53.5 months of follow-up (median 29.9 months). During follow-up, 31 participants (11%) experienced a first episode of suicidality, producing an incidence density of 4.42 per 100 person-years (95% CI 3.10 to 6.30). The median age was 36 (IQR 29–42); 16% identified as gender or sexual minorities, 33% as indigenous, and 25% reported homelessness in the last 6 months. Nearly half solicited clients on the street and 37% in indoor venues. Childhood physical and/or sexual abuse was reported by 47% of the sample and was more common among those who developed suicidality (77% vs 43%, p<0.001). Lifetime substance use was common: 63% reported ever using crack, 56% cocaine, 49% heroin and 31% crystal methamphetamine. Overall, 27% reported ever using a psychedelic substance; among these, the majority reported MDMA/ecstasy (75%), with other psychedelics also reported though the extracted text truncates the full breakdown. In bivariate analyses, most classes of illicit drugs were associated with increased hazard of suicidality except psychedelics. In multivariable extended Cox regression, lifetime psychedelic drug use was associated with a substantially reduced hazard for incident suicidality (adjusted HR 0.40; 95% CI 0.17 to 0.94), indicating a 60% lower hazard compared with those who had never used psychedelics. Crystal methamphetamine use (adjusted HR 3.25; 95% CI 1.47 to 7.21) and childhood physical/sexual abuse (adjusted HR 3.54; 95% CI 1.49 to 8.40) remained independent predictors associated with more than a threefold increased hazard. The extracted text does not provide the complete list of covariates in the final multivariable model or full model fit statistics beyond the reported adjusted HRs and confidence intervals.

Argento and colleagues interpret their findings as evidence that naturalistic lifetime psychedelic use was independently associated with a reduced hazard of incident suicidality among marginalised women, while crystal methamphetamine use and childhood abuse increased suicide risk. The authors emphasise the high prevalence of suicidality in this population—almost half reporting lifetime suicidality at baseline and 11% experiencing a first episode during follow-up—and position their results within growing observational and clinical literature suggesting therapeutic potential for psychedelics in mood and trauma-related disorders. Limitations acknowledged by the investigators include reliance on self-reported data for highly stigmatised experiences, which may introduce recall, social desirability or reporting bias, and the observational design, which precludes causal inference despite temporal ordering ensured by excluding individuals with baseline suicidality. The authors note limited statistical power to examine frequency, recency or dose/context of psychedelic use and to separate ideation from attempts, and they recognise potential unmeasured confounding (for example, personality traits or spirituality) that might explain both psychedelic use and lower suicidality. Additionally, the extraction did not contain detailed information on the doses or settings of psychedelic use among participants, which the authors state are important given the role of 'set and setting' in safety and outcomes. In terms of implications, the paper calls for further investigation into the therapeutic utility of psychedelics for mental health and suicide prevention, while underscoring the need for trauma-informed, community-led and structural interventions to address the high burden of suicidality among sex workers. The authors also highlight the importance of safer work environments, noting a lower risk of suicidality among women working indoors in bivariate analysis, and argue that any clinical development of psychedelic-assisted treatments should be co-developed with affected communities.

The authors conclude that the high rate of suicidality observed among marginalised women is a critical public health concern. Their longitudinal analysis indicated that naturalistic lifetime psychedelic use was independently associated with reduced incidence of suicidal ideation or attempts, whereas other illicit drug use and childhood trauma increased suicide risk. While stressing the observational nature of the findings and the need for further research, Argento and colleagues suggest that these results support continued investigation into psychedelic-assisted approaches alongside community-driven, trauma-informed interventions to improve mental health and reduce suicidality in vulnerable populations.