Despite the multifaceted structural and social inequities that shape poor mental health burden among marginalised and street-involved sex workers, there remains a paucity of data on suicide rates and research that systematically examines factors that potentiate or mitigate suicidality among sex workers, particularly in the global north. Some evidence suggests that psychedelic drug use may be protective with regard to suicidality 33–35 and is associated with significant improvements in psychological well-being and reductions in depression and anxiety in clinical settings, 36–41 yet existent research is characterised by large gaps. Given the urgency of addressing and preventing suicide and calls for prioritising innovative interventions, this study aimed to longitudinally investigate whether lifetime psychedelic drug use is associated with a reduced incidence of suicidality (suicide ideation or attempts) among a community-based prospective cohort of marginalised women. We postulated that psychedelic drug use would have an independent protective effect on suicidality over the study period.

A number of psychedelic drug therapies are being revisited following a 40-year hiatus in research into their potential for the treatment of depression, anxiety, PTSD, eating disorders and addiction. 23 Psychedelic drugs include the classic serotonergic psychedelics or ‘hallucinogens’ lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine and mescaline, as well as the ‘enactogen’ or ‘empathogen’ methylenedioxymethamphetamine (MDMA), 23–25 all of which are being investigated in clinical/preclinical studies for their neuropharmacological functions and potential as adjuncts to psychotherapy. 26–28 While renewed interest in psychedelic medicine is challenged by various funding and methodological and legal impediments, the emerging evidence indicating improved outcomes for some individuals suffering from mental health and addiction issues has generated new scientific inquiry and an imposing obligation to advance this research. 23 29 30 Recent observational studies in the USA demonstrate significant associations between lifetime psychedelic use and reduced recidivism and intimate partner violence among populations of prison inmates 31 32 and reduced psychological distress and suicidality among the general adult population. 33–35

Various biological, interpersonal and sociostructural factors (eg, social exclusion/isolation, education level and employment) contribute to our understanding of suicidal behaviours. 1 19 While evidence has demonstrated that some forms of cognitive behavioural therapy and pharmacological interventions may reduce suicidality, the literature is hampered by publication bias and significant heterogeneity of strategies and outcome measures. 14 20 Due to ethical challenges and limitations to studying suicide and its proxies (ie, ideation and attempts), there remains a paucity of evidence from randomised controlled trials to support the efficacy of prevention interventions. 20 Researchers have largely focused on examining suicidality outcomes (rather than suicide itself), which may not be fully generalisable to understanding suicide or accurately evaluating treatment approaches. 21 Furthermore, stigma continues to hinder research and reporting of suicidality. 21 There remains an urgency to better understand pathways to suicidality, with literature highlighting the need for innovative psychological and psychosocial treatments 14 and tailored intervention approaches for key marginalised populations. 20 21 Given the complex aetiological pathways to suicide and limited effectiveness of well-established evidence-based interventions to reduce the burden of suicidality, the US National Institute of Mental Health has called for innovative research on suicide prevention and treatment for suicidality. 22

Despite efforts to improve mental health over the last 60 years, suicide remains a critical public health concern worldwide. 1 2 Suicide was the second leading cause of death globally in 2012 among individuals aged 15–29 years, 2 with an estimated 80%–90% of suicide deaths attributable to mental health or substance use disorders. 3 4 Significant gaps remain in empirical research examining suicidality among marginalised populations. Marginalised women, such as sex workers who are street involved or use drugs, experience disproportionately high levels of social and health-related risks and harms, including stigma, discrimination and violence 5–7 as a result of dynamic structural drivers including poverty, criminalisation and racism. While sex workers are a diverse population working from indoor in-call and out-call venues to street-based settings, previous studies highlight substantial unmet mental health needs of more marginalised and street-involved sex workers. Studies among street-based sex workers and those who use drugs underscore the associations of social exclusion, depression and post-traumatic stress disorder (PTSD) with suicidality. 8–12 Research demonstrates greater risk for suicidality among those with a history of trauma 1 13 14 and among street-involved sex workers who report historical experiences of violence and childhood abuse. 8–10 15 16 Furthermore, indigenous women are vastly over-represented among street-based sex workers in North America and face devastating and multigenerational effects of trauma and socioeconomic dislocation (eg, high burden of mental illness and suicidality) as a result of colonialism, racialised policies and displacement from land and home communities. 17 18

Using extended Cox regression, unadjusted hazard ratios (HR) and adjusted hazard ratios(AHR) and 95% CI were calculated to identify predictors of suicidality. Psychedelic drug use, hypothesised a priori to be a predictor of suicidality, and variables that were significantly correlated with the outcome at the p<0.10 level in bivariate analyses were subsequently fitted into a multivariable Cox model. Backward model selection was used to determine the final multivariable model with the best overall fit, as indicated by the lowest Akaike information criterion value. A complete case analysis was used, where observations with missing data were excluded from analyses, and participants who were lost to follow-up were right censored at their most recent study visit. All statistical analyses were performed using SAS software V.9.4. Two-sided p values are reported.

The outcome of interest was a first episode of suicidality, defined as responding ‘yes’ to having thought about or attempted suicide in the last 6 months. Time-fixed variables examined included age (continuous), gender/sexual minority (lesbian, gay, bisexual, trans or two-spirit), indigenous ancestry (inclusive of First Nations, Métis, and Inuit), being an immigrant/migrant worker (vs Canadian born), education (high school or greater) and physical and/or sexual childhood abuse (before age 18 years). Variables treated as time-updated covariates based on biannual follow-up data included HIV/STI serostatus, recent homelessness, recent physical and/or sexual violence by clients, recent police harassment and/or arrest and primary place to solicit clients in the last 6 months. Time-updated injection and non-injection drug use variables included lifetime use of psychedelics (including LSD/acid, magic mushrooms/psilocybin, ecstasy/MDMA), cannabis, pharmaceutical opioids (any street methadone/suboxone, dilaudid, morphine, oxycontin, percocet/vicodin/demerol or T3s/T4s), crack, cocaine, crystal methamphetamine and heroin.

To capture initial episodes of suicidality, analyses for this study were restricted to AESHA participants who had never thought about or attempted suicide at baseline and completed at least one follow-up visit between January 2010 and August 2014. Those with missing observations for suicidality at baseline (n=50/766; 6.5%) were excluded from analysis, and one additional participant was excluded because reported suicidality was missing at follow-up.

The main interview questionnaire elicits responses related to sociodemographics (eg, sexual and gender identities, ethnicity and housing), the work environment (eg, access to services, violence/safety, policing and incarceration), client characteristics (eg, types/fees of services and male condom use), intimate partners (eg, sexual history, cohabitation and financial support), trauma and violence (eg, lifetime and childhood trauma and exposure to intimate partner and workplace violence) and comprehensive injection and non-injection drug use patterns. The clinical questionnaire relates to overall physical, mental and emotional health, and HIV testing and treatment experiences to support education, referral and linkages with care. The research team works in close partnership with the affected community and a diversity of stakeholders (eg, legal/human rights experts, community-based organisations, service providers, health authorities, government officials and international policy bodies) and regularly engages in knowledge exchange efforts. AESHA is monitored by a Community Advisory Board of over 15 sex work, women’s health and HIV service agencies, as well as representatives from the health authority and policy experts, and holds ethical approval through Providence Health Care/University of British Columbia Research Ethics Board. All participants receive an honorarium of $C40 at each biannual visit for their time, expertise and travel.

Data for this study were drawn from a large, community-based, prospective cohort of women sex workers initiated in 2010, known as An Evaluation of Sex Workers Health Access (AESHA). Eligibility criteria for study participants included cisgender or transgender women, 14 years of age or older, who exchanged sex for money within the last 30 days. AESHA participants completed interviewer-administered questionnaires and HIV/sexually transmitted infection (STI)/hepatitis C virus (HCV) serology testing at enrolment and biannually. Experiential staff (current/former sex workers) are represented across interview, outreach and nursing teams, including coordinators with substantial community experience. Participants were recruited across Metro Vancouver using time–location sampling and community mapping strategies, with day and late-night outreach to outdoor sex work locations (ie, streets and alleyways), indoor sex work venues (ie, massage parlours, microbrothels and in-call locations) and online. Weekly outreach by experiential staff is conducted to over 100 sex work venues by outreach/nursing teams operating a mobile van, with regular contact as well as encouraging drop-in to women-only spaces at the research office, contributing to an annual retention rate of >90% for AESHA participants.

Over half of participants reported ever using crack (63%, n=184) or cocaine (56%; n=162), with higher proportions of crack and cocaine use among those reporting suicidality than those who did not (p=0.003). Close to half (49%, n=141) reported lifetime heroin use, which was significantly higher among those who reported suicidality than those who did not (68% vs 46%, p=0.02). Approximately one-third (31%, n=90) of participants had ever used crystal methamphetamine, and this was significantly higher among those who reported suicidality than those who did not (58% vs 28%, p<0.001). Overall, 27% (n=79) of participants reported ever using a psychedelic substance, and of those, 75% (n=59) had used MDMA/ecstasy, 35% (n=28) had used LSD/acid and 30% (n=24) had used psilocybin/magic mushrooms.

Overall, 11% (n=31) thought about or attempted suicide for the first time during follow-up, with 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) and 16% (n=45) of participants identified as gender or sexual minorities. One-third (n=93) identified as indigenous and one-quarter (n=73) had been homeless in the last 6 months. Half of the participants (49%; n=142) solicited clients on the streets, and 37% (n=106) solicited clients in indoor establishments. In terms of workplace violence and harassment, 14% (n=41) and 37% (n=107) reported recent exposure to physical and/or sexual violence from clients/dates and recent police harassment without arrest, respectively. Nearly half (47%; n=136) of participants reported ever being physically and/or sexually abused before age 18 years, and among those who reported suicidality, 77% (n=24/31) experienced childhood abuse compared with 43% (n=112/259) among those who did not report suicidality (p<0.001).

Of the total 766 women who completed the baseline questionnaire, 46% (n=355) reported ever experiencing suicidality (45%; n=343 reported suicidal thoughts, 32%; n=245 attempted suicide) and were thus excluded from this analysis. A total of 290 women without suicidality who completed at least one follow-up visit were eligible for inclusion in the present analysis. Participants were followed for a total of 53.5 months (median=29.9 months). Baseline characteristics of participants who reported suicidality during follow-up compared with those who did not are displayed in table 1 .

Discussion

This study demonstrated that among marginalised women, many of whom are street-involved and experience a disproportionate burden of violence, trauma, psychological distress and suicide, naturalistic psychedelic drug use predicted a significantly reduced hazard for suicidality. Crystal methamphetamine use and childhood abuse predisposed women to suicidality corresponding to more than a threefold increased hazard. Suicidality was highly prevalent, with almost half of women reporting lifetime suicidality at baseline, and 11% reporting a first episode of suicidality in the last 6 months during follow-up. Few studies have longitudinally examined predictors of suicidality among marginalised sex workers, and of the available data, most are cross-sectional and/or conducted in lower-income and middle-income settings.8 16 42 43 The present study, based on a community-based, prospective cohort of marginalised women, adds to a growing body of literature documenting the protective and therapeutic potentials of psychedelic substances.23 29 39 44 45

Data were self-reported, and questions pertaining to events that occurred in the past may be subject to recall bias. Variables examined included sensitive and highly stigmatised topics such as childhood trauma, violence and illicit drug use, which introduce the potential for social desirability and reporting bias. However, the likelihood of these biases is reduced by the community-based nature of the study. While lifetime psychedelic drug use was found to reduce the hazard of suicidality, the associations uncovered in this analysis cannot be determined as causal. However, the use of Cox regression analysis in this study was able to determine a temporal relationship between psychedelic use and suicidality. The sample was restricted to participants who had not experienced suicidal ideation or attempt at baseline, ensuring that psychedelic use preceded suicidality and thus providing evidence that psychedelics have a protective effect. Due to a lack of statistical power, analyses evaluating the effects of more nuanced indicators of psychedelic use (eg, frequency of use or recent use), as well as separate analyses for ideation and attempt outcomes, were not feasible. Further examination of these variables would certainly be interesting and important in future analyses with additional data from follow-up questionnaires. Suicidality is influenced by complex individual, interpersonal and structural variables, and not all potential confounding variables could be controlled for in this study. For example, women who use psychedelics may also possess some characteristic(s) associated with a reduced likelihood of being suicidal (eg, openness to experience, curiosity or spirituality), which were not examined in this study. Despite the relative safety of psychedelic drug use as evidenced from the clinical and non-clinical literature,36 46–49 it should be noted that the use of psychedelics, particularly with unknown doses sourced from unregulated street markets, is not without risk, highlighting the importance of set and setting23; the doses and contexts of psychedelic use among women in the present study could not be determined. The SE for the association between psychedelic use and suicidality was somewhat high, resulting in a wider CI. However, a large and significant protective effect was demonstrated in multivariable analysis, despite the relatively small number of events for suicidality over follow-up. With a larger sample size, we would expect a narrower CI for this association. The study population included women from a wide-ranging representation of sex work environments, yet findings may not be fully generalisable to sex workers in other settings. The mapping of working areas and time–location sampling helped to ensure a representative sample and to minimise selection bias.

To the best of our knowledge, this study is the first to longitudinally investigate associations with suicidality among marginalised and street-involved sex workers in North America and builds on prior cross-sectional research highlighting significantly elevated rates of suicidality and unmet mental health needs in this population. For example, a study conducted in Sydney, Australia demonstrated significant links between depression, trauma, and suicidality, where an estimated 42% of street-based female sex workers reported attempting suicide and 74% reported lifetime suicidal ideation.10 42 While estimates of mental illness vary significantly across sex work settings, up to three-quarters of street-involved and drug-involved sex workers in a US study reported severe depression, anxiety or PTSD.12 Notably, our study demonstrated a lower risk of suicidality among women working indoors in bivariate analysis (HR 0.19, p=0.009), lending support to the critical role of safer workplace environments in mitigating risk. In studies conducted in Asia, recent suicide attempts ranged from 19% among sex workers in Goa, India16 to 38% among sex workers in China,8 11 50 many of whom work in marginalised settings with few workplace protections. Transgender women involved in sex work, a subpopulation experiencing significant psychosocial vulnerability and discrimination, report notably further elevated rates of suicidality: three-quarters of participants in San Francisco reported suicide ideation, of whom 64% attempted suicide.51 The global evidence is unequivocal that in settings where sex work is criminalised, sex workers are unable to access essential social, health and legal protections (eg, against violence), highlighting the need for structural (eg, decriminalisation) and community-led interventions to improve health and human rights.5 A structural approach to mitigating suicidality risk requires a reform of laws and policies that perpetuate stigma, discrimination, violence and unequal access to health and social supports among sex workers. Increased support for community-driven interventions that are gender and culturally appropriate are urgently needed, and any clinical treatment utilising psychedelics must be developed alongside sex worker-led interventions and community empowerment.

Our findings extend on research on associations between lifetime use of illicit drugs and increased risk for suicidality: in bivariate analysis, all classes of illicit drugs were demonstrated to increase the hazard of suicidality with the exception of psychedelics. In multivariable analysis, psychedelics were independently associated with a 60% reduced hazard for suicidality, contributing to emergent evidence on the potential of psychedelics to mitigate risks for suicide.

Among the various scientific studies examining the potential benefits of psychedelic drug use, a recent and large (n>190 000) population study conducted among adult respondents in the USA demonstrated that psychedelics are associated with reduced psychological distress and suicidality.33 A recent open-label trial conducted in the UK demonstrated the safety and efficacy of psilocybin for treating major depression,36 and another open-label trial in Brazil found rapid and sustained antidepressant effects from the Amazonian psychedelic brew ayahuasca administered in a clinical setting.38 The ways in which psychedelics may alleviate suffering associated with some mental illness is undoubtedly a complex phenomenon. It has been hypothesised that psychedelics modify neurobiological processes that may be involved in suicidality by downregulating 5-HT 2A serotonin receptors, as increased binding (and upregulation) of this receptor has been implicated in major depression and suicide.39 45 52 Furthermore, there is evidence that psychedelics alter neural network connectivity and enhance recall of autobiographical memories, which may facilitate positive reprocessing of trauma.26 53 54 Recent randomised, placebo-controlled, crossover studies found that psilocybin (among n=25 adults) and LSD (among n=20 adults) were associated with increased positive mood and psychological well-being,37 39 supporting other work demonstrating the antidepressive/anxiolytic effects of psychedelics.27 40 46 55 The potential of psychedelics to elicit ‘mystical-type’ experiences, with profound and sustained positive changes in attitudes and mood, may play a key role in addiction treatment interventions.41 45 56 57 For example, psilocybin-assisted psychotherapy demonstrated high success in smoking cessation outcomes at 6 months follow-up (abstinence rates of 80%), and mystical experiences generated from the psilocybin sessions were significantly correlated with elevated ratings of personal meaningfulness, well-being and life satisfaction.58 Randomised control trials in the USA and Switzerland have demonstrated significant long-term improvements among patients with treatment-resistant PTSD following MDMA-assisted psychotherapy,28 59 and further research is continuing in an international multisite phase t3 clinical trial.

Marginalised and street-based sex workers experience complex and synergistic effects between trauma, lack of workplace safety and mental health/substance use comorbidities that elevate risk of suicidality. Marginalised women and sex workers who use drugs report high rates of childhood abuse,60–62 which is associated with an increased likelihood of experiencing subsequent physical or sexual violence, as well as initiating injection drug use.63–65 For those suffering from emotional trauma stemming from violence, including indirect violence (ie, witnessing violence), there may be a proclivity to use drugs for self-medication.66 67 Violence and sexual coercion have been found to be significantly associated with suicidality among sex worker populations in China and India.8 9 16 68 As demonstrated in this study, having an early traumatic life event is a key risk factor for suicide among sex workers, a high proportion of whom are Indigenous, and experiencing historical trauma can have harmful intergenerational impacts.1 17 Given that historical experiences of violence and trauma denote significant risk for suicide, there is an urgent need to provide integrated, trauma-informed intervention services for sex workers and other marginalised populations. Currently available interventions and pharmacological treatments for suicidality show limited efficacy, and concerted efforts should be made to increase access to evidence-based treatments and to explore alternative approaches to improving mental health and well-being. Emerging research and evidence show positive outcomes with psychedelic-assisted treatments, which have demonstrated an excellent record of safety with few to no serious adverse effects reported.1 This study suggests psychedelic substances may hold promise as useful tools in addressing mental health issues and remediating risks for psychological distress and suicide.