Acute and enduring effects of naturalistic psychedelic use among Indigenous peoples in Canada and the United States

De La Salle and colleagues situate this study within growing interest in psychedelic-assisted therapies alongside a recognition that Indigenous peoples of North America have long-standing relationships with psychedelic plant medicines and also face pervasive, racially based trauma. Earlier research has shown beneficial effects of psychedelics for conditions such as depression, anxiety, PTSD-like syndromes, and substance misuse, and recent cross-sectional work in people of colour linked acute psychedelic experiences to reductions in racial trauma symptoms. However, modern psychedelic clinical research has had limited representation of Indigenous participants and has not specifically examined psychedelic effects on racial trauma within Indigenous communities. This study therefore set out to examine whether recalled changes in mental health and trauma-related symptoms (comparing the 30 days before versus 30 days after a memorable naturalistic psychedelic experience) were associated with substance type, country of residence, residency on Tribal lands/reservations/reserves, strength of ethnic identity, severity/frequency of discrimination-related stress, and participant sex in a sample of self-identified Indigenous adults in Canada and the United States. The work also aims to frame considerations for culturally respectful research and policy concerning psychedelic medicines for Indigenous peoples.

The investigators used a cross-sectional, internet-based survey drawn from a larger observational study of nonclinical psychedelic use among people of colour. Recruitment and survey administration were performed via Qualtrics panels; responses were anonymous and participants received compensation. From the larger sample, after exclusions for poor or inconsistent responding, 66 participants who self-identified as Native or Indigenous comprised the analytic subsample. Inclusion required having taken a dose of a psychedelic that produced moderate-to-strong psychoactive effects and that the participant believed had contributed to relief from the challenging effects of ethnic discrimination. Demographic data (age, sex, ethnicity, country, education, income, Tribal/residency status) and details of the most memorable psychedelic experience were collected (substance type, route, dose category, co-administration, duration, and age at experience). Participants were asked to recall a single most memorable experience that they judged to have helped relieve the effects of ethnic discrimination and to report symptom levels for the 30 days before and the 30 days after that experience. Validated self-report instruments were used to assess constructs of interest: a modified General Ethnic Discrimination Scale (GEDS) for frequency and stress of discrimination, the six-item Multigroup Ethnic Identity Measure (MEIM-6), the Acceptance and Action Questionnaire II (AAQ-II) for psychological flexibility, shortened AUDIT-C and DUDIT-C for alcohol and drug use, the DASS-21 for depression, anxiety and stress, and the Trauma Symptoms of Discrimination Scale (TSDS) for discrimination-related trauma symptoms. Internal consistencies (Cronbach's alpha) for these scales in this sample were reported as acceptable to excellent. Statistical analyses were conducted in SPSS v25. Change scores were computed as 30 days post minus 30 days pre for each measure; normality was checked with Shapiro-Wilk. Because AAQ and substance-use change scores were non-normal, nonparametric Kruskal-Wallis tests were used for those measures, while one-way ANOVAs were used for normally distributed change scores. Between-subjects factors included substance consumed (three largest categories: psilocybin, LSD, MDMA), country (Canada, United States), residency on Tribal lands/reserve (Yes/No), and participant sex. Bonferroni-corrected post hoc tests followed significant ANOVAs. Correlations (Pearson or Spearman rho) explored associations with MEIM-6 and GEDS. Finally, exploratory stepwise multiple linear regressions (probability-of-F-to-enter ≤.05) predicted change scores from substance, residency, MEIM-6, GEDS (frequency and stress), country, and sex.

The analytic sample included 66 Indigenous-identifying participants, 74.2% of whom resided in Canada and 25.8% in the United States. Mean age was 35.9 years (SD = 12.2) and 59.1% identified as female. Most participants identified as First Nations (56.1%) and 53.0% reported living on, or having family living on, Tribal lands/reservation/reserve. The memorable psychedelic experience occurred at a mean age of 22.3 years (SD = 7.2, range 13–47). Reported substances were predominantly oral psilocybin mushrooms, MDMA, or LSD; over 70% described taking a moderately high or high dose, and about 60% reported no other psychoactive substances at the time (excluding caffeine and nicotine). Approximately 51.5% reported the experience lasted ≤5 hours. On measures of discrimination and identity, participants reported frequent lifetime experiences of ethnic discrimination (GEDS lifetime sum mean = 36.4, SD = 18.9) and high stress from discrimination (GEDS stress sum mean = 38.7, SD = 18.1). Mean MEIM-6 ethnic identity was 4.1 (SD = 0.8), indicating moderate ethnic-group affiliation. Comparing recalled symptom levels 30 days before versus 30 days after the psychedelic experience, the sample replicated prior findings from the larger study: statistically significant recalled decreases in discrimination-related trauma (TSDS), depression, anxiety, stress (DASS-21 subscales), alcohol use (AUDIT-C), drug use (DUDIT-C), and a significant recalled increase in psychological flexibility (AAQ-II). No differences were observed by country of residence for any outcome. Substance-specific analyses found that participants who reported psilocybin consumption recalled greater changes on several outcomes compared with MDMA and LSD. Post hoc tests indicated greater recalled change in TSDS for psilocybin versus MDMA (p = .03); similar patterns were reported for AAQ and DASS-21 subscales (Depression, Anxiety, Stress). For AAQ, AUDIT-C, and DUDIT-C change scores analyses used Kruskal-Wallis due to non-normality. Residency on Tribal lands was associated with group differences: greater recalled decreases in drug use (ΔDUDIT) and anxiety (ΔDASS Anxiety) were observed in participants who did not live (or whose family did not live) on Tribal lands/reserves compared with those who did. Sex differences emerged, with female participants recalling greater improvements in discrimination-related trauma (ΔTSDS) and anxiety (ΔDASS Anxiety) after the psychedelic experience. Correlation analyses found a negative association between ΔTSDS and GEDS stress (r = -0.28, p < .03, N = 66), indicating that participants who had experienced greater stress from discrimination recalled greater reductions in discrimination-related trauma symptoms. MEIM-6 and GEDS frequency did not correlate significantly with change scores. Exploratory stepwise multiple regression models identified several predictors of change scores. For ΔTSDS the final model included substance consumed, GEDS stress, and residency on Tribal lands and explained 27% of variance. Substance consumed alone explained 8% of variance in ΔAUDIT and 10% in ΔDASS21 Depression. Residency on Tribal lands alone explained 8% of variance in ΔDUDIT. For ΔDASS21 Anxiety a three-variable final model including participant sex, residency on Tribal lands, and substance consumed explained 24% of variance. Regression diagnostics reported no multicollinearity (VIF < 10) and acceptable assumptions for the fitted models.

De La Salle and colleagues interpret their findings to indicate that, among this heterogeneous subsample of 66 Indigenous participants recalling naturalistic psychedelic experiences, there were consistent retrospective reports of reduced symptoms of discrimination-related trauma, depression, anxiety, stress, and substance use, alongside increased psychological flexibility in the 30 days after the experience compared with the 30 days before. The authors emphasise that psilocybin was associated with the largest recalled improvements relative to MDMA and LSD, and they suggest multiple possible explanations including cultural perceptions of psilocybin as a naturally derived, ceremonial medicine shaping participants' set and expectations, and potential pharmacological differences (for example, additional compounds in natural sources). The investigators also discuss subgroup findings: smaller recalled improvements in drug use and anxiety among those living on Tribal lands/reserves may reflect unique social determinants of health and contextual factors that shape the setting of psychedelic use, and thus outcomes; this requires further study. Greater recalled reductions in discrimination-related trauma among participants reporting higher stress from discrimination might reflect a self-medication motive or indicate that those most affected by discrimination may derive more perceived benefit. Female sex predicted greater anxiety reductions; the authors note limited existing data on sex and gender effects in psychedelic responses and propose that greater help-seeking by women could partly explain this observation. Key limitations acknowledged by the authors include the retrospective, cross-sectional design and reliance on participant recall for both the memorable psychedelic event and pre/post symptom levels, which introduces potential recall and positivity biases. The Indigenous subsample was drawn from a larger non‑targeted survey and the psychedelic experience questionnaire was not designed specifically for Indigenous contexts; important contextual details such as ceremonial framing, community involvement, and timing of the experience were not captured. The sample was small and heterogeneous with participants from multiple Tribes and identities, reducing the ability to examine within-group differences. Negative or neutral psychedelic experiences were not assessed. The authors therefore call for prospective, culturally informed, and community‑engaged research designs to validate and extend these findings. Finally, the paper provides practical recommendations directed at researchers, clinicians, and policymakers, stressing the need for consultation, consent, reciprocity, accountability, and culturally competent policy development to avoid repetition of historical harms to Indigenous peoples in the advancement of psychedelic science.

The authors conclude that, based on retrospective reports of naturalistic psychedelic use among Indigenous participants in Canada and the United States, psychedelic substances were associated with recalled improvements in trauma-related symptoms, mood, substance use, and psychological flexibility, with psilocybin showing the largest recalled effects in this sample. They underscore that further work must proceed only with explicit consultation and approval from Indigenous communities and that future research should employ prospective, culturally sensitive methods to validate these preliminary, retrospective findings while protecting Indigenous cultural practices and addressing historical injustices.