Longitudinal changes in depressive symptoms following naturalistic ayahuasca use: A prospective cohort study in Las Vegas, Nevada
Krista Whitley, Kai Davide Castellarin, Kumar Dave, Taylor Parrott, Andre Craig Christie, Lisa Durette, Yusuf Khan, Kidus Yohannes, Rayan Muneer, Kristina Domanski
medRxiv August 27, 2026 preprint DOI: 10.64898/2026.08.24.26361280 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Prospective observational cohort Longitudinal |
|---|---|
| Sample size | 87 |
| Population | Adults participating in naturalistic ayahuasca use in Las Vegas, Nevada |
| Intervention | Ayahuasca |
| Duration | 90-day follow-up |
| Measures | Patient Health Questionnaire-9 (PHQ-9) |
| Topics | Ayahuasca |
| Key findings | PHQ-9 scores decreased from a mean of 8.06 at baseline to 3.65 at 90 days, with significant reductions at all time points in a mixed-effects model. Among those with baseline scores ≥5, 69.2% showed at least a 5-point reduction at 90 days. |
Abstract
Abstract Ayahuasca use has expanded beyond its traditional Amazonian contexts, yet prospective longitudinal data examining depressive symptoms following naturalistic use in the United States remain limited. We conducted an interim analysis of an ongoing prospective observational cohort of adults participating in naturalistic ayahuasca use in Las Vegas, Nevada. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), with higher scores indicating greater depressive symptom severity, at baseline and approximately 48 hours, 30 days, 60 days, and 90 days following exposure. At interim analysis, PHQ-9 data were available for 87 participants at baseline, 61 at 48 hours, 41 at 30 days, 33 at 60 days, and 26 at 90 days. Mean PHQ-9 scores decreased from 8.06 (SD 5.96) at baseline to 4.39 at 48 hours, 3.76 at 30 days, 3.97 at 60 days, and 3.65 at 90 days. Among participants with matched baseline and follow-up assessments, mean changes were −3.58 points at 48 hours, −4.47 at 30 days, −4.48 at 60 days, and −4.76 at 90 days. In a mixed-effects model accounting for repeated observations, PHQ-9 scores remained significantly lower than baseline at 48 hours (β=−3.70; 95% CI −5.09 to −2.31), 30 days (β=−4.34; 95% CI −6.01 to −2.67), 60 days (β=−3.97; 95% CI −5.77 to −2.18), and 90 days (β=−4.25; 95% CI −6.18 to −2.33; all p<0.001). Among participants with baseline PHQ-9 scores ≥5 and matched follow-up data, 69.2% demonstrated a reduction of at least 5 points at 90 days. These interim findings provide preliminary evidence of a sustained longitudinal association between naturalistic ayahuasca exposure and lower depressive symptom scores through 90 days in a U.S.-based cohort. The observational design, self-selection, incomplete follow-up, and absence of a control group preclude causal inference. Continued longitudinal follow-up is needed to determine the durability of this association.
Comparable studies
Other observational and cohort studies on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Patients with a depressive disorder | 2015 | Observational study | |
| The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network Experienced subjects | 2015 | Observational cohort | n = 10 |
| Human Psychopharmacology of Hoasca, A Plant Hallucinogen Used in Ritual Context in Brazil Long-term members of a syncretic church that uses hoasca as a psychoactive sacrament... | 1996 | Observational cohort with matched controls | n = 30 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study Regular ayahuasca users and active controls in non-ayahuasca religions | 2012 | Observational cohort | n = 242 |