Longitudinal changes in depressive symptoms following naturalistic ayahuasca use: A prospective cohort study in Las Vegas, Nevada

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 ({beta}=-3.70; 95% CI -5.09 to -2.31), 30 days ({beta}=-4.34; 95% CI -6.01 to -2.67), 60 days ({beta}=-3.97; 95% CI -5.77 to -2.18), and 90 days ({beta}=-4.25; 95% CI -6.18 to -2.33; all p<0.001). Among participants with baseline PHQ-9 scores [&ge;]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.