Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination

The investigation comprised two observational sub-studies conducted in naturalistic ritual settings. Sub-study 1 was a prospective longitudinal cohort of ayahuasca-naïve volunteers recruited via ceremony leaders in Spain; 40 participants (28 women) enrolled and completed baseline assessments prior to their first ayahuasca ceremony. Follow-up assessments were conducted at approximately 1 month (n = 28) and 6 months (n = 15). Participants attended a variety of ceremony types (neoshamanic, religious, psychotherapeutic); the study did not implement experimental dosing or laboratory control of the brew. Psychiatric and psychometric instruments used in sub-study 1 included the Mini-International Neuropsychiatric Interview (MINI) for diagnostic status, the Hamilton Depression Rating Scale (HAM-D), the Symptom Check-List-90-Revised (SCL-90-R), the Community Assessment of Psychic Experiences (CAPE), the Acceptance and Action Questionnaire (AAQ-II), the Temperament and Character Inventory (TCI-R-67), the SF-36 Health Survey, and the WHOQOL-Bref. Sociodemographic and motivation data were recorded. Effect sizes (Cohen’s d), t-tests and confidence-interval comparisons are reported in the extracted text; intention-to-treat or mixed-model procedures are not described in the available extraction. Sub-study 2 was a cross-sectional comparison using the same interview and questionnaire battery administered to long-term ayahuasca users (n = 23; 10 women, 13 men). The long-term group reported a mean of 70 ceremonies (range 50–100). The baseline data from the naïve group (sub-study 1) were compared with the long-term users to investigate whether observed differences could reflect pre-existing traits or consequences of prolonged use. The extracted text does not provide full procedural details for recruitment, timing of assessment relative to last ceremony for long-term users, or complete statistical modelling for between-group comparisons.

Sub-study 1 (longitudinal naïve sample): At baseline 40 participants (mean age approximately 35 years; 70% women; majority Spanish) were assessed. Eighteen participants (45%) met criteria for one or more psychiatric disorders on the MINI, with generalized anxiety disorder and substance use diagnoses most common; 50% of those diagnosed had comorbidity. Motivations for attending ceremonies were primarily therapeutic (59.2%), with other motives including self-exploration and curiosity. Attrition occurred across follow-ups: 28 participants at 1 month and 15 at 6 months. Diagnostic outcomes: Of the 18 participants who met diagnostic criteria at baseline and were re-interviewed at 1 month, 11 (61%) no longer met criteria for any psychiatric disorder and 4 (22.2%) had fewer diagnoses; one participant (5.5%) had a different psychiatric diagnosis at 1 month and one participant who was well at baseline met criteria for generalized anxiety disorder at follow-up. At 6 months, among the 8 of the original 18 who were re-interviewed, only 2 still met diagnostic criteria; overall, 3 participants met criteria for a psychiatric disorder at 6 months according to the available interviews. Questionnaire outcomes: At 1 month there were reductions on SCL-90-R subscales for anxiety (d = 0.54) and hostility (d = 0.62). At 6 months significant decreases were reported for HAM-D (d = 0.72) and the role-emotional subscale of SF-36 (d = 0.74). The authors note that many questionnaire CIs overlapped between assessments, indicating that while tendencies toward improvement were observable, not all reached statistical significance. Subgroup analyses focusing on those with baseline psychiatric diagnoses showed trends toward reduced symptom scores over time, but confidence intervals overlapped, suggesting limited power to detect significant change. An analysis comparing drop-outs and completers found no statistically significant differences overall, though at 1 month drop-outs tended (statistically) to have lower CAPE depression frequency and lower SCL-90-R depression scores (t and p values reported in the text), indicating some systematic attrition patterns. Sub-study 2 (cross-sectional long-term users): Twenty-three long-term users (mean age about 45 years; mean ~70 ceremonies) completed the battery. Only two (≈9%) met criteria for a psychiatric disorder. Comparison with the naïve baseline indicated that long-term users scored significantly lower on HAM-D (specific test statistics were truncated in the extracted text). The long-term group also had higher self-transcendence scores on the TCI-R and showed better quality-of-life metrics consistent with sub-study findings, although some between-group statistics in the extraction are incomplete. Adverse events: the extracted text reports no general mid-term adverse effects in the cohort; isolated acute reactions (for example transient anxiety) occurred in some individuals and are to be described in a separate report.

Jiménez-Garrido and colleagues interpret their findings as indicating that initiation of ritual ayahuasca use in naïve participants was followed by clinically meaningful reductions in psychiatric diagnoses and symptomatology, particularly for depression. The MINI interviews suggested that 61% of those meeting diagnostic criteria at baseline no longer met criteria at 1 month, with improvements persisting up to 6 months in most cases; questionnaire data showed the most consistent change for depression (HAM-D), which decreased at both follow-ups. The authors note that many other psychopathology scales showed short-term improvement at 1 month that attenuated by 6 months, suggesting that some benefits may be transient unless use is maintained. Positioning these results relative to prior work, the paper notes concordance with clinical trials that reported rapid antidepressant effects after single administrations in depressed patients and with observational studies reporting better mental-health indices among regular ritual users. The long-term users in sub-study 2 scored lower on depression and higher on self-transcendence and quality-of-life measures than the naïve sample, which the authors consider consistent with both pharmacological (e.g. DMN connectivity changes) and psychological mechanisms (enhanced mindfulness-like capacities, integration of experience, community effects, and mystical-type experiences) proposed in earlier research. Key limitations acknowledged by the investigators include the absence of a randomised control group, small sample sizes, and attrition across follow-ups. The authors also note incomplete ability to separate pharmacological effects from contextual or ceremony-type influences in a naturalistic design and recommend larger studies that consider ceremony setting and frequency. Despite these constraints, they report no general mid-term adverse effects in the sample, while recognising isolated acute adverse reactions occurred in individual cases. The investigators conclude that ritualistic ayahuasca use in controlled settings may offer therapeutic benefits—most notably for depressive symptoms—but that larger, controlled and naturalistic studies are needed to clarify risks, mechanisms, duration of effect and which users are most likely to benefit.