Acute Psychological Adverse Reactions in First-Time Ritual Ayahuasca Users

Ayahuasca is a botanical decoction containing Banisteriopsis caapi (β-carbolines such as harmine) combined with plants that supply N,N-dimethyltryptamine (DMT). The β-carbolines inhibit peripheral monoamine oxidase A (MAO-A), permitting orally ingested DMT to exert central psychedelic effects. In Amazonian cultures ayahuasca has longstanding spiritual and therapeutic roles, and in recent decades ceremonial use has spread globally. Previous retrospective and controlled studies have generally reported acceptable tolerability, potential therapeutic benefits (for example in depression and substance use), and few enduring neuropsychiatric harms, yet prospective research that uses clinical interviews and follows ayahuasca‑naive ceremony participants over time remains limited. Gómez-Sousa and colleagues sought to address this gap by analysing a subsample drawn from a previously published prospective cohort of 40 first‑time ayahuasca ceremony participants. The present paper describes seven cases from that cohort who experienced acute, distressing psychological reactions during ceremonies, and reports clinical and psychometric outcomes assessed before exposure and at 1 and 6 months afterwards. The primary aim was to characterise the content, short‑term and longer‑term course of these challenging experiences and to explore contextual factors that might have contributed to adverse reactions.

The investigators selected a subsample of seven participants from an initial cohort of 40 ayahuasca‑naive individuals because these seven reported clearly negative, distressing acute experiences as judged by the research team. Selection emphasised experiences that were unambiguously distressful rather than transient anxiety commonly associated with psychedelics. Data were collected at three time points: baseline (before the ceremony), and at 1 month and 6 months after the index ceremony. Clinical assessment used the Mini‑International Neuropsychiatric Interview (MINI) version 5.0 administered by interviewers. In addition, self‑report psychometric instruments were applied: the Hamilton Depression Rating Scale (HAM‑D), the Community Assessment of Psychic Experiences (CAPE), the Symptom Checklist‑90‑Revised (SCL‑90‑R), the Acceptance and Action Questionnaire II (AAQ‑II), the Short Form‑36 Health Survey (SF‑36) and the WHOQOL‑Bref. During follow‑up interviews participants were also asked to describe their subjective experiences in detail; these narrative reports were recorded manually. Statistical analysis was descriptive, focused on demographic and clinical characterisation. Ethical approval was obtained from the Autonomous University of Madrid Research Ethics Committee and written informed consent was obtained from all volunteers.

Seven of the 40 participants (17.5%) reported intense, challenging psychological reactions during their first ayahuasca ceremony. The initial cohort comprised 40 participants (28 women); follow‑up attendance fell to 26 participants (20 women) at 1 month and to 15 participants (9 women) at 6 months. The extracted text indicates some attrition bias analyses in the parent study but does not provide full detail here. At baseline, four of the seven case subjects met diagnostic criteria for at least one psychiatric disorder according to the MINI. By 1 month two of the subjects no longer met diagnostic criteria and two showed substantial reductions in psychiatric symptoms; at 6 months those improvements largely persisted and only one subject continued to meet a baseline diagnosis. One participant (patient 1) met criteria for hypomanic disorder at the 1‑month assessment despite having previously met criteria for depressive disorders; the role of increased alcohol consumption in this case was noted as a confounder. Two participants (patients 2 and 6) showed marked increases on certain SCL‑90‑R scales at follow‑up, with T scores above 70 (considered clinical range) reported for specific subscales (for example patient 2: depression 71.5 at 1 month, somatisation 74.1 and obsessive‑compulsive 77 at 6 months; patient 6: interpersonal sensitivity 73, depression 72.3 and paranoid ideation 75 at 6 months). Case summaries convey the diversity of experiences. Patient 1 had baseline major depression and dysthymia, increased alcohol use after the ceremony and later reported subjective improvement after attending further ceremonies. Patient 2 had multiple baseline diagnoses (including major depression, panic disorder and benzodiazepine dependence), reported feelings of being observed after the ceremony and by follow‑up only met ‘‘low risk of suicide’’ criteria. Patient 3, with no baseline disorder and prior psilocybin experience, briefly lost consciousness during the first ceremony and later (after repeating ceremony attendance) experienced an intense ‘‘bad trip’’ including aggressive behaviour toward a caregiver; she did not meet diagnostic criteria at follow‑ups. Patient 4 had distressing visual hallucinations in a poorly managed setting (the guide reportedly fell asleep), but no subsequent psychiatric diagnosis. Patient 5 had baseline dysthymia, obsessive‑compulsive disorder, generalised anxiety disorder and a history of epilepsy (on Depakene); despite being advised of contraindication she attended, experienced seizures and transient loss of consciousness, required psychological support for two days and subsequently described positive lifestyle changes while not returning to ceremonies. Patient 6 described overwhelming sadness and strong effects that nevertheless prompted some positive changes; no MINI diagnoses were met, but SCL‑90‑R pathology scores rose at follow‑up. Patient 7 experienced a paranoid episode during the ceremony and contact with ‘‘invisible people’’ but reported beneficial effects and met no diagnostic criteria at follow‑ups. The extracted text contains inconsistent statements about repeat use: an earlier summary claimed that most (6 of 7) did not take ayahuasca again during the study period, but individual case reports indicate at least two participants attended additional ceremonies. Two cases involved transient loss of consciousness and one reported seizure activity; the team highlighted that causality for seizures could not be firmly established. Contextual deficiencies (for example inadequate screening of epilepsy and poor supervision by guides) were identified in several cases.

Gómez‑Sousa and colleagues interpret these case series as evidence that acute, challenging psychological reactions to ayahuasca ceremonies are not rare in an unscreened, naturalistic sample—17.5% in this cohort—and that context and screening practices may substantially influence risk. The authors emphasise that because participants in this study were not preselected or excluded for psychiatric history, the observed incidence may better reflect real‑world prevalence than tightly controlled clinical trials. It is also noted that most participants without prior psychiatric disorder did not develop persistent disorders after a challenging experience, and several participants with baseline disorders showed symptomatic improvement at follow‑up. At the same time, the investigators acknowledge concerning outcomes: one participant developed hypomanic symptoms after the ceremony (with concurrent increased alcohol use), and two participants showed clinically elevated psychopathology scores on self‑report measures at follow‑up despite apparent improvements on the MINI and other scales. The authors discuss plausible mechanisms (for example a role for MAO‑inhibiting β‑carbolines and serotonergic activity) but do not assert causality, noting confounders such as alcohol use and repeat ceremony attendance. They also highlight seizure risk and transient loss of consciousness as potential harms, particularly in individuals with epilepsy, and suggest a possible neurobiological route via glutamate release after 5‑HT2A receptor activation. Contextual factors received substantial emphasis: inadequate screening (for example allowing a person with epilepsy to participate) and poor on‑site supervision (for example guides falling asleep) likely contributed to some adverse events. The authors argue that post‑experience integration processes and the ritual setting may be protective, but that integration practices are inconsistent across providers. They call for prospective, naturalistic research to identify profiles of increased vulnerability and to clarify which contextual practices mitigate risk. Finally, the authors acknowledge the study limitations—small case number, heterogeneity of ceremonial contexts, inability to measure alkaloid content or dose, reliance on subjective reports and questionnaires, and the observational design that precludes definitive attribution of long‑term effects to ayahuasca exposure—and recommend development of harm‑reduction strategies and better screening by ceremony organisers.

The case series documents that challenging psychological reactions occurred in 17.5% of an unscreened sample of first‑time ayahuasca ceremony participants, yet many of those affected later reported positive influence and symptom reductions. Conversely, three subjects demonstrated concerning outcomes (two with elevated psychopathology scores and one who met criteria for hypomanic disorder after the ceremony). The authors conclude that these findings underline the need for harm‑reduction measures, improved screening and supervision in ceremony contexts, and further prospective naturalistic studies to identify predictors of adverse versus beneficial outcomes.