Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report

Ayahuasca is a traditional botanical hallucinogenic brew composed of Banisteriopsis caapi and Psychotria viridis, containing DMT and β-carbolines that together permit oral DMT to become systemically active. Earlier human and animal studies suggest anxiolytic and antidepressant effects of ayahuasca, and controlled administrations in healthy volunteers are generally well tolerated; the acute psychoactive window typically begins within 30–40 minutes, peaks around 1.5–2 hours, and resolves by 4–6 hours. While transient dysphoric reactions such as anxiety or paranoia can occur during the acute effects, prolonged or subacute anxiety-related adverse events have not been commonly reported in controlled settings, and long-term ritual users generally do not show increased psychopathology in observational studies, although selection biases may limit those findings. Santos and colleagues report a single-case description to document what they consider an uncommon prolonged anxiety-like reaction following ritual ayahuasca ingestion in a young woman with a prior diagnosis of generalized anxiety disorder (GAD). The report aims to characterise the clinical course, contextual factors, and possible mechanisms of the event, and to highlight implications for the use of ayahuasca in people with anxiety histories. This case is presented as, to the authors’ knowledge, the first scientific description of a subacute/prolonged anxiety reaction temporally associated with ayahuasca intake.

This paper is a descriptive single-case report based on retrospective self-report from the participant, who contacted the investigators by e-mail after reading the authors’ publications. No face-to-face clinical assessment, direct clinical records review, or chemical analysis of the ayahuasca sample was performed. The investigators could not verify the original psychiatric diagnoses with the treating psychiatrist and were unable to apply standard diagnostic interviews because the participant was travelling and contact was limited to e-mail. The case history includes antecedent psychiatric diagnoses reported by the patient (GAD and chronic insomnia diagnosed at age 20), family psychiatric history (mother with panic disorder), substance use history (occasional LSD and psilocybin, intermittent MDMA use for about a year, and daily cannabis use for 8 years), and pharmacological treatments previously received (paroxetine, zolpidem, alprazolam for 8 months). The participant reported a spontaneous remission of anxiety symptoms after a non-drug ‘‘spiritual awakening’’ and discontinued medication four months prior to the ayahuasca ceremony. She attended a ritual at a local ayahuasca centre, where she ingested two consecutive doses separated by approximately 2 hours. The report describes symptom onset, qualitative symptom characteristics, time course over hours and days, any supportive measures available during the ritual, and the participant’s subsequent resumption of psychiatric treatment. No structured outcome measures, objective physiological recordings, or laboratory data are reported. The analysis is narrative and interpretive, with acknowledgement of major methodological limitations including remote data collection, inability to confirm diagnoses or drug composition, and potential confounding by prior substance use and medication discontinuation.

The participant, a 25-year-old Brazilian woman with a reported history of GAD and chronic insomnia, experienced intense anxiety, panic and hopelessness after the second of two ayahuasca doses taken within a 2-hour interval in a ritual setting. She reported no psychoactive effect after the first dose; after the second dose she described being ‘‘100 times more anxious than normal,’’ marked panic about not returning to her baseline mental state, an inability to stay still, and persistent feelings of hopelessness lasting for hours. Arrhythmia was also reported and increased her concern; no physician was reportedly present at the ritual. Support from organisers and attempts to reduce distress (including taking a shower) did not resolve her suffering during the ceremony, which continued intensely for about 8 hours and then gradually diminished. Residual anxiety and hopelessness persisted for the following 3 days, after which she resumed psychiatric treatment. At the time of reporting she was taking mirtazapine, clonazepam and zolpidem daily, with improvement in anxiety and insomnia. The participant denied using cannabis or other drugs in the 2 days prior to or during the episode and reported no prior adverse reactions to recreational hallucinogens or MDMA. She attributed some beneficial changes following the experience, including reductions in alcohol and cannabis use and increased engagement with yoga and meditation. The extracted text notes that no chemical analysis of the ayahuasca sample was possible and that details about the ceremonial setting, screening or integration procedures were not provided by the participant.

Santos and colleagues interpret this case as a rare but notable example of an acute and subacute anxiety-related reaction after ritual ayahuasca use. They situate the event within the broader literature showing that ayahuasca and other 5-HT2A agonist hallucinogens are generally associated with low rates of prolonged psychiatric adverse events, while acknowledging that uncommon subacute or prolonged negative reactions have been reported after other psychedelics (for example, a pooled psilocybin dataset in which 7 of 110 subjects reported negative psychological effects in the days or weeks following administration, and one required professional help). Possible mechanisms discussed include DMT’s agonist activity at cortical 5-HT2A receptors, which modulate frontal and limbic circuits implicated in mood and emotion, whereas the β-carbolines in ayahuasca are less likely to be directly hallucinogenic at typical concentrations. The authors also consider patient-specific vulnerability factors that might have contributed: a family history of panic disorder, a prior GAD diagnosis, and abrupt discontinuation of anxiolytic/antidepressant medication four months earlier. They note that certain pharmacotherapies (for example, selective serotonin reuptake inhibitors) can increase anxiety early in treatment, and that other recreational substances (cannabis, MDMA) can also produce anxiogenic effects in susceptible individuals. Contextual factors related to set and setting are mentioned as potential contributors, although the participant did not emphasise these elements and provided few details about ceremony preparation, guidance or integration. The authors concede that the episode could be a self-limited ‘‘bad trip’’ but argue that the subacute nature of symptoms and the need to restart pharmacological treatment suggest a more prolonged reaction in this case. They also acknowledge that the reported arrhythmia may have been an important factor exacerbating anxiety and cannot be ruled out as causal. Finally, the discussion highlights selection bias concerns in observational studies of long-term ayahuasca users and calls for prospective research following novice users to better characterise both therapeutic and adverse outcomes. The authors conclude that, given the potential morbidity of prolonged drug-induced anxiety and ongoing clinical interest in psychedelic therapies, ayahuasca should be used with caution in individuals with a history of anxiety disorders.