Switch to mania after ayahuasca consumption in a man with bipolar disorder: a case report

Ayahuasca is a psychotropic, hallucinogenic Amazonian brew most commonly prepared from Banisteriopsis caapi and Psychotria viridis. The B. caapi component contains β-carbolines (harmine, tetrahydroharmine, and to a lesser extent harmaline and related alkaloids) that act as reversible, selective MAO-A inhibitors, while P. viridis supplies the tryptamine N,N-dimethyltryptamine (DMT). Because DMT is normally inactivated by intestinal MAO-A, its oral psychoactivity depends on co‑administration with MAO-A inhibitors, and some β-carbolines have also been implicated in serotonergic modulation and possible antidepressant actions. This paper presents a single case report of a man with a history suggestive of bipolar spectrum illness who developed a manic episode with psychotic features in temporal relation to participation in a multi‑day ayahuasca ritual. The authors use the case to examine diagnostic implications in the psychiatric setting, consider pharmacodynamic mechanisms that might precipitate a mood switch, and highlight gaps in the literature regarding ayahuasca’s effects in people with mood disorders.

This is an individual case report based on clinical assessment and patient/family history. The subject was a 30‑year‑old Argentinian man who presented to the authors’ emergency service after recent hospitalisation in Brazil for an acute psychotic episode that followed participation in a 4‑day ayahuasca ritual. Information was obtained from the patient, his mother, hospital records from the Brazilian admission as reported, and a contemporaneous mental state examination performed after transfer back to Argentina. Key clinical details reported include a family history of bipolar disorder type I in the patient’s father, the patient’s prior history of multiple hypomanic episodes (including a 10‑day period of increased energy and decreased need for sleep occurring two weeks before travel to Brazil), and the absence of a documented substance use disorder. The timeline reported by the patient and his mother indicates that two days after the last ayahuasca session the patient developed mystical and paranoid delusions, auditory hallucinations, racing thoughts, disorganised behaviour, elevated energy and euphoria. Treatment during the Brazilian hospital admission comprised risperidone 2 mg/day and clonazepam 2 mg/day; the patient was reportedly asymptomatic after approximately one month and was discharged on the same medications. Subsequent assessment in Argentina documented a depressive episode after remission of the psychotic/manic symptoms. The extracted text does not report objective laboratory tests, ayahuasca dose or exact alkaloid content, nor does it provide toxicology results.

Two days after completing a 4‑day ayahuasca ritual, the patient developed prominent manic and psychotic features: mystical and paranoid delusional ideas, auditory hallucinations, pressured thoughts, disorganised behaviour, increased energy and euphoria. These psychotic symptoms were described as congruent with an elevated mood. He was admitted to a psychiatric hospital in Brazil and treated with risperidone 2 mg/day and clonazepam 2 mg/day; after one month he was reported as asymptomatic and was discharged on the same medications. On return to Argentina and at the authors’ hospital assessment, the patient was in a depressive state that began after the remission of the earlier episode. The mental state examination showed decreased amount and speed of speech, depressed affect, ideas of hopelessness, anhedonia, apathy, clinophilia, and otherwise normal sleep and appetite; no current delusions or hallucinations were present. Two weeks prior to travelling to Brazil the patient had experienced a 10‑day period of hypomanic symptoms (increased energy and goal‑directed activity, decreased need for sleep, pressured speech and elevated self‑esteem) and reported having had similar episodes previously but no documented full manic or major depressive episodes. The authors reiterate pharmacological features of ayahuasca relevant to the case: DMT is orally inactive without peripheral MAO‑A inhibition, and β‑carbolines in B. caapi act as reversible, selective MAO‑A inhibitors and have been proposed to possess serotonergic effects including serotonin reuptake inhibition and 5‑HT1A agonism. Citing prior reviews, they note that ayahuasca‑related psychotic episodes are reported to be uncommon (under 1%) and typically transient, resolving within hours in most cases. The authors also report literature estimates that MAO inhibitor treatment in bipolar patients is associated with a 4.58% to 15% risk of switching to mania, and state that β‑carboline half‑lives are reported as approximately 1 to 5 hours.

The authors interpret the clinical picture as a manic episode with psychotic features occurring in a patient with an underlying bipolar diathesis and temporal relation to ayahuasca consumption. They discuss diagnostic framing under DSM‑5, noting that a diagnosis of a substance‑induced mental disorder is conventionally applied when characteristic symptoms arise during or up to one month after substance use and when there is no evidence for a primary disorder preceding the exposure. Given the patient’s prior hypomanic history and a first‑degree family history of bipolar disorder, the investigators argue that the episode is better understood as a switch to mania precipitated by the antidepressant properties of ayahuasca constituents rather than a transient ayahuasca‑intoxication psychosis. In support of this view, Szmulewicz and colleagues highlight the pharmacodynamics of β‑carbolines (reversible MAO‑A inhibition and potential serotonergic actions) and cite the reported low incidence and short duration of typical ayahuasca‑related psychotic reactions. They invoke DSM‑5 guidance that a manic episode emerging during antidepressant treatment but persisting beyond the physiological effect of the treatment constitutes evidence of a manic episode and therefore supports a diagnosis of bipolar I disorder; using reported β‑carboline half‑life estimates (1–5 hours), the authors judge the clinical course consistent with this criterion. The discussion acknowledges lack of specificity in applying the substance‑induced diagnosis and emphasises that compounds with antidepressant action may lower the threshold for manic switching in bipolar patients. The authors conclude that this single case illustrates a potential mechanism of toxicity for ayahuasca in patients with bipolar vulnerability and recommend caution in psychiatric settings. The extracted text does not present systematic limitations beyond diagnostic uncertainty and does not provide objective toxicological confirmation of exposure or quantitative dosing information.

Szmulewicz and colleagues conclude that, in this patient, manic symptoms were most plausibly caused by the antidepressant effects of ayahuasca constituents in the context of an underlying bipolar disorder. They argue the case demonstrates limited specificity of the substance‑induced psychotic disorder diagnosis, suggests that compounds with antidepressant properties can lower the threshold for mania in bipolar patients, and supports the DSM‑5 approach that antidepressant‑induced persistent mania should count as evidence for bipolar I disorder. Finally, the authors emphasise the need for caution when ayahuasca or similar compounds are used by people with mood disorder vulnerability.