A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT)

DMT (N,N-dimethyltryptamine) is a naturally occurring psychoactive compound found in plants such as Psychotria viridis and is a primary active ingredient in the South American brew ayahuasca. Recent years have seen renewed interest in DMT's potential antidepressant effects and a rise in recreational and therapeutic use, including travel to spiritual retreats. Population survey data cited in the extracted text indicate a relatively high proportion of new users (24%) and a lifetime prevalence of 8.9% for DMT, but the neuropsychiatric effects of chronic use and its utility in treating depression remain speculative and incompletely characterised. Brown and colleagues present a single-patient case report describing a retired 40-year-old psychiatrist with bipolar I disorder who chronically self-administered vaporised DMT, later combined with the monoamine oxidase inhibitor phenelzine, in an attempt to treat refractory depression. The report aims to document his acute presentation of altered mental status, mania, and psychosis, to explore possible mechanisms linking DMT to these neuropsychiatric manifestations, and to highlight the hazards of self-medication, particularly among physicians.

This paper is an individual case report based on clinical observation, medical investigations, collateral history from family, and hospital course documentation. The subject was a 40-year-old retired male psychiatrist with a diagnosis of bipolar I disorder who presented to hospital with severe behavioural disturbance. Emergency care and inpatient medical records provided details of the acute management: initial violent and nonverbal behaviour requiring multiple staff to restrain him, administration of several sedative agents (propofol 1,000 mg IV, ketamine 500 mg IM, midazolam 5 mg IV, diazepam 20 mg IV, fentanyl 4 mg IV) which had minimal effect, a subsequent seizure and one day of intubation. Laboratory testing and imaging included liver enzymes, creatine kinase, head CT, blood and urine testing, vitamin B12 and folate, serology for syphilis, HIV and hepatitis, thyroid-stimulating hormone, and lumbar puncture; the extracted text reports all of these as unremarkable except for elevated transaminases and creatine kinase. Collateral history from family members and psychiatric assessment established the exposure details: up to 1 g of vaporised DMT daily for six months, addition of phenelzine 60 mg daily three weeks before admission to potentiate antidepressant effects, and intermittent clonazepam 4–6 mg daily as needed. The patient obtained both phenelzine and DMT via online illicit sources described as the “dark net.” Psychiatric treatment in hospital targeted mania and psychosis with lithium (later reported at 600 mg twice daily with a serum level of 0.8 mmol/L), paliperidone 6 mg/day, and clonazepam as needed. Outcome data are limited to the inpatient course; outpatient follow-up was arranged but the extracted text does not clearly report long-term follow-up.

On presentation the patient was nonverbal, combative and required six security guards to restrain him. Multiple sedative agents were administered with limited effect, after which he seized and required intubation for one day. Laboratory abnormalities included elevated transaminases (peak ALT 151 IU/L, AST 237 IU/L) and a markedly raised creatine kinase (3,868 IU/L). Other diagnostic tests reported in the record — head CT, blood cultures, urinalysis, vitamin B12 and folate levels, syphilis, HIV and hepatitis screens, thyroid-stimulating hormone, and lumbar puncture — were reported as unremarkable. Following medical stabilisation and resolution of delirium, psychiatric assessment identified pressured speech, hyperreligiosity and delusional beliefs (for example, that demons were leeching into his soul). Family history revealed chronic high-dose DMT use (up to 1 g vaporised daily for six months) and the recent addition of phenelzine 60 mg daily three weeks prior to admission. The family also reported some hypomanic features (decreased sleep, increased religiosity, erratic spending) in the month preceding admission, but the patient had no documented prior history of psychosis. According to the extracted text, his DMT, phenelzine and clonazepam were abruptly discontinued 2–3 days before hospitalisation. Inpatient psychiatric management consisted of lithium for mood stabilisation (reported dosing 600 mg twice daily with level 0.8 mmol/L), paliperidone 6 mg/day for psychosis and clonazepam for sleep. By treatment day 7 the patient's psychotic symptoms had resolved, though he remained hypomanic. He left hospital against medical advice on the medications above; the extracted text does not report his condition after discharge.

Brown and colleagues considered multiple explanations for the presentation, including activation of mania by DMT or phenelzine, phenelzine withdrawal, serotonin syndrome, and the natural course of bipolar disorder. They interpret the case as most consistent with DMT-related psychosis and mania given the patient's prolonged, very-high-dose DMT exposure, the absence of prior psychotic episodes, and the temporal relationship between chronic use and the acute presentation. The authors discuss pharmacological mechanisms that may link DMT to both hallucinations and antidepressant effects. DMT is structurally related to serotonin and acts as an agonist at serotonin receptor subtypes 5-HT2A, 5-HT1A and 5-HT2C; 5-HT2A agonism in particular has been implicated in visual hallucinations. Normally DMT has limited oral activity because monoamine oxidase (MAO) enzymes rapidly metabolise it; concomitant MAO inhibition (in this case phenelzine, a nonselective MAOI) prolongs and potentiates DMT's effects by preventing its breakdown. The authors note that the patient’s self-administered dosing (up to 1 g/day inhaled) is orders of magnitude higher than doses reported in clinical or recreational dose guides (reported smoked doses of 25 mg per session, with threshold inhaled doses cited as 2–5 mg and strong doses 40–60 mg). Evidence cited in the discussion is described as preliminary: small open-label and experimental studies have reported short-term increases in positive mood or relaxation after DMT or ayahuasca administration, and a small trial of 17 patients with recurrent major depressive disorder found reductions in several depression scales after a single oral ayahuasca dose. By contrast, there are no controlled studies of DMT specifically in bipolar depression and only sparse case literature linking ayahuasca/DMT to mania or psychosis. A 2017 systematic review identified three case series and six case reports of ayahuasca or DMT associated with psychosis, and the review authors reported that prolonged psychosis was not observed in controlled research settings; prolonged cases tended to have risk factors such as a personal or family psychiatric history, concurrent substance use, or repeated exposure. Finally, the report highlights the phenomenon of self-treatment among physicians: a cited survey of psychiatrists indicated substantial willingness to self-medicate for depression and a nontrivial proportion who had self-treated. The authors use this case to emphasise practical implications: clinicians should be aware of the psychiatric and physiological presentations associated with DMT use, patients with personal or family histories of psychosis or nonpsychotic mania or who use other substances should avoid hallucinogens, and the risks of self-medication among healthcare professionals merit attention.