Ayahuasca

Uncontrolled hypertension, Arrhythmia, Recent cardiac events

Ayahuasca produces moderate sympathomimetic cardiovascular effects including tachycardia and diastolic blood pressure increase of approximately 9 mmHg at 0.85 mg DMT/kg. While these effects are not comparable in magnitude to sympathomimetic stimulants, they pose risk for individuals with pre-existing severe cardiovascular disease, uncontrolled hypertension, or recent cardiac events. Clinical trial protocols systematically exclude cardiovascular-compromised participants.

Concurrent lithium use

Seizure risk with concurrent lithium and ayahuasca has been noted in harm reduction literature and clinical practice guidelines. The mechanism is plausible given lithium's effects on serotonin neurotransmission combined with ayahuasca's MAO-A inhibition and 5-HT2A agonism. However, specific peer-reviewed case reports documenting this interaction with ayahuasca were not identified in this review. This contraindication is flagged for human review.

Active psychosis, Schizophrenia, Schizotypal personality disorder, Family history of psychotic disorders

Ayahuasca's primary psychedelic mechanism — DMT partial agonism at 5-HT2A receptors — carries risk of precipitating or exacerbating psychotic episodes in individuals with personal or family history of psychotic spectrum disorders. This is a class-level contraindication shared with all serotonergic psychedelics. No published prevalence estimate specific to ayahuasca-induced psychosis was identified, but the mechanism is well-established and consistently applied in clinical trial exclusion criteria.

Acute bipolar disorder (mania), Bipolar I disorder, Bipolar II disorder

Mania risk with ayahuasca is not fully characterized in the literature but is mechanistically plausible given serotonergic activation via DMT's 5-HT2A agonism and beta-carboline MAO-A inhibition. Individuals in acute manic episodes or with history of manic episodes should exercise caution. This is treated as a relative contraindication pending further clinical characterization.

Severe hepatic impairment, Cirrhosis, Acute liver failure

Harmine and harmaline are primarily metabolized via hepatic CYP2D6 and CYP1A2. Severe hepatic impairment may reduce clearance of beta-carboline alkaloids, prolonging the window of MAO-A inhibition and increasing DMT plasma exposure. No clinical case reports of hepatotoxicity from ayahuasca were identified in the literature. This contraindication is based on mechanistic pharmacokinetic reasoning only.

Pregnancy, Planned pregnancy

Da Motta et al. (2018) administered ayahuasca orally to rats on gestation days 6–20. At 2× human equivalent dose, neuronal loss was observed in the hippocampal CA1 region. At 4× and 8× doses, maternal mortality reached 44–52% with kidney injury; the 8× dose produced neuronal loss in hippocampus and raphe nuclei, embryo deaths, and fetal anomalies. While formal extrapolation to humans is limited, these findings constitute a clear developmental toxicity signal and an absolute contraindication for use during pregnancy.

SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), SNRIs (venlafaxine, duloxetine), MAOIs (phenelzine, tranylcypromine, moclobemide), Tramadol

Beta-carboline alkaloids in ayahuasca reversibly inhibit MAO-A. Co-administration with serotonergic medications creates dual risk: pharmacokinetic (PBPK modeling predicts fluoxetine and paroxetine significantly increase DMT and harmine plasma exposure via CYP2D6 inhibition) and pharmacodynamic (serotonin accumulation from combined MAO-A inhibition and reuptake blockade). This combination carries risk of serotonin syndrome — a potentially fatal emergency characterized by hyperthermia, neuromuscular rigidity, autonomic instability, and altered mental status. Minimum washout of 2 weeks from most SSRIs/SNRIs is recommended; fluoxetine requires 5 weeks due to long-half-life active metabolite norfluoxetine.