Anadenanthera peregrina

Ischemic heart disease, Cardiac arrhythmias, Uncontrolled hypertension

Ischemic heart disease, cardiac arrhythmias, and uncontrolled hypertension are absolutely contraindicated. Psychoactive doses of yopo produce clinically significant tachycardia, hypertension, and intense peripheral vasoconstriction (documented as facial purpling/cyanosis in historical human administration studies). These effects are inherent to the pharmacological profile and cannot be separated from the psychoactive dose range.

Epilepsy, History of seizures

Seizure disorders are a speculative relative contraindication based on general serotonergic agent class effects. Seizure threshold lowering has not been specifically documented for bufotenine but applies broadly to serotonergic agents.

Schizophrenia, Schizoaffective disorder, Family history of psychosis

Personal or family history of psychosis, schizophrenia, or schizoaffective disorder constitutes an absolute contraindication. Bufotenine is psychotomimetic at psychoactive doses. This contraindication is a class-level effect shared by all classical serotonergic psychedelics.

Bipolar I disorder, Bipolar II disorder, Active mania

Bipolar disorder, especially during manic phases, is a relative contraindication. This is a class-level contraindication for classical serotonergic psychedelics; no bufotenine-specific data exist.

Panic disorder, Severe generalized anxiety disorder

Severe anxiety disorders represent a relative contraindication given yopo's rapid onset, intense somatic effects (nausea, cardiovascular stimulation), and acute perceptual disruption. Risk of panic and acute distress is elevated outside traditional ritual contexts.

Hepatic impairment, Liver disease

Hepatic impairment is a relative contraindication. MAO-A is a primary inactivation pathway for all three seed alkaloids, and reduced hepatic MAO-A activity could increase exposure. No substance-specific hepatic safety data exist for bufotenine or yopo.

Pregnancy

Pregnancy is absolutely contraindicated. No published safety data exist for any A. peregrina preparation during pregnancy. The low molecular weight of all three alkaloids (188–218 Da) predicts placental transfer. This is a structural inference, not a substance-specific finding.

MAOI use, Banisteriopsis caapi co-administration, Syrian rue co-administration

Concurrent use of any MAO-A inhibitor — including botanical sources (Banisteriopsis caapi, Syrian rue/Peganum harmala) and pharmaceutical MAOIs (phenelzine, tranylcypromine, moclobemide) — is absolutely contraindicated. Animal pharmacokinetic studies demonstrate 3.6–4.4-fold increases in systemic 5-MeO-DMT exposure and 9.9-fold increases in bufotenine exposure with harmaline co-administration. Serotonin toxicity is the primary clinical risk.

SSRI use, SNRI use

Concurrent SSRI or SNRI use is a relative contraindication requiring taper and physician-supervised washout before yopo administration. The dual risk includes serotonin syndrome from pharmacodynamic serotonergic addition and unpredictable efficacy changes from chronic 5-HT₂A modulation. No clinical case report specific to yopo exists.

Fluoxetine use, Paroxetine use, Bupropion use

Concurrent use of CYP2D6 inhibitors alters the metabolic conversion of 5-MeO-DMT to bufotenine, producing unpredictable changes in alkaloid exposure ratios. This is particularly relevant for seeds with higher 5-MeO-DMT content (immature seeds).