5-APB

Any pre-existing valvular heart disease, including mitral valve prolapse, aortic stenosis, or regurgitation of any valve, represents an absolute contraindication. 5-APB's potent 5-HT₂B full agonism drives the same fibrotic pathway responsible for fenfluramine-associated valvulopathy.

Pre-existing cardiac arrhythmias including atrial fibrillation, long QT syndrome, and Wolff-Parkinson-White syndrome are absolute contraindications. Case reports document significant tachycardia, ECG changes, and elevated troponin T during intoxication.

Epilepsy or other seizure disorders represent a relative contraindication. Seizures are documented in the first published fatal case (Adamowicz et al. 2014) and are a recognized feature of stimulant-entactogen toxicity.

Active or historical psychotic disorders including schizophrenia and schizoaffective disorder are absolute contraindications. 5-APB's 5-HT₂A agonist activity exceeds MDMA, and hallucinations are documented at high doses.

Pre-existing liver disease, hepatic insufficiency, or active hepatitis is an absolute contraindication. 5-APB demonstrated greater hepatotoxicity than both 6-APB and MDMA in vitro, with CYP3A4 confirmed as mediating toxic activation.

Pregnancy and breastfeeding are absolute contraindications. No reproductive safety data exist. Class-level risks from amphetamine-type compounds include vasoconstriction, hyperthermia, and disrupted monoamine signaling during fetal development.

Concurrent use of any monoamine oxidase inhibitor — pharmaceutical (phenelzine, tranylcypromine, moclobemide) or botanical (harmine, harmaline in ayahuasca) — is absolutely contraindicated. The additive MAO inhibition layered on 5-APB's serotonin release creates maximal serotonin toxicity risk.

Concurrent serotonin or serotonin-norepinephrine reuptake inhibitor therapy is an absolute contraindication. The triple serotonergic mechanism of 5-APB makes any additional serotonergic input potentially dangerous.