6-APB

Any history of valvular heart disease, including mitral valve prolapse, aortic stenosis, or prosthetic valves, represents an absolute contraindication due to the established mechanism of 5-HT2B agonist-induced valvulopathy.

Pre-existing cardiac arrhythmias or conditions predisposing to arrhythmia (including long QT syndrome) increase risk from 6-APB's sympathomimetic cardiovascular effects.

Personal or family history of psychotic disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder) constitutes a relative contraindication. The Chan et al. (2013) case report of 6-APB-associated psychosis supports caution.

Bipolar disorder (types I and II) is a relative contraindication due to the risk of monoamine-triggered mood destabilization.

Pre-existing liver disease, including cirrhosis, hepatitis, or significantly elevated liver enzymes, warrants caution. In vitro data demonstrate CYP-mediated formation of hepatotoxic metabolites from 6-APB.

Pregnancy and breastfeeding are absolute contraindications. No reproductive or developmental toxicity data exist for 6-APB. Monoamine disruption during fetal development carries established risks from related compound classes.

Concurrent use of any monoamine oxidase inhibitor (including moclobemide, phenelzine, tranylcypromine, selegiline, and the ayahuasca component harmaline) is an absolute contraindication. This combination creates extreme risk of serotonin syndrome and hypertensive crisis.

Concurrent use of SSRIs, SNRIs, triptans, lithium, or other serotonin-modulating medications increases the risk of serotonin syndrome. SSRIs may also blunt the entactogenic effects by blocking SERT-mediated release.