2C-B-FLY

Uncontrolled hypertension, coronary artery disease, or cerebrovascular disease. The identified vasoconstriction risk from 5-HT2B agonism compounds baseline cardiovascular vulnerability.

Pre-existing peripheral vascular disease or Raynaud's phenomenon. The tetrahydrobenzodifuran scaffold's vasoconstrictive properties pose direct risk to compromised peripheral circulation.

History of seizure disorders. The 5-HT2A-mediated increase in cortical excitability may lower seizure threshold.

Personal or family history of schizophrenia, schizoaffective disorder, or other psychotic spectrum disorders. 5-HT2A agonists are contraindicated due to the risk of triggering acute psychotic episodes or worsening chronic psychotic conditions.

Bipolar I and II disorder, particularly with history of mania. Risk of triggering manic episodes. The extended 7-12 hour duration of 2C-B-FLY increases the window of psychiatric vulnerability.

Significant hepatic impairment may reduce CYP2D6-mediated metabolism of 2C-B-FLY, leading to elevated plasma concentrations, prolonged duration, and increased adverse effect risk.

Pregnancy and breastfeeding are absolute contraindications. No reproductive or developmental toxicity data exist for 2C-B-FLY. Vasoactive properties and serotonergic activity pose theoretical risks to fetal development.

Concurrent use of monoamine oxidase inhibitors (pharmaceutical or botanical, including ayahuasca/harmaline) is contraindicated due to serotonin syndrome risk.

Concurrent tramadol use is contraindicated due to dangerous serotonin syndrome risk from converging serotonergic mechanisms.