25I-NBOH

coronary artery disease, uncontrolled hypertension, aortic aneurysm, recent cerebrovascular accident

The N-benzylphenethylamine class produces pronounced sympathomimetic cardiovascular activation including tachycardia, hypertension, and vasoconstriction. These hemodynamic stresses are hazardous in the setting of pre-existing cardiovascular compromise. Evidence is inferred from 25I-NBOMe case series documenting cardiovascular complications (Zawilska et al. 2020) and the known sympathomimetic profile of the NBOH/NBOMe class.

epilepsy, seizure disorder, history of febrile seizures

Seizures have been documented as a complication of severe N-benzylphenethylamine intoxication in multiple case reports and reviews (Halberstadt 2017; Zawilska et al. 2020). Individuals with pre-existing seizure disorders or reduced seizure thresholds face compounded risk. No 25I-NBOH-specific seizure data exists; classification is inferred from the NBOMe class.

schizophrenia, schizoaffective disorder, bipolar disorder, family history of psychotic disorders

Serotonergic psychedelics as a class carry risk of precipitating acute psychotic episodes or destabilizing mood disorders in vulnerable individuals. No 25I-NBOH-specific psychiatric adverse event data exists. The risk is inferred from class-level evidence for serotonergic psychedelics broadly and from case reports of agitation, confusion, and excited delirium with NBOMe compounds (Zawilska et al. 2020).

CYP2D6 poor metabolizer genotype, concurrent strong CYP2D6 inhibitor use

Nielsen et al. (2017) established CYP2D6 as the primary cytochrome P450 enzyme for 25I-NBOH metabolism, with intrinsic clearance of 118.7 mL/min/kg. Approximately 5-10% of European-ancestry individuals are CYP2D6 poor metabolizers. Reduced or absent CYP2D6 activity is expected to substantially increase systemic exposure and prolong effects. Direct glucuronidation may partially compensate but the net impact is unstudied in vivo. This contraindication is specific to 25I-NBOH within the NBOH/NBOMe series, as 25I-NBOMe is metabolized by CYP3A4 instead.

MAOI use, SSRI use, SNRI use, tramadol use

25I-NBOH is a potent full agonist at 5-HT2A/2C receptors. Combination with any agent that elevates intrasynaptic serotonin (MAOIs, SSRIs, SNRIs) or provides additive serotonergic stimulation (tramadol) creates risk of serotonin syndrome — a potentially life-threatening condition. Additionally, fluoxetine and paroxetine are strong CYP2D6 inhibitors, compounding pharmacokinetic risk with pharmacodynamic risk. Tramadol independently lowers seizure threshold.