CBN

severe hepatic impairment, cirrhosis, acute liver failure

CBN is extensively metabolized by multiple hepatic CYP enzymes and was identified as the most rapidly biotransformed phytocannabinoid in the Havlasek et al. 2023 panel. Severe hepatic impairment would be expected to substantially reduce CBN clearance, increasing systemic exposure and potentially crossing psychoactive thresholds. No hepatic impairment PK studies for CBN have been conducted.

tacrolimus, cyclosporine, sirolimus, atorvastatin, simvastatin, ritonavir, efavirenz, midazolam

CBN is a potent human PXR agonist (17-fold activation at 10 µM, MEC 0.3 µM). PXR-mediated CYP3A4 induction could reduce plasma levels of narrow-therapeutic-index CYP3A4 substrates including immunosuppressants, statins, and antiretrovirals. Dose adjustments or therapeutic drug monitoring may be necessary. This mechanism has been characterized in vitro only — no human pharmacokinetic interaction studies exist for CBN.

warfarin, phenytoin, celecoxib

As a CYP2C9 substrate (Havlasek et al. 2023, Stout & Cimino 2014), CBN may competitively inhibit metabolism of co-administered CYP2C9 substrates. Warfarin is of particular concern: even modest inhibition of CYP2C9-mediated metabolism can produce clinically significant INR changes. All interaction data derive from in vitro assays — no human pharmacokinetic interaction studies exist.

pregnancy, lactation

No CBN-specific reproductive or developmental toxicity data have been published. Consistent with general cannabinoid class precautions — CB1 receptors are expressed in developing neural tissue, and lipophilic cannabinoids cross the placenta and enter breast milk — CBN should be considered contraindicated in pregnancy and lactation until safety data are available.

operating vehicles, operating heavy machinery

While CBN is minimally psychoactive at typical commercial doses (≤5–10 mg oral), theoretical concern exists at higher pharmacological doses. The CUPID trial protocol explicitly includes simulated driving as a safety endpoint, reflecting recognition of this concern. No controlled human data on CBN's effects on psychomotor performance currently exist.

alcohol, benzodiazepines, opioids, barbiturates, sedating antihistamines

Additive sedation is theoretically possible when CBN is combined with other CNS depressants. This concern is based on CB1 partial agonism and putative GABA_A allosteric modulation — both of which contribute to CNS depression. No clinical data characterize this interaction for CBN specifically. The concern is extrapolated from the cannabinoid class.