Clinical Study to Evaluate Drug Interactions of Cannabidiol with Citalopram and Morphine in Healthy Adults

Cannabidiol (CBD) is one of the most abundant bioactive cannabinoids. Research has demonstrated CBD's ability to inhibit metabolic enzymes like cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT), potentially leading to drug interactions. However, clinical knowledge gaps remain, particularly with regard to drugs that are more commonly taken by consumers of unregulated CBD products. This study aimed to characterize the effects of daily CBD consumption, at doses typical of unregulated CBD products, on the pharmacokinetics of citalopram and morphine. These two commonly prescribed medications are metabolized by CYPs and UGTs, respectively. This open-label, sequential study involved two cohorts of 20 healthy participants. Cohort one received a single dose of citalopram (20 mg) on days 1 and 13, with CBD (2.5 mg/kg twice daily) administered for 12 days. Cohort two received a single dose of morphine (15 mg) on days 1, 4, and 11, with CBD (2.5 mg/kg twice daily) given for 9 days. The geometric mean ratio (GMR, [90% confidence interval]) for citalopram with and without CBD for 12 days was 1.43 (1.34-1.52) for the area under the plasma concentration-time curve (AUC_0-inf) and 1.12 (1.06-1.17) for the maximum observed plasma concentration (C_max). The GMR for AUC_0-inf and C_max for morphine coadministered with CBD compared to morphine alone was 1.06 (0.96-1.16) and 1.19 (1.05-1.35), respectively. For morphine with CBD for 9 days compared to morphine alone, the GMR for AUC_0-inf and C_max was 1.12 (1.00-1.26) and 1.11 (0.94-1.30), respectively. While a significant pharmacokinetic interaction between CBD and citalopram was observed, interactions between CBD and morphine, as well as its metabolites, were limited.