A Randomized, Single-Dose, Single-Sequence, Two-Arm (Fasting and Fed), Open-Label Study on the Oral Pharmacokinetics...

Cannabidiol (CBD), a non-psychoactive phytocannabinoid, attributed to its therapeutic benefits and positive safety profile is being studied for its potential to treat various medical conditions. The low oral bioavailability and significant first-pass metabolism present pharmacokinetic (PK) challenges. The present study aimed to evaluate the PK profile of a novel nanodispersible CBD oral solution (150 mg/mL) under fasting and fed conditions in healthy male subjects.

In this randomized, single-dose, two-arm (fasting and fed), open-label trial, 18 subjects (9 fasting and 9 fed) received 300 mg of CBD (2 mL of 150 mg/mL). Plasma concentrations of CBD and its major metabolites, specifically 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD) were quantified and the PK parameters including C_max, time to reach maximum concentration (T_max), AUC_0-∞, and t½ were analyzed using non-compartmental modeling methods.

The fed state significantly increased the area under the curve (AUC_0-∞) for CBD by 3.0-fold (p < 0.0001) and prolonged the T_max. C_max was moderately higher in the fed state (1.3-fold). The 7-COOH-CBD metabolite reached the highest plasma concentration, followed by the parent CBD and 7-OH-CBD. The administration of nanodispersible CBD oral solution was well tolerated, with no major adverse events.

The nanodispersible CBD oral solution showed enhanced bioavailability under fed conditions and was well tolerated in healthy subjects. Food intake increased CBD's C_max and AUC and delayed T_max. Further studies are required to confirm the therapeutic efficacy in patient populations.