Impact of Dietary Fat and Oral Delivery System on Cannabigerol Pharmacokinetics in Adults

Background and Aims: Cannabigerol (CBG) is a nonintoxicating cannabinoid synthesized in the Cannabis sativa plant that is incorporated into dietary supplements. This study investigated the influence of dietary fat and an emulsified delivery vehicle on CBG pharmacokinetics (PKs) after oral ingestion by adults. Materials and Methods: Consented participants were enrolled in a double-crossover pilot study and were blinded to the delivery vehicle type (isolate or emulsification) and isocaloric meal condition (low-fat=<5 g fat/meal or high-fat [HF]=>30 g fat/meal). The concentration of CBG in human plasma was measured after a single 25 mg dose of CBG using liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using noncompartmental analysis. Results: The PKs of the two delivery systems (emulsified vs. non-emulsified) were significantly impacted by the HF meal condition. Participants in the HF meal group exhibited significantly higher area under the plasma concentration time curve from time 0 to last quantifiable value, maximum concentration, and terminal half-life. Participants in the HF meal group also had a significantly lower terminal elimination rate constant and time to maximum concentration (T_max), in addition to decreased T_max variation. The threshold for bioequivalence between conditions was not met. An exploratory aim correlated anthropometric measures and previous day's dietary intake on PK parameters which yielded inconsistent results across dietary fat conditions. Conclusions: In aggregate, dietary fat had a greater effect on CBG PKs than the emulsified delivery vehicle. This supports accounting for dietary intake in development of therapeutics and administration guidelines for orally delivered CBG.