Safety, pharmacodynamics, and pharmacokinetics of oral cannabigerol in healthy adults.

Cannabigerol (CBG) is a minor cannabinoid that has been considered as a potential therapeutic, yet basic acute pharmacodynamics and pharmacokinetics across commercially available doses have not been examined. To complete this critical step, healthy adults (n = 12) were enrolled in a single ascending dose human laboratory study where they consumed 0, 25, 50, 100, and 200 mg of CBG isolate suspended in medium-chain triglyceride oil. The placebo administration occurred randomly within the dosing sequence. Standardizing flavor and solution volume facilitated blinding. Adverse events were recorded throughout to characterize safety and tolerability. Pharmacodynamic outcomes (ie, subjective, cognitive, and physiological responses) and plasma samples were collected at baseline and regular intervals after drug administration (0.5-, 1-, 1.5-, 2-, 3-, 4- , 5-, 6-, and 8-hours). Pharmacokinetic parameters (eg, peak plasma CBG concentration) were also measured. Liver function tests were characterized at baseline and after acute administration of the 2 highest doses. No drug-related adverse events occurred. Subjective effects associated with CBG administration were minimal with the exception of significant decreases in self-reported ratings of Jittery and Active associated with 50 mg, significant decreases in Calm associated with 100 mg, and increases in Appetite associated with 200 mg of CBG. Pharmacokinetics were dose-orderly, but significant individual variability was observed. Liver function tests never exceeded the upper limit of normal following acute administration of the highest doses. Overall CBG was well-tolerated with no robust pharmacodynamic effects; chronic dosing studies are needed to more fully characterize the safety and pharmacodynamic profile of oral CBG. SIGNIFICANCE STATEMENT: Cannabigerol has garnered attention as a potential therapeutic for many diagnoses before the fundamental studies investigating its pharmacokinetics and pharmacodynamics have been completed. We aimed to provide this information through a single ascending dose study, finding that cannabigerol is well-tolerated while yielding few pharmacodynamic or psychoactive effects.