Identification of genetic biomarker signatures associated with cannabis pharmacokinetics and tolerability

Medical cannabis has been increasingly prescribed for a range of conditions including epilepsy, chronic neuropathic pain, and chemotherapy-induced nausea and vomiting. The benefits and possible adverse events of medical-grade cannabis products vary between patients, suggesting that genetics may play a role in the pharmacokinetics of the cannabinoids, yet regulatory restrictions have led to limited clinical studies. This study is aimed at identifying a genetic signature that is predictive of the pharmacokinetics of tetrahydrocannabinol (THC), the principal intoxicating chemical compound derived from cannabis. We have identified 55 variants among 38 genes that were overrepresented in either the Low-THC or High-THC groups. Saliva samples were obtained from 28 healthy subjects who consented to the genetics sub-study after participating in a controlled pharmacokinetic study on a THC extract capsule. Subjects were grouped as ‘Low-THC’ or ‘High-THC’ based on the profile of their plasma THC concentration over various timepoints following intake of 5 mg or 10 mg THC under fed and fasting conditions. DNA, extracted from their saliva, was then analyzed using Illumina's Infinium DrugDev microarray.