A phase I trial of the safety, tolerability and pharmacokinetics of cannabidiol administered as single-dose oil solution and single and multiple doses of a sublingual wafer in healthy volunteers

Aims This study investigated the safety, tolerability and pharmacokinetics after administration of a specific Cannabis sativa cultivar extract, standardised to cannabidiol (CBD) content as sublingual wafer or oil formulation compared to nabiximols oromucosal spray. Methods For the single-dose study, the design was an open-label, 4-way crossover in 12 healthy volunteers randomised to receive a sequence of 4 different single doses of CBD as a sublingual wafer (25 or 50 mg CBD), oil solution (50 mg CBD), or nabiximols oromucosal spray (20 mg CBD, 21.6 mg tetrahydrocannabinol). For the multiple-dose study, sublingual wafer (50 mg CBD) was administered twice a day for 5 days. Results The extract was generally well tolerated by participants when administered in either wafer or oil form, with some adverse events, including mild or moderate somnolence, sedation and altered mood. The relative bioavailability of CBD after administration as a sublingual wafer was comparable with that of oil solution with 90% confidence interval of 83-131%. The median maximum concentrations of CBD after administration of oil solution and wafer was 9.4 and 11.9 ng mL(-1), respectively. Maximum concentrations of CBD occurred 4 hours after administration, with an estimated terminal elimination half-life of 6 hours. There was no statistically significant difference between the AUC(0-tau) of CBD after administration of oil solution or wafer compared with nabiximols oromucosal spray. Conclusion Oil solution and sublingual wafer formulations of the extract standardised with CBD were well tolerated and achieved equivalent concentrations of CBD when compared to an available commercial nabiximols formulation.

Automated summary

The study investigated the safety, tolerability, and pharmacokinetics of a specific Cannabis sativa cultivar extract standardized to cannabidiol (CBD) content administered as sublingual wafer or oil compared to nabiximols oromucosal spray. The extract was well tolerated with mild adverse events, and the relative bioavailability of CBD was comparable between wafer and oil formulations. Maximum concentrations of CBD occurred 4 hours after administration, with an estimated terminal elimination half-life of 6 hours, and no significant difference in CBD concentrations was found between oil solution, wafer, and nabiximols oromucosal spray.