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.
Hosseini et al.·British Journal of Clinical PharmacologyImpact 2.1
MixedGRADELow38 citations
Samplen = 12 Pat.
DurationSingle dose as well as multiple…
ControlNabiximols oromucosal spray
EndpointPharmacokinetics
Blindingoffen
DesignPhase-I-RCT (open-label, 4-way-crossover)
Cannabinoidcbd
Max. dose100.0 mg
Routeoromukosal
”Key finding
CBD wafer and oil solution were well tolerated and showed comparable bioavailability to nabiximols, with mild to moderate adverse events such as somnolence and mood changes.
Summary
Phase I safety study (n=12 healthy volunteers): CBD as sublingual wafer (25/50 mg) or oil solution (50 mg) vs. nabiximols spray. Adverse events: mild to moderate somnolence, sedation and mood changes; no serious events. Relative bioavailability wafer vs. oil: 90% CI 83–131% (equivalent). Maximum CBD plasma concentration: 9,4 ng/mL (oil) vs. 11,9 ng/mL (wafer); half-life approx. 6 hours. No statistically significant difference in AUC compared to nabiximols.
P
PopulationHealthy volunteers, n=12
I
InterventionCBD extract (Cannabis sativa) as sublingual wafer (25 or 50 mg) or oil solution (50 mg), single dose and multiple dose (50 mg twice daily over 5 days)
OutcomeComparable relative bioavailability of CBD between wafer and oil solution (90% CI: 83–131%); no statistically significant difference in AUC₀₋τ between wafer/oil solution and nabiximols; Cmax after oil solution 9,4 ng/mL, after wafer 11,9 ng/mL; Tmax approx. 4 hours; t½ approx. 6 hours
Confidence in the evidence
Very lowLowModerateHigh
Low
The second of four GRADE levels, the effect estimate is of limited reliability.
<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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<sup>-1</sup> , 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<sub>0-τ</sub> of CBD after administration of oil solution or wafer compared with nabiximols oromucosal spray.<h4>Conclusion</h4>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.