A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray.
OBJECTIVE
To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects.


METHODS
Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).


RESULTS
Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2-2.5 h. Only mild adverse events were reported.


CONCLUSIONS
The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.
GW Pharma Ltd, Porton Down Science Park, Salisbury, Wiltshire, UK. cgs@gwpharm.com
C G
CG
Stott
L
L
White
S
S
Wright
D
D
Wilbraham
G W
GW
Guy
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D062408:Breakfast; D002185:Cannabidiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage; D013759:Dronabinol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005215:Fasting; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism*; D058993:Oral Sprays; D055815:Young Adult
D004041:Dietary Fats; D004338:Drug Combinations; D058993:Oral Sprays; D002185:Cannabidiol; D013759:Dronabinol