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European Journal of Clinical Pharmacology

, Volume 69, Issue 4, pp 825–834 | Cite as

A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray

  • C. G. StottEmail author
  • L. White
  • S. Wright
  • D. Wilbraham
  • G. W. Guy
Pharmacokinetics and Disposition

Abstract

Purpose

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.

Keywords

Cannabidiol Cannabinoid Delta-9-tetrahydrocannabinol Endocannabinoid THC/CBD spray Pharmacokinetics 

Notes

Conflicts of interest

Darren Wilbraham had support from GW Pharmaceuticals Ltd. for the submitted work. Darren Wilbraham was employed by Quintiles, who were contracted to perform the clinical study by GW Pharmaceuticals Ltd. Colin Stott, Linda White, Stephen Wright and Geoffrey Guy are shareholders of GW Pharmaceuticals Ltd.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • C. G. Stott
    • 1
    Email author
  • L. White
    • 1
  • S. Wright
    • 1
  • D. Wilbraham
    • 2
  • G. W. Guy
    • 1
  1. 1.GW Pharma Ltd, Porton Down Science ParkSalisburyUK
  2. 2.Quintiles Drug Research Unit at Guy’s HospitalLondonUK

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