Introduction: Vaporised medicinal cannabis has the potential to improve anorexia in people with advanced cancer however, pharmacokinetic studies are lacking. This Phase I study assessed the pharmacokinetics, safety and tolerability of vaporised botanical cannabis flower bud. 

Methods: In an advanced cancer population with anorexia, placebo/Bedrobinol® was vaporised three times a day, one hour before meals and escalated over seven days (average 0–6.96 mg delta-9-tetrahydrocannabinol (∆-9-THC)). Bloods were collected at pre-dose, 1, 5, 20, 40, 60 mins and 4 hours post dose. Safety was measured using a numerical rating scale (NRS), Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Assessment (GAD-7) and National Cancer Institute Common Terminology for Adverse Events (NCICTCAE).  Vaporiser tolerability was surveyed.

Results: Twelve participants (7 females; mean age: 66.6 years) completed the study. The dose-concentration relationship of vaporised ∆-9-THC followed standard first order pharmacokinetics, with an exponential increase between 16 and 32 mg and displayed linear kinetics on elimination. A dose-exposure relationship became relatively linear after 16 mg, with significant inter- but not intra-participant variability. A two-compartment pharmacokinetics model identified ∆-9-THC dose as a significant covariate for bioavailability. The NRS reported grade 3 “intoxicated” for 48 mg, with a general increase for “relaxed” and “drowsy”. There was a significant decrease (p<0.05) for PHQ-9 at Days 8 and 14 compared to baseline. NCICTCAE reported grade 3 hypertension on Day 1, 6 (n=2), 8 and 14 (n=1) and grade 4 constipation on Day 14 (n=1). Overall tolerability was 99.2%.

Conclusions: These findings provide robust pharmacokinetic parameters for vaporised ∆-9-THC to guide future research and is relatively safe and well tolerated at these doses for people with advanced cancer.