Poster Presentation NSW State Cancer Conference 2023

Phase I/IIb dose-ranging study and development of a two-compartment model of vaporised cannabis flower bud in people with advanced cancer experiencing anorexia (#231)

Valentina Naumovski 1 , Jennifer Martin 2 , Peter Galettis 2 , Zheng Liu 2 , Richard Chye 3 , Nicholas Lintzeris 4 , Jane Phillips 5 , Nadia Solowij 6 , Melanie Lovell 7 , Linda Brown 8 , Belinda Fazekas 8 , Meera Agar 8
  1. University of New South Wales, Kensington, NSW, Australia
  2. Discipline of Clinical Pharmacology, Hunter Medical Research Institute (HMRI), University of Newcastle, Newcastle, NSW, Australia
  3. Sacred Heart Palliative Care Service, St Vincent's Hospital, Sydney, NSW, Australia
  4. Discipline of Addiction Medicine, University of Sydney, Sydney, NSW, Australia
  5. Faculty of Health, Queensland University of Technology , Brisbane, QLD, Australia
  6. School of Psychology , University of Wollongong, Wollongong, , NSW, Australia
  7. Greenwich Palliative and Supportive Care Services, HammondCare, Sydney, NSW, Australia
  8. Faculty of Health, University of Technology Sydney, Sydney, NSW, Australia

PURPOSE Vaporised medicinal cannabis has potential to improve anorexia in advanced cancer however, studies are lacking. This Phase I/IIb study assessed the pharmacokinetics, safety and feasibility of delta-9-tetrahydrocannabinol (∆-9-THC)-dominant vaporised cannabis flower bud.

PARTICIPANTS AND METHODS In an inpatient, advanced cancer population with anorexia, placebo/cannabis combination (50 mg) was vaporised one hour before meals, three times a day for seven days (dose escalation 0–6.96/7.39 mg ∆-9-THC). Blood sampling occurred at pre-dose, 1, 5, 20, 40, 60 and 240 minutes post-dose. Safety endpoints were numerical rating scale (NRS), Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Assessment (GAD-7), National Cancer Institute Common Terminology for Adverse Events (NCICTCAE) and vaporiser tolerability. Feasibility included completion of all measures at all time points and vaporiser usage and acceptance.

RESULTS Twelve participants (seven females; mean age: 66.6±8.1 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 linear kinetics on elimination. A dose-exposure relationship becomes 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 score was 3 “intoxicated” for 48 mg, with a significant increase for “relaxed” and “drowsy” (both p=0.012). There was a significant decrease (p<0.05) for PHQ-9 at Days 8 and 14 compared to baseline. NCICTCAE recorded grade 3 hypertension on Days 1, 6 (both n=2), 8 and 14 (n=1) and grade 4 constipation on Day 14 (n=1). Tolerability was 99.2% of the time. For feasibility, >97% of the measures were answered. Vaporiser usage and acceptance was “very easy/easy” and “acceptable”, respectively (n=11).

CONCLUSION: This study shows that vaporised ∆-9-THC is relatively safe and well tolerated at these doses and provides robust parameters to guide future research for people with advanced cancer-related anorexia.