Post Notification Withdrawal Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Pilot clinical and pharmacokinetic study of a water soluble nanoparticle cannabis-based medicine in advanced cancer with intractable pain. (#219)

Stephen Clarke 1 2 3 , Belinda Butcher 4 5 , Andrew J McLachlan 6 , Jeremy D Henson 7 8 , David Rutolo 8 , Sean Hall 8 , Luis Vitetta 1 8
  1. Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
  2. Northern Clinical School Kolling Institute of Medical Research, Sydney, NSW, Australia
  3. Oncology, GenesisCare, Sydney, New South Wales, Australia
  4. WriteSource Medical Pty Ltd., , Lane Cove , New South Wales, Australia
  5. The University of New South Wales, School of Medical Sciences, Sydney, New South Wales, Australia
  6. The University of Sydney, School of Pharmacy, Sydney, NSW, Australia
  7. The University of New South Wales, Prince of Wales Clinical School, Sydney, NSW, Australia
  8. Medlab Clinical, Sydney, NSW, Australia

Relief from chronic pain has been a common reason cited by patients for the medical use of cannabis.1-3 A two-stage open label single arm study (n=30) assessed a single ascending dose (SAD; Stage 1) and multiple ascending doses (MAD; Stage 2) of a standardised and purified mixture of Δ9-Tetrahydrocannabinol (Δ9-THC)/Cannabidiol (CBD) in a water-soluble nanoparticle oro-buccal spray formulation for the management of intractable pain in people with advanced cancer. On day 1 Stage I participants received 2.5 mg Δ9THC and 2.5 mg CBD (two sprays); escalating to 7.5 mg Δ9-THC and 7.5 mg CBD (six sprays) on day 2.  In Stage II, participants administered daily Δ9-THC/CBD as one spray containing 1.25 mg Δ9-THC and 1.25 mg CBD; two sprays; or three sprays every four hours unless asleep. Δ9-THC and CBD were rapidly absorbed. As single and multiple doses were increased, maximum observed plasma concentrations (Cmax) of all analytes were proportional to dose. The bioavailability of Δ9-THC and CBD in this water-soluble nanoparticle formulation was approximately twice the bioavailability reported for a Δ9-THC/CBD spray that uses ethanol as the vehicle. The water-soluble cannabis-based medicine resulted in a higher bioavailability of Δ9-THC than CBD (bioavailability from 2.5 mg each of Δ9-THC and CBD was 2.8 ng/mL.h and 1.5, respectively).  In a subgroup of participants diagnosed with breast and prostate cancer with bone metastases, the mean pain scores improvement from baseline was approximately 40% (unadjusted) and 33% adjusted for rescue medication use. For all patients the most commonly reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided adequate bioavailability for Δ9-THC and CBD, appears safe and tolerable in people with cancer and uncontrolled pain with preliminary evidence of analgesic efficacy.

  1. Fraguas-Sanchez, A.I.; Torres-Suarez, A.I. Medical Use of Cannabinoids. Drugs 2018, 78, 1665-1703.
  2. Borgelt, L.M.; Franson, K.L.; Nussbaum, A.M.; Wang, G.S. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 2013, 33, 195-209.
  3. National Academies of Sciences, E.; Medicine; Health; Medicine, D.; Board on Population, H.; Public Health, P.; Committee on the Health Effects of Marijuana: An Evidence, R.; Research, A. The National Academies Collection: Reports funded by National Institutes of Health. In The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, National Academies Press (US) 2017 by the National Academy of Sciences. All rights reserved.: Washington (DC).