An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics

J Pain Symptom Manage. 2013 Aug;46(2):207-18. doi: 10.1016/j.jpainsymman.2012.07.014. Epub 2012 Nov 8.

Abstract

Context: Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.

Objectives: This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.

Methods: In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit.

Results: The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study.

Conclusion: This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

Keywords: Cancer; THC/CBD oromucosal spray; cannabinoid; delta-9-tetrahydrocannabinol; pain.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aerosols / administration & dosage
  • Aerosols / adverse effects
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Belgium / epidemiology
  • Dose-Response Relationship, Drug
  • Dronabinol / administration & dosage*
  • Dronabinol / adverse effects*
  • Drug Tolerance
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / diagnosis
  • Neoplasms / nursing*
  • Pain Measurement / drug effects
  • Pain, Intractable / diagnosis
  • Pain, Intractable / drug therapy*
  • Pain, Intractable / etiology*
  • Palliative Care / methods*
  • Terminal Care / methods
  • Treatment Failure
  • Treatment Outcome
  • United Kingdom / epidemiology

Substances

  • Aerosols
  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Dronabinol