title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Shropshire and Mid-Wales Hospice, Shrewsbury, Shropshire, United Kingdom. jeremyjohnson@severnhospice.org.uk
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Dominique
authors.initials: D
authors.lastname: Lossignol
authors.forename: Mary
authors.initials: M
authors.lastname: Burnell-Nugent
authors.forename: Marie T
authors.initials: MT
authors.lastname: Fallon
mesh_terms: D000284:Administration, Oral; D000336:Aerosols / Q000008:administration & dosage / Q000009:adverse effects; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use; D001530:Belgium / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000009:adverse effects*; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000451:nursing*; D010147:Pain Measurement / Q000187:drug effects; D010148:Intractable Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D010166:Palliative Care / Q000379:methods*; D013727:Terminal Care / Q000379:methods; D017211:Treatment Failure; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000336:Aerosols; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D013759:Dronabinol
keywords: Cancer; THC/CBD oromucosal spray; cannabinoid; delta-9-tetrahydrocannabinol; pain