It has been estimated that two thirds of patients with advanced metastatic cancer and over half of all patients receiving anti-cancer medication experience pain (1). Furthermore, despite the availability of standard of care (SOC) pain medications, it has been reported that 1 in 3 patients do not receive adequate medication for the level of pain experienced (1). Medicinal cannabis has been proposed as a potential therapy for the treatment of cancer pain. Compelling preclinical work, (both in vitro and in animal models), has demonstrated the existence of a biochemical link between central cannabinoid receptors, THC and pain pathways (2).
Sativex, a THC, CBD formulation, has received a Notice of Compliance in Canada for its use in adult patients with cancer pain unresponsive to opioids (3). In the US, it was granted Fast Track designation in 2014 by the US FDA in order to accelerate the drug’s approval for cancer pain.
Evidence of cannabinoids effectiveness in cancer pain will remain limited until large scale controlled clinical trials are performed. From the evidence available, cannabinoids are reported to be modestly effective and a safe treatment option for cancer related pain.
Efficacy and Safety Data
Nabiximols for Opioid–Treated Cancer Patients With Poorly–Controlled Chronic Pain: A Randomized, Placebo–Controlled, Graded–Dose Trial. Portenoy et al 2012. (4)
Objective: To evaluate the safety and analgesic efficacy of adjunct nabiximol therapy (cannabinoid formulation of THC and CBD) in 3 dose ranges.
Eligible participants: Adult cancer patients with chronic pain despite a stable opioid regimen, (patients receiving methadone therapy were excluded). Total n = 263 patients. 1 x 100ul spray = THC7mg and CBD 2.5mg.
Dose: (i) Low dose: 1-4 sprays per day, n = 71 (ii) Medium dose: 6-10 sprays per day n = 67, (iii) High dose: 11-16 sprays per day n= 59 (iv) Placebo, n= 66
Results: although the 30% responder rate analysis was not statistically significant (primary endpoint), the low and medium dose groups were reported to be more analgesic when compared to placebo (P – .008 and P = 0.38). The low dose group achieved an improvement in pain by 26% compared to baseline. Improvements in sleep were reported by the low and medium dose participants.
Adverse events (AE’s): were dose related. Only the high dose group was not well tolerated.
Multicenter, Double–Blind, Randomized, Placebo–Controlled, Parallel–Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients With Intractable Cancer–Related Pain. Johnson et al 2009 (5).
Objective: To compare the efficacy of adjunct THC:CBD or THC therapy in cancer pain relief.
Eligible participants: Adult cancer patients with moderate to severe pain using strong opioids for at least 1 week. Total n = 177 (i) Group 1 THC:CBD (n = 60) (ii) Group 2, THC (n = 58) (iii) Group 3, Placebo (n = 59).
Results: THC:CBD group demonstrated a statistically significantly reduction in pain when compared to placebo. THC:CBD showed a more promising efficacy profile than THC alone.
Safety: Both THC:CBD and THC treatments were well tolerated and no safety concerns were identified.
Adjunctive Nabilone in Cancer Pain and Symptom Management: A Prospective Observational Study Using Propensity Scoring. Madia et al. (6)
Study: Prospective, observational study to assess nabilone (synthetic THC) as an adjunct analgesic therapy for cancer pain.
Cohort: Total n = 112 patients (i) Nabilone treated n = 47 (n=24 for pain, n= 12 for nausea and n=11 for anorexia. (ii) Untreated n = 65. Mean daily dose of nabilone was79mg
Resuts: Propensity-adjusted pain scores and total morphine-sulfate-equivalent use in treated patients were significantly lower than in untreated patients (both P < 0.0001). Nausea, anxiety and overall distress scores were also improved in patients receiving nabilone (P<0.0001, P<0.0284 and P< 0.0208 respectively). Patients using nabilone were less likely to start NSAIDs, gabapentin, tricyclic antidepressants, metoclopramide, dexamethasone and ondansetron and were more likely to discontinue baseline medications.
Safety: Nabilone was found to be well tolerated.
Cannabinoid-opioid interaction in Chronic Pain (Abrams et al) (7)
Interaction Study: Data were collected for 21 patients, 10 of which were on morphine treatment and 11 were receiving oxycodone.
Results: Participants in both groups reported statistically significant reductions in pain ratings by day 5 of inhaling vaporized cannabis. There were no statistically significant changes in the AUC for either opiate. Cannabis had no effect on oxycodone kinetics or metabolite levels. Cannabis exposure did decrease the Cmax of morphine sulfate but still resulted in an average pain reduction of 27%.
Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS) (Ware et al) (8)
Study: The first long term safety study of medical cannabis use by patients suffering from chronic. Evaluated across 7 clinics in Canada and involved 431 patients.
Cohort: (i) Cannabis group (n = 215), (ii) Control group (n = 216). Average dose of5g herbal cannabis per day.
Results: No difference in the risk for serious AEs between patients receiving cannabis treatment compared with placebo. Significant reduction in average pain intensity over 1 year was observed in the cannabis group in comparison to the control group.
Safety: higher rate of mild-moderate AEs, were reported in the cannabis group.
Of note, a recent survey performed in Canada on patients who are registered to purchase cannabis from Tilray, perceived cannabis to be an effective treatment for pain. Survey participants also reported cannabis use as a substitute for other prescription drugs (63%), particularly pharmaceutical opioids (30%) (9).
- Chwistek M. Recent advances in understanding and managing cancer pain. F1000Research 2017, 6(F1000 Faculty Rev):945.
- Manzanare, Julian and Carrascosa. Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes. Current Neuropharmacology, 2006, 4, 239-257
- Sativex Product Monograph. http://omr.bayer.ca/omr/online/sativex-pm-en.pdf
- Portenoy, Ganae-Motan, Allende, Yanagihara, Shaiova, Weinstein, McQuade, Wright and Fallonet. Nabiximols for Opioid-Treated Cancer Patients With Poorly-Controlled Chronic Pain: A Randomized, Placebo-Controlled, Graded-Dose Trial. The Journal of Pain. 2012
- Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. 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.
- Maida, Ennis, Irani, Corbo and Dolzhykov. Adjunctive Nabilone in Cancer Pain andSymptom Management: A Prospective Observational Study Using Propensity Scoring. J Support Oncol 2008;6:119–124.
- Abrams, Couey, Shade, Kelly and Benowitz. Cannabinoid–Opioid Interaction in chronic Pain. Nature. Vol. 90 N0. 6.
- Ware, Wang, Shapiro, Collet. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). The Journal of Pain, Vol 16, No 12 (December), 2015: pp 1233-1242
- Philippe Lucas, Zach Walsh. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. International Journal of Drug Policy 42 (2017) 30–35