Chronic Non-Cancer Pain

Chronic non-cancer pain is highly prevalent in Australia, reportedly affecting 17% of males and 20% of females (1). Opioids have long been considered the gold standard for pain relief, however, potentially dangerous dose-limiting side effects often limits their use at higher doses (2). Despite the availability of opioids and other classes of pain medications, there still exists an unmet need for safe, more efficacious methods of chronic pain management.

Medicinal cannabis has been proposed as a potential therapy for the treatment of chronic 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 (3). Robust human data however, will remain limited until large scale controlled clinical trials are performed. From the evidence available, cannabinoids are reported to be modestly effective at most and a safe treatment option for chronic non-cancer pain.

Efficacy and Safety Data

1. Retrospective analysis of 614 Italian patients treated with cannabinoids for chronic pain (4).

  • 2% of patients used cannabinoid therapy as an adjunct to their current analgesic therapy.
  • At initial follow-up, 76.2% of patients continued the cannabinoid therapy while8% discontinued.
  • Of those that continued, an improvement associated with the therapy was reported in7%, while 34.1% reported neither an improvement nor worsening of their condition.
  • Overall, no serious adverse events (AE’s) were reported and the treatment was reported to be effective and safe in the majority of patients.

 2. Systematic review of randomized controlled trials (RCTinvestigating cannabinoids as a treatment in noncancer pain (5). 

  • 18 published trials between 2003 and 2010 were analysed.
  • 15 out of the 18 trials demonstrated a significant analgesic effect for the cannabinoid under investigation and many reported an improvement in sleep.
  • No serious AE’s were reported.
  • The majority of AE’s reported were described as mild, transient and well tolerated.
  • This current paper also refutes a claim by a previously published systematic review (6) that cannabinoid treatment for chronic pain may cause serious harm, the claim was viewed as outdated and not consistent with their clinical experience.

3. Systematic review of RCTs investigating cannabinoids as a treatment in noncancer painan updated report (7).

  • 11 additional RCTs published since previous report (5).
  • 7 reports demonstrated significant analgesic effects of the cannabinoids studied.
  • AE’s were mild to moderate and well tolerated.
  • Overall, cannabinoid treatments were found to be safe and modestly analgesic.

 4. Cannabinoidopioid interaction study (8).

  • Data were collected for 21 patients, 10 of which were on morphine treatment and 11 were receiving oxycodone.
  • Participants in both groups reported statistically significant reductions in pain ratings by day 5 of inhaling vaporised 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%.

The main limitations to these findings are short trial duration, small sample sizes and modest effect sizes.

The first long term safety study of medical cannabis use by patients suffering from chronic pain was evaluated across 7 clinics in Canada and involved 431 patients (215 in the cannabis group and 216 controls). At an average dose of 2.5g herbal cannabis per day, there was no difference in the risk for serious AEs between patients receiving cannabis treatment compared with placebo. A higher rate of mild-moderate AEs however, were reported in the cannabis group. Furthermore, a significant reduction in average pain intensity over 1 year was observed in the cannabis group in comparison to the control group (9).

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%) (10).

Products most prescribed for this condition:
  1. Currow, Phillips and Clark. Using opioids in general practice for chronic non-cancer pain: an overview of current evidence. Med J Aust 2016; 204 (8): 305-309.
  2. Deshpande, Mailis-Gagnon, Zoheiry,  Lakha. Efficacy and adverse effects of medical marijuana for chronic noncancer pain. Systematic review of randomized controlled trials.
  3. Manzanares, 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, Bentham Science Publishers Ltd.
  4. Guido Fanelli, Giuliano De Carolis, Claudio Leonardi, Adele Longobardi, Ennio Sarli, Massimo Allegri, Michael E Schatman. Cannabis and intractable chronic pain: an explorative retrospective analysis of Italian cohort of 614 patients. 2015. Canadian Family Physician Vol. 60.
  5. Lynch & Campbell. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. 2011.Br J Clin Pharmacol 72:5,  735–744.
  6. Martin-Sanchez E, Furukawa TA, Taylor J, Martin JLR. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med 2009; 10: 1353–68.
  7. Lynch & Ware. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. 2015. J. Neuroimmune Pharmacol.
  8. Abrams, Couey, Shade, Kelly and Benowitz. Cannabinoid–Opioid Interaction in chronic Pain. Nature. Vol. 90 N0. 6
  9. Ware, Wang, Shapiro and Collet. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS)
  10. Lucas and  Walsh. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. 2017 Int. Drug Policy.


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