Research in Focus: Cannabis and Cannabinoids for Chronic Noncancer Pain Conditions

  •   December 6, 2018

Full Citation: Stockings E, Campbell G, Hall WD, Nielsen S, Zagic D, Rahman R, Murnion B, Farrell M, Weiler M, Degenhardt L. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: A systematic review and meta-analysis of controlled and observational studies. Pain 2018; 159(10):1932-1954.

Background

Chronic noncancer pain conditions (CNPC), (including neuropathic pain, arthritic pain, fibromyalgia, and general chronic noncancer pain) are common and “rank among the most significant causes of disability globally.”1 Cannabis and cannabinoids have been suggested as potential treatments for the management of chronic noncancer pain conditions, as an alternative or an adjunct to other medications. This systematic review summarizes the available evidence for the effectiveness of cannabis and cannabinoids across a range of core outcomes including pain intensity, 30% reduction in pain, 50% reduction in pain, physical and emotional functioning, and patient global impression of change.

Methods

  • Systematic review of reviews
    • Databases searched: MEDLINE, Embase, PsychINFO, and the Cochrane Database of Systematic Reviews.
  • Supplemented by four additional systematic searches of primary studies
    • Databases searched: MEDLINE, Embase, PsychINFO, the Cochrane Database of Systematic Reviews and clinicaltrials.gov.
  • Publication date: 1980-July 2017
  • Inclusion Criteria:
    • Intervention – Cannabis and cannabinoids as a primary or secondary intervention for pain.
    • Population – at least 80% of the study population experiencing one of the included pain conditions; or if less than 80% had one of the conditions, study included if subsample data could be extracted.
    • Outcome – measured at least one of three primary pain outcomes (pain intensity, 30% reduction in pain, 50% reduction in pain).
  • Cochrane Collaboration tools were used to assess risk of bias of included studies.
  • Evidence was graded using an adapted version of the GRADE tool.
  • 104 studies included (47 RCTs and 57 observational studies).
  • A total of 9,958 study participants (median study size N=42).

Findings

Pain Intensity

  • 45 RCTs reported on pain intensity.
  • Overall cannabinoids “produced a larger reduction in pain intensity than placebo groups.”
  • Calculated to be a reduction of pain intensity of 2.9mm on the 100mm VAS scale.
  • “Observational studies found no significant evidence of effect of cannabinoids in reducing pain intensity.”

30% reduction in pain

  • Among 13 RCTs, across all cannabinoids and CNCP conditions, cannabinoids were more likely than placebo to produce a 30% pain reduction.
  • Among observational studies with a comparison group, the cannabinoid nabilone was “significantly more likely to produce a 30% reduction in pain relative to placebo.”

50% reduction in pain    

  • Among five RCTs, there was “no significant evidence that cannabinoids reduced pain by 50% compared with placebo.”
  • However, three RCTs that included 390 participants found that there was a “significant effect found for non-MS related neuropathic pain.” Two observational studies also found a significant effect, however the GRADE rating of the evidence was “very low.”

Physical and emotional functioning

  • 18 RCTs found no significant effect of cannabinoids on overall physical functioning.
  • “Patients receiving any cannabinoids did not report any difference… in overall emotional functioning, or in depressive or anxiety symptoms specifically.”

Patient global impression of change (PGIC)

  • Four RCTs reported a significant increase in PGIC among patients receiving any cannabinoid compared with placebo, however confidence in these findings was rated as low to very low.

Adverse events (AEs) and study withdrawal

  • Patients receiving cannabinoids were 2.33 times more likely to experience an AE, including “dizziness, cognitive attention or disturbance, and confusion and disorientation.”
  • Patients receiving cannabinoids were 3.47 times more likely to withdraw from a study due to AEs.

Discussion

The study found moderate evidence for a reduction in pain when using cannabinoids as compared to placebo. However, 24 people needed to be treated with cannabis or cannabinoids in order for one person to achieve a 30% reduction in pain (Number Needed to Benefit or NNTB). Furthermore, only six people needed to be treated with cannabis or cannabinoids for one person to experience any adverse event (Number Needed to Harm or NNTH). The NNTB compares unfavorably to the NNTB for opioids, pregabalin and antidepressants previously reported in the literature. The NNTH in this review “was similar to that for opioids for CNCP.” Furthermore, the pooled standardized mean difference in pain intensity as measured on the 100mm VAS “was equivalent to a 3mm greater reduction on this scale compared with placebo, which is well below the 30mm reduction regarded to represent a clinically important difference in pain intensity.”

In summary, the authors state that “these medicines are unlikely to be effective in the treatment of pain.”

Limitations

The findings are limited by a high risk of bias due to small sample size and lack of reporting detail of study design in many of the publications reviewed. Most included studies evaluated cannabinoids as an adjunct to other analgesics, effecting the ability to assess their independent effect on the outcomes in question.

Relevance to physiotherapy practice in Alberta

The recent legalization of cannabis in Canada may result in increased use of cannabis and cannabinoids for pain management by patients with CNCP. Although physiotherapists do not make recommendations about or prescribe medications, they should be aware of the evidence related to these substances and be able to provide accurate patient education regarding their effects when asked.

Disclaimer: The purpose of this summary is to highlight recently published research findings. Every effort is made to ensure accuracy and clarity of the summary. Readers are encouraged to review the published article in full for further information.