Cannabis and/or cannabinoids, when consumed through certain routes of administration, may reduce pain levels significantly, according to a systematic review and meta-analysis published in the Journal of the American Pharmacists Association.

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the 2 active ingredients in cannabis responsible for pain mitigation, with bioavailability and analgesic effect that depend on the administration route. Although cannabis has proven effective for managing pain secondary to neuropathy, cancer, HIV, multiple sclerosis, diabetes, and spinal injuries, more studies are needed to characterize the effects of cannabis and its routes of administration on analgesic safety and efficacy. Investigators sought to describe the current understanding of these effects by reviewing the literature.

In this systematic literature review and meta-analysis, a total of 39 and 25 studies were examined for qualitative synthesis and quantitative analysis, respectively (n=2270 patients). The PubMed, Embase, ClinicalTrials.gov, ScienceDirect, Scopus, and Cochrane Library databases were searched through June 2017 for relevant studies. All studies were randomized controlled trials in which the use of cannabis (dosage range, 2-96 mg/day) in pain management was examined and was assessed in the majority of studies using a visual analog scale or numeric rating scale for pain. The primary efficacy and safety outcomes were pain scores and psychiatric adverse events, respectively.

Two main reviewers assessed study quality using the Cochrane risk for bias tool. Standardized mean differences (SMDs) were calculated to indicate effect sizes, and a random effects model was used to pool treatment effects. Relative risk (RR) was also calculated to determine the incidence of adverse euphoria, which was the review’s safety outcome.

Neuropathic pain scores were found to be reduced for the following drugs and routes of administration: a combination of THC and CBD (THC/CBD) by the oromucosal route (SMD, -0.41; 95% CI, -0.7 to -0.1); THC alone by the oromucosal route (SMD -0.61; 95% CI, -1.2 to -0.02); and standardized dried cannabis with THC (SCT) by the inhalation route (SMD, -0.77; 95% CI, -1.4 to -0.2). Nociceptive pain scores were lowered by standardized cannabis extract with THC (SCET) by the oral route (SMD, -1.8; 95% CI, -2.4 to -1.2). Cancer pain was alleviated by THC/CBD by the oromucosal route (SMD, -0.7; 95% CI, -1.2 to -0.2), and THC by the oral or oromucosal route (SMD, -2.1; 95% CI, -2.8 to -1.4). In a mean rank analysis, SCET was found to provide the most benefit for pain control, followed by SCT, THC, and THC/CBD, in that order.

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No evidence was found in any study regarding the safety and efficacy of THC/CBD (oral or inhalation route) or THC (inhalation route) for nociceptive or cancer pain, THC (oromucosal route) for nociceptive pain, SCET (oromucosal or inhalation route) for neuropathic or cancer pain, or SCT (oral or oromucosal route) for neuropathic, nociceptive, or cancer pain.

The risk for euphoria was increased with THC by the oromucosal route vs placebo (RR, 4.36; 95% CI, 1.21-15.68), THC/CBD by the oromucosal route (RR, 4.16; 95% CI, 1.27-13.59), and SCT by the inhalation route (RR, 1.74; 95% CI, 1.13-2.67). A total of 28 and 11 studies were found to have a low and high risk for bias, respectively.

Study strengths include disease specificity and inclusion of more randomized controlled trials than in prior reviews. Study limitations include the use of a single study to assess the effect of cannabinoids on nociceptive pain.

“Product developers could consider our findings as part of their product design so that the effective route of cannabis and cannabinoids for pain control can be achieved,” noted the authors.

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Reference

Rabgay K, Waranuch N, Chaiyakunapruk N, Sawangjit R, Ingkaninan K, Dilokthornsakul P. The effects of cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: A systematic review and network meta-analysis [published online September 5, 2019]. J Am Pharm Assoc (2003). doi:10.1016/j.japh.2019.07.015