Association of Cannabinoid Administration With Experimental Pain in Healthy Adults: A Systematic Review and Meta-analysis.

Importance: Cannabinoid drugs are widely used as analgesics, but experimental pain studies have produced mixed findings. The analgesic properties of cannabinoids remain unclear. Objective: To conduct a systematic review and meta-analysis of the association between cannabinoid drug administration and experimental pain outcomes in studies of healthy adults. Design, Setting, and Participants: A systematic search of PubMed, EMBASE, MEDLINE, PsycINFO, and CINAHL was conducted from the inception of each database to September 30, 2017. Studies were eligible for inclusion if they met criteria, including healthy participants and an experimentally controlled administration of any cannabinoid preparation in a quantified dose. Studies that used participants with chronic pain were excluded. Data extracted included study characteristics, cannabinoid types and doses, sex composition, and outcomes. Study quality was assessed using a validity measure previously established in published reviews. Random-effects meta-analyses were used to pool data and generate summary estimates. Main Outcomes and Measures: Experimental pain threshold, pain tolerance, pain intensity, pain unpleasantness, and mechanical hyperalgesia. Results: Eighteen placebo-controlled studies (with 442 participants) were identified. Of the 442 participants, 233 (52.7%) were male and 209 (47.3%) were female. For sample ages, 13 (72%) of the 18 studies reported a mean sample age (26.65 years), 4 (22%) reported a range, and 1 (6%) reported a median value. The search yielded sufficient data to analyze 18 pain threshold comparisons, 22 pain intensity comparisons, 9 pain unpleasantness comparisons, 13 pain tolerance comparisons, and 9 mechanical hyperalgesia comparisons. Cannabinoid administration was associated with small increases in pain threshold (Hedges g = 0.186; 95% CI, 0.054-0.318; P = .006), small to medium increases in pain tolerance (Hedges g = 0.225; 95% CI, 0.015-0.436; P = .04), and a small to medium reduction in the unpleasantness of ongoing experimental pain (Hedges g = 0.288; 95% CI, 0.104-0.472; P = .002). Cannabinoid administration was not reliably associated with a decrease in experimental pain intensity (Hedges g = 0.017; 95% CI, -0.120 to 0.154; P = .81) or mechanical hyperalgesia (Hedges g = 0.093; 95% CI, -0.059 to 0.244; P = .23). The mean quality rating across studies was good. Conclusions and Relevance: Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes. Cannabis-induced improvements in pain-related negative affect may underlie the widely held belief that cannabis relieves pain.