Cannabinoid-Associated Analgesia May Be Mediated Through Modulation of Affective Processes

Cannabis Sativa
Cannabis Sativa
The analgesic effects of cannabinoid drugs may be mediated by a modulation of affective vs sensory processes.

The analgesic effects of cannabinoid drugs may be mediated by a modulation of affective vs sensory processes, according to a study published in JAMA Psychiatry.

The researchers conducted a systematic search of PubMed, EMBASE, MEDLINE, PsycINFO, and CINAHL from the inception of each database through September 30, 2017. They included studies in which healthy participants (but not individuals with chronic pain) were enrolled and in which a cannabinoid was administered in an experimentally controlled and quantified manner.

In total, 18 placebo-controlled studies with 442 participants were included and examined a total of 18 pain threshold comparisons, 22 pain intensity comparisons, 9 pain unpleasantness comparisons, 13 pain tolerance comparisons, and 9 mechanical hyperalgesia comparisons. 

To palliate variations in the way in which experimental pain outcomes were assessed across studies, a Hedges g factor was calculated to standardize effect size (Hedges g of 0.20, 1.50, and 0.80 indicating small, medium, and large effect sizes, respectively; positive and negative Hedge g values indicating analgesia and hyperalgesia, respectively).

Cannabinoid administration was found to be 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).

No associations were established between cannabinoid administration and 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).

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“The long-term association of regular cannabinoid use with pain is poorly understood, and future research should investigate whether chronic use dysregulates pathophysiologic pain processes that increase the risk for chronic pain development,” the researchers wrote.


De Vita MJ, Moskal D, Maisto SA, Ansell EB. Association of cannabinoid administration with experimental pain in healthy adults: a systematic review and meta-analysis [published online September 19, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.2503