Cannabinoids Don't Relieve Pain So Much as Boost Tolerance

Cannabinoids appear to help people handle more pain but don't reduce pain intensity, according to a meta-analysis of experimental human studies.

Across 18 placebo-controlled studies, cannabinoids increased pain thresholds (Hedges g 0.186, 95% CI 0.054-0.318, P=0.006), but did not reduce the intensity of pain already felt by participants (g 0.017, 95% CI −0.120 to 0.154, P=0.81), according to Martin De Vita, MS, of Syracuse University in New York, and colleagues.

Instead, cannabinoids appear to make pain feel less unpleasant (g 0.288, 95% CI 0.104-0.472, P=0.002) and more tolerable (g 0.225, 95% CI 0.015-0.436, P = 0.04), which implies cannabinoids are influencing the affective component of pain rather than the sensory aspect, the authors wrote in JAMA Psychiatry. (Hedges g values indicate effect sizes on a standardized scale, "with 0.20 corresponding to small size, 0.50 corresponding to medium size, and 0.80 corresponding to large size," the authors explained.)

"If you think of pain as a noxious sound coming from a radio, the volume is the intensity of that pain," De Vita told MedPage Today. "After using cannabinoid drugs, it may not decrease the volume of the noxious noise, but it may tune it to a station that's a little less unpleasant. It won't be the most beautiful music you've ever heard -- it will still be pain -- but it will be a little less unpleasant."

The group's study sought to consolidate data from a growing body of research examining the role of cannabinoids in pain management. Despite cannabis having been legalized for pain management treatment in many U.S. states, some previous studies found little solid evidence that cannabinoids are effective in treating pain. In general, there are numerous confounding factors -- such as dosage and type of cannabinoid administered, as well as patient characteristics like sex -- that can influence results.

De Vita told MedPage Today that most previous studies have examined patients with chronic pain, which often occurs alongside depression, anxiety, or other conditions that could influence the effectiveness of cannabinoid treatment.

"When you're looking at [cannabinoid treatment] in healthy patients, you're going back to those basic pain processes that should be functioning and seeing how cannabinoids actually work on those processes without those additional factors," he said.

Taking data from PubMed, EMBASE, MEDLINE, PsycINFO, and CINAHL databases, De Vita and colleagues identified 26 full-text articles, excluding eight because they included participants with chronic pain. Studies were restricted to those enrolling generally healthy individuals who were subjected to standardized pain stimuli in laboratory settings.

The authors took several measures to ensure accurate effect sizes, including pooling effect sizes when studies used multiple pain-induction methods; treating each cannabinoid type tested as an individual comparison; and extracting "peak effects" from studies that measured pain after cannabis was administered.

Quality and validity scores were high across measures of pain threshold, tolerance, intensity, and unpleasantness, as well as across mechanical hyperalgesia (average: 9.8 out of 12), with 17 studies (94%) using randomization and 16 (89%) using blinding techniques.

Just over half of study participants were male. Among those studies reporting a mean age for participants (some did not), the average was 27.

The reports examined were conducted in the United States, Canada, and Europe from 1974 to 2016. Six studies administered plant-based cannabis (33%), while others administered different forms of synthetic tetrahydrocannabinol (THC), cannabis extract, or synthetic cannabinoids.

Reduced mechanical hyperalgesia, which reflects central sensitization, was not associated with the intake of cannabinoids (g 0.093, 95% CI −0.059 to 0.244, P=0.23) across all studies.

In their analysis of pain threshold, researchers found that relatively high cannabinoid dosages were associated with improved pain management, whereas low doses were not (g 0.334 versus g -0.023; P<0.001 versus P=0.77).

The association was also stronger between reduced unpleasantness and cannabinoid administration when participants were given plant-based cannabis (g 0.499, P<0.001), as opposed to synthetic THC substances (g 0.298, P=0.10). The administration of plant-based cannabis (g 0.471, P<0.001) and dronabinol (g 0.313, P=0.002) were both associated with improved pain tolerance as well.

The composition of males and females in the studies did not significantly affect the study's results (P>0.05).

Further research needs to be conducted in order to determine neuropathic pain data and specifically test which forms of cannabinoid treatment, at which doses, and in which populations, are most effective, De Vita said. He also encouraged future studies that administer non-psychoactive cannabinoids, such as cannabidiol, to reduce bias.

The authors cited the psychoactive nature of cannabinoids as a study limitation, since participants "feel high" when given the active treatment and thus blinding can be comprised. Additionally, the data only recorded static pain measurements and did not assess patient pain across a period of time. For some studies examined, the data was collected at "peak effect" points, which may mean the results were underestimated. The type and dose of cannabinoids distributed across participants also differed, which limits this study's generalizability.

"Everyone is saying we need more research and that we need to catch up," De Vita said. "This is a first step in doing that, starting from the fundamentals of how cannabinoids affect basic pain processes, and now we need to determine some of these follow-up questions."

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