Cannabinoid Fares Well for Pain Threshold and Tolerance, But Not Decreases

Cannabinoid drugs may have potential for a single avenue in pain management therapy, according to a new systematic review and meta-analysis.

In a study conducted by investigators with the Syracuse University Department of Psychology and Program in Neuroscience, the plant-based cannabis therapies were found to be beneficial in varying improvements to patient tolerance and threshold for pain across 18 placebo-controlled studies.

The new analysis comes at a time of increasing interest in cannabinoid analgesia, investigators—led by Martin J. De Vita, MS—noted. As US public policies have opened the door for legal cannabis therapy, refined research into the anagelsic properties of the compound drug is in demand. In some cases of previous studies, cannabis has been associated with increased pain, despite being predominately researched and prescribed for pain management.

“To our knowledge, the varied findings from the literature have never been quantitatively synthesized,” investigators wrote. “This systematic review aimed to use meta-analysis to evaluate the evidence for cannabinoid analgesia in healthy adult participants in experimental pain studies.”

Investigators conducted a systematic search of 5 online databases from the date of the databases’ inception to September 30, 2017. Eligible studies involved healthy participants and a controlled administration of any cannabinoid preparation, in quantified doses. They excluded studies involving participants with chronic pain.

Among the 18 studies assessed for the meta-analysis, 12 (66.67%) tested for threshold outcomes, and 6 (33.33%) tested for combined outcomes. The leading types of cannabinoid featured in the studies were plant-based cannabis (n = 6 [33.33%]) tetrahydrocannabinol (THC) (5 [27.78%]), and dronabinol (3 [16.67%]). A majority of the therapies were administered in capsule (n = 10 [55.56%]), as well as in cigarettes (4 [22.22%]).

Just 13 studies reported a mean sample age (26.65 years); 4 reported a range, and just 1 reported a median value. However, investigators collected enough data to assess 18 pain threshold comparisons, 22 pain intensity comparisons, 9 pain unpleasantness comparisons, 13 pain tolerance comparisons, and 9 hyperalgesia comparisons.

Cannabinoid administration was associated with incremental increases in pain threshold (Hedges g = .186; 95% CI; .054-.318; P = .006), greater increases in pain tolerance (Hedges g = .225; 95% CI; .0150-.436; P = .04), and even greater increases in reduction of ongoing experimental pain reduction (Hedges g = .288; 95% CI; .104-.472; P = .002).

But investigators also found cannabinoid was not reliably associated with decreases in experimental pain intensity (Hedges g = .017; 95% CI; -.120 - .154; P = .81) or mechanical hyperalgesia (Hedges g = .093; 95% CI; -.059 - .244; P = .23). The differing results led investigators to believe that cannabinoids’ most direct influence is on the patient’s affective processes. They also found through moderation analysis that plant-based cannabis was more strongly associated with pain unpleasantness and pain tolerance than synthetic forms of the drug.

Though validity scores were good, the GRADE ratings for pain threshold, intensity, unpleasantness, and tolerance were low, investigators noted—though this was mostly due to inconsistency and indirectness domains. They concluded that, though cannabinoid does not have preventive effects for experimental pain, it can make the experience more tolerable and less unpleasant, indicating its benefits for the affective processes. In a multiple-dimension condition, cannabinoids’ effect on pain is possibly singular.

“Pain is a complex phenomenon with multiple dimensions that can be affected separately,” investigators wrote. “Meta-analyses revealed that although the cannabinoids examined in this review may prevent the onset of laboratory-induced pain by increasing pain thresholds, they do not appear to reduce the intensity of experimental pain that is already being experienced.”

The study, "Association of Cannabinoid Administration With Experimental Pain in Healthy Adults," was published online in JAMA on Wednesday.