THC reduced pain and enhanced a specific pain inhibition pathway in fibromyalgia patients

THC (0.2 mg/kg sublingual) significantly reduced spontaneous pain ratings on the McGill scale compared to both baseline and placebo. THC also enhanced offset analgesia relative to placebo (P=0.008) but had no effect on conditioned pain modulation (P=0.27). Baseline offset analgesia magnitude predicted who would respond to THC treatment (R²=0.404, P=0.003).

Randomized, double-blind, placebo-controlled crossover design with 23 fibromyalgia patients. Each participant completed two sessions with McGill Pain Questionnaire, VAS assessments, and evaluations of offset analgesia and conditioned pain modulation before and after sublingual THC or placebo.

This is the first study to test whether THC affects different central pain modulation mechanisms differently, finding that it selectively enhances offset analgesia. If baseline offset analgesia can predict who responds to THC, it could help match the right patients to cannabinoid therapy.

Fibromyalgia involves dysfunctional central pain processing, and treatments that restore normal pain inhibition pathways are a priority. This finding that THC selectively targets one pathway but not another suggests cannabinoids work through specific neural mechanisms rather than general pain suppression.

Very small sample (23 patients). Single-dose acute study does not reflect chronic use. Only tested one THC dose (0.2 mg/kg sublingual). No long-term safety or efficacy data.