Correlation of tetrahydrocannabinol plasma levels with pain reduction in diabetic peripheral neuropathy

There is emerging evidence that inhaled cannabis is effective in the treatment of neuropathic pain. However, few studies have looked at the correlation between THC plasma concentration and pain relief. A randomized, double-blinded, placebo controlled crossover study was conducted in sixteen patients with painful diabetic peripheral neuropathy. Subjects participated in four sessions where they were exposed to placebo, low (1% tetrahydrocannabinol, THC), medium (4% THC), or high (7% THC) dose of cannabis. Subjects were administered aerosolized cannabis or placebo and the spontaneous and evoked (von frey and stroking) pain intensity was measured and a blood sample for plasma THC levels were taken at 5, 15, 30, 45, 60minutes and then every 30 minutes for an additional 3 hours. Analysis was done for both the administered dose and peak plasma concentrations. Within each dose level, subjects were divided into those with peak plasma concentration < 15 ng/ml or>15 ng/ml. There was a significant dose dependent reduction in both spontaneous and evoked pain with the highest dose being most effective. Evoked pain showed the tightest correlation and was used to analyze THC concentration and pain reduction. There was a significant correlation between pain reduction between 5- 15 ng/ml (p=0.0319) which was lost at>15 ng/ml THC (p=0.9111). There appears to be a therapeutic window for the analgesic effects of THC and patients should be counseled that more is not better.