Effect of smoked cannabis on capsaicin induced pain in healthy volunteers
      Although the preclinical literature suggests that the cannabinoids produce antinociception and antihyperalgesic effects, the efficacy in the human pain state is unclear due to difficulties in conducting clinical trials with cannabinoids. Experimental pain models have been used to assess the analgesic efficacy in normal volunteers. This study sought to evaluate the effects of three doses of smoked cannabis on the pain and cutaneous hyperalgesia induced by intradermal capsaicin in healthy volunteers. A randomized, double-blinded, placebo controlled crossover design methodology was conducted in fifteen healthy volunteers (4 women, 11 men). Subjects participated in four sessions where they were exposed to placebo, low, medium, or high dose of cannabis. Capsaicin was injected into opposite forearms 5 and 45 minutes after drug exposure and pain, hyperalgesia and side effects were assessed. Five minutes after cannabis exposure, there was no effect on capsaicin induced pain at any dose. However, 45 minutes after cannabis exposure, there was a significant decrease in capsaicin induced pain with the medium dose and a significant increase in capsaicin induced pain with the high dose. There was no effect seen with the low dose nor was there an effect on area of hyperalgesia at any dose. There was a dose dependent increase in the subjective highness score reported after cannabis exposure which persisted into the late time course. There was no significant difference in the neuropsychological tests (PASAT, Trail Making Test) before and after cannabis exposure. This study suggests that there is a therapeutic window of analgesia for smoked cannabis with lower doses decreasing pain and higher doses increasing pain. Further studies are required to determine this therapeutic window and time course of analgesia.