Diabetic peripheral neuropathy (DPN) has been increasing, now affecting an estimated 366 million individuals worldwide. Preclinical studies have shown that a major cannabinoid receptor, CB1, is expressed in regions involved in the dorsal root ganglion, periaqueductal gray, raphe nucleus and forebrain. In addition, animal models of neuropathic pain, including diabetic neuropathy, suggest that cannabinoids may be effective in reducing pain. This study evaluated the effects of low, medium and high dose inhaled cannabis on the pain and hyperalgesia of DPN.

This randomized, double-blind, placebo-controlled, crossover trial studied 16 patients with painful DPN. All subjects participated in four sessions, separated by two weeks, involving exposure to a placebo or low (one percent THC), medium (four percent THC) or high (seven percent THC) doses of cannabis. Pain was assessed with a 10-point visual analogue scale at baseline and at five, 15, 30, 45 and 60 minutes, and then every 30 minutes for an additional three hours. Cognitive testing, using the Trail Making Test, Parts A and B, and the Paced Auditory Attention Test, was performed at five and 30 minutes, and then every 30 minutes, for three hours.

Spontaneous pain was reduced by an average of 1.1 points with greater reduction with higher doses (P＝0.001). In addition, for evoked pain conditions, significant differences over placebo were noted in medium and high doses. Neuropsychological test results demonstrated impaired performance on two of three neuropsychological tests among patients who received the high-dose.

This small, placebo-controlled trial of inhaled cannabis demonstrated a dose dependent reduction in diabetic peripheral neuropathy pain.