Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy

Abstract

A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis. In a crossover design, each participant was exposed to 4 single dosing sessions of placebo or to low (1% tetrahydrocannabinol [THC]), medium (4% THC), or high (7% THC) doses of cannabis. Baseline spontaneous pain, evoked pain, and cognitive testing were performed. Subjects were then administered aerosolized cannabis or placebo and the pain intensity and subjective "highness" score was measured at 5, 15, 30, 45, and 60 minutes and then every 30 minutes for an additional 3 hours. Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes for an additional 3 hours. The primary analysis compared differences in spontaneous pain over time between doses using linear mixed effects models. There was a significant difference in spontaneous pain scores between doses (P < .001). Specific significant comparisons were placebo versus low, medium, and high doses (P = .031, .04, and <.001, respectively) and high versus low and medium doses (both P < .001). There was a significant effect of the high dose on foam brush and von Frey evoked pain (both P < .001). There was a significant negative effect (impaired performance) of the high dose on 2 of the 3 neuropsychological tests (Paced Auditory Serial Addition Test, Trail Making Test Part B.

Perspective: This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain. This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain.

Keywords: Diabetic peripheral neuropathy; cannabis; clinical trial.

Figure 1

Raw (left panel) and predicted (right panel) mean pain scores (±SE) for (A) Spontaneous pain, (B) Evoked pain (Foam Brush), and (C) Evoked pain (von Frey) from the randomized, double-blinded, placebo controlled crossover study on effect of inhaled cannabis on diabetic peripheral neuropathy pain (n=16). Raw mean scores are means of actual values recorded during the experiment. Predicted mean scores are estimates obtained from the mixed effects models.

Figure 2

Observed mean scaled scores (±SE) for (A) Trails Making Part A, (B) Trails Making Part B, and (C) PASAT-50 tests from a brief neuropsychological test battery that assessed changes in participants’ cognitive abilities after cannabis inhalation (N=16). Using a pair-wise approach, significant differences (p<0.05) are detected between [a] high and placebo doses, [b] medium and placebo doses.