Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis

Background: Central pain in multiple sclerosis (MS) is common and often refractory to treatment. Methods:
We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled,
parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant
cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment. Each spray delivered 2.7 mg of THC and 2.5 of CBD, and patients could
gradually self-titrate to a maximum of 48 sprays in 24 hours. Results: Sixty-four patients (97%) completed the trial, 34
received CBM. In week 4, the mean number of daily sprays taken of CBM (n 32) was 9.6 (range 2 to 25, SD 6.0) and
of placebo (n 31) was 19.1 (range 1 to 47, SD 12.9). Pain and sleep disturbance were recorded daily on an 11-point
numerical rating scale. CBM was superior to placebo in reducing the mean intensity of pain (CBM mean change 2.7, 95%
CI: 3.4 to 2.0, placebo –1.4 95% CI: 2.0 to 0.8, comparison between groups, p 0.005) and sleep disturbance (CBM
mean change –2.5, 95% CI: 3.4 to 1.7, placebo – 0.8, 95% CI: 1.5 to 0.1, comparison between groups, p 0.003).
CBM was generally well tolerated, although more patients on CBM than placebo reported dizziness, dry mouth, and
somnolence. Cognitive side effects were limited to long-term memory storage. Conclusions: Cannabis-based medicine is
effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is
mostly well tolerated.