Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.

Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS. The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex) oromucosal spray in CNP associated with MS. This uncontrolled, open-label trial was an indefinite-duration extension of a previously reported 5-week randomized study in patients with MS and CNP. In the initial trial, patients were randomized to placebo or THC/CBD. All patients (placebo and THC/CBD) who completed the randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25 mg/mL). The primary end point of the trial was the number, frequency, and type of adverse events (AEs). Secondary end points included changes from baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score. Sixty-six patients were enrolled in the randomized trial; 64 (97%) completed and 63 (95%) entered the open-label extension. Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 (44%) patients who completed the 2-year follow up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0). Fifty-eight (92%) patients experienced >=1 treatment-related AE. The most commonly reported AEs were dizziness (27%), nausea (18%), and feeling intoxicated (11%). THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n=28).