Substantial evidence has shown nabiximols, a complex botanical mixture containing delta-9-tetrahydrocannabinol and cannabidiol as the principal cannabinoids, can reduce spasticity associated with MS. This analysis assesses whether nabiximols affects other patient outcomes such as depressive symptoms, suicidality, and cognition.
Report the effect of nabiximols on depression, suicidality, and cognition using data from 2 placebo-controlled randomized controlled trials, GWSP0604 (12 weeks) and GWMS1137 (48 weeks), in patients with spasticity due to MS.
Mood and suicidality were assessed using the Beck Depression Inventory-II (BDI-II) in both trials. In GWMS1137, suicidality was assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) and working memory/processing speed using the Paced Auditory Serial Addition Test (PASAT). The combined PASAT total score was calculated combining both PASAT-3 and -2 tests scores (total of 120 points). Outcome differences between nabiximols and placebo are summarized.
241 patients from GWSP0604 and 121 from GWMS1137 were included. The baseline and end-of-treatment mean BDI-II total scores were 8.7 vs 9.5 for nabiximols and 9.7 vs 10.4 for placebo in GWSP0604, and 15.7 vs 12.5 for nabiximols and 13.5 vs 11.1 for placebo in GWMS1137. Differences between nabiximols and placebo of the BDI-II change from baseline adjusted means were -0.06 (-1.62, 1.49) in GWSP0604 (no significant difference) and -0.29 (-2.91, 2.33) in GWMS1137 (statistically non-inferior). Question 9 of BDI-II (suicidal thoughts or wishes) showed no notable treatment differences in either trial, with only 1 patient treated with nabiximols reporting a score ≥2. On the Columbia-Suicide Severity Rating Scale, 3 (5.1%) patients randomized to placebo and 1 (1.6%) to nabiximols had a ‘flag’ (ie, ‘Yes’ as a response), but further questioning revealed no emergent suicidal ideations or behavior in any of these patients. For GWMS1137, the baseline and end-of-treatment PASAT total score means were 71.3 vs 78.6 for nabiximols and 74.5 vs 82.7 for placebo; increases may reflect practice effects. Treatment difference of the adjusted mean was -1.47 (-6.41, 3.48), indicating nabiximols does not adversely affect working memory/cognitive processing speed in MS patients over a 48-week period compared with placebo.
Nabiximols had no notable effects on depression, suicidality, or working memory/processing speed in patients with MS. Funding: Greenwich Biosciences, Inc.