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 PwMS with inadequately managed spasticity.

Substantial evidence has shown nabiximols, a complex botanical mixture containing delta-9-tetrahydrocannabinol, cannabidiol, and other cannabinoid and non-cannabinoid constituents, can reduce spasticity associated with 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); working memory/processing speed using the Paced Auditory Serial Addition Test (PASAT). Combined PASAT total score was calculated combining PASAT-3 and -2 tests scores (total: 120 points). Outcome differences between nabiximols and placebo are summarized.

241 PwMS 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; 9.7 vs 10.4 for placebo in GWSP0604 and 15.7 vs 12.5 for nabiximols; 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); -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. On the C-SSRS, 3 (5.1%) PwMS randomized to placebo and 1 (1.6%) to nabiximols had a ‘flag’; further questioning revealed no emergent suicidal ideations or behavior in any. For GWMS1137, the baseline and end-of-treatment PASAT total score means were 71.3 vs 78.6 for nabiximols; 74.5 vs 82.7 for placebo. 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 PwMS over a 48-week period compared with placebo.

Nabiximols had no notable effects on depression, suicidality, or working memory/processing speed in PwMS. Funding: Greenwich Biosciences, Inc.