A Multicentre, Double-Blind, Randomised, Parallel-Group, Placebo-Controlled Study of Effect of Long-Term Sativex® Treatment on Cognition and Mood of Patients with Spasticity Due to Multiple Sclerosis

Objective: When Sativex  THC:CBD cannabinoid-based oromucosal spray was first approved as a prescription medicine for multiple sclerosis (MS) spasticity, there was some concern about its possible long-term impact on cognition and mood. The objective of this study was therefore to assess the long-term impact of Sativex on cognitive function and mood in MS patients with spasticity. Methods: 121 patients were randomly assigned Sativex or placebo in a double-blind manner. Patients selfadministered treatment daily for 48 weeks while maintaining anti-spasticity therapy. The primary endpoint was the difference between treatments in Paced Auditory Serial Addition Test (PASAT) score from baseline to end of treatment. Secondary measures included Beck Depression Inventory-II (BDI-II), Subject-, Physicianand Caregiver Global Impression of Change, and Columbia-Suicide Severity Rating Scale. Results: 62 patients were randomised to Sativex and 59 to placebo. There was no difference in the effect of Sativex on PASAT and BDI-II scores compared with placebo. Subject-, Physicianand Caregiver-rated improvements in spasticity with Sativex were all statistically significant. The mean daily dose of Sativex declined gradually to 6.4 sprays per day. Conclusion: Long-term treatment with Sativex was not associated with cognitive decline or significant changes in mood in this prone population sample. Sativex was efficacious and well tolerated across the study period and no new safety concerns were identified.