Non‐Motor Symptoms in Parkinson's Disease are Reduced by Nabilone

Abstract

Objective To assess the efficacy and safety of nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non‐motor symptoms (NMS) in Parkinson´s Disease (PD). Methods This was a phase II placebo‐controlled, double‐blind, parallel‐group, enriched enrollment randomized withdrawal trial at the Medical University Innsbruck. A random sample of 47 PD patients with stable motor disease and disturbing NMS defined by a score of ≥4 points on the Movement Disorder Society‐Unified PD Rating Scale‐I (MDS‐UPDRS‐I) underwent open‐label nabilone titration (0.25mg once daily‐1mg twice daily, Phase 1). Responders were randomized 1:1 to continue with nabilone or switch to placebo for four weeks (Phase 2). The primary efficacy criterion was the change of the MDS‐UPDRS‐I between randomization and week four. Safety was analyzed in all patients who received at least one nabilone dose. Results Between October 2017 and July 2019, 19 patients received either nabilone (median dose=0.75mg) or placebo. At week four, mean change of the MDS‐UPDRS‐I was 2.63 (95%CI 1.53‐3.74, p=0.002, effect size=1.15) in the placebo versus 1.00 (95%CI ‐0.16‐2.16, p=0.280, effect size=0.42) in the nabilone‐group (difference:1.63, 95%CI 0.09‐3.18, p=0.030, effect size=0.66). Seventy‐seven percent of patients had adverse events (AEs) during open‐label titration, most of them were transient. In the double‐blind phase, similar proportions of patients in each group had AEs (42% placebo‐group, 32% nabilone‐group). There were no serious AEs. Interpretation Our results highlight the potential efficacy of nabilone for PD patients with disturbing NMS, which appears to be driven by positive effects on anxious mood and night‐time sleep problems. Trial registry: ClinicalTrials.gov (NCT03769896) and EudraCT (2017‐000192‐86)