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

Abstract

Objective: The objective of this study was 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 conducted at the Medical University Innsbruck. A random sample of 47 patients with PD 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 (0.25 mg once daily to 1 mg twice daily, phase I). Responders were randomized 1:1 to continue with nabilone or switch to placebo for 4 weeks (phase II). The primary efficacy criterion was the change of the MDS-UPDRS-I between randomization and week 4. 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 = 0.75 mg) or placebo. At week 4, mean change of the MDS-UPDRS-I was 2.63 (95% confidence interval [CI] 1.53 to 3.74, p = 0.002, effect size = 1.15) in the placebo versus 1.00 (95% CI -0.16 to 2.16, p = 0.280, effect size = 0.42) in the nabilone-group (difference: 1.63, 95% CI 0.09 to 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% in the placebo group and 32% in the nabilone group). There were no serious AEs.

Interpretation: Our results highlight the potential efficacy of nabilone for patients with PD 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). ANN NEUROL 2020;88:712-722.

FIGURE 1

Schedule of trial activities. All patients received nabilone during phase I of the trial. The mean durations of phase I (including the open‐label titration phase and open‐label phase with stable nabilone dosage) and phase II (ie, double‐blind withdrawal phase) were 39.90 days ± 12.10 (median 37.00 days) and 28.37 days ± 3.23 (median 28.00 days), respectively. OL, open‐label; SFU, safety follow‐up.

FIGURE 2

Flow chart (adapted from CONSORT 2010). n, number.

FIGURE 3

Data representing the change of MDS‐UPDRS‐I during the study and CGI‐I during double‐blind treatment. (A) Change of MDS‐UPDRS‐I during the study; (B) Change of CGI‐I during double‐blind treatment. CGI‐I, Clinical Global Impression – Improvement Scale; MDS‐UPDRS, Movement Disorder Society ‐ Unified Parkinson's Disease Rating Scale; SE, standard error.