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.

• Authors: Marina Peball, Florian Krismer, Hans-Günther Knaus, Atbin Djamshidian, Mario Werkmann, Federico Carbone, Philipp Ellmerer, Beatrice Heim, Kathrin Marini, Dora Valent, Georg Goebel, Hanno Ulmer, Heike Stockner, Gregor K Wenning, Raphaela Stolz, Kurt Krejcy, Werner Poewe, Klaus Seppi, Collaborators of the Parkinson's Disease Working Group Innsbruck
• Journal: Annals of neurology (Ann Neurol) Vol. 88 Issue 4 Pg. 712-722 (10 2020) ISSN: 1531-8249 [Electronic] United States
• PMID: 32757413 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Chemical References

• nabilone
• Dronabinol

Topics

• Aged
• Anxiety (etiology)
• Double-Blind Method
• Dronabinol (analogs & derivatives, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Parkinson Disease (complications, drug therapy)
• Sleep Wake Disorders (etiology)
• Treatment Outcome