nabilone and Parkinson-Disease

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).. 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.. 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.. 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.. ClinicalTrials.gov (NCT03769896) and EudraCT (2017-000192-86). ANN NEUROL 2020;88:712-722.

Topics: Aged; Anxiety; Double-Blind Method; Dronabinol; Female; Humans; Male; Middle Aged; Parkinson Disease; Sleep Wake Disorders; Treatment Outcome

Although open-label observations report a positive effect of cannabinoids on non-motor symptoms (NMS) in Parkinson's disease (PD) patients, these effects remain to be investigated in a controlled trial for a broader use in NMS in PD patients. Therefore, we decided to design a proof-of-concept study to assess the synthetic cannabinoid nabilone for the treatment of NMS. We hypothesize that nabilone will improve NMS in patients with PD and have a favorable safety profile. The NMS-Nab Study is as a mono-centric phase II, randomized, placebo-controlled, double-blind, parallel-group, enriched enrollment withdrawal study. The primary efficacy criterion will be the change in Movement Disorders Society-Unified Parkinson's Disease-Rating Scale Part I score between baseline (i.e. randomization) and week 4. A total of 38 patients will have 80% power to detect a probability of 0.231 that an observation in the treatment group is less than an observation in the placebo group using a Wilcoxon rank-sum test with a 0.050 two-sided significance level assuming a true difference of 2.5 points between nabilone and placebo in the primary outcome measure and a standard deviation of the change of 2.4 points. The reduction of harm through an ineffective treatment, the possibility of individualized dosing, the reduction of sample size, and the possible evaluation of the influence of the placebo effect on efficacy outcomes justify this design for a single-centered placebo-controlled investigator-initiated trial of nabilone. This study should be the basis for further evaluations of long-term efficacy and safety of the use of cannabinoids in PD patients.

Topics: Antiparkinson Agents; Cannabinoid Receptor Agonists; Clinical Trial Protocols as Topic; Double-Blind Method; Dronabinol; Female; Humans; Male; Parkinson Disease; Patient Selection; Proof of Concept Study; Treatment Outcome

The lateral segment of the globus pallidus (GPl) is thought to be overactive in levodopa-induced dyskinesia in PD. Stimulation of cannabinoid receptors in the GPl reduces gamma-aminobutyric acid (GABA) reuptake and enhances GABA transmission and may thus alleviate dyskinesia. In a randomized, double-blind, placebo-controlled, crossover trial (n = 7), the authors demonstrate that the cannabinoid receptor agonist nabilone significantly reduces levodopa-induced dyskinesia in PD.

Topics: Aged; Animals; Cross-Over Studies; Culture Techniques; Double-Blind Method; Dronabinol; Dyskinesia, Drug-Induced; Female; gamma-Aminobutyric Acid; Globus Pallidus; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug

Topics: Aged; Cannabinoids; Delusions; Dronabinol; Dystonia; Female; Hallucinations; Humans; Parkinson Disease; Psychoses, Substance-Induced