Cannabinoid May Improve Nonmotor Symptoms in Parkinson Disease

September 12, 2020
Matt Hoffman
Matt Hoffman

Matt Hoffman, Senior Editor for NeurologyLive, has covered medical news for MJH Life Sciences, NeurologyLive’s parent company, since 2017. He hosts the Mind Moments podcast. Follow him on Twitter @byMattHoffman or email him at

Results from a phase 2 pilot study of nabilone in Parkinson disease suggest that the synthetic cannabinoid might hold therapeutic potential for nonmotor symptoms.

Patients with Parkinson disease who were treated with nabilone in a recent phase 2, randomized pilot study (NCT03769896) experienced improvements in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I scores compared with those administered placebo, pointing towards nabilone’s therapeutic potential for the treatment of nonmotor symptoms.

Presented as a poster by Marina Peball, MD, resident and research fellow, Department of Neurology, Medical University Innsbruck, and colleagues at the 2020 MDS Virtual Congress, September 12–16, 2020, the data compared 38 patients randomized 1:1 to either AOP Orphan’s synthetic cannabinoid nabilone (n = 19) or placebo (n = 19).1

Ultimately, the mean change in MDS-UPDRS Part I scores at Week 4 was 2.63 (95% CI, 1.53–3.74; P = .002; effect size, 1.15) in the placebo group compared with 1.00 (95% CI, –0.16 to 2.16; P = .280; effect size, 0.42) in the nabilone group, for a difference of 1.63 (95% CI, 0.09–3.18; P = .030; effect size, 0.66).

“Our results highlight the potential efficacy of nabilone for patients with PD and disturbing nonmotor symptoms, which appears to be driven by positive effects on anxious mood and night-time sleep problems,” Peball and colleagues wrote.

Patients in this single-center withdrawal trial were evaluated between October 2017 and July 2019. In Phase 1 of the study, 48 patients received nabilone on a stable dose during the open-label titration period (0.25 mg once daily to 1 mg twice daily). Then, in Phase 2, the 38 patients who responded to treatment were randomized to either treatment or placebo switch for 4 weeks. Nine patients discontinued prior to this randomization phase—1 dropped out, 3 halted due to adverse events (AEs), and 5 due to lack of response.

READ MORE: Directional Deep Brain Stimulation Linked to Wider Therapeutic Window in Parkinson Disease

This selection of open‐label responders could raise concerns about the generalizability of the findings, Peball and colleagues noted, writing that they in turn could impact external validity. “In this study, most patients enrolled in the open‐label phase were responders, therefore, selection bias can be considered small. The inclusion of responders only can lead to overestimation of the effect of a novel treatment. However, restriction to responders reflects clinical practice by limiting long‐term treatment to patients who might benefit from it, in line with a personalized medicine approach,” they wrote.2

Change on the Clinical Global Impression–Improvement (CGI-I) scale was also observed, with patients rated as having no change, being minimally worse, or much worse. For the nabilone group, 63.16% experienced no change, 31.58% were minimally worse, and 5.26% were much worse, compared with 26.32%, 52.63%, and 21.05% of the placebo group, respectively.

Mean change on the Non‐Motor Symptoms Scale (NMSS) was assessed at the termination visit, which was reported as 11 points (95% CI, 4.68–17.32; P = .004; effect size, 0.84) in the placebo group compared with 4.05 points (95% CI, −0.65 to 8.75; P = .096; effect size, 0.42) in the nabilone group. The difference between groups was 6.95 points (95% CI −0.66 to 14.55; P = .147; effect size, 0.58).2

“The change of the NMSS during the randomized double‐blind phase was not significant in the nabilone group. The placebo group, however, worsened significantly with a large effect size,” Peball et al. wrote. “Of note, the between‐group effect size of deterioration was also medium to the disadvantage of the placebo arm for the NMSS.”

As for safety, there were similar proportions of patients in both groups that reported adverse events (AEs), with 42% of the placebo group and 32% of the nabilone group in the double-blind phase. Overall, 4 patients reported insomnia (nabilone: n = 2; placebo: n = 2), 3 reported upper respiratory tract infection (nabilone: n = 0; placebo: n = 3), 3 reported pain (nabilone: n = 1; placebo: n = 2), 2 reported a fall or recurrent falls (nabilone: n = 1; placebo: n = 1), and 2 reported syncope (nabilone: n = 0; placebo: n = 2).

There were no serious AEs reported. The most common AEs during the open-label phase were fatigue (n = 17; 15 mild, 2 moderate), dizziness (n = 9; 8 mild, 1 moderate), daytime sleepiness (n = 5; 4 mild, 1 moderate), and upper respiratory tract infection (n = 5; 4 mild, 1 moderate).

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1. Peball M, Krismer F, Knaus HG, et al. Effects of nabilone on non-motor symptoms of Parkinson’s Disease: A randomized placebo-controlled study (the NMS-Nab Study). Presented at: MDS Virtual Congress; September 12–16, 2020. Abstract 933.
2. Peball M, Krismer F, Knaus HG, et al. Non‐Motor Symptoms in Parkinson's Disease are Reduced by Nabilone. Annals Neurol. Published online August 5, 2020. doi: 10.1002/ana.25864