Long-term safety and efficacy of open-label nabilone on sleep and pain in Parkinson´s Disease

Marina Peball; Beatrice Heim; Federico Carbone; Oliver Schorr; Mario Werkmann; Philipp Ellmerer; Kathrin Marini; Florian Krismer; Hans-Günther Knaus; Werner Poewe; Atbin Djamshidian; Klaus Seppi

doi:10.1038/s41531-024-00665-7

Long-term safety and efficacy of open-label nabilone on sleep and pain in Parkinson´s Disease

NPJ Parkinsons Dis. 2024 Mar 15;10(1):61. doi: 10.1038/s41531-024-00665-7.

Authors

Affiliations

¹ Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. Marina.peball@i-med.ac.at.
² Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
³ Department for Medical Genetics, Molecular, and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. Klaus.Seppi@bkh-kufstein.at.
⁵ Department of Neurology, District Hospital of Kufstein, Kufstein, Austria. Klaus.Seppi@bkh-kufstein.at.

Abstract

The synthetic tetrahydrocannabinol-analog nabilone improved non-motor symptoms (NMS) in Parkinson's disease (PD) patients in a placebo-controlled, double-blind, parallel-group, randomized withdrawal trial with enriched enrollment (NMS-Nab-study). This was a single-center open-label extension study to assess the long-term safety and efficacy of nabilone for NMS in PD. To be eligible for this study, patients had to be treatment responders during the previous NMS-Nab-trial and complete its double-blind phase without experiencing a drug-related serious/severe/moderate adverse event (AE). Patients were re-introduced to nabilone during an up-titration phase until their overall NMS burden improved. Nabilone was continued for six months with clinic visits every 3 months. Evaluation of AEs was based on self-report and clinical assessment. Twenty-two patients participated in the NMS-Nab2-study (age-median 68.33 y, 52% females, disease duration-median 7.42 y). Nabilone was well tolerated with concentration difficulties as the most common treatment-related AE (possibly/not related n = 1 each). One in two drop-outs discontinued because of an AE for which a prohibited concomitant medication needed to be introduced (night-time sleep problems). Efficacy evaluation showed a significant and lasting improvement in NMS burden according to the CGI-I (79% at V3). Nabilone improved overall sleep (NMSS Domain-2: -8.26 points; 95%CI -13.82 to -2.71; p = 0.004; ES = -0.72), night-time sleep problems (MDS-UPDRS-1.7: -1.42 points; 95 CI -2.16 to -0.68; p = 0.002; ES = -0.92), and overall pain (KPPS Total Score: -8.00 points; 95%CI -15.05 to -0.95; p = 0.046; ES -0.55 and MDS-UPDRS-1.9: -0.74 points; 95%CI -1.21 to -0.26; p = 0.008; ES = -0.74). This study demonstrates continuous long-term safety and efficacy in PD patients responding early to nabilone without intolerable side effects.