doi: 10.1016/j.psychres.2023.115135.
- PMID: 36878177
- DOI: 10.1016/j.psychres.2023.115135
Abstract
Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21·9%) vs. 3/33 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.
Keywords: ADHD, Cannabis-based medicine, Nabiximols, OCD, Randomized-controlled trial, Tics, Tourette syndrome
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest This study was funded by the DFG (MU 1527/2-1). KMV has received financial or material research support from the EU (FP7-HEALTH-2011 No. 278367, FP7-PEOPLE-2012-ITN No. 316978), the German Research Foundation (DFG: GZ MU 1527/3-1), the German Ministry of Education and Research (BMBF: 01KG1421), the National Institute of Mental Health (NIMH), the Tourette Gesellschaft Deutschland e.V., the Else-Kroner Fresenius-Stiftung, and GW, Abide Therapeutics, Lundbeck, Syneos Health, Therapix Biosciences Ltd, Almirall Hermal GmbH, GW pharmaceuticals. She has received consultant’s honoraria from Abide Therapeutics, Tilray, Resalo Vertrieb GmbH, Columbia Care, Bionorica Ethics GmbH, Lundbeck and Eurox Deutschland GmbH. She is a consultant or advisory board member for Abide Therapeutics, Alirio, The Academy of Medical Cannabis Limited, CannaMedical Pharma GmbH, CannaXan GmbH, Columbia Care, Canopy Growth, Leafly Deutschland GmbH, Lundbeck, Nomovo Pharm, Nuvelution TS Pharma Inc., Resalo Vertrieb GmbH, Sanity Group, Syqe Medical Ltd., Therapix Biosciences Ltd., Tilray, Wayland Group, Zynerba Pharmaceuticals, and CTC Communications Corporation. She has received speaker’s fees from Tilray, Wayland Group, Emalex, Eurox group, PR Berater, Aphria, Ever pharma GmbH, and Cogitando GmbH. She has received royalties from Medizinisch Wissenschaftliche Verlagsgesellschaft Berlin, Elsevier, and Kohlhammer. She holds shares of Nomovo Pharm. She served as a Guest editor for Frontiers in Neurology on the research topic “The neurobiology and genetics of Gilles de la Tourette syndrome: new avenues through large-scale collaborative projects,” is Associate editor for “Cannabis and Cannabinoid Research” and Editorial Board Member for “Medical Cannabis and Cannabinoids.” The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. AM received commercial research support from Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion, honoraria for lectures from GlaxoSmithKline, Desitin, Teva, Takeda and consultancies from Desitin, Merz Pharmaceuticals, Admedicum, PTC Therapeutics, Novartis, Barmer. He was supported by the Possehl-Stiftung (Lübeck, Germany), the Margot und Jürgen Wessel Stiftung (Lübeck, Germany), the Tourette Syndrome Association (Germany), the Interessenverband Tourette Syndrom (Germany), CHDI, and the Damp-Stiftung (Kiel, Germany). He received academic research support by the Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1, SFB 936, and FOR 2698 (project numbers 396914663, 396577296, 396474989), by the European Reference Network – Rare Neurological Diseases (ERN – RND; Project ID No 739510). He receives royalties for the book Neurogenetics (Oxford University Press). AM is member of the advisory boards of the German Tourette syndrome Association and the alliance of patients with chronic rare diseases. RM has received financial research support from the EU (H2020 No. 754740), the Tourette Gesellschaft Deutschland e.V., Abide Therapeutics, Böhringer-Ingelheim, Emalex, Lundbeck, Nuvelution TS Pharma Inc., Otsuka Pharmaceuticals, Therapix Biosciences. He has received speakers’ honoraria from Otsuka Pharmaceuticals and Lundbeck. RM is member of the advisory board of the Tourette Gesellschaft Deutschland e.V. NS has received financial or material research support by Polish Ministry of Health, Polish Neurological Society, Foundation for Polish Science, American Academy of Neurology, Tourette Association of America, American Brain Foundation and European Stroke Organisation. She received speakers’ honoraria from Biogen and 90 Consulting and was supported to attend meetings by Biogen. She is the Secretary of the European Society for the Study of Tourette Syndrome. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
