Abstract
Anecdotal references, preclinical, and non-randomized studies support the therapeutic potential of cannabinoids for movement disorders (MD). To create an evidenced-based point of view for patients and physicians, we performed a systematic review of randomized controlled trials (RCT) on the use of cannabinoids in MD. The seven RCTs found on PD used different cannabis formulations. No improvement of motor symptoms was shown in any of the two RCTs with this as primary outcome (PO), but in the nabilone group, an improvement in quality of life was documented. Of the three RCTs having levodopa-induced dyskinesia as PO, only one using nabilone showed a reduction. Anxiety and anxiety-induced tremor could be reduced in the cannabidiol group as well as anxiety and sleeping problems in the nabilone group in another RCT. In two RCTs with Tourette syndrome, an improvement in tics was revealed. From three RCTs on Huntington’s disease only one found symptoms relief using nabilone. No reduction of dystonia could be shown in the two included RCTs. The limited number of available but small and inhomogeneous RCTs precludes reliable conclusions. Therefore, more and smartly designed RCTs are urgently needed.
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Abbreviations
- MD:
-
Movement disorders
- RCT:
-
Randomized controlled trials
- PO:
-
Primary outcome
- CBM:
-
Cannabis-based medicine
- CB 1 and/or CB2:
-
Cannabinoid receptor (CB) 1 and/or CB2
- ECS:
-
Endocannabinoid system
- THC:
-
Delta-9-tetrahydrocannabinol
- CBD:
-
Cannabidiol
- PD:
-
Parkinson’s disease
- APS:
-
Atypical Parkinson Syndrome
- HD:
-
Huntington’s disease
- TS:
-
Tourette syndrome
- LID:
-
Levodopa-induced dyskinesia
- UPDRS:
-
Unified Parkinson’s Disease Rating Scale
- PDQ-39:
-
Parkinson’s Disease Questionnaire
- REM:
-
Rapid eye movement
- RBD:
-
REM sleep behaviour disorder
References
Bahji A, Breward N, Duff W, Absher N, Patten SB, Alcorn J, Mousseau DD (2022) Cannabinoids in the management of behavioral, psychological, and motor symptoms of neurocognitive disorders: a mixed studies systematic review. J Cannabis Res 4(1):11. https://doi.org/10.1186/s42238-022-00119-y
Balint B, Mencacci NE, Valente EM, Pisani A, Rothwell J, Jankovic J, Vidailhet M, Bhatia KP (2018) Dystonia Nat Rev Dis Primers 4(1):25. https://doi.org/10.1038/s41572-018-0023-6.
Bloem BR, Okun MS, Klein C (2021) Parkinson’s disease. Lancet 397(10291):2284–2303. https://doi.org/10.1016/S0140-6736(21)00218-X
Bougea A, Koros C, Simitsi AM, Chrysovitsanou C, Leonardos A, Stefanis L (2020) Medical cannabis as an alternative therapeutics for Parkinsons’ disease: SYSTEMATIC review. Complement Ther Clin Pract 39:101154. https://doi.org/10.1016/j.ctcp.2020.101154
Bravo-Soto GA, Juri C (2017) Are cannabinoids effective for Parkinson’s disease? Medwave 17(Suppl 2):e6974. https://doi.org/10.5867/medwave.2017.6974
Brodie MJ, Ben-Menachem E (2018) Cannabinoids for epilepsy: what do we know and where do we go? Epilepsia 59(2):291–296. https://doi.org/10.1111/epi.13973
Buhmann C, Mainka T, Ebersbach G, Gandor F (2019) Evidence for the use of cannabinoids in Parkinson’s disease. J Neural Transm (vienna) 126(7):913–924. https://doi.org/10.1007/s00702-019-02018-8
Carroll CB, Bain PG, Teare L, Liu X, Joint C, Wroath C, Parkin SG, Fox P, Wright D, Hobart J, Zajicek JP (2004) Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology 63(7):1245–1250. https://doi.org/10.1212/01.wnl.0000140288.48796.8e
Chagas MH, Zuardi AW, Tumas V, Pena-Pereira MA, Sobreira ET, Bergamaschi MM, dos Santos AC, Teixeira AL, Hallak JE, Crippa JA (2014) Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J Psychopharmacol 28(11):1088–1098. https://doi.org/10.1177/0269881114550355
Chung YC, Shin WH, Baek JY, Cho EJ, Baik HH, Kim SR, Won SY, Jin BK (2016) CB2 receptor activation prevents glial-derived neurotoxic mediator production, BBB leakage and peripheral immune cell infiltration and rescues dopamine neurons in the MPTP model of Parkinson’s disease. Exp Mol Med 48(1):e205. https://doi.org/10.1038/emm.2015.100
Consroe P, Laguna J, Allender J, Snider S, Stern L, Sandyk R, Kennedy K, Schram K (1991) Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 40(3):701–708. https://doi.org/10.1016/0091-3057(91)90386-g
Curtis A, Mitchell I, Patel S, Ives N, Rickards H (2009) A pilot study using nabilone for symptomatic treatment in Huntington’s disease. Mov Disord 24(15):2254–2259. https://doi.org/10.1002/mds.22809
Curtis A, Clarke CE, Rickards HE (2009) Cannabinoids for Tourette’s Syndrome. Cochrane Database Syst Rev 2009(4):CD006565. https://doi.org/10.1002/14651858.CD006565.pub2
de Almeida CMO, Brito MMC, Bosaipo NB, Pimentel AV, Tumas V, Zuardi AW, Crippa JAS, Hallak JEC, Eckeli AL (2021) Cannabidiol for rapid eye movement sleep behavior disorder. Mov Disord 36(7):1711–1715. https://doi.org/10.1002/mds.28577
de Faria SM, de Morais FD, Tumas V, Castro PC, Ponti MA, Hallak JE, Zuardi AW, Crippa JAS, Chagas MHN (2020) Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson’s disease. J Psychopharmacol 34(2):189–196. https://doi.org/10.1177/0269881119895536
Deeb W, Malaty IA, Mathews CA (2019) Tourette disorder and other tic disorders. Handb Clin Neurol 165:123–153. https://doi.org/10.1016/B978-0-444-64012-3.00008-3
Dickson DW (2018) Neuropathology of Parkinson disease. Parkinsonism Relat Disord 46:S30–S33. https://doi.org/10.1016/j.parkreldis.2017.07.033
Fahn S, Jankovic J, Hallett M (2011) Principles and practice of movement disorders. Elsevier Health Sciences, Amsterdam
Feeney MP, Bega D, Kluger BM, Stoessl AJ, Evers CM, De Leon R, Beck JC (2021) Weeding through the haze: a survey on cannabis use among people living with Parkinson’s disease in the US. NPJ Parkinsons Dis 7(1):21. https://doi.org/10.1038/s41531-021-00165-y
Figura M, Koziorowski D, Sławek J (2022) Cannabis in Parkinson’s Disease - the patient’s perspective versus clinical trials: a systematic literature review. Neurol Neurochir Pol 56(1):21–27. https://doi.org/10.5603/PJNNS.a2022.0004 (Epub 2022 Jan 5 PMID: 34985112)
Fox SH, Kellett M, Moore AP, Crossman AR, Brotchie JM (2002) Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord 17(1):145–149. https://doi.org/10.1002/mds.1280
García K, Rada G (2016) Do cannabinoids have a role to play in Tourette’s syndrome? Medwave 16(Suppl5):e6793. https://doi.org/10.5867/medwave.2016.6793
García MC, Cinquina V, Palomo-Garo C, Rábano A, Fernández-Ruiz J (2015) Identification of CB2 receptors in human nigral neurons that degenerate in Parkinson’s disease. Neurosci Lett 5(587):1–4. https://doi.org/10.1016/j.neulet.2014.12.003
Greydanus DE, Tullio J (2020) Tourette’s disorder in children and adolescents. Transl Pediatr 9(1):S94–S103. https://doi.org/10.21037/tp.2019.09.11
Ibeas Bih C, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ (2015) Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics 12(4):699–730. https://doi.org/10.1007/s13311-015-0377-3
Kluger B, Triolo P, Jones W, Jankovic J (2015) The therapeutic potential of cannabinoids for movement disorders. Mov Disord 30(3):313–327. https://doi.org/10.1002/mds.26142
Koppel BS (2015) Cannabis in the Treatment of Dystonia, Dyskinesias, and Tics. Neurotherapeutics 12(4):788–792. https://doi.org/10.1007/s13311-015-0376-4
Koppel BS, Brust JC, Fife T, Bronstein J, Youssof S, Gronseth G, Gloss D (2014) Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 82(17):1556–1563. https://doi.org/10.1212/WNL.0000000000000363
Lim K, See YM, Lee J (2017) A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clin Psychopharmacol Neurosci 15(4):301–312. https://doi.org/10.9758/cpn.2017.15.4.301
López-Sendón MJL, García Caldentey J, Trigo Cubillo P, Ruiz Romero C, García Ribas G, Alonso Arias MA, García de Yébenes MJ, Tolón RM, Galve-Roperh I, Sagredo O, Valdeolivas S, Resel E, Ortega-Gutierrez S, García-Bermejo ML, Fernández Ruiz J, Guzmán M, de Yébenes G, Prous J (2016) A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease. J Neurol. https://doi.org/10.1007/s00415-016-8145-9
Lucas CJ, Galettis P, Schneider J (2018) The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol 84(11):2477–2482. https://doi.org/10.1111/bcp.13710
McColgan P, Tabrizi SJ (2018) Huntington’s disease: a clinical review. Eur J Neurol 25(1):24–34. https://doi.org/10.1111/ene.13413
Mesnage V, Houeto JL, Bonnet AM, Clavier I, Arnulf I, Cattelin F, Le Fur G, Damier P, Welter ML, Agid Y (2004) Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease. Clin Neuropharmacol 27(3):108–110. https://doi.org/10.1097/00002826-200405000-00003
Müller-Vahl KR, Schneider U, Koblenz A, Jöbges M, Kolbe H, Daldrup T, Emrich HM (2002) Treatment of Tourette’s syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry 35(2):57–61. https://doi.org/10.1055/s-2002-25028
Müller-Vahl KR, Prevedel H, Theloe K, Kolbe H, Emrich HM, Schneider U (2003) Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. Neuropsychopharmacology 28(2):384–388. https://doi.org/10.1038/sj.npp.1300047
Müller-Vahl KR, Schneider U, Prevedel H, Theloe K, Kolbe H, Daldrup T, Emrich HM (2003) Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry 64(4):459–465. https://doi.org/10.4088/jcp.v64n0417
O’Donnell B, Meissner H, Gupta V (2022) Dronabinol. StatPearls Publishing, Treasure Island (FL)
Oikonomou P, Jost WH (2022) Commentary: roles of the cannabinoid system in the Basal Ganglia in Parkinson’s Disease. Front Cell Neurosci 9(16):897930. https://doi.org/10.3389/fncel.2022.897930
Peball M, Werkmann M, Ellmerer P, Stolz R, Valent D, Knaus HG, Ulmer H, Djamshidian A, Poewe W, Seppi K (2019) Nabilone for non-motor symptoms of Parkinson’s disease: a randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study (The NMS-Nab Study). J Neural Transm (vienna) 126(8):1061–1072. https://doi.org/10.1007/s00702-019-02021-z
Peball M, Krismer F, Knaus HG, Djamshidian A, Werkmann M, Carbone F, Ellmerer P, Heim B, Marini K, Valent D, Goebel G, Ulmer H, Stockner H, Wenning GK, Stolz R, Krejcy K, Poewe W, Seppi K, Collaborators of the Parkinson’s Disease Working Group Innsbruck (2020) Non-Motor symptoms in Parkinson’s Disease are reduced by Nabilone. Ann Neurol 88(4):712–722. https://doi.org/10.1002/ana.25864
Poyatos L, Pérez-Acevedo AP, Papaseit E, Pérez-Mañá C, Martin S, Hladun O, Siles A, Torrens M, Busardo FP, Farré M (2020) Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) preparations: a systematic review. Medicina (kaunas) 56(6):309. https://doi.org/10.3390/medicina56060309
Prakash S, Carter WG (2021) The neuroprotective effects of cannabis-derived phytocannabinoids and resveratrol in Parkinson’s Disease: a systematic literature review of pre-clinical studies. Brain Sci 11(12):1573. https://doi.org/10.3390/brainsci11121573
Sieradzan KA, Fox SH, Hill M, Dick JP, Crossman AR, Brotchie JM (2001) Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: a pilot study. Neurology 57(11):2108–2111. https://doi.org/10.1212/wnl.57.11.2108
Sulcova A (2019) Pharmacodynamics of cannabinoids. Arch Pharm Pharma Sci 3:011–018. https://doi.org/10.29328/journal.apps.1001013
Szejko N (2022) Neurology—to be or not to be of the cannabis-based medicine? Neurol Neurochir Pol 56(1):1–3. https://doi.org/10.5603/PJNNS.2022.0021
Szejko N, Jakubovski E, Müller-Vahl K (2019) Possible role of the endocannabinoid system in Tourette syndrome. In: Laprairie RB, Costain WJ (eds) Recent advances in cannabinoid research. Intechopen, London
Szejko N, Saramak K, Lombroso A, Müller-Vahl K (2022) Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome. Neurol Neurochir Pol 56(1):28–38. https://doi.org/10.5603/PJNNS.a2021.0081
Thanabalasingam SJ, Ranjith B, Jackson R, Wijeratne DT (2021) Cannabis and its derivatives for the use of motor symptoms in Parkinson’s disease: a systematic review and meta-analysis. Ther Adv Neurol Disord 25(14):17562864211018560. https://doi.org/10.1177/17562864211018561.PMID:34104218;PMCID:PMC8161868
Urbi B, Corbett J, Hughes I, Owusu MA, Thorning S, Broadley SA, Sabet A, Heshmat S (2022) Effects of Cannabis in Parkinson’s Disease: a systematic review and meta-analysis. J Parkinsons Dis 12(2):495–508. https://doi.org/10.3233/JPD-212923
Vermersch P (2011) Sativex(®) (tetrahydrocannabinol + cannabidiol), an endocannabinoid system modulator: basic features and main clinical data. Expert Rev Neurother 11(4 Suppl):15–19. https://doi.org/10.1586/ern.11.27
Walker FO (2007) Huntington’s disease. Lancet 369(9557):218–228. https://doi.org/10.1016/S0140-6736(07)60111-1
Wang M, Liu H, Ma Z (2022) Roles of the cannabinoid system in the Basal Ganglia in Parkinson’s Disease. Front Cell Neurosci 21(16):832854. https://doi.org/10.3389/fncel.2022.832854
Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AF, Rodriguez-Violante M, Schrag A (2022) The neuropsychiatry of Parkinson’s disease: advances and challenges. Lancet Neurol 21(1):89–102. https://doi.org/10.1016/S1474-4422(21)00330-6
Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J (2015) Cannabinoids for Medical Use: a systematic review and meta-analysis. JAMA 313(24):2456–2473. https://doi.org/10.1001/jama.2015.6358
Yenilmez F, Fründt O, Hidding U, Buhmann C (2021) Cannabis in Parkinson’s Disease: the patients’ view. J Parkinsons Dis 11(1):309–321. https://doi.org/10.3233/JPD-202260
Zadikoff C, Wadia PM, Miyasaki J, Chen R, Lang AE, So J et al (2011) Cannabinoid, CB1 agonists in cervical dystonia: failure in a phase IIa randomized controlled trial. Basal Ganglia 1:91–95
Zhai S, Shen W, Graves SM, Surmeier DJ (2019) Dopaminergic modulation of striatal function and Parkinson’s disease. J Neural Transm (vienna) 126(4):411–422. https://doi.org/10.1007/s00702-019-01997-y
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Oikonomou, P., Jost, W.H. Randomized controlled trials on the use of cannabis-based medicines in movement disorders: a systematic review. J Neural Transm 129, 1247–1256 (2022). https://doi.org/10.1007/s00702-022-02529-x
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DOI: https://doi.org/10.1007/s00702-022-02529-x