Download PDF
Neurology International Open 2017; 01(04): E307-E311
DOI: 10.1055/s-0043-115359
Review
© Georg Thieme Verlag KG Stuttgart · New York

Cannabinoids in the Treatment of Parkinson’s Disease

Florin Gandor
1   Neurologisches Fachkrankenhaus für Bewegungsstörungen und Parkinson, Kliniken Beelitz GmbH, Beelitz-Heilstätten, Germany
,
Georg Ebersbach
1   Neurologisches Fachkrankenhaus für Bewegungsstörungen und Parkinson, Kliniken Beelitz GmbH, Beelitz-Heilstätten, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
25 October 2017 (online)

   Permissions and Reprints

Abstract

Due to the changing legal status of medical cannabis and derivatives in numerous countries, this therapeutic option has moved into the field of public debate. Neurologists treating patients with idiopathic Parkinson’s disease are increasingly confronted with questions regarding cannabis as a treatment alternative, especially for levodopa-resistant Parkinson’s symptoms. A number of single case reports and case series suggested improvement of Parkinsonian symptoms after cannabinoid intake, but the small number of available randomized clinical trials failed to reproduce the extent of these findings. Only one trial found a reduction of levodopa-induced dyskinesia with cannabinoid treatment, the remaining three trials showed no effect on Parkinsonian symptoms. This article gives an overview on the effects of cannabis, and reviews experimental and clinical trials studying the effects of cannabinoids in idiopathic Parkinson’s disease.

Key words

Parkinson’s disease - THC - cannabinoids
 

  • References

  • 1 Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646-1647
    CrossrefPubMedGoogle Scholar
  • 2 Di Marzo V, Melck D, Bisogno T. et al. Endocannabinoids: Endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 1998; 21: 521-528
    CrossrefPubMedGoogle Scholar
  • 3 Parker LA, Rock EM, Limebeer CL. Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. Eur J Pharmacol 2014; 722: 134-146
    CrossrefPubMedGoogle Scholar
  • 4 Pacher P, Kunos G. Modulating the endocannabinoid system in human health and disease – Successes and failures. FEBS J 2013; 280: 1918-1943
    CrossrefPubMedGoogle Scholar
  • 5 Kendall DA, Yudowski GA, Wang H. et al. Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Front Cell Neurosci 2017; 10: 1-10
    PubMedGoogle Scholar
  • 6 Scotter EL, Abood ME, Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol 2010; 160: 480-498
    CrossrefPubMedGoogle Scholar
  • 7 Koppel BS, Brust JCM, Fife T. et al. Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders. Neurology 2014; 82: 1556-1563
    CrossrefPubMedGoogle Scholar
  • 8 2017; Cannabisagentur. www.bfarm.de/DE/Bundesopiumstelle/ Cannabis/Cannabisagentur/_node.html
    PubMed
  • 9 2016; Ride with Larry. https://www.youtube.com/watch?v = LHvPIXGsrHk& list = PL6wHuRfu1deQ2BZ_yLddvdQfKEJbjFkLg
    PubMed
  • 10 2016; Lindenstrasse, Folge 1581. http://www1.wdr.de/daserste/ lindenstrasse/folgen/2016/ende-und-anfang-100~_compage-4.html
    PubMed
  • 11 Mechoulam R, Shvo Y, Hashish I. The structure of cannabidiol. Tetrahedron 1963; 19: 2073-2078
    CrossrefPubMedGoogle Scholar
  • 12 Matsuda LA, Lolait SJ, Brownstein MJ. et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561-564
    CrossrefPubMedGoogle Scholar
  • 13 Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61-65
    CrossrefPubMedGoogle Scholar
  • 14 Rogers N. Cannabinoid receptor with an “identity crisis” gets a second look. Nat Med 2015; 21: 966-967
    CrossrefPubMedGoogle Scholar
  • 15 Onaivi ES. Neuropsychobiological evidence for the functional presence and expression of cannabinoid CB2 receptors in the brain. Neuropsychobiology 2006; 54: 231-246
    CrossrefPubMedGoogle Scholar
  • 16 Van Sickle MD, Duncan M, Kingsley PJ. et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 2005; 310: 329-332
    CrossrefPubMedGoogle Scholar
  • 17 Valjent E, Pagès C, Rogard M. et al. Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission. Eur J Neurosci 2001; 14: 342-352
    CrossrefPubMedGoogle Scholar
  • 18 Moranta D, Esteban S, García-Sevilla JA. Acute, chronic and withdrawal effects of the cannabinoid receptor agonist WIN55212-2 on the sequential activation of MAPK/Raf-MEK-ERK signaling in the rat cerebral frontal cortex: Short-term regulation by intrinsic and extrinsic pathways. J Neurosci Res 2007; 85: 656-667
    CrossrefPubMedGoogle Scholar
  • 19 Howlett AC, Blume LC, Dalton GD. CB(1) cannabinoid receptors and their associated proteins. Curr Med Chem 2010; 17: 1382-1393
    CrossrefPubMedGoogle Scholar
  • 20 Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 2011; 75: 50-83
    CrossrefPubMedGoogle Scholar
  • 21 Garriott JC, King LJ, Forney RB. et al. Effects of some tetrahydrocannabinols on hexobarbital sleeping time and amphetamine induced hyperactivity in mice. Life Sci 1967; 6: 2119-2128
    CrossrefPubMedGoogle Scholar
  • 22 Howes J, Osgood P. The effect of delta9-tetrahydrocannabinol on the uptake and release of 14C-dopamine from crude striatal synaptosoma; preparations. Neuropharmacology 1974; 13: 1109-1114
    CrossrefPubMedGoogle Scholar
  • 23 Herkenham M, Lynn AB, de Costa BR. et al. Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 1991; 547: 267-274
    CrossrefPubMedGoogle Scholar
  • 24 Hershkowitz M, Szechtman H. Pretreatment with delta 1-tetrahydrocannabinol and psychoactive drugs: Effects on uptake of biogenic amines and on behavior. Eur J Pharmacol 1979; 59: 267-276
    CrossrefPubMedGoogle Scholar
  • 25 Bloom AS, Dewey WL. A comparison of some pharmacological actions of morphine and delta9-tetrahydrocannabinol in the mouse. Psychopharmacology (Berl) 1978; 57: 243-248
    CrossrefPubMedGoogle Scholar
  • 26 Bloomfield MAP, Ashok AH, Volkow ND. et al. The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature 2016; 539: 369-377
    CrossrefPubMedGoogle Scholar
  • 27 Fernández-Ruiz J, Moreno-Martet M, Rodríguez-Cueto C. et al. Prospects for cannabinoid therapies in basal ganglia disorders. Br J Pharmacol 2011; 163: 1365-1378
    CrossrefPubMedGoogle Scholar
  • 28 Gómez-Gálvez Y, Palomo-Garo C, Fernández-Ruiz J. et al. Potential of the cannabinoid CB2 receptor as a pharmacological target against inflammation in Parkinson’s disease. Prog Neuro-Psychopharmacology Biol Psychiatry 2016; 64: 200-208
    CrossrefPubMedGoogle Scholar
  • 29 Lastres-Becker I, Cebeira M, de Ceballos ML. et al. Increased cannabinoid CB1 receptor binding and activation of GTP-binding proteins in the basal ganglia of patients with Parkinson’s syndrome and of MPTP-treated marmosets. Eur J Neurosci 2001; 14: 1827-1832
    CrossrefPubMedGoogle Scholar
  • 30 Di Marzo V, Hill MP, Bisogno T. et al. Enhanced levels of endogenous cannabinoids in the globus pallidus are associated with a reduction in movement in an animal model of Parkinson’s disease. FASEB J 2000; 14: 1432-1438
    CrossrefPubMedGoogle Scholar
  • 31 van der Stelt M, Fox SH, Hill M. et al. A role for endocannabinoids in the generation of parkinsonism and levodopa-induced dyskinesia in MPTP-lesioned non-human primate models of Parkinson’s disease. FASEB J 2005; 19: 1140-1142
    CrossrefPubMedGoogle Scholar
  • 32 Gubellini P, Picconi B, Bari M. et al. Experimental parkinsonism alters endocannabinoid degradation: implications for striatal glutamatergic transmission. J Neurosci 2002; 22: 6900-6907
    CrossrefPubMedGoogle Scholar
  • 33 Maccarrone M, Gubellini P, Bari M. et al. Levodopa treatment reverses endocannabinoid system abnormalities in experimental parkinsonism. J Neurochem 2003; 85: 1018-1025
    CrossrefPubMedGoogle Scholar
  • 34 Meschler JP, Howlett AC, Madras BK. Cannabinoid receptor agonist and antagonist effects on motor function in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human primates. Psychopharmacology (Berl) 2001; 156: 79-85
    CrossrefPubMedGoogle Scholar
  • 35 Kreitzer AC, Malenka RC. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s disease models. Nature 2007; 445: 643-647
    CrossrefPubMedGoogle Scholar
  • 36 Fernandez-Espejo E, Caraballo I, Rodriguez de Fonseca F. et al. Experimental parkinsonism alters anandamide precursor synthesis, and functional deficits are improved by AM404: A modulator of endocannabinoid function. Neuropsychopharmacol 2004; 29: 1134-1142
    CrossrefPubMedGoogle Scholar
  • 37 Fox SH, Henry B, Hill M. et al. Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 2002; 17: 1180-1187
    CrossrefPubMedGoogle Scholar
  • 38 Carroll CB, Zeissler M-L, Hanemann CO. et al. Δ9-tetrahydrocannabinol (Δ9-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson’s disease. Neuropathol Appl Neurobiol 2012; 38: 535-547
    CrossrefPubMedGoogle Scholar
  • 39 Klein TW. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol 2005; 5: 400-411
    CrossrefPubMedGoogle Scholar
  • 40 Lastres-Becker I, Molina-Holgado F, Ramos JA. et al. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: Relevance to Parkinson’s disease. Neurobiol Dis 2005; 19: 96-107
    CrossrefPubMedGoogle Scholar
  • 41 Fernández-Ruiz J, García C, Sagredo O. et al. The endocannabinoid system as a target for the treatment of neuronal damage. Expert Opin Ther Targets 2010; 14: 387-404
    CrossrefPubMedGoogle Scholar
  • 42 Venderová K, Růzicka E, Vorísek V. et al. Survey on cannabis use in Parkinson’s disease: subjective improvement of motor symptoms. Mov Disord 2004; 19: 1102-1106
    CrossrefPubMedGoogle Scholar
  • 43 Lotan I, Treves TA, Roditi Y. et al. Cannabis (Medical Marijuana) Treatment for motor and non–motor symptoms of Parkinson disease. Clin Neuropharmacol 2014; 37: 41-44
    CrossrefPubMedGoogle Scholar
  • 44 Frankel JP, Hughes A, Lees AJ. et al. Marijuana for parkinsonian tremor. J Neurol Neurosurg Psychiatry 1990; 53: 436
    PubMedGoogle Scholar
  • 45 Chagas MH, Zuardi AW, Tumas V. et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial. J Psychopharmacol 2014; 28: 1088-1098
    CrossrefPubMedGoogle Scholar
  • 46 Sieradzan KA, Fox SH, Hill M. et al. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: A pilot study. Neurology 2001; 57: 2108-2111
    CrossrefPubMedGoogle Scholar
  • 47 Carroll CB, Bain PG, Teare L. et al. Cannabis for dyskinesia in Parkinson disease: A randomized double-blind crossover study. Neurology 2004; 63: 1245-1250
    CrossrefPubMedGoogle Scholar
  • 48 Mesnage V, Houeto JL, Bonnet AM. et al. Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease. Clin Neuropharmacol 2004; 27: 108-110
    CrossrefPubMedGoogle Scholar
  • 49 Zuardi AW, Crippa JAS, Hallak JEC. et al. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol 2009; 23: 979-983
    CrossrefPubMedGoogle Scholar
  • 50 Seppi K, Weintraub D, Coelho M. et al. The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord 2001; 26 (Suppl. 03) S42-S80
    PubMedGoogle Scholar
  • 51 Sidney S. Cardiovascular consequences of marijuana use. J Clin Pharmacol 2002; 42: 64S-70S
    CrossrefPubMedGoogle Scholar
  • 52 Prakash R, Aronow WS, Warren M. et al. Effects of marihuana and placebo marihuana smoking on hemodynamics in coronary disease. Clin Pharmacol Ther 1975; 18: 90-95
    CrossrefPubMedGoogle Scholar
  • 53 Aronow WS, Cassidy J. Effect of marihuana and placebo-marihuana smoking on angina pectoris. N Engl J Med 1974; 291: 65-67
    CrossrefPubMedGoogle Scholar
  • 54 Jouanjus E, Lapeyre-Mestre M, Micallef J. French Association of the Regional Abuse and Dependence Monitoring Centres (CEIP-A) Working Group on Cannabis Complications* Cannabis Use: Signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc 2014; 3: e000638-e000638
    CrossrefPubMedGoogle Scholar
  • 55 Mittleman MA, Lewis RA, Maclure M. et al. Triggering myocardial infarction by marijuana. Circulation 2001; 103: 2805-2809
    CrossrefPubMedGoogle Scholar