Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?

Fernanda F Peres, Alvaro C Lima, Jaime E C Hallak, José A Crippa, Regina H Silva, Vanessa C Abílio, Fernanda F Peres, Alvaro C Lima, Jaime E C Hallak, José A Crippa, Regina H Silva, Vanessa C Abílio

Abstract

Movement disorders such as Parkinson's disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field.

Keywords: Huntington's disease; Parkinson's disease; cannabidiol; cannabinoids; dystonic disorders; movement disorders.

Figures

Figure 1
Figure 1
CBD's mechanisms of action. CBD acts as agonist of the receptors TRPV1, PPARγ, and 5-HT1A, and as antagonist of the receptor GPR55. CBD is an inverse agonist of the receptors GPR3, GPR6, and GPR12. Moreover, CBD antagonizes the action of CB1 and CB2 receptors agonists, and is suggested to act as an inverse agonist and a negative allosteric modulator of these receptors. CBD also inhibits FAAH, which results in increased anandamide levels. Anandamide activates CB1, CB2, and TRPV1 receptors. By acting on mitochondria, CBD increases the activity of mitochondrial complexes. In addition, CBD displays antioxidant and anti-inflammatory effects—that are partially mediated by CBD's actions on TRPV1, mitochondria and PPARγ. 5-HT1A, serotonin receptor 1A; CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type 2; FAAH, fatty acid amide hydrolase; GPR3, G-protein-coupled receptor 3; GPR6, G-protein-coupled receptor 6; GPR12, G-protein-coupled receptor 12; GPR55, G-protein-coupled receptor 55; PPARγ, peroxisome proliferator-activated receptor gamma; ROS, reactive oxygen species; TRPV1, transient receptor potential vanilloid type 1.

References

    1. Adams R., Hunt M., Clark J. (1940). Structure of cannabidiol, a product isolated from the marihuana extract of Minnesota wild hemp. I. J. Am. Chem. Soc. 62, 196–200. 10.1021/ja01858a058
    1. Aiken C. T., Tobin A. J., Schweitzer E. S. (2004). A cell-based screen for drugs to treat Huntington's disease. Neurobiol. Dis. 16, 546–555. 10.1016/j.nbd.2004.04.001
    1. Ammal Kaidery N., Thomas B. (2018). Current perspective of mitochondrial biology in Parkinson's disease. Neurochem. Int. [Epub ahead of print]. 10.1016/j.neuint.2018.03.001
    1. Aragona M., Onesti E., Tomassini V., Conte A., Gupta S., Gilio F., et al. . (2009). Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study. Clin. Neuropharmacol. 32, 41–47. 10.1097/WNF.0B013E3181633497
    1. Bergamaschi M. M., Queiroz R. H., Zuardi A. W., Crippa J. A. (2011). Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr. Drug Saf. 6, 237–249. 10.2174/157488611798280924
    1. Bisogno T., Hanus L., De Petrocellis L., Tchilibon S., Ponde D. E., Brandi I., et al. . (2001). Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol. 134, 845–852. 10.1038/sj.bjp.0704327
    1. Bové J., Prou D., Perier C., Przedborski S. (2005). Toxin-induced models of Parkinson's disease. NeuroRx 2, 484–494. 10.1602/neurorx.2.3.484
    1. Breakefield X. O., Blood A. J., Li Y., Hallett M., Hanson P. I., Standaert D. G. (2008). The pathophysiological basis of dystonias. Nat. Rev. Neurosci. 9, 222–234. 10.1038/nrn2337
    1. Breese G. R., Traylor T. D. (1971). Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine. Br. J. Pharmacol. 42, 88–99. 10.1111/j.1476-5381.1971.tb07089.x
    1. Brouillet E., Jacquard C., Bizat N., Blum D. (2005). 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease. J. Neurochem. 95, 1521–1540. 10.1111/j.1471-4159.2005.03515.x
    1. Brown K. J., Laun A. S., Song Z. H. (2017). Cannabidiol, a novel inverse agonist for GPR12. Biochem. Biophys. Res. Commun. 493, 451–454. 10.1016/j.bbrc.2017.09.001
    1. Campos A. C., Brant F., Miranda A. S., Machado F. S., Teixeira A. L. (2015). Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria. Neuroscience 289, 166–180. 10.1016/j.neuroscience.2014.12.051
    1. Campos A. C., Fogaca M. V., Sonego A. B., Guimaraes F. S. (2016). Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol. Res. 112, 119–127. 10.1016/j.phrs.2016.01.033
    1. Castelli L., Prosperini L., Pozzilli C. (2018). Balance worsening associated with nabiximols in multiple sclerosis. Mult. Scler. J. [Epub ahead of print]. 10.1177/1352458518765649
    1. Celorrio M., Rojo-Bustamante E., Fernandez-Suarez D., Saez E., Estella-Hermoso de Mendoza A., Muller C. E., et al. . (2017). GPR55: a therapeutic target for Parkinson's disease? Neuropharmacology 125, 319–332. 10.1016/j.neuropharm.2017.08.017
    1. Chagas M. H., Eckeli A. L., Zuardi A. W., Pena-Pereira M. A., Sobreira-Neto M. A., Sobreira E. T., et al. . (2014a). Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J. Clin. Pharm. Ther. 39, 564–566. 10.1111/jcpt.12179
    1. Chagas M. H., Zuardi A. W., Tumas V., Pena-Pereira M. A., Sobreira E. T., Bergamaschi M. M., et al. . (2014b). Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J. Psychopharmacol. 28, 1088–1098. 10.1177/0269881114550355
    1. Chen J., Hou C., Chen X., Wang D., Yang P., He X., et al. (2016). Protective effect of cannabidiol on hydrogen peroxide induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells. Mol. Med. Rep. 14, 2321–2327. 10.3892/mmr.2016.5513
    1. Cheng D., Low J. K., Logge W., Garner B., Karl T. (2014). Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1E9 mice. Psychopharmacology 231, 3009–3017. 10.1007/s00213-014-3478-5
    1. Cherif H., Argaw A., Cecyre B., Bouchard A., Gagnon J., Javadi P., et al. . (2015). Role of GPR55 during axon growth and target innervation. eNeuro 2:ENEURO.0011-15.2015. 10.1523/ENEURO.0011-15.2015
    1. Colizzi M., Bhattacharyya S. (2017). Does cannabis composition matter? differential effects of delta-9-tetrahydrocannabinol and cannabidiol on human cognition. Curr. Addict. Rep. 4, 62–74. 10.1007/s40429-017-0142-2
    1. Connolly B. S., Lang A. E. (2014). Pharmacological treatment of Parkinson disease: a review. JAMA 311, 1670–1683. 10.1001/jama.2014.3654
    1. Consroe P., Laguna J., Allender J., Snider S., Stern L., Sandyk R., et al. . (1991). Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacol. Biochem. Behav. 40, 701–708. 10.1016/0091-3057(91)90386-G
    1. Consroe P., Sandyk R., Snider S. R. (1986). Open label evaluation of cannabidiol in dystonic movement disorders. Int. J. Neurosci. 30, 277–282. 10.3109/00207458608985678
    1. Crabtree-Hartman E. (2018). Advanced symptom management in multiple sclerosis. Neurol. Clin. 36, 197–218. 10.1016/j.ncl.2017.08.015
    1. Crook Z. R., Housman D. (2011). Huntington's disease: can mice lead the way to treatment? Neuron 69, 423–435. 10.1016/j.neuron.2010.12.035
    1. 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, 2254–2259. 10.1002/mds.22809
    1. da Silva V. K., de Freitas B. S., Dornelles V. C., Kist L. W., Bogo M. R., Silva M. C., et al. . (2018). Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: reversal by cannabidiol. Brain Res. Bull. 139, 1–8. 10.1016/j.brainresbull.2018.01.014
    1. Dauer W., Przedborski S. (2003). Parkinson's disease: mechanisms and models. Neuron 39, 889–909. 10.1016/S0896-6273(03)00568-3
    1. Dickey A. S., La Spada A. R. (2017). Therapy development in Huntington disease: from current strategies to emerging opportunities. Am. J. Med. Genet. A 176, 842–861. 10.1002/ajmg.a.38494
    1. Dos-Santos-Pereira M., da-Silva C. A., Guimaraes F. S., Del-Bel E. (2016). Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: possible mechanism of action. Neurobiol. Dis. 94, 179–195. 10.1016/j.nbd.2016.06.013
    1. El-Alfy A. T., Ivey K., Robinson K., Ahmed S., Radwan M., Slade D., et al. . (2010). Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol. Biochem. Behav. 95, 434–442. 10.1016/j.pbb.2010.03.004
    1. ElSohly M., Gul W. (2014). Constituents of Cannabis sativa, in Handbook of Cannabis, ed Pertwee R. G. (New York, NY: Oxford University Press; ), 1093.
    1. Englund A., Freeman T. P., Murray R. M., McGuire P. (2017). Can we make cannabis safer? Lancet Psychiatry 4, 643–648. 10.1016/S2215-0366(17)30075-5
    1. Espejo-Porras F., Fernandez-Ruiz J., Pertwee R. G., Mechoulam R., Garcia C. (2013). Motor effects of the non-psychotropic phytocannabinoid cannabidiol that are mediated by 5-HT1A receptors. Neuropharmacology 75, 155–163. 10.1016/j.neuropharm.2013.07.024
    1. Esposito G., Scuderi C., Savani C., Steardo L., Jr., De Filippis D., Cottone P., et al. . (2007). Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br. J. Pharmacol. 151, 1272–1279. 10.1038/sj.bjp.0707337
    1. Esposito G., Scuderi C., Valenza M., Togna G. I., Latina V., De Filippis D., et al. . (2011). Cannabidiol reduces Abeta-induced neuroinflammation and promotes hippocampal neurogenesis through PPARgamma involvement. PLoS ONE 6:e28668. 10.1371/journal.pone.0028668
    1. Fagherazzi E. V., Garcia V. A., Maurmann N., Bervanger T., Halmenschlager L. H., Busato S. B., et al. . (2012). Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders. Psychopharmacology 219, 1133–1140. 10.1007/s00213-011-2449-3
    1. Farooqui T., Farooqui A. A. (2011). Lipid-mediated oxidative stress and inflammation in the pathogenesis of Parkinson's disease. Parkinsons. Dis. 2011:247467. 10.4061/2011/247467
    1. Flachenecker P., Henze T., Zettl U. K. (2014). Spasticity in patients with multiple sclerosis–clinical characteristics, treatment and quality of life. Acta Neurol. Scand. 129, 154–162. 10.1111/ane.12202
    1. Garcia C., Palomo-Garo C., Garcia-Arencibia M., Ramos J., Pertwee R., Fernandez-Ruiz J. (2011). Symptom-relieving and neuroprotective effects of the phytocannabinoid Delta(9)-THCV in animal models of Parkinson's disease. Br. J. Pharmacol. 163, 1495–1506. 10.1111/j.1476-5381.2011.01278.x
    1. García-Arencibia M., Gonzalez S., de Lago E., Ramos J. A., Mechoulam R., Fernandez-Ruiz J. (2007). Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res. 1134, 162–170. 10.1016/j.brainres.2006.11.063
    1. Giacoppo S., Bramanti P., Mazzon E. (2017a). Sativex in the management of multiple sclerosis-related spasticity: an overview of the last decade of clinical evaluation. Mult. Scler. Relat. Disord. 17, 22–31. 10.1016/j.msard.2017.06.015
    1. Giacoppo S., Pollastro F., Grassi G., Bramanti P., Mazzon E. (2017b). Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis. Fitoterapia 116, 77–84. 10.1016/j.fitote.2016.11.010
    1. Gomes F. V., Del Bel E. A., Guimaraes F. S. (2013). Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 46, 43–47. 10.1016/j.pnpbp.2013.06.005
    1. Gomes F. V., Llorente R., Del Bel E. A., Viveros M. P., Lopez-Gallardo M., Guimaraes F. S. (2015). Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol. Schizophr. Res. 164, 155–163. 10.1016/j.schres.2015.01.015
    1. Grlic L. (1976). A comparative study on some chemical and biological characteristics of various samples of cannabis resin. Bull. Narc. 14, 37–46.
    1. Hampson A. J., Grimaldi M., Axelrod J., Wink D. (1998). Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc. Natl. Acad. Sci. U.S.A. 95, 8268–8273. 10.1073/pnas.95.14.8268
    1. Hassan S., Eldeeb K., Millns P. J., Bennett A. J., Alexander S. P., Kendall D. A. (2014). Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br. J. Pharmacol. 171, 2426–2439. 10.1111/bph.12615
    1. Hayakawa K., Mishima K., Hazekawa M., Sano K., Irie K., Orito K., et al. . (2008). Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism. Brain Res. 1188, 157–164. 10.1016/j.brainres.2007.09.090
    1. Hecker M., Paap B. K., Goertsches R. H., Kandulski O., Fatum C., Koczan D., et al. . (2011). Reassessment of blood gene expression markers for the prognosis of relapsing-remitting multiple sclerosis. PLoS ONE 6:e29648. 10.1371/journal.pone.0029648
    1. Hind W. H., England T. J., O'Sullivan S. E. (2016). Cannabidiol protects an in vitro model of the blood-brain barrier from oxygen-glucose deprivation via PPARgamma and 5-HT1A receptors. Br. J. Pharmacol. 173, 815–825. 10.1111/bph.13368
    1. Hindocha C., Freeman T. P., Schafer G., Gardener C., Das R. K., Morgan C. J., et al. . (2015). Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users. Eur. Neuropsychopharmacol. 25, 325–334. 10.1016/j.euroneuro.2014.11.014
    1. Hodges A., Strand A. D., Aragaki A. K., Kuhn A., Sengstag T., Hughes G., et al. . (2006). Regional and cellular gene expression changes in human Huntington's disease brain. Hum. Mol. Genet. 15, 965–977. 10.1093/hmg/ddl013
    1. Iffland K., Grotenhermen F. (2017). An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2, 139–154. 10.1089/can.2016.0034
    1. Iuvone T., Esposito G., Esposito R., Santamaria R., Di Rosa M., Izzo A. A. (2004). Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J. Neurochem. 89, 134–141. 10.1111/j.1471-4159.2003.02327.x
    1. Jacobs D. S., Kohut S. J., Jiang S., Nikas S. P., Makriyannis A., Bergman J. (2016). Acute and chronic effects of cannabidiol on Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-induced disruption in stop signal task performance. Exp. Clin. Psychopharmacol. 24, 320–330. 10.1037/pha0000081
    1. Jankovic J. (2005). Motor fluctuations and dyskinesias in Parkinson's disease: clinical manifestations. Mov Disord 20 (Suppl. 11), S11–S16. 10.1002/mds.20458
    1. Juknat A., Rimmerman N., Levy R., Vogel Z., Kozela E. (2012). Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells. Neurochem. Int. 61, 923–930. 10.1016/j.neuint.2011.12.002
    1. Kaplan J. S., Stella N., Catterall W. A., Westenbroek R. E. (2017). Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proc. Natl. Acad. Sci. U.S.A. 114, 11229–11234. 10.1073/pnas.1711351114
    1. Klockgether T. (2004). Parkinson's disease: clinical aspects. Cell Tissue Res. 318, 115–120. 10.1007/s00441-004-0975-6
    1. Kozela E., Pietr M., Juknat A., Rimmerman N., Levy R., Vogel Z. (2010). Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferon-beta/STAT proinflammatory pathways in BV-2 microglial cells. J. Biol. Chem. 285, 1616–1626. 10.1074/jbc.M109.069294
    1. Laprairie R., Bagher A., Kelly M., Denovan-Wright E. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br. J. Pharmacol. 172, 4790–4805. 10.1111/bph.13250
    1. Lastres-Becker I., Hansen H. H., Berrendero F., De Miguel R., Perez-Rosado A., Manzanares J., et al. . (2002). Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington's disease. Synapse 44, 23–35. 10.1002/syn.10054
    1. Lastres-Becker I., Molina-Holgado F., Ramos J. A., Mechoulam R., Fernandez-Ruiz J. (2005). Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease. Neurobiol. Dis. 19, 96–107. 10.1016/j.nbd.2004.11.009
    1. Laun A. S., Song Z. H. (2017). GPR3 and GPR6, novel molecular targets for cannabidiol. Biochem. Biophys. Res. Commun. 490, 17–21. 10.1016/j.bbrc.2017.05.165
    1. Lee J. L. C., Bertoglio L. J., Guimaraes F. S., Stevenson C. W. (2017). Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. Br. J. Pharmacol. 174, 3242–3256. 10.1111/bph.13724
    1. Lerner P. P., Miodownik C., Lerner V. (2015). Tardive dyskinesia (syndrome): current concept and modern approaches to its management. Psychiatry Clin. Neurosci. 69, 321–334. 10.1111/pcn.12270
    1. Leweke F. M., Piomelli D., Pahlisch F., Muhl D., Gerth C. W., Hoyer C., et al. . (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl. Psychiatry 2:e94. 10.1038/tp.2012.15
    1. Long L. E., Malone D. T., Taylor D. A. (2006). Cannabidiol reverses MK-801-induced disruption of prepulse inhibition in mice. Neuropsychopharmacology 31, 795–803. 10.1038/sj.npp.1300838
    1. López-Sendón Moreno J. L., Garcia Caldentey J., Trigo Cubillo P., Ruiz Romero C., Garcia Ribas G., Alonso Arias M. A., et al. . (2016). A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington's disease. J. Neurol. 263, 1390–1400. 10.1007/s00415-016-8145-9
    1. MacDonald M. E., Barnes G., Srinidhi J., Duyao M. P., Ambrose C. M., Myers R. H., et al. (1993). Gametic but not somatic instability of CAG repeat length in Huntington's disease. J. Med. Genet. 30, 982–986. 10.1136/jmg.30.12.982
    1. Martínez-Pinilla E., Varani K., Reyes-Resina I., Angelats E., Vincenzi F., Ferreiro-Vera C., et al. . (2017). Binding and signaling studies disclose a potential allosteric site for cannabidiol in cannabinoid CB2 receptors. Front. Pharmacol. 8:744. 10.3389/fphar.2017.00744
    1. Martín-Moreno A. M., Reigada D., Ramirez B. G., Mechoulam R., Innamorato N., Cuadrado A., et al. . (2011). Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer's disease. Mol. Pharmacol. 79, 964–973. 10.1124/mol.111.071290
    1. Mason S. L., Barker R. A. (2016). Advancing pharmacotherapy for treating Huntington's disease: a review of the existing literature. Expert Opin. Pharmacother. 17, 41–52. 10.1517/14656566.2016.1109630
    1. McColgan P., Tabrizi S. J. (2018). Huntington's disease: a clinical review. Eur. J. Neurol. 25, 24–34. 10.1111/ene.13413
    1. McGuire P., Robson P., Cubala W. J., Vasile D., Morrison P. D., Barron R., et al. . (2018). Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am. J. Psychiatry 175, 225–231. 10.1176/appi.ajp.2017.17030325
    1. Mecha M., Torrao A. S., Mestre L., Carrillo-Salinas F. J., Mechoulam R., Guaza C. (2012). Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress. Cell Death Dis. 3:e331. 10.1038/cddis.2012.71
    1. Mechoulam R., Shvo Y. (1963). Hashish—I: the structure of cannabidiol. Tetrahedron 19, 2073–2078. 10.1016/0040-4020(63)85022-X
    1. Meredith G. E., Totterdell S., Potashkin J. A., Surmeier D. J. (2008). Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol. Parkinsonism Relat. Disord. 14(Suppl. 2), S112–115. 10.1016/j.parkreldis.2008.04.012
    1. Molderings G. J., Bonisch H., Hammermann R., Gothert M., Bruss M. (2002). Noradrenaline release-inhibiting receptors on PC12 cells devoid of alpha(2(-)) and CB(1) receptors: similarities to presynaptic imidazoline and edg receptors. Neurochem. Int. 40, 157–167. 10.1016/S0197-0186(01)00076-6
    1. Morales P., Isawi I., Reggio P. H. (2018). Towards a better understanding of the cannabinoid-related orphan receptors GPR3, GPR6, and GPR12. Drug Metab. Rev. 50, 74–93. 10.1080/03602532.2018.1428616
    1. Morales P., Reggio P. H. (2017). An update on non-CB1, non-CB2 cannabinoid related g-protein-coupled receptors. Cannabis Cannabinoid Res. 2, 265–273. 10.1089/can.2017.0036
    1. Murphy M., Mills S., Winstone J., Leishman E., Wager-Miller J., Bradshaw H., et al. (2017). Chronic adolescent delta(9)-tetrahydrocannabinol treatment of male mice leads to long-term cognitive and behavioral dysfunction, which are prevented by concurrent cannabidiol treatment. Cannabis Cannabinoid Res. 2, 235–246. 10.1089/can.2017.0034
    1. Myers A. M., Siegele P. B., Foss J. D., Tuma R. F., Ward S. J. (2018). Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice. Br. J. Pharmacol. [Epub ahead of print]. 10.1111/bph.14147
    1. Nielsen S., Germanos R., Weier M., Pollard J., Degenhardt L., Hall W., et al. . (2018). The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews. Curr. Neurol. Neurosci. Rep. 18:8. 10.1007/s11910-018-0814-x
    1. Niranjan R. (2014). The role of inflammatory and oxidative stress mechanisms in the pathogenesis of Parkinson's disease: focus on astrocytes. Mol. Neurobiol. 49, 28–38. 10.1007/s12035-013-8483-x
    1. Oeckl P., Ferger B. (2016). Increased susceptibility of G-protein coupled receptor 6 deficient mice to MPTP neurotoxicity. Neuroscience 337, 218–223. 10.1016/j.neuroscience.2016.09.021
    1. Oeckl P., Hengerer B., Ferger B. (2014). G-protein coupled receptor 6 deficiency alters striatal dopamine and cAMP concentrations and reduces dyskinesia in a mouse model of Parkinson's disease. Exp. Neurol. 257, 1–9. 10.1016/j.expneurol.2014.04.010
    1. Osborne A. L., Solowij N., Weston-Green K. (2017). A systematic review of the effect of cannabidiol on cognitive function: relevance to schizophrenia. Neurosci. Biobehav. Rev. 72, 310–324. 10.1016/j.neubiorev.2016.11.012
    1. O'Sullivan S. E., Sun Y., Bennett A. J., Randall M. D., Kendall D. A. (2009). Time-dependent vascular actions of cannabidiol in the rat aorta. Eur. J. Pharmacol. 612, 61–68. 10.1016/j.ejphar.2009.03.010
    1. Pan H., Mukhopadhyay P., Rajesh M., Patel V., Mukhopadhyay B., Gao B., et al. . (2009). Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. J. Pharmacol. Exp. Ther. 328, 708–714. 10.1124/jpet.108.147181
    1. Patti F., Messina S., Solaro C., Amato M. P., Bergamaschi R., Bonavita S., et al. . (2016). Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity. J. Neurol. Neurosurg. Psychiatry 87, 944–951. 10.1136/jnnp-2015-312591
    1. Pazos M. R., Mohammed N., Lafuente H., Santos M., Martinez-Pinilla E., Moreno E., et al. . (2013). Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors. Neuropharmacology 71, 282–291. 10.1016/j.neuropharm.2013.03.027
    1. Pedrazzi J. F., Issy A. C., Gomes F. V., Guimaraes F. S., Del-Bel E. A. (2015). Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine. Psychopharmacology 232, 3057–3065. 10.1007/s00213-015-3945-7
    1. Peres F. F., Levin R., Suiama M. A., Diana M. C., Gouvea D. A., Almeida V., et al. . (2016). Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats. Front. Pharmacol. 7:343. 10.3389/fphar.2016.00343
    1. Perez-Reyes M., Timmons M. C., Davis K. H., Wall E. M. (1973). A comparison of the pharmacological activity in man of intravenously administered delta9-tetrahydrocannabinol, cannabinol, and cannabidiol. Experientia 29, 1368–1369. 10.1007/BF01922823
    1. Pertwee R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br. J. Pharmacol. 153, 199–215. 10.1038/sj.bjp.0707442
    1. Pertwee R. G., Ross R. A. (2002). Cannabinoid receptors and their ligands. Prostaglandins Leukot. Essent. Fatty Acids 66, 101–121. 10.1054/plef.2001.0341
    1. Rajan T. S., Giacoppo S., Iori R., De Nicola G. R., Grassi G., Pollastro F., et al. . (2016). Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia 112, 104–115. 10.1016/j.fitote.2016.05.008
    1. Rekand T. (2014). THC:CBD spray and MS spasticity symptoms: data from latest studies. Eur. Neurol. 71(Suppl. 1), 4–9. 10.1159/000357742
    1. Richter A., Loscher W. (2002). Effects of pharmacological manipulations of cannabinoid receptors on severity of dystonia in a genetic model of paroxysmal dyskinesia. Eur. J. Pharmacol. 454, 145–151. 10.1016/S0014-2999(02)02477-9
    1. Rock E. M., Bolognini D., Limebeer C. L., Cascio M. G., Anavi-Goffer S., Fletcher P. J., et al. . (2012). Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br. J. Pharmacol. 165, 2620–2634. 10.1111/j.1476-5381.2011.01621.x
    1. Ross R. A. (2003). Anandamide and vanilloid TRPV1 receptors. Br. J. Pharmacol. 140, 790–801. 10.1038/sj.bjp.0705467
    1. Ross R. A. (2009). The enigmatic pharmacology of GPR55. Trends Pharmacol. Sci. 30, 156–163. 10.1016/j.tips.2008.12.004
    1. Russo E. B., Burnett A., Hall B., Parker K. K. (2005). Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem. Res. 30, 1037–1043. 10.1007/s11064-005-6978-1
    1. Russo E., Guy G. W. (2006). A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med. Hypotheses 66, 234–246. 10.1016/j.mehy.2005.08.026
    1. Russo M., De Luca R., Torrisi M., Rifici C., Sessa E., Bramanti P., et al. . (2016). Should we care about sativex-induced neurobehavioral effects? A 6-month follow-up study. Eur. Rev. Med. Pharmacol. Sci. 20, 3127–3133.
    1. Ryberg E., Larsson N., Sjogren S., Hjorth S., Hermansson N. O., Leonova J., et al. . (2007). The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol. 152, 1092–1101. 10.1038/sj.bjp.0707460
    1. Saft C., von Hein S. M., Lücke T., Thiels C., Peball M., Djamshidian A., et al. . (2018). Cannabinoids for treatment of dystonia in Huntington's disease. J. Huntingtons Dis. [Epub ahead of print]. 10.3233/JHD-170283
    1. Sagredo O., Pazos M. R., Satta V., Ramos J. A., Pertwee R. G., Fernandez-Ruiz J. (2011). Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease. J. Neurosci. Res. 89, 1509–1518. 10.1002/jnr.22682
    1. Sagredo O., Ramos J. A., Decio A., Mechoulam R., Fernandez-Ruiz J. (2007). Cannabidiol reduced the striatal atrophy caused 3-nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV1 and adenosine A2A receptors. Eur. J. Neurosci. 26, 843–851. 10.1111/j.1460-9568.2007.05717.x
    1. Sánchez-López F., Tasset I., Aguera E., Feijoo M., Fernandez-Bolanos R., Sanchez F. M., et al. . (2012). Oxidative stress and inflammation biomarkers in the blood of patients with Huntington's disease. Neurol. Res. 34, 721–724. 10.1179/1743132812Y.0000000073
    1. Sandyk R., Snider S. R., Consroe P., Elias S. M. (1986). Cannabidiol in dystonic movement disorders. Psychiatry Res. 18:291. 10.1016/0165-1781(86)90117-4
    1. Santos N. A., Martins N. M., Sisti F. M., Fernandes L. S., Ferreira R. S., Queiroz R. H., et al. . (2015). The neuroprotection of cannabidiol against MPP(+)-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease. Toxicol. In Vitro 30(1 Pt B), 231–240. 10.1016/j.tiv.2015.11.004
    1. Sartim A. G., Guimaraes F. S., Joca S. R. (2016). Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors. Behav. Brain Res. 303, 218–227. 10.1016/j.bbr.2016.01.033
    1. Schapira A. H., Cooper J. M., Dexter D., Clark J. B., Jenner P., Marsden C. D. (1990). Mitochondrial complex I deficiency in Parkinson's disease. J. Neurochem. 54, 823–827. 10.1111/j.1471-4159.1990.tb02325.x
    1. Schiavon A. P., Soares L. M., Bonato J. M., Milani H., Guimaraes F. S., Weffort de Oliveira R. M. (2014). Protective effects of cannabidiol against hippocampal cell death and cognitive impairment induced by bilateral common carotid artery occlusion in mice. Neurotox. Res. 26, 307–316. 10.1007/s12640-014-9457-0
    1. Schrag A., Horsfall L., Walters K., Noyce A., Petersen I. (2015). Prediagnostic presentations of Parkinson's disease in primary care: a case-control study. Lancet Neurol. 14, 57–64. 10.1016/S1474-4422(14)70287-X
    1. Sonego A. B., Gomes F. V., Del Bel E. A., Guimaraes F. S. (2016). Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice. Behav. Brain Res. 309, 22–28. 10.1016/j.bbr.2016.04.042
    1. Stern C. A. J., da Silva T. R., Raymundi A. M., de Souza C. P., Hiroaki-Sato V. A., Kato L., et al. . (2017). Cannabidiol disrupts the consolidation of specific and generalized fear memories via dorsal hippocampus CB1 and CB2 receptors. Neuropharmacology 125, 220–230. 10.1016/j.neuropharm.2017.07.024
    1. Tysnes O. B., Storstein A. (2017). Epidemiology of Parkinson's disease. J. Neural Transm. 124, 901–905. 10.1007/s00702-017-1686-y
    1. Valdeolivas S., Sagredo O., Delgado M., Pozo M. A., Fernandez-Ruiz J. (2017). Effects of a sativex-like combination of phytocannabinoids on disease progression in R6/2 mice, an experimental model of Huntington's disease. Int. J. Mol. Sci. 18:E684. 10.3390/ijms18040684
    1. Valdeolivas S., Satta V., Pertwee R. G., Fernandez-Ruiz J., Sagredo O. (2012). Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington's disease: role of CB1 and CB2 receptors. ACS Chem. Neurosci. 3, 400–406. 10.1021/cn200114w
    1. Valvassori S. S., Bavaresco D. V., Scaini G., Varela R. B., Streck E. L., Chagas M. H., et al. . (2013). Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain. Rev. Bras. Psiquiatr. 35, 380–386. 10.1590/1516-4446-2012-0886
    1. Watzl B., Scuderi P., Watson R. R. (1991). Influence of marijuana components (THC and CBD) on human mononuclear cell cytokine secretion in vitro, in Drugs of Abuse, Immunity, and Immunodeficiency, eds Friedman H., Klein T. W., Specter S. (Boston, MA: Springer; ), 63–70.
    1. Weiss L., Zeira M., Reich S., Har-Noy M., Mechoulam R., Slavin S., et al. . (2006). Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39, 143–151. 10.1080/08916930500356674
    1. Wright M. J., Jr., Vandewater S. A., Taffe M. A. (2013). Cannabidiol attenuates deficits of visuospatial associative memory induced by Delta(9) tetrahydrocannabinol. Br. J. Pharmacol. 170, 1365–1373. 10.1111/bph.12199
    1. Zhang X. Y., Tan Y. L., Zhou D. F., Cao L. Y., Wu G. Y., Haile C. N., et al. . (2007). Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenic patients with tardive dyskinesia. J. Clin. Psychiatry 68, 754–760. 10.4088/JCP.v68n0513
    1. Zuardi A. W. (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev. Bras. Psiquiatr. 30, 271–280. 10.1590/S1516-44462008000300015
    1. Zuardi A. W., Crippa J. A., Hallak J. E., Pinto J. P., Chagas M. H., Rodrigues G. G., et al. . (2009). Cannabidiol for the treatment of psychosis in Parkinson's disease. J. Psychopharmacol. 23, 979–983. 10.1177/0269881108096519

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