Cannabinoids for the Treatment of Movement Disorders

  • Briony Catlow
  • Juan Sanchez-RamosEmail author
Movement Disorders (O Suchowersky and A Videnovic, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Movement Disorders

Opinion statement

Use of cannabinoids as medications has a long history. Unfortunately, the prohibition of cannabis and its classification in 1970 as a schedule 1 drug has been a major obstacle in studying these agents in a systematic, controlled manner. The number of class 1 studies (randomized, double-blind, placebo-controlled) in patients with movement disorders is limited. Hence, it is not possible to make recommendations on the use of these cannabinoids as primary treatments for any of the movement disorders at this time. Fortunately, there is an expanding body of research in animal models of age-dependent and disease-related changes in the endocannabinoid system that is providing new targets for drug development. Moreover, there is growing evidence of a “cannabinoid entourage effect” in which a combination of cannabinoids derived from the plant are more effective than any single cannabinoid for a number of conditions. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will expand.


Cannabinoids Cannabis Schedule 1 drug THC CBD Movement disorders Endocannabinoid system Cannabis preparations Compassionate use Therapeutic application 


Compliance with Ethics Guidelines

Conflict of Interest

The authors declare that they have no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Russo EB. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers. 2007;4(8):1614–48.CrossRefPubMedGoogle Scholar
  2. 2.
    Gowers W. A manual of diseases of the nervous system. Philadelphia: P. Blakiston Son and Co.; 1888.Google Scholar
  3. 3.••
    Kluger B et al. The therapeutic potential of cannabinoids for movement disorders. Mov Disord. 2015;30(3):313–27. Excellent review of both clinical and pre-clinical literature.CrossRefPubMedGoogle Scholar
  4. 4.
    Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344–64.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Mechoulam R et al. Early phytocannabinoid chemistry to endocannabinoids and beyond. Nat Rev Neurosci. 2014;15(11):757–64.CrossRefPubMedGoogle Scholar
  6. 6.
    Pertwee RG. The central neuropharmacology of psychotropic cannabinoids. Pharmacol Ther. 1988;36(2–3):189–261.CrossRefPubMedGoogle Scholar
  7. 7.
    Egertova M, Elphick MR. Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CB. J Comp Neurol. 2000;422(2):159–71.CrossRefPubMedGoogle Scholar
  8. 8.
    Van Laere K et al. Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [(18)F]MK-9470 PET. Neuroimage. 2008;39(4):1533–41.CrossRefPubMedGoogle Scholar
  9. 9.
    Fernandez-Ruiz J et al. Prospects for cannabinoid therapies in basal ganglia disorders. Br J Pharmacol. 2011;163(7):1365–78.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Van Laere K et al. Widespread decrease of type 1 cannabinoid receptor availability in Huntington disease in vivo. J Nucl Med. 2010;51(9):1413–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Garcia-Arencibia M, Garcia C, Fernandez-Ruiz J. Cannabinoids and Parkinson’s disease. CNS Neurol Disord Drug Targets. 2009;8(6):432–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Hurley MJ, Mash DC, Jenner P. Expression of cannabinoid CB1 receptor mRNA in basal ganglia of normal and parkinsonian human brain. J Neural Transm. 2003;110(11):1279–88.CrossRefPubMedGoogle Scholar
  13. 13.
    Walsh S et al. Loss of cannabinoid CB1 receptor expression in the 6-hydroxydopamine-induced nigrostriatal terminal lesion model of Parkinson’s disease in the rat. Brain Res Bull. 2010;81(6):543–8.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Lanciego JL et al. Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of Macaca fascicularis. J Psychopharmacol. 2011;25(1):97–104.CrossRefPubMedGoogle Scholar
  15. 15.
    Fernandez-Ruiz J et al. Cannabinoid CB2 receptor: a new target for controlling neural cell survival? Trends Pharmacol Sci. 2007;28(1):39–45.CrossRefPubMedGoogle Scholar
  16. 16.
    Szabo B, Schlicker E. Effects of cannabinoids on neurotransmission. Handb Exp Pharmacol. 2005;168:327–65.CrossRefPubMedGoogle Scholar
  17. 17.
    Julian MD et al. Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia. Neuroscience. 2003;119(1):309–18.CrossRefPubMedGoogle Scholar
  18. 18.
    Engler B et al. Effects of exogenous and endogenous cannabinoids on GABAergic neurotransmission between the caudate-putamen and the globus pallidus in the mouse. J Pharmacol Exp Ther. 2006;316(2):608–17.CrossRefPubMedGoogle Scholar
  19. 19.
    Sanudo-Pena MC, Tsou K, Walker JM. Motor actions of cannabinoids in the basal ganglia output nuclei. Life Sci. 1999;65(6–7):703–13.CrossRefPubMedGoogle Scholar
  20. 20.
    Freiman I, Szabo B. Cannabinoids depress excitatory neurotransmission between the subthalamic nucleus and the globus pallidus. Neuroscience. 2005;133(1):305–13.CrossRefPubMedGoogle Scholar
  21. 21.
    Polissidis A et al. The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate release region dependently. Int J Neuropsychopharmacol. 2013;16(2):393–403.CrossRefPubMedGoogle Scholar
  22. 22.
    Drews E, Schneider M, Koch M. Effects of the cannabinoid receptor agonist WIN 55,212-2 on operant behavior and locomotor activity in rats. Pharmacol Biochem Behav. 2005;80(1):145–50.CrossRefPubMedGoogle Scholar
  23. 23.
    Rodvelt KR et al. WIN-55,212-2 and SR-141716A alter nicotine-induced changes in locomotor activity, but do not alter nicotine-evoked [3H]dopamine release. Life Sci. 2007;80(4):337–44.CrossRefPubMedGoogle Scholar
  24. 24.
    Sanudo-Pena MC et al. Activational role of cannabinoids on movement. Eur J Pharmacol. 2000;391(3):269–74.CrossRefPubMedGoogle Scholar
  25. 25.
    Long LE et al. A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice. Int J Neuropsychopharmacol. 2010;13(7):861–76.CrossRefPubMedGoogle Scholar
  26. 26.
    Blankman JL, Cravatt BF. Chemical probes of endocannabinoid metabolism. Pharmacol Rev. 2013;65(2):849–71.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Kathuria S et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med. 2003;9(1):76–81.CrossRefPubMedGoogle Scholar
  28. 28.
    Piomelli D et al. Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev. 2006;12(1):21–38.CrossRefPubMedGoogle Scholar
  29. 29.
    Chaperon F, Thiebot MH. Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol. 1999;13:243–81.PubMedGoogle Scholar
  30. 30.
    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(1):79–85.CrossRefGoogle Scholar
  31. 31.
    Brotchie JM. Adjuncts to dopamine replacement: a pragmatic approach to reducing the problem of dyskinesia in Parkinson’s disease. Mov Disord. 1998;13(6):871–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Fernandez-Espejo E et al. Experimental parkinsonism alters anandamide precursor synthesis, and functional deficits are improved by AM404: a modulator of endocannabinoid function. Neuropsychopharmacology. 2004;29(6):1134–42.CrossRefPubMedGoogle Scholar
  33. 33.
    Kreitzer AC, Malenka RC. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s disease models. Nature. 2007;445(7128):643–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Sanudo-Pena MC et al. Cannabinoid effects in basal ganglia in a rat model of Parkinson’s disease. Neurosci Lett. 1998;248(3):171–4.CrossRefPubMedGoogle Scholar
  35. 35.
    Segovia G et al. Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high-dose levodopa in the reserpine-treated rat model of Parkinson’s disease. Mov Disord. 2003;18(2):138–49.CrossRefPubMedGoogle Scholar
  36. 36.
    van Vliet SA et al. Therapeutic effects of Delta9-THC and modafinil in a marmoset Parkinson model. Eur Neuropsychopharmacol. 2008;18(5):383–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Fernandez-Espejo E et al. Cannabinoid CB1 antagonists possess antiparkinsonian efficacy only in rats with very severe nigral lesion in experimental parkinsonism. Neurobiol Dis. 2005;18(3):591–601.CrossRefPubMedGoogle Scholar
  38. 38.
    Garcia-Arencibia M et al. Enhanced striatal glutamate release after the administration of rimonabant to 6-hydroxydopamine-lesioned rats. Neurosci Lett. 2008;438(1):10–3.CrossRefPubMedGoogle Scholar
  39. 39.
    Gonzalez S et al. Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat model of Parkinson’s disease. Brain Res. 2006;1073–1074:209–19.CrossRefPubMedGoogle Scholar
  40. 40.
    Kelsey JE, Harris O, Cassin J. The CB(1) antagonist rimonabant is adjunctively therapeutic as well as monotherapeutic in an animal model of Parkinson’s disease. Behav Brain Res. 2009;203(2):304–7.CrossRefPubMedGoogle Scholar
  41. 41.
    van der Stelt 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(9):1140–2.PubMedGoogle Scholar
  42. 42.
    Di Marzo V 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(10):1432–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Cao X et al. Blockade of cannabinoid type 1 receptors augments the antiparkinsonian action of levodopa without affecting dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys. J Pharmacol Exp Ther. 2007;323(1):318–26.CrossRefPubMedGoogle Scholar
  44. 44.
    Morgese MG et al. Anti-dyskinetic effects of cannabinoids in a rat model of Parkinson’s disease: role of CB(1) and TRPV1 receptors. Exp Neurol. 2007;208(1):110–9.PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Walsh S et al. The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats. Brain Res. 2010;1363:40–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Lastres-Becker I et al. Loss of mRNA levels, binding and activation of GTP-binding proteins for cannabinoid CB1 receptors in the basal ganglia of a transgenic model of Huntington’s disease. Brain Res. 2002;929:236–42.CrossRefPubMedGoogle Scholar
  47. 47.
    Lastres-Becker I et al. Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington’s disease. Synapse. 2002;44:23–35.CrossRefPubMedGoogle Scholar
  48. 48.•
    Valdeolivas S et al. 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. 2012;3:400–6. Neuroprotective effects are well demonstrated in this pre-clinical study. Worth reading despite being an animal study, because studies of neuroprotection in humans are expensive, require large numbers of subjects and many years of observation.PubMedCentralCrossRefPubMedGoogle Scholar
  49. 49.
    Pintor A et al. The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum. Neuropharmacology. 2006;51:1004–12.CrossRefPubMedGoogle Scholar
  50. 50.
    Sagredo O et al. Cannabinoids and neuroprotection in basal ganglia disorders. Mol Neurobiol. 2007;36:82–91.CrossRefPubMedGoogle Scholar
  51. 51.
    de Lago E et al. UCM707, an inhibitor of the anandamide uptake, behaves as a symptom control agent in models of Huntington’s disease and multiple sclerosis, but fails to delay/arrest the progression of different motor-related disorders. Eur Neuropsychopharmacol. 2006;16:7–18.CrossRefPubMedGoogle Scholar
  52. 52.
    Scotter EL, Abood ME, Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol. 2010;160(3):480–98.PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Lastres-Becker I et al. Effects of cannabinoids in the rat model of Huntington’s disease generated by an intrastriatal injection of malonate. Neuroreport. 2003;14:813–6.CrossRefPubMedGoogle Scholar
  54. 54.
    Lastres-Becker I et al. Compounds acting at the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington’s disease. J Neurochem. 2003;84:1097–109.CrossRefPubMedGoogle Scholar
  55. 55.
    Fox SH et al. Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord. 2002;17:145–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Richter A, Löscher W. (+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters. Eur J Pharmacol. 1994;264:371–7.CrossRefPubMedGoogle Scholar
  57. 57.
    Richter A, Löscher W. Effects of pharmacological manipulations of cannabinoid receptors on severity of dystonia in a genetic model of paroxysmal dyskinesia. Eur J Pharmacol. 2002;454:145–51.CrossRefPubMedGoogle Scholar
  58. 58.
    Martínez-Orgado J et al. The seek of neuroprotection: introducing cannabinoids. Recent Pat CNS Drug Discov. 2007;2:131–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Sagredo O et al. 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. 2007;26:843–51.CrossRefPubMedGoogle Scholar
  60. 60.
    Garcia-Arencibia M et al. 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. 2007;1134:162–70.CrossRefPubMedGoogle Scholar
  61. 61.
    Lastres-Becker I 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
  62. 62.
    Carroll CB 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;38:535–47.CrossRefPubMedGoogle Scholar
  63. 63.
    Klein TW. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol. 2005;5:400–11.CrossRefPubMedGoogle Scholar
  64. 64.
    Sagredo O et al. Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington’s disease. J Neurosci Res. 2011;89:1509–18.CrossRefPubMedGoogle Scholar
  65. 65.
    Romero J, Orgado JM. Cannabinoids and neurodegenerative diseases. CNS Neurol Disord Drug Targets. 2009;8:440–50.CrossRefPubMedGoogle Scholar
  66. 66.
    Beitz JM. Parkinson’s disease: a review. Front Biosci (Schol Ed). 2014;6:65–74.CrossRefGoogle Scholar
  67. 67.
    Chagas MH et al. 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. 2014;39(5):564–6.CrossRefPubMedGoogle Scholar
  68. 68.•
    Lotan I et al. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clin Neuropharmacol. 2014;37(2):41–4. Worth reading despite being an open label study because it shows the potential of cannabis to treat both motor and non-motor symptoms of PD.CrossRefPubMedGoogle Scholar
  69. 69.
    Muller-Vahl KR et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry. 2003;64(4):459–65.CrossRefPubMedGoogle Scholar
  70. 70.
    Carroll CB et al. Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology. 2004;63:1245–50.CrossRefPubMedGoogle Scholar
  71. 71.
    Muller-Vahl KR. Cannabinoids reduce symptoms of Tourette’s syndrome. Expert Opin Pharmacother. 2003;4(10):1717–25.CrossRefPubMedGoogle Scholar
  72. 72.
    Venderova K et al. Survey on cannabis use in Parkinson’s disease: subjective improvement of motor symptoms. Mov Disord. 2004;19(9):1102–6.CrossRefPubMedGoogle Scholar
  73. 73.
    Chagas MH et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J Psychopharmacol. 2014;28(11):1088–98.CrossRefPubMedGoogle Scholar
  74. 74.
    Zuardi AW et al. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol. 2009;23(8):979–83.CrossRefPubMedGoogle Scholar
  75. 75.
    Uribe Roca MC, Micheli F, Viotti R. Cannabis sativa and dystonia secondary to Wilson’s disease. Mov Disord. 2005;20(1):113–5.CrossRefPubMedGoogle Scholar
  76. 76.
    Sieradzan KA et al. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: a pilot study. Neurology. 2001;57:2108–11.CrossRefPubMedGoogle Scholar
  77. 77.
    Curtis A, Clarke CE, Rickards HE. Cannabinoids for Tourette’s Syndrome. Cochrane Database Syst Rev. 2009(4):CD006565. doi: 10.1002/14651858.CD006565.pub2.
  78. 78.••
    Muller-Vahl KR. Treatment of Tourette syndrome with cannabinoids. Behav Neurol. 2013;27(1):119–24. Excellent review of the effects of cannabinoids in treatment of Tourette’s syndrome.CrossRefPubMedGoogle Scholar
  79. 79.
    Consroe P, Sandyk R, Snider SR. Open label evaluation of cannabidiol in dystonic movement disorders. Int J Neurosci. 1986;30(4):277–82.CrossRefPubMedGoogle Scholar
  80. 80.
    Fox SH 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(6):1180–7.CrossRefPubMedGoogle Scholar
  81. 81.
    Zadikoff C et al. Cannabinoid, CB1 agonists in cervical dystonia: Failure in a phase IIa randomized controlled trial. Basal Ganglia. 2011;1(2):91–5.CrossRefGoogle Scholar
  82. 82.
    Consroe P et al. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav. 1991;40(3):701–8.CrossRefPubMedGoogle Scholar
  83. 83.
    Koppel BS et al. 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. 2014;82:1556–63.PubMedCentralCrossRefPubMedGoogle Scholar
  84. 84.
    Bergamaschi MM et al. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011;6:237–49.CrossRefPubMedGoogle Scholar
  85. 85.
    Cunha JM et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology. 1980;21:175–85.CrossRefPubMedGoogle Scholar
  86. 86.
    Frisher M et al. Assessing the impact of cannabis use on trends in diagnosed schizophrenia in the United Kingdom from 1996 to 2005. Schizophr Res. 2009;113:123–8.CrossRefPubMedGoogle Scholar
  87. 87.
    Proal AC et al. A controlled family study of cannabis users with and without psychosis. Schizophr Res. 2014;152:283–8.PubMedCentralCrossRefPubMedGoogle Scholar
  88. 88.
    Volkow ND, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;371:879.PubMedGoogle Scholar
  89. 89.
    Zajicek JP et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry. 2005;76:1664–9.PubMedCentralCrossRefPubMedGoogle Scholar
  90. 90.
    Seamon MJ et al. Medical marijuana and the developing role of the pharmacist. Am J Health Syst Pharm. 2007;64:1037–44.CrossRefPubMedGoogle Scholar
  91. 91.
    Lindsay AC et al. Cannabis as a precipitant of cardiovascular emergencies. Int J Cardiol. 2005;104:230–2.CrossRefPubMedGoogle Scholar
  92. 92.
    Moore BA et al. Respiratory effects of marijuana and tobacco use in a U.S. sample. J Gen Intern Med. 2005;20:33–7.PubMedCentralCrossRefPubMedGoogle Scholar
  93. 93.
    Pletcher MJ et al. ASsociation between marijuana exposure and pulmonary function over 20 years. JAMA. 2012;307:173–81.CrossRefPubMedGoogle Scholar
  94. 94.
    Russo E et al. Chronic cannabis use in the Compassionate Investigational New Drug program: An examination of benefits and adverse effects of legal clinical Cannabis. J Cannabis Ther. 2002;2:3–57.CrossRefGoogle Scholar
  95. 95.••
    Benbadis SR et al. Medical marijuana in neurology. Expert Rev Neurother. 2014;14:1453–65. Excellent review of the literature on the efficacy and safety of cannabinoids for treatment of the entire spectrum of neurological diseases.CrossRefPubMedGoogle Scholar
  96. 96.
    Sanchez-Ramos J. The entourage effect of the phytocannabinoids. Ann Neurol. 2015;77:1083.CrossRefPubMedGoogle Scholar
  97. 97.
    Ben-Shabat S et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol. 1998;353:23–31.CrossRefPubMedGoogle Scholar
  98. 98.
    Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat Prod Rep. 1999;16:131–43.CrossRefPubMedGoogle Scholar
  99. 99.
    Elfawal MA et al. Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin. Proc Natl Acad Sci U S A. 2015;112:821–6.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Lieber Institute for Brain DevelopmentBaltimoreUSA
  2. 2.Department of NeurologyUniversity of South FloridaTampaUSA

Personalised recommendations