Skip to main content
SpringerLink
Log in

Potential Role of Cannabinoids in Parkinson’s Disease

  • Leading Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder caused by a progressive loss of dopaminergic neurons of the substantia nigra, resulting from an oxidative stress. The lack of dopaminergic neurons is reflected by a disturbed balance of the neural circuitry in the basal ganglia. Cannabinoids might alleviate some parkinsonian symptoms by their remarkable receptor-mediated modulatory action in the basal ganglia output nuclei. Moreover, it was recently observed that some cannabinoids are potent antioxidants that can protect neurons from death even without cannabinoid receptor activation. It seems that cannabinoids could delay or even stop progressive degeneration of brain dopaminergic systems, a process for which there is presently no prevention. In combination with currently used drugs, cannabinoids might represent, qualitatively, a new approach to the treatment of PD, making it more effective.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Standaert DG, Young AB. Treatment of central nervous system degenerative disorders. In: Hardmann JG, Goodman Gilman A, Limbird LE, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996: 503–19

    Google Scholar 

  2. Gerlach M, Riederer P, Youdim MBH. Neuroprotective therapeutic strategies: comparison of experimental and clinical results. Biochem Pharmacol 1995 Jun; 50(1): 1–16

    Article  PubMed  CAS  Google Scholar 

  3. Youdim MBH, Riederer P. Understanding Parkinson’s disease. Sci Am 1997 Jan; 276(1): 38–45

    Article  Google Scholar 

  4. Schapira AH, Mann VM, Cooper JM, et al. Anatomic and disease specificity of NADH CoQ 1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 1990 Dec; 55(6): 2142–5

    Article  PubMed  CAS  Google Scholar 

  5. Beal MR Excitotoxicity and nitric oxide in Parkinson’s disease pathogenesis. Ann Neurol 1998 Sep; 44 (3 Suppl. 1): S110–4

    Google Scholar 

  6. Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 1994 Mar 3; 330(9): 613–22

    Article  PubMed  CAS  Google Scholar 

  7. Akaike A. Glutamate neurotoxicity and neuroprotective factors. Nippon Yakurigaku Zasshi 1994 May; 103(5): 193–201

    Article  PubMed  CAS  Google Scholar 

  8. Cohen G, Werner P. Free radicals, oxidative stress and neurodegeneration. In: Calne DB, editor. Neurodegenerative diseases. Philadelphia (PA): W.B. Saunders, 1994: 139–61

    Google Scholar 

  9. Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 1992 Dec; 32(6): 804–12

    Article  PubMed  CAS  Google Scholar 

  10. Olanow CW. Oxidation reactions in Parkinson’s disease. Neurology 1990 Oct; 40 (10 Suppl. 3): 32–7

    PubMed  Google Scholar 

  11. Jenner P. Oxidative stress as acause of Parkinson’s disease. Acta Neurol Scand Suppl. 1991; 136: 6–15

    Article  PubMed  CAS  Google Scholar 

  12. Parkinson’s Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1993 Jan 21; 328(3): 176–83

    Article  Google Scholar 

  13. Mechoulam R. The pharmacohistory of Cannabis sativa. In: Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton (FL): CRC, 1986: 1–19

    Google Scholar 

  14. Gowers, WR. A manual of diseases of the nervous system. Vol. II. London: Churchill, 1888

    Google Scholar 

  15. Annas GJ. Reefer madness: the federal response to California’s medical-marijuana law. N Engl J Med 1997 Aug 7; 337(6): 435–9

    Article  PubMed  CAS  Google Scholar 

  16. Mechoulam R, Vogel Z, Barg J. CNS cannabinoid receptors: role and therapeutic implications for CNS disorders. CNS Drugs 1994; 2(4): 255–60

    Article  CAS  Google Scholar 

  17. Devane WA. New dawn of cannabinoid pharmacology. Trends Pharmacol Sci 1994 Feb; 15(2): 40–1

    Article  PubMed  CAS  Google Scholar 

  18. Devane WA, Dysarz III FA, Johnson MR, et al. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988 Nov; 34(5): 605–13

    PubMed  CAS  Google Scholar 

  19. Klein TW, Newton C, Friedman H. Cannabinoid receptors and immunity. Immunol Today 1998 Aug; 19(8): 373–81

    Article  PubMed  CAS  Google Scholar 

  20. Jeon YJ, Yang KH, Pulaski JT, et al. Attenuation of inducible nitric oxide synthase gene expression by delta 9-tetrahydro-cannabinol is mediated through the inhibition of nuclear factor- kappa B/Rel activation. Mol Pharmacol 1996 Aug; 50(2): 334–41

    PubMed  CAS  Google Scholar 

  21. Bloom FE. Neurotransmission and the central nervous system. In: Hardmann JG, Goodman Gilman A, Limbird LE, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996: 267–93

    Google Scholar 

  22. Skaper SD, Buriani A, Dal Toso R, et al. The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proc Natl Acad Sci U S A 1996 Apr 30; 93(9): 3984–9

    Article  PubMed  CAS  Google Scholar 

  23. Hampson AJ, Bornheim LM, Scanziani M, et al. Dual effects of anandamide on NMDA receptor-mediated responses and neurotransmission. J Neurochem 1998 Feb; 70(2): 671–6

    Article  PubMed  CAS  Google Scholar 

  24. Shen M, Thayer SA. Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol Pharmacol 1998 Sep; 54(3): 459–62

    PubMed  CAS  Google Scholar 

  25. Biegon A. Neuroprotective activity of HU-211, a novel nonpsychotropic synthetic cannabinoid. Ann N Y Acad Sci 1995 Sep 15; 765: 314

    Article  PubMed  CAS  Google Scholar 

  26. Eshhar N, Striem S, Kohen R, et al. Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist. Eur J Pharmacol 1995 Sep 5; 283(1–3): 19–29

    Article  PubMed  CAS  Google Scholar 

  27. Hampson AJ, Grimaldi M, Axelrod J, et al. Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A 1998 Jul 7; 95(14): 8268–73

    Article  PubMed  CAS  Google Scholar 

  28. Mansbach RS, Rovetti CC, Winston EN, et al. Effects of the cannabinoid CB1 receptor antagonist SR141716A on the behavior of pigeons and rats. Psychopharmacology (Berl) 1996 Apr; 124(4): 315–22

    Article  CAS  Google Scholar 

  29. Cunha JM, Carlini EA, Pereira AE, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 1980; 21(3): 175–85

    Article  PubMed  CAS  Google Scholar 

  30. Consroe P, Laguna J, Allender J, et al. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 1991 Nov; 40(3): 701–8

    Article  PubMed  CAS  Google Scholar 

  31. Sanudo-Pena MC, Patrick SL, Patrick RL, et al. Effects of intranigral cannabinoids on rotational behavior in rats: interactions with the dopaminergic system. Neurosci Lett 1996 Mar 8; 206(1): 21–4

    Article  PubMed  CAS  Google Scholar 

  32. Sanudo-Pena MC, Walker JM. Role of the subthalamic nucleus on cannabinoid actions in the substantia nigra of the rat. J Neurophysiol 1997 Mar; 77(3): 1635–8

    PubMed  CAS  Google Scholar 

  33. Sanudo-Pena MC, Walker JM. Effects of intrapallidal cannabinoids on rotational behavior in rats: interactions with the dopaminergic system. Synapse 1998 Jan; 28(1): 27–32

    Article  PubMed  CAS  Google Scholar 

  34. 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

    Article  PubMed  CAS  Google Scholar 

  35. Sanudo-Pena MC, Patrick SL, Khen S, et al. Cannabinoid effects in basal ganglia in a rat model of Parkinson’s disease. Neurosci Lett 1998 Jun 5; 248(3): 171–4

    Article  PubMed  CAS  Google Scholar 

  36. Muller-Vahl KR, Kolbe H, Schneider U, et al. Cannabis in movement disorders. Forschende Komplementarmedi 1999 Oct; 6Suppl. 3: 23–7

    Article  Google Scholar 

  37. Brotchie JM. Adjuncts to dopamine replacement: a pragmatic approach to reducing the problem of dyskinesia in Parkinson’s disease. Mov Disord 1998 Nov; 13(6): 871–6

    Article  PubMed  CAS  Google Scholar 

  38. Frankel JP, Hughes A, Lees AJ, et al. Marijuana for Parkinsonian tremor. J Neurol Neurosurg Psychiatry 1990 May; 53(5): 436–42

    Article  PubMed  CAS  Google Scholar 

  39. Agid Y, Chase T, Marsden D. Adverse reactions to levodopa: drug toxicity or progression of disease? Lancet 1998 Mar 21; 351(9106): 851–2

    Article  PubMed  CAS  Google Scholar 

  40. Stix G. Herb remedy. Sci Am 1998 Sep; 279(3): 11–12

    Google Scholar 

  41. Grotenhermen F. Therapeutic use of cannabis. Lancet 1998 Mar 7; 351(9104): 758–9

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4, Czech Republic

    Jan Ševčík & Karel Mašek

Authors
  1. Jan Ševčík
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karel Mašek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jan Ševčík.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ševčík, J., Mašek, K. Potential Role of Cannabinoids in Parkinson’s Disease. Drugs & Aging 16, 391–395 (2000). https://doi.org/10.2165/00002512-200016060-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200016060-00001

Keywords

Search

Navigation