Skip to main content
SpringerLink
Log in

CNS Cannabinoid Receptors

Role and Therapeutic Implications for CNS Disorders

  • Leading Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Summary

Cannabinoid receptors have recently been identified in both the CNS and the periphery, and endogenous ligands for these receptors (anandamides) have been found in the CNS. Both natural and synthetic cannabinoids have promising therapeutic effects in various clinical conditions, including neurological disorders such as multiple sclerosis and Huntington’s chorea. As a result of these findings, rapid progress in this new and exciting field can be expected over the next few years. This will further the understanding of the physiological role of the an-andamide-cannabinoid system and allow the development of new pharmacological tools and clinically useful drugs.

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

    Google Scholar 

  2. Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646–7

    Article  CAS  Google Scholar 

  3. Razdan RK. The total synthesis of cannabinoids. In: Apsimon J, editor. The total synthesis of natural products, Vol. 4. New York: Wiley, 1981: 186–262

    Google Scholar 

  4. Martin BR. Cellular effects of cannabinoids. Pharmacol Rev 1986; 38: 45–74

    PubMed  CAS  Google Scholar 

  5. Dewey WL. Cannabinoid pharmacology. Pharmacol Rev 1986; 38: 151–78

    PubMed  CAS  Google Scholar 

  6. Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton: CRC, 1986

    Google Scholar 

  7. Mechoulam R, Feigenbaum JJ. Towards cannabimimetic drugs. Prog Med Chem 1987; 24: 159–207

    Article  PubMed  CAS  Google Scholar 

  8. Mechoulam R, Devane WA, Glaser R. Cannabinoid geometry and biological activity. In: Murphy L, Bartke A, editors. Mari-juana/cannabinoids: neurobiology and neurophysiology. Boca Raton: CRC, 1992: 1–33

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  10. Compton DR, Rice KC, De Costa BR, et al. Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. J Pharmacol Exp Ther 1993; 265: 218–26

    PubMed  CAS  Google Scholar 

  11. Howlett AC, Bidaut-Russell M, Devane WA. The cannabinoid receptor: biochemical, anatomical and behavioral characterization. Trends Neurosci 1990; 13: 420–3

    Article  PubMed  CAS  Google Scholar 

  12. Mackie K, Hille B. Cannabinoids inhibit N-type calcium current in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 1992; 89: 3825–9

    Article  PubMed  CAS  Google Scholar 

  13. Matsuda LA, Lolait SJ, Brownstein MJ, et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990: 346: 561–4

    Article  PubMed  CAS  Google Scholar 

  14. Gerard CM, Mollereau C, Vassart G, et al. Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 1991; 279: 129–34

    PubMed  CAS  Google Scholar 

  15. Kaminski NE, Abood ME, Kessler FK, et al. Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid mediated immune modulation. Mol Pharmacol 1992; 42: 736–42

    PubMed  CAS  Google Scholar 

  16. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61–4

    Article  PubMed  CAS  Google Scholar 

  17. Devane WA, Breuer A, Sheskin T, et al. A novel probe for the cannabinoid receptor. J Med Chem 1992; 35: 2065–9

    Article  PubMed  CAS  Google Scholar 

  18. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258: 1946–9

    Article  PubMed  CAS  Google Scholar 

  19. Hanus L, Gopher A, Almog S, et al. Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J Med Chem 1993; 36: 3032–4

    Article  PubMed  CAS  Google Scholar 

  20. Fride E, Mechoulam R. Pharmacological activity of the cannabinoid agonist anandamide, a brain constituent. Eur J Pharmacol 1993; 231: 313–4

    Article  PubMed  CAS  Google Scholar 

  21. Vogel Z, Barg J. Levy R, et al. Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. J Neurochem 1993; 61: 352–5

    Article  PubMed  CAS  Google Scholar 

  22. Felder CC, Briley EM, Axelrod J, et al. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc Natl Acad Sci USA 1993; 90: 7656–60

    Article  PubMed  CAS  Google Scholar 

  23. Mackie K, Devane W, Hille B. Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N18 neuroblastoma cells. Mol Pharmacol 1993; 44: 498–503

    PubMed  CAS  Google Scholar 

  24. Pertwee RG. In vivo interactions between psychotropic cannabinoids and other drugs involving central and peripheral neurochemical mediators. In: Murphy L, Bartke A, editors. Marijuana/cannabinoids: neurobiology and neurophysiology. Boca Raton: CRC, 1992: 165–218

    Google Scholar 

  25. Wickens AP, Pertwee RG. △9-Tetrahydrocannabinol and anandamide enhance the ability of muscimol to induce catalepsy in the globus pallidus of rats. Eur J Pharmacol 1993; 250: 205–8

    Article  PubMed  CAS  Google Scholar 

  26. Mailleux P, Vanderhaeghen JJ. Dopaminergic regulation of cannabinoid receptor messenger RNA levels in the rat caudate-putamen: an in situ hybridization study. J Neurochem 1993; 61: 1705–12

    Article  PubMed  CAS  Google Scholar 

  27. Mailleux P, Vanderhaeghen JJ. Delta-9-tetrahydrocannabinol regulates substance P and enkephalin messenger RNA levels in caudate-putamen. Eur Pharmacol Mol Pharmacol Section 1993; 267: R1–R3

    Article  Google Scholar 

  28. Kinoshita H, Hasegawa T, Katsumata Y, et al. Effect of dizocilpine (MK-801) on the catalepsy induced by delta(9)-tetrahydrocannabinol in mice. J Neural Transm Gen Sect 1994; 95: 137–43

    Article  PubMed  CAS  Google Scholar 

  29. Mailleux P, Vanderhaeghen JJ. Glucorticoid regulation of cannabinoid receptor messenger RNA levels in the rat caudate pu-tamen - an in situ hybridization study. Neurosci Lett 1993; 156: 51–3

    Article  PubMed  CAS  Google Scholar 

  30. Weidenfeld J, Feldman S, Mechoulam R. The effect of the brain constituent anandamide, a cannabinoid receptor agonist, on the hypothalamo-pituitary-adrenal axis in the rat. Neuroendocrinology 1994; 59: 110–2

    Article  PubMed  CAS  Google Scholar 

  31. Herkenham M, Lynn AB, Little MD, et al. Cannabinoid receptor localization in the brain. Proc Natl Acad Sci USA 1990; 87: 1932–6

    Article  PubMed  CAS  Google Scholar 

  32. Consroe P, Snider SR. Therapeutic potential of cannabinoids in neurological disorders. In: Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton: CRC, 1986: 21–49

    Google Scholar 

  33. Malec J, Harvey RF, Cayner JJ. Cannabis effect on spasticity in spinal cord injury. Arch Phys Med Rehabil 1982; 63: 116–8

    PubMed  CAS  Google Scholar 

  34. Petro DJ, Ellenberger C. Treatment for human spasticity with △99-tetrahydrocannabinol. J Clin Pharmacol 1981; 21: 413S–416S

    PubMed  CAS  Google Scholar 

  35. Clifford DB. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann Neurol 1983; 13: 669–671

    Article  PubMed  CAS  Google Scholar 

  36. Meinck HM, Shonle PW, Conrad B. Effects of cannabinoids on spasticity and ataxia in multiple sclerosis. J Neurol 1989; 236: 120–2

    Article  PubMed  CAS  Google Scholar 

  37. Lyman WD, Sonett JR, Brosnan CF, et al. △9Tetrahydrocannabinol: a novel treatment for experimental encephalomyelitis. J Neuroimmunol 1989; 23: 73–81

    Article  PubMed  CAS  Google Scholar 

  38. Glass M, Faull RLM, Dragunow M. Loss of cannabinoid receptors in the substantia nigra in Huntington’s disease. Neurosci-ence 1993; 56: 523–7

    Article  CAS  Google Scholar 

  39. Feigenbaum JJ, Bergmann F, Richmond SA, et al. A non-psychotropic cannabinoid acts as a functional N-methyl-D-aspartate (NMDA) receptor blocker. Proc Natl Acad Sci USA 1989; 86: 9584–7

    Article  PubMed  CAS  Google Scholar 

  40. Little PJ, Compton DR, Mechoulam R, et al. Stereochemical effects of II-OH-delta-8-THC-dimethylheptyl in mice and dogs. Pharmacol Biochem Behav 1989; 32: 661–6

    Article  PubMed  CAS  Google Scholar 

  41. Howlett AC, Champion TM, Wilken GH, et al. Stereochemical effects of II-OH-delta-8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinol receptor. Neuropharmacology 1990; 29: 161–5

    Article  PubMed  CAS  Google Scholar 

  42. Nadler V, Mechoulam R, Sokolovsky M. Blockage of 45Ca2+ influx through the N-methyl-D-aspartate receptor ion channel by the nonpsychoactive cannabinoid HU-211. Brain Res 1993; 622: 79–85

    Article  PubMed  CAS  Google Scholar 

  43. Nadler V, Mechoulam R, Sokolovksy M. The nonpsychotropic cannabinoid (+)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol 1,1-dimethylheptyl (HU-211) attenuates N-methyl-D-aspartate-receptor-mediated neurotoxicity in primary cultures of rat forebrain. Neurosci Lett 1993; 162: 43–5

    Article  PubMed  CAS  Google Scholar 

  44. Eshhar N, Striem S, Biegon A. HU-211, a non-psychotropic cannabinoid, rescues cortical neurones from excitatory amino acid toxicity in culture. Neuroreport 1993; 5: 237–40

    Article  PubMed  CAS  Google Scholar 

  45. Shohami E, Novikov M, Mechoulam R. A non-psychotropic cannabinoid, HU-211, has cerebroprotective effects after closed head injury in the rat. J Neurotrauma 1993; 10: 109–19

    Article  PubMed  CAS  Google Scholar 

  46. Plasse TF, Gorter RW, Kransnow SH, Recent clinical experience with dronabinol. Pharmacol Biochem Behav 1991; 40: 695–700

    Article  PubMed  CAS  Google Scholar 

  47. Feigenbaum JJ, Richmond SA, Weissman Y, et al. Inhibition of cisplatin induced emesis in the pigeon by a non-psychotropic synthetic cannabinoid. Eur J Pharmacol 1989; 169: 159–65

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Natural Products, The Hebrew University, Ein Kerem Campus, Jerusalem, 91120, Israel

    Raphael Mechoulam (Faculty of Medicine)

  2. Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel

    Zvi Vogel & Jacob Barg

Authors
  1. Raphael Mechoulam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zvi Vogel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacob Barg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mechoulam, R., Vogel, Z. & Barg, J. CNS Cannabinoid Receptors. CNS Drugs 2, 255–260 (1994). https://doi.org/10.2165/00023210-199402040-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199402040-00001

Keywords

Search

Navigation