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Cannabinoids for the pharmaceutical industry

Summary

Cannabis sativa, is a rich source of a variety of compounds, including cannabinoids, terpenoids and flavonoids. Their content depends upon the plant genetics, growth conditions, time of harvest and drying conditions. To date, more than 60 different cannabinoids have been identified in the plant. Cannabis has been used medicinally for 4000 years and remained in the British pharmacopaeia until 1932, and in the British Pharmaceutical Codex until 1949. Medical use has been prohibited in the UK since 1973. The principal cannabinoid, delta-9-tetrahydrocannabinol (THC) was first isolated in 1964; the first cannabinoid pharmaceutical product Marinol® (a synthetic THC product) was approved in the USA in 1985. The discovery of specific cannabinoid receptors in the early 1990s and subsequent identification of the endocannabinoids anandamide and 2-arachadonoylglycerol, led to a resurgence of interest in the field of cannabinoid medicine, especially within the pharmaceutical industry. Cannabidiol (CBD), as a non-psychoactive, cannabinoid is currently a cannabinoid of significant interest, showing a wide range of pharmacological activity. The other classes of compounds present in cannabis also have their own pharmacology (e.g. terpenoids, flavonoids). The potential for interaction and synergy between compounds within the plant, may play a role in the therapeutic potential of cannabis. This may explain why a cannabis-based medicine using extracts containing multiple cannabinoids, in defined ratios, and other non-cannabinoid fractions, may provide better therapeutic success and be better tolerated than the single synthetic cannabinoid medicines currently available. The development and employment of one of these medicines, Sativex®, is described.

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References

  • Aldrich, M.R., 1997. History of therapeutic cannabis. In: M.L. Mathre (Ed.), Cannabis in Medical Practice: A Legal, Historical and Pharmacological Overview of the Therapeutic Use of Marijuana. McFarland.

    Google Scholar 

  • Berman, J., J. Lee, A. Cannon, J. Sach, S. Tripp, S. McKerral, M. {Taggart}, C.P. Symonds, K. Fisher & R. Birch, 2004. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: Results of a randomized controlled trial. PAIN 112(3): 299–306.

    Google Scholar 

  • Brady, C.M., R. DasGupta, C. Dalton, O.J. Wiseman, K.J. Berkley & C.J. Fowler, 2004. An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Multiple Sclerosis 10: 425–433.

    Google Scholar 

  • Browne, R.G. & A. Weissman, 1981. Discriminative stimulus properties of delta-9-tetrahydrocannabinol: Mechanistic studies. J Clin Pharmacol 21 (8–9 Suppl): 227S–234S.

    Google Scholar 

  • Carlini, E.A., I.G. Karniol, P.F. Renault & C.R. Schuster, 1974. Effects of marihuana in laboratory animals and man. Br J Pharmacol 50: 299–309.

    Google Scholar 

  • Devane, W.A., F.A. Dysarz 3rd, M.R. Johnson, L.S. Melvin & A.C. Howlett, 1988. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34(5): 605– 613.

    CAS  PubMed  Google Scholar 

  • Devane, W.A., L. Hanus, A. Breuer, R.G. Pertwee, L.A. {Stevenson}, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger & R. {Mechoulam}, 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258(5090): 1946–1949.

    CAS  PubMed  Google Scholar 

  • Elphick, M. & M.R. Ergetova, 2001. The neurobiology and evolution of cannabinoid signalling. Phil Trans R Soc Lond Ser B Biol Sci 356(1407): 381–408.

    Google Scholar 

  • Fairbairn, J.W. & J.T. Pickens, 1981. Activity of cannabis in relation to its delta-1-trans-tetrahydro-cannabinol content. Br J Pharmacol 72: 401–409.

    Google Scholar 

  • Food & Drug Administration, 2004. Guidance for Industry: Botanical Drug Products. Drug Information Branch (HFD-210), Center for Drug Evaluation and Research (CDER), FDA, Rockville, MD 20857, USA.

    Google Scholar 

  • Freund, T.F., I. Katona & D. Piomelli, 2003. Role of endogenous cannabinoids in synaptic signalling. Physiol Rev 83(3): 1017–1066.

    CAS  PubMed  Google Scholar 

  • Gaoni, Y. & R. Mechoulam, 1964. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 86: 1646–1647.

    Google Scholar 

  • Grinspoon, L. & J.B. Bakalar, 1993. Marihuana, the Forbidden Medicine. Yale University Press, New Haven.

    Google Scholar 

  • Grinspoon, L. & J.B. Bakalar, 1997. Marihuana, the forbidden medicine, revised edition. Yale University Press, New Haven.

    Google Scholar 

  • Hanus, L., S. Abu-Lafi, E. Fride, A. Breuer, Z. Vogel, D.E. Shalev, I. Kustanovich & R. Mechoulam, 2001. 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98(7): 3662–3665.

    Google Scholar 

  • Howlett, A.C. & M.R. Fleming, 1984. Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. Mol Pharmacol 26(3): 532–538.

    CAS  PubMed  Google Scholar 

  • Howlett, A.C., 1984. Inhibition of neuroblastoma adenylate cyclase by cannabinoid and nantradol compounds. Life Sci 35(17): 1803–1810.

    Article  CAS  PubMed  Google Scholar 

  • Huang, S.M., T. Bisogno, M. Trevisani, A. Al-Hayani, De L. Petrocellis, F. Fezza, M. Tognetto, T.J. Petros, J.F. Krey, C.J. Chu, J.D. Miller, S.N. Davies, P. Geppetti, J.M. Walker, Di V. Marzo, 2002. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99(12): 8400–8405.

    Google Scholar 

  • Matsuda, L.A., S.J. Lolait, M.J. Brownstein, A.C. Young & T.I. Bonner, 1990. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346(6284): 561–564.

    Article  CAS  PubMed  Google Scholar 

  • McPartland, J. & E.B. Russo, 2001. Cannabis and cannabis extracts: Greater than the sum of their parts? J Cannabis Ther 1(3–4): 103–132.

    Google Scholar 

  • McPartland, J., 2003. Neurobiological effects of cannabinoids. American Academy of Pain Management (AAPM), Lecture, 4 September 2003.

  • Mechoulam, R., Z.A. Ben-Zvi, H. Shani Zemler & S. Levy, 1972. Cannabinoids and cannabis activity. In: W.D.M. Paton & J. Crown, (Eds.), Cannabis and its Derivatives, pp. 1–13. Oxford University Press, London.

    Google Scholar 

  • Munro, S., K.L. Thomas, M. Abu-Shaar, 1993. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365(6441): 61–65.

    Article  CAS  PubMed  Google Scholar 

  • Notcutt, W., M. Price, R. Miller, S. Newport, C. Phillips, S. Simmons & C. Sansom, 2004. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34′ N of 1′ studies. Anaesthesia 59(5): 440–452.

    Google Scholar 

  • Pertwee, R.G., 1997. Pharmacology of CB1 and CB2 receptors. Pharmacol Ther 74(2): 129–180.

    Article  CAS  PubMed  Google Scholar 

  • Pertwee, R.G., 2004. The pharmacology and therapeutic potential of cannabidiol. In: V. Di Marzo (Ed.), Cannabinoids. Kluwer Academic/Plenum Publishers.

  • Porter, A.C., J.M. Sauer, M.D. Knierman, G.W. Becker, M.J. Berna, J. Bao, G.G. Nomikos, P. Carter, F.P. Bymaster, A.B. Leese & C.C. Felder, 2002. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301(3): 1020–1024.

    Article  CAS  PubMed  Google Scholar 

  • Potter, D.J., 2004. Growth and morphology of medicinal cannabis. In: G.W. Guy, B.A. Whittle, P.J. Robson, (Eds.), The Medicinal Uses of Cannabis and Cannabinoids. Pharmaceutical Press, London.

    Google Scholar 

  • Robson, P.J., 2001. The therapeutic uses of cannabis. Abstracts of the 17th Association of Nurses in Substance Abuse (ANSA) UK National Conference, April 2001.

  • Rog, D.J. & C.A. Young, 2003. Randomised controlledtrial of cannabis based medicinal extracts in central neuropathic pain due to multiple sclerosis. Abstracts of the 19th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (September 17–20, Milan, Italy).

  • Russo, E.B. & J. McPartland, 2003. Cannabis is more than simply delta-9-tetrahydrocannabinol. Psychopharmacology 165: 431–432.

    Google Scholar 

  • Russo, E.B., 2001. Hemp for headache: An in-depth historical and scientific review of cannabis in migraine treatment. J Cannabis Ther 1(2): 21–92.

    Google Scholar 

  • Russo, E.B., 2002. Cannabis treatments in obstetrics and gynaecology: A historical review. J Cannabis Ther 2(3–4): 5– 35.

    Google Scholar 

  • Serpell, M., E. Smith, N. Sarantis, Sativex in the treatment of pain of neurological origin or symptoms of Multiple Sclerosis: Interim analysis of a long-term, open lable, safety and tolerability study. Abstracts of the 8th Congress of EFNS, 04–07 September 2004, Paris, France.

  • Sharief, M.K., 2004. Sativex® in the treatment of patients with chronic refractory pain due to MS or other defects of neurological function. Abstracts of the Spring Scientific Meeting of the Association of British Neurologists, 14–16 April, London, UK.

  • The House of Lords Science and Technology Committee, 1998. Ninth Report. “Cannabis: The Scientific Evidence”. HMG The Stationery Office.

  • Wade, D.T., P. Makela, P.J. Robson, H. House & C. Bateman, 2004. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo controlled study on 160 patients. Multiple Sclerosis 10: 434–441.

    Google Scholar 

  • Wade, D.T., P.J. Robson, H. House, P. Makela & J. Aram, 2002. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil 17: 21–29.

    Google Scholar 

  • Walton, R.P., 1938. Marihuana, America’s New Drug Problem. Philadelphia, J.B. Lippincott Co.

    Google Scholar 

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Correspondence to Colin G. Stott.

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Stott, C.G., Guy, G.W. Cannabinoids for the pharmaceutical industry. Euphytica 140, 83–93 (2004). https://doi.org/10.1007/s10681-004-4757-8

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  • DOI: https://doi.org/10.1007/s10681-004-4757-8

Key words

  • cannabidiol
  • cannabinoids
  • Cannabis sativa L.
  • delta-9-tetrahydrocannabinol
  • endocannabinoids
  • Sativex®