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1 - The cannabinoid system: from the point of view of a chemist

Published online by Cambridge University Press:  07 December 2009

Raphael Mechoulam
Affiliation:
Hebrew University Medical Faculty, Israel
Lumir Hanuš
Affiliation:
Hebrew University Medical Faculty, Israel
David Castle
Affiliation:
Mental Health Research Institute, Melbourne
Robin Murray
Affiliation:
Institute of Psychiatry, London
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Summary

This book is about cannabis (marijuana) and psychotic illnesses; more specifically, it outlines how our increasing understanding of cannabis itself, the effects of cannabis on the brain and psychic functions and of the cannabinoid system can inform our understanding of the relationships between cannabis and psychosis. This chapter serves as an introduction to this topic, with a brief historical overview of the psychic effects of cannabis, followed by an exposition on the cannabinoid system.

Cannabis and mental illness

J. J. Moreau, the first nineteenth-century psychiatrist with an interest in psychopharmacology, described in great detail his experiments with hashish (Moreau, 1973). He took the drug himself and asked his students to follow his example. He also administered it to his patients. By modern standards the doses used were enormously high. The effects on one of his assistants, who swallowed 16 g of an extract – presumably containing several hundred milligrams of tetrahydrocannabinol (THC), which we know today to be the major psychotropic principal of cannabis – were intense agitation, incoherence, delirium and hallucinations. On the basis of numerous such experiments, Moreau declared that ‘there is not a single, elementary manifestation of mental illness that cannot be found in the mental changes caused by hashish, from simple manic excitement to frenzied delirium, from the feeblest impulse, the simplest fixation, the merest injury to the senses, to the most irresistible drive, the wildest delirium, the most varied disorders of feelings’.

Type
Chapter
Information
Marijuana and Madness
Psychiatry and Neurobiology
, pp. 1 - 18
Publisher: Cambridge University Press
Print publication year: 2004

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References

Abadji, V., Lin, S., Taha, G.et al. (1994). (R)-methanandamide: a chiral novel anandamide possessing higher potency and metabolic stability. J. Med. Chem, 37, 1889–1893CrossRefGoogle ScholarPubMed
Adams, R. (1941–1942). Marihuana. Harvey Lect., 37, 168–197Google Scholar
Beltramo, M., Stella, N., Calignano, A.et al. (1997). Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science, 227, 1094–1097CrossRefGoogle Scholar
Ben-Shabat, S., Fride, E., Sheskin, T.et al. (1998). An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur. J. Pharmacol., 353, 23–31CrossRefGoogle ScholarPubMed
Bisogno, T., Hanuš, L., Petrocellis, L.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., 135, 845–852CrossRefGoogle Scholar
Boger, D. L., Henriksen, S. J. and Cravatt, B. F. (1998). Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules. Curr. Pharm. Design, 4, 303–314Google ScholarPubMed
Breivogel, C. S., Griffin, G., Di Marzo, V. and Martin, B. R. (2001). Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol. Pharmacol., 60, 155–163CrossRefGoogle Scholar
Carlini, E. A. and Cunha, J. M. (1981). Hypnotic and antiepileptic effects of cannabidiol. J. Clin. Pharmacol., 21, 417S–427SCrossRefGoogle ScholarPubMed
Carlini, E. A., Leite, J. R., Tanhauser, M. and Bernardi, A. C. (1973). Cannabidiol and Cannabis sativa extract protect mice and rats against convulsive agents. J. Pharm. Pharmacol., 25, 664–665CrossRefGoogle ScholarPubMed
Consroe, P. (1998). Brain cannabinoid system as targets for the therapy of neurological disorders. Neurobiol. Dis., 5, 534–551CrossRefGoogle ScholarPubMed
Cunha, J. M., Carlini, E. A., Pereira, A. E.et al. (1980). Chronic administration of CBD to healthy volunteers and epileptic patients. Pharmacologia, 21, 175–185Google ScholarPubMed
Deutsch, D. G., Ueda, N. and Yamamoto, S. (2002). The fatty acid amide hydrolase (FAAH). Prostaglandins Leukot. Essent. Fatty Acids, 66, 201–210CrossRefGoogle Scholar
Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S. and Howlett, A. C. (1988). Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol., 34, 605–613Google ScholarPubMed
Devane, W. A., Breuer, A., Sheskin, T.et al. (1992a). A novel probe for the cannabinoid receptor. J. Med. Chem., 35, 2065–2069CrossRefGoogle Scholar
Devane, W. A., Hanu, L., Breuer, A.et al. (1992b). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 258, 1946–1949CrossRefGoogle Scholar
Di Marzo, V., Petrocellis, L., Bisogno, T. and Melck, D. (1999). Metabolism of anandamide and 2-arachidonoylglycerol: an historical overview and some recent developments. Lipids, 34, S319–S325CrossRefGoogle ScholarPubMed
Di Marzo, V., Petrocellis, L., Fezza, F., Ligresti, A. and Bisogno, T. (2002). Anandamide receptors. Prostaglandins Leukot. Essent. Fatty Acids, 66, 377–391CrossRefGoogle ScholarPubMed
Donovan, M. (1845). On the physical and medicinal qualities of Indian hemp (Cannabis indica). Dublin J. Med. Sci., 26, 368–402CrossRefGoogle Scholar
Elphick, M. R. and Egertova, M. (2001). The neurobiology and evolution of cannabinoid signalling. Philos. Trans. R. Soc. Lond., 356, 381–408CrossRefGoogle ScholarPubMed
Feigenbaum, J. J., Bergman, F., Richmond, S. A.et al. (1989). Nonpsychotropic cannabinoid acts as a functional N-methyl-d-asparate (NMDA) receptor blocker. Proc. Natl Acad. Sci. USA, 86, 9584–9587CrossRefGoogle Scholar
Felder, C. C. and Glass, M. (1998). Cannabinoid receptors and their endogenous agonists. Annu. Rev. Pharmacol. Toxicol., 38, 179–200CrossRefGoogle ScholarPubMed
Field, B. I. and Arndt, R. R. (1980). Cannabinoid compounds in South African Cannabis sativa L. J. Pharm. Pharmacol., 32, 21–24CrossRefGoogle ScholarPubMed
Ford, W. R., Honan, S. A., White, R. and Hiley, C. R. (2002). Evidence of a novel site mediating anandamide-induced negative inotropic and coronary vasodilator responses in rat isolated hearts. Br. J. Pharmacol., 135, 1191–1198CrossRefGoogle Scholar
Fowler, J. J. and Jacobsson, S. O. P. (2002). Cellular transport of anandamide, 2-arachidonoylgly cerol and palmitoylethanolamide – targets for drug development?Prostaglandin Leukot. Essent. Fatty Acids, 66, 193–200CrossRefGoogle Scholar
Fowler, C. J., Jonsson, K. O. and Tiger, G. (2001). Fatty acid amide hydrolase: biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem. Pharmacol., 62, 517–526CrossRefGoogle ScholarPubMed
Gaoni, Y. and Mechoulam, R. (1964). Isolation, structure and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc., 86, 1646CrossRefGoogle Scholar
Gerard, C. M., Mollereau, C., Vassart, G. and Parmentier, M. (1991). Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem. J., 279 (Pt 1), 129–134CrossRefGoogle ScholarPubMed
Gerth, C. W., Schultze-Lutter, F., Mauss, C.et al. (2002). The natural cannabinoid cannabidiol in the treatment of acute schizophrenia. Schizophr. Res. (Suppl.), 53, 192, B113Google Scholar
Giuffrida, A., Beltramo, M. and Piomelli, D. (2001). Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology. J. Pharmacol. Exp. Ther., 298, 7–14Google ScholarPubMed
Grinspoon, L. and Bakalar, J. B. (1997). Marihuana, the Forbidden Medicine. New Haven, CT: Yale University Press
Guimaraes, F. S., Chiaretti, T. M., Graeff, F. G. and Zuardi, A. W. (1990). Antianxiety effect of cannabidol in the elevated plus-maze. Psychopharmacology, 100, 558–559CrossRefGoogle Scholar
Hanu, L., Gopher, A., Almog, S. and Mechoulam, R. (1993). Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J. Med. Chem., 36, 3032–3034CrossRefGoogle Scholar
Hanuš, L., Breuer, A., Tchilibon, S.et al. (1999). HU-308: a specific agonist for CB2, a peripheral cannabinoid receptor. Proc. Natl Acad. Sci. USA, 96, 14228–14233CrossRefGoogle Scholar
Hanuš, L., Abu-Lafi, S., Fride, E.et al. (2001). 2-Arachidonyl glyceryl ether, a novel endogenous agonist of the cannabinoid CB1 receptor. Proc. Natl Acad. Sci. USA, 98, 3662–3665CrossRefGoogle Scholar
Hillard, C. J. (2000). Biochemistry and pharmacology of the endocannabinoids arachidonylethanolamide and 2-arachidonylglycerol. Prostagladins Other Lipid Mediat., 61, 3–18CrossRefGoogle Scholar
Howlett, A. C. (1998). The CB1 cannabinoid receptor in the brain. Neurobiol. Dis., 5, 405–416CrossRefGoogle Scholar
Howlett, A. C. and Fleming, R. M. (1984). Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. Mol. Pharmacol., 26, 532–538Google ScholarPubMed
Howlett, A. C., Champion, T. M., Wilken, G. H. and Mechoulam, R. (1990). Stereochemical effects of 11-OH-Δ8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor. Neuropharmacology, 29, 161–165CrossRefGoogle Scholar
Huffman, J. W. (2000). The search for selective ligands for the CB2 receptor. Curr. Pharm. Des., 6, 1323–1337CrossRefGoogle ScholarPubMed
Kaminski, N. E., Abood, M. E., Kessler, F. K., Martin, B. R. and Schatz, A. R. (1992). Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation. Mol. Pharmacol., 42, 736–742Google ScholarPubMed
Knoller, N., Levi, L., Shoshan, I.et al. (2002). Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled phase II clinical trial. Crit. Care Med., 30, 548–554CrossRefGoogle ScholarPubMed
Kozak, K. R. and Marnett, L. J. (2002). Oxidative metabolism of endocannabinoids. Prostaglandins Leukot. Essent. Fatty Acids, 66, 211–220CrossRefGoogle ScholarPubMed
Kunos, G., Jarai, Z., Varga, K.et al. (2000). Cardiovascular effects of endocannabinoids – the plot thickens. Prostaglandins Other Lipid Mediat., 61, 71–84CrossRefGoogle ScholarPubMed
Lan, R., Liu, Q., Fan, P.et al. (1999). Structure–activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J. Med. Chem., 42, 769–776CrossRefGoogle ScholarPubMed
Leweke, F. M., Schneider, U., Radwan, M., Schmidt, E. and Emrich, H. M. (2000). Different effects of nabilone and cannabidiol in binocular depth inversion in man. Pharmacol. Biochem. Behav., 66, 175–181CrossRefGoogle ScholarPubMed
Lutz, B. (2002). Molecular biology of cannabinoid receptors. Prostaglandin Leukot. Essent. Fatty Acids, 66, 123–142CrossRefGoogle ScholarPubMed
Maccarrone, M., Valensise, H., Bari, M.et al. (2000). Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage. Lancet, 355, 1326–1329CrossRefGoogle ScholarPubMed
Maccarrone, M., Pauselli, R., Rienzo, M. D. and Finazzi-Agro, A. (2002). Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells. Biochem. J., 15, 137–144CrossRefGoogle Scholar
Malfait, A. M., Gallily, R., Sumariwalla, P. F.et al. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc. Natl Acad. Sci. USA, 97, 9561–9566CrossRefGoogle ScholarPubMed
Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C. and Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346, 561–564CrossRefGoogle ScholarPubMed
Mechoulam, R. (1973). Cannabinoid chemistry. In Marijuana Chemistry, Metabolism, Pharmacology and Clinical Effects, ed. R. Mechoulam, pp. 1–99. New York: Academic Press
Mechoulam, R. (1986). The pharmacohistory of Cannabis sativa. In Cannabinoids as Therapeutic Agents, pp. 1–19. Boca Raton, FL. CRC Press
Mechoulam, R. and Edery, H. (1973). Structure–activity relationships in the cannabinoid series. In Marijuana Chemistry, Metabolism, Pharmacology and Clinical Effects, ed. R. Mechoulam, pp. 101–136. New York: Academic Press
Mechoulam, R. and Hanuš, L. (2002). Cannabidiol: an overview of some chemical and pharmacological aspects. Part I. Chemical aspects. Chem. Phys. Lipids, 121, 35–43CrossRefGoogle ScholarPubMed
Mechoulam, R. and Shvo, Y. (1963). The structure of cannabidiol. Tetrahedron, 19, 2073–2078CrossRefGoogle ScholarPubMed
Mechoulam, R., Shani, A., Edery, H. and Grunfeld, Y. (1970). The chemical basis of hashish activity. Science, 169, 611–612CrossRefGoogle ScholarPubMed
Mechoulam, R., Feigenbaum, J. J., Lander, N.et al. (1988). Enantiomeric cannabinoids: stereo-specificity of psychotropic activity. Experientia, 44, 762–764CrossRefGoogle Scholar
Mechoulam, R., Ben-Shabat, S., Hanuš, L.et al. (1995). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to the peripheral cannabinoid receptors. Biochem. Pharmacol., 50, 83–90CrossRefGoogle Scholar
Mechoulam, R., Fride, E. and Di Marzo, V. (1998). Endocannabinoids. Eur. J. Pharmacol., 359, 1–18CrossRefGoogle ScholarPubMed
Moreau, J-J. (1973). Hashish and Mental Illness. Translated from the French original (1845). New York: Raven Press
Munro, S., Thomas, K. L. and Abu-Shaar, M. (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365, 61–65CrossRefGoogle ScholarPubMed
Onaivi, E. S., Green, M. R. and Martin, B. R. (1990). Pharmacological characterization of cannabinoids in the elevated plus maze. J. Pharmacol. Exp. Ther., 253, 1002–1009Google ScholarPubMed
O'Shaugnessy, W. B. (1841). Cannabis. In The Bengal Dispensatory and Pharmacopoeia, pp. 579–604. Calcutta: Bishop's College Press
O'Shaugnessy, W. B. (1843). On the Cannabis indica or Indian hemp. Pharmacol. J. Trans., 2, 594–595Google Scholar
Ottani, A. and Giuliani, D. (2001). HU 210: a potent tool for investigations of the cannabinoid system. CNS Drug Rev., 7, 131–45CrossRefGoogle ScholarPubMed
Panikashvili, D., Simeonidou, C., Ben-Shabat, S.et al. (2001). An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature, 413, 527–531CrossRefGoogle ScholarPubMed
Parker, L. A., Mechoulam, R. and Schlievert, C. (2002). Cannabidiol, a non-psychoactive component of cannabis, and its dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport, 13, 567–570CrossRefGoogle Scholar
Pertwee, R. G. and Ross, R. A. (2002). Cannabinoid receptors and their ligands. Prostaglandins Leukot. Essent. Fatty Acids, 66, 101–121CrossRefGoogle ScholarPubMed
Pertwee, R. G., Stevenson, L. A., Elrick, D. B., Mechoulam, R. and Corbett, A. D. (1992). Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea-pig small intestine. Br. J. Pharmacol., 105, 980–984CrossRefGoogle ScholarPubMed
Pickens, J. T. (1981). Sedative activity of cannabis in relation to its delta-1-trans-tetrahydrocannabinol and cannabidiol content. Br. J. Pharmacol., 72, 649–656CrossRefGoogle Scholar
Piomelli, D., Giuffrida, A., Calignano, A. and Fonseca, F. R. (2000). The endocannabinoid system as a target for therapeutic drugs. Trends Pharmacol. Sci., 21, 218–223CrossRefGoogle ScholarPubMed
Porter, A. C., Sauer, J. M., Knierman, M. D.et al. (2002). Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J. Pharmacol. Exp. Ther., 301, 1020–1024CrossRefGoogle ScholarPubMed
Reynolds, J. R. (1890). Therapeutic uses and toxic effects of Cannabis indica. Lancet, 1, 637–638CrossRefGoogle Scholar
Rinaldi-Carmona, M., Barth, F., Heaulme, M.et al. (1994). SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett., 350, 240–244CrossRefGoogle ScholarPubMed
Rinaldi-Carmona, M., Barth, F., Millan, J.et al. (1998). SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J. Pharmacol. Exp. Ther., 284, 644–650Google ScholarPubMed
Rottanburg, D., Robins, A. H., Ben-Arie, O., Teggin, A. and Elk, R. (1982). Cannabis-associated psychosis with hypomanic features. Lancet, 2, 1364–1366CrossRefGoogle ScholarPubMed
Schlicker, E. and Kathmann, M. (2001). Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol. Sci., 22, 565–572CrossRefGoogle ScholarPubMed
Schmid, H. H. (2000). Pathways and mechanisms of N-acylethanolamine biosynthesis: can anandamide be generated selectively?Chem. Phys. Lipids, 108, 71–87CrossRefGoogle ScholarPubMed
Schmid, H. H. O. and Berdyshev, E. V. (2002). Cannabinoid receptor-inactive N-acylethanolamines and other fatty acid amides: metabolism and function. Prostaglandins Leukot. Essent. Fatty Acids, 66, 363–376CrossRefGoogle ScholarPubMed
Shohami, E. and Mechoulam, R. (2000). Dexanabinol (HU-211): a non-psychotropic cannabinoid with neuroprotective properties. Drug Dev. Res., 50, 211–2153.0.CO;2-G>CrossRefGoogle Scholar
Srivastava, M. D., Srivastava, B. I. and Brouhard, B. (1998). Delta-9-tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology, 40, 179–185CrossRefGoogle ScholarPubMed
Sugiura, T., Kondo, S., Sukagawa, A.et al. (1995). 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun., 215, 89–97CrossRefGoogle ScholarPubMed
Sugiura, T., Kobayashi, Y., Oka, S. and Waku, K. (2002). Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot. Essent. Fatty Acids, 66, 173–192CrossRefGoogle ScholarPubMed
Todd, A. R. (1946). Hashish. Experientia, 2, 55–60CrossRefGoogle Scholar
Turkanis, S. A., Cely, W., Olsen, D. M. and Karler, R. (1974). Anticonvulsant properties of cannabidiol. Res. Commun. Chem. Pathol. Pharmacol., 8, 231–246Google ScholarPubMed
Turner, C. E., Elsohly, M. A. and Boeren, E. G. (1980). Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J. Nat. Prod., 43, 169–234CrossRefGoogle ScholarPubMed
Stelt, M., van-Kuik, J. A., Bari, M.et al. (2002). Oxygenated metabolites of anandamide and 2-arachidonylglycerol: conformational analysis and interaction with cannabinoid receptors, membrane transporter, and fatty acid amide hydrolase. J. Med. Chem., 45, 3709–3720CrossRefGoogle ScholarPubMed
Wachtel, S. R., ElSohly, M. A., Ross, S. A., Ambre, J. and 'de Wit, H. (2002). Comparison of the subjective effects of Δ9-tetrahydrocannabinol and marijuana in humans. Psychopharmacology, 161, 331–339Google ScholarPubMed
Wagner, J. A., Varga, K., Jarai, Z. and Kunos, G. (1999). Mesenteric vasodilation mediated by endothelial anandamide receptors. Hypertension, 33, 429–434CrossRefGoogle ScholarPubMed
Wallace, M. J., Wiley, J. L., Martin, B. R. and DeLorenzo, R. J. (2001). Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. Eur. J. Pharmacol., 28, 51–57CrossRefGoogle Scholar
Watzl, B., Scuderi, P. and Watson, R. R. (1991). Marijuana components stimulate human peripheral blood mononuclear cell secretion of interferon-gamma and suppress interleukin-1 alpha in vitro. Int. J. Immunopharmacol., 13, 1091–1097CrossRefGoogle ScholarPubMed
Zuardi, A. W., Shirakawa, I., Finkelfarb, E. and Karniol, I. G. (1982). Action of cannabidiol on the anxiety and other effects produced by delta-9-THC in normal subjects. Psychopharmacology, 76, 245–250CrossRefGoogle ScholarPubMed
Zuardi, A. W., Rodrigues, J. A. and Cunha, J. M. (1991). Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology, 104, 260–264CrossRefGoogle ScholarPubMed
Zuardi, A. W., Morais, S. L., Guimaraes, F. S. and Mechoulam, R. (1995). Antipsychotic effect of cannabidiol. J. Clin. Psychiatry, 56, 485–486Google ScholarPubMed
Zuardi, A. W., Guimaraes F. S., Guimaraes, V. M. C. and Del Bel, E. A. (2002). Cannabidiol: possible therapeutic application. In Cannabis and Cannabinoids, ed. F. Grotenhermen and E. Russo, pp. 359–369. New York: Haworth Press

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