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Chapter 3 - The Endocannabinoids

from Section 1 - An Introduction to Cannabinoid Science

Published online by Cambridge University Press:  12 October 2020

Steven James
Steven James
Affiliation:
University of California, San Diego
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Summary

As we have discussed previously in Chapters 1 and 2, cannabinoids have been very difficult to isolate and study due to their significant lipophilic properties. Once it was finally determined that (-)Δ9-tetrahydrocannabinol (THC) was the psychoactive component in cannabis (Gaoni and Mechoulam, 1964), attention quickly focused on understanding how THC worked in the brain. Many believed cannabinoids acted directly on membranes and did not bind specifically to receptors because of the high lipophilicity of THC.

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A Clinician's Guide to Cannabinoid Science , pp. 27 - 40
Publisher: Cambridge University Press
Print publication year: 2020

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References

Ahluwalia, J. et al. (2003) ‘Anandamide regulates neuropeptide release from capsaicin-sensitive primary sensory neurons by activating both the cannabinoid 1 receptor and the vanilloid receptor 1 in vitro’, European Journal of Neuroscience, 17(12), 2611–2618. https://doi.org/10.1046/j.1460-9568.2003.02703.x.CrossRefGoogle ScholarPubMed
Alger, B. E. (2002). ‘Retrograde signalling in the regulation of synaptic transmission: focus on endocannabinoids’, Progress in Neurobiology, 68(4), 247–286.CrossRefGoogle ScholarPubMed
Basavarajappa, B. S. (2017) ‘Cannabinoid receptors and their signaling mechanisms’, in Murillo-Rodríguez, E (ed.), The Endocannabinoid System: Genetics, Biochemistry, Brain Disorders, and Therapy. London: Academic Press. pp. 25–62.Google Scholar
Cantini, G. et al. (2010) ‘Peroxisome-proliferator-activated receptor gamma (PPARγ) is required for modulating endothelial inflammatory response through a nongenomic mechanism’, European Journal of Cell Biology, 89(9), 645–653. https://doi.org/10.1016/j.ejcb.2010.04.002.CrossRefGoogle ScholarPubMed
Carman, C. V and Benovic, J. L. (1998) ‘G-protein-coupled receptors: turn-ons and turn-offs’, Current Opinion in Neurobiology, 8(3), 335–344.CrossRefGoogle ScholarPubMed
Christopoulos, A. and Kanakin, T. (2002). ‘G protein-coupled receptor allosterism and complexing’, Pharmacological Reviews, 54(2), 323–374.CrossRefGoogle ScholarPubMed
Collins, S., Caron, M. G. and Lefkowitz, R. J. (1992) ‘From ligand binding to gene expression: new insights into the regulation of G-protein-coupled receptors’, Trends in Biochemical Sciences, 17(1), 37–39. https://doi.org/10.1016/0968-0004(92)90425-9.CrossRefGoogle ScholarPubMed
Cravatt, B. F. et al. (1996) ‘Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides’, Nature, 384(6604), 83–87. https://doi.org/10.1038/384083a0.Google Scholar
Davis, G. W. and Goodman, C. S. (1998) ‘Synapse-specific control of synaptic efficacy at the terminals of a single neuron’, Nature, 392(6671), 82–86. doi:10.1038/32176.CrossRefGoogle ScholarPubMed
Davis, G. W. and Murphey, R. K. (1994) ‘Retrograde signaling and the development of transmitter release properties in the invertebrate nervous system’, Journal of Neurobiology, 25(6), 740–756. https://doi.org/10.1002/neu.480250612.Google Scholar
De Petrocellis, L. et al. (2011). ‘Effects of cannabinoids and cannabinoid‐enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes’, British Journal of Pharmacology, 163, 1479–1494.Google Scholar
Devane, W. A. (1994) ‘New dawn of cannabinoid pharmacology’, Trends in Pharmacological Sciences, 15(2), 40–41. https://doi.org/10.1016/0165-6147(94)90106-6.CrossRefGoogle ScholarPubMed
Devane, W. A. et al. (1988) ‘Determination and characterization of a cannabinoid receptor in rat brain’, Molecular Pharmacology, 34(5), 605–613.Google ScholarPubMed
Devane, W. A. et al. (1992) ‘Isolation and structure of a brain constituent that binds to the cannabinoid receptor’, Science, 258(5090), 1946–1949. https://doi.org/10.1126/science.1470919.CrossRefGoogle Scholar
Devane, W. A. and Axelrod, J. (1994) ‘Enzymatic synthesis of anandamide, an endogenous ligand for the cannabinoid receptor, by brain membranes’, Proceedings of the National Academy of Sciences of the United States of America, 91(14), 6698–6701. https://doi.org/10.1073/pnas.91.14.6698.Google Scholar
Dinh, T. P., Kathuria, S. and Piomelli, D. (2004) ‘RNA interference suggests a primary role for monoacylglycerol lipase in the degradation of the endocannabinoid 2-arachidonoylglycerol’, Molecular Pharmacology, 66(5), 1260–1264.CrossRefGoogle ScholarPubMed
Duan, S. Z., Usher, M. G. and Mortensen, R. M. (2009) ‘PPARs: the vasculature, inflammation and hypertension’, Current Opinion in Nephrology and Hypertension, 18(2), 128–133. https://doi.org/10.1097/MNH.0b013e328325803b.CrossRefGoogle ScholarPubMed
Elphick, M. R. and Egertova, M. (2001) ‘The neurobiology and evolution of cannabinoid signalling’, Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 356(1407), 381–408. https://doi.org/10.1098/rstb.2000.0787.CrossRefGoogle ScholarPubMed
Gaoni, Y. and Mechoulam, R. (1964) ‘Isolation, structure, and partial synthesis of an active constituent of hashish’, Journal of the American Chemical Society, 86(8), 1646–1647. https://doi.org/10.1021/ja01062a046.CrossRefGoogle Scholar
Hanus, L. et al. (2001) ‘2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor’, Proceedings of the National Academy of Sciences of the United States of America, 98, 3662–3665.Google Scholar
Henstridge, C. M., et al. (2009) ‘The GPR55 ligand L-α-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation’, FASEB Journal, 23(1), 183–193. https://doi.org/10.1096/fj.08-108670.CrossRefGoogle ScholarPubMed
Hermanson, D. J. et al. (2013) ‘Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation’, Nature Neuroscience, 16(9), 1291–1298. doi:10.1038/nn.3480.CrossRefGoogle ScholarPubMed
Höller, C., Freissmuth, M. and Nanoff, C. (1999) ‘G proteins as drug targets’, Cellular and Molecular Life Sciences CMLS, 55(2), 257–270. https://doi.org/10.1007/s000180050288.Google Scholar
Howlett, A. C. (1998) ‘The CB1cannabinoid receptor in the brain’, Neurobiology of Disease, 5(6), 405–416. https://doi.org/10.1006/nbdi.1998.0215.CrossRefGoogle Scholar
Huang, S. M. et al. (2002) ‘An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors’, Proceedings of the National Academy of Sciences of the United States of America, 99, 8400–8405.CrossRefGoogle ScholarPubMed
Kreitzer, A. C. and Regehr, W. G. (2001) ‘Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells’, Neuron, 29, 717–727. https://doi.org/10.1016/S0896-6273(01)00246-X.CrossRefGoogle ScholarPubMed
Lauckner, J. E. et al. (2008) ‘GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current’, Proceedings of the National Academy of Sciences of the United States of America, 105(7), 2699–2704. https://doi.org/10.1073/pnas.0711278105.CrossRefGoogle ScholarPubMed
Llano, I., Leresche, N. and Marty, A. (1991) ‘Calcium entry increases the sensitivity of cerebellar purkinje cells to applied GABA and decreases inhibitory synaptic currents’, Neuron, 6(4), 565–574. doi:10.1016/0896-6273(91)90059-9.CrossRefGoogle ScholarPubMed
Mackie, K. (2005) ‘Distribution of cannabinoid receptors in the central and peripheral nervous system’, Handbook of Experimental Pharmacology, 168(1), 299–325. https://doi.org/10.1007/3-540-26573-2_10.CrossRefGoogle Scholar
Mackie, K. (2008) ‘Cannabinoid receptors: where they are and what they do’, Journal of Neuroendocrinology, 20(s1), 10–14. https://doi.org/10.1111/j.1365-2826.2008.01671.x.Google Scholar
Maresz, K. et al. (2005) ‘Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli’, Journal of Neurochemistry, 95(2), 437–445. https://doi.org/10.1111/j.1471-4159.2005.03380.x.CrossRefGoogle ScholarPubMed
Matsuda, L. A. et al. (1990). ‘Structure of a cannabinoid receptor and functional expression of the cloned cDNA’, Nature, 346, 561–564.CrossRefGoogle ScholarPubMed
McPartland, J. M. et al. (2006a) ‘Cannabinoid receptors in invertebrates’, Journal of Evolutionary Biology, 19(2), 366–373. https://doi.org/10.1111/j.1420-9101.2005.01028.x.Google Scholar
McPartland, J. M. et al. (2006b) ‘Evolutionary origins of the endocannabinoid system’, Gene, 370(1–2), 64–74. https://doi.org/10.1016/j.gene.2005.11.004.CrossRefGoogle ScholarPubMed
Mechoulam, R. et al. (1995) ‘Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors’, Biochemical Pharmacology, 50(1), 83–90. https://doi.org/10.1016/0006-2952(95)00109-D.CrossRefGoogle ScholarPubMed
Mechoulam, R. and Parker, L. A. (2013) ‘The endocannabinoid system and the brain’, Annual Review of Psychology, 64, 21–47. https://doi.org/10.1146/annurev-psych-113011-143739.CrossRefGoogle ScholarPubMed
Michalik, L. et al. (2006) ‘International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors’, Pharmacological Reviews, 58(4), 726–741. doi:10.1124/pr.58.4.5.CrossRefGoogle ScholarPubMed
Morales, P., Reggio, P. H. and Jagerovic, N. (2017) ‘An overview on medicinal chemistry of synthetic and natural derivatives of cannabidiol’. Frontiers in Pharmacology, 8, 422. https://doi.org/10.3389/fphar.2017.00422.Google Scholar
Moriconi, A. et al. (2010) ‘GPR55: current knowledge and future perspectives of a purported cannabinoid receptor’, Current Medicinal Chemistry, 17(14), 1411–1429. https://doi.org/10.2174/092986710790980069.Google Scholar
Munro, S., Thomas, K. L. and Abu-Shaar, M. (1993) ‘Molecular characterization of the peripheral receptor for cannabinoids’, Nature, 365(6441), 61–65.CrossRefGoogle ScholarPubMed
Neubig, R. R. et al. (2003) ‘International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on Terms and Symbols in Quantitative Pharmacology’, Pharmacological Reviews, 55, 597–606.Google Scholar
Nguyen, T. et al. (2018) ‘Allosteric modulation: an alternative approach targeting the cannabinoid CB1 receptor’, Medical Research Reviews, 37(3), 441–474. https://doi.org/10.1002/med.21418.CrossRefGoogle Scholar
Onaivi, E. S. et al. (2002) ‘Endocannabinoids and cannabinoid receptor genetics’, Progress in Neurobiology, 66(5), 307–344. https://doi.org/10.1016/S0301-0082(02)00007-2.CrossRefGoogle ScholarPubMed
Onaivi, E. S. et al. (2012) ‘CNS effects of CB2 cannabinoid receptors: beyond neuro-immuno-cannabinoid activity’, Journal of Psychopharmacology, 26(1), 92–103.CrossRefGoogle ScholarPubMed
Pacher, P. and Mechoulam, R. (2011) ‘Is lipid signaling through cannabinoid 2 receptors part of a protective system?’, Progress in Lipid Research, 50, 193–211.CrossRefGoogle ScholarPubMed
Parker, L. A. (2017) Cannabinoids and the Brain. Cambridge, MA: MIT Press.CrossRefGoogle Scholar
Pertwee, R. G. (1999) ‘Evidence for the presence of CB1 cannabinoid receptors on peripheral neurones and for the existence of neuronal non-CB1 cannabinoid receptors’, Life Sciences, 65(6–7), 597–605. https://doi.org/10.1016/S0024-3205(99)00282-9.Google Scholar
Pertwee, R. G. et al. (2010) ‘International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2’, Pharmacological Reviews, 62(4), 588–631. https://doi.org/10.1124/pr.110.003004CrossRefGoogle ScholarPubMed
Pertwee, R.G. and Ross, R. A. (2002) ‘Cannabinoid receptors and their ligands’, Prostaglandins, Leukotrienes and Essential Fatty Acids, 66(2–3), 101–121. https://doi.org/10.1054/plef.2001.0341CrossRefGoogle ScholarPubMed
Piomelli, D. (2003) ‘The molecular logic of endocannabinoid signalling’, Nature Reviews Neuroscience, 4(11), 873–884. https://doi.org/10.1038/nrn1247.CrossRefGoogle ScholarPubMed
Pitler, T. A. and Alger, B. E. (1992) ‘Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells’, Journal of Neuroscience, 12, 4122–4132. doi:10.1523/JNEUROSCI.12-10-04122.1992.Google Scholar
Porter, A. C. et al. (2002) ‘Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor’, Journal of Pharmacology and Experimental Therapeutics, 301, 1020–1024.Google Scholar
Regehr, W. G., Carey, M. R. and Best, A. R. (2009) ‘Activity-dependent regulation of synapses by retrograde messengers’, Neuron, 63(2), 154–170. https://doi.org/10.1016/j.neuron.2009.06.021.CrossRefGoogle ScholarPubMed
Rodbell, M. (1997) ‘The complex regulation of receptor-coupled G-proteins’, Advances in Enzyme Regulation, 37, 427–435. https://doi.org/10.1016/S0065-2571(96)00020-9.CrossRefGoogle ScholarPubMed
Sawzdargo, M. et al. (1999) ‘Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain’, Brain Research. Molecular Brain Research, 64(2), 193–198. doi:10.1016/s0169-328x(98)00277-0.Google Scholar
Starowicz, K., Nigam, S. and Di Marzo, V. (2007) ‘Biochemistry and pharmacology of endovanilloids’, Pharmacology & Therapeutics, 114(1), 13–33. https://doi.org/10.1016/j.pharmthera.2007.01.005.Google Scholar
Sugiura, T. et al. (2002) ‘Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible significance’, Prostaglandins, Leukotrienes and Essential Fatty Acids, 66, 173–192.Google Scholar
Sylantyev, S. et al. (2013) ‘Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses’, Proceedings of the National Academy of Sciences of the United States of America, 110(13), 5193–5198. doi:10.1073/pnas.1211204110.CrossRefGoogle ScholarPubMed
Williams, J. H. (1996) ‘Retrograde messengers and long-term potentiation: a progress report’, Journal of Lipid Mediators and Cell Signalling, 14(1–3), 331–339.Google Scholar
Yates, M. L. and Barker, E. L. (2009) ‘Inactivation and biotransformation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol’, Molecular Pharmacology, 76(1), 11–17.Google Scholar
Zoerner, A. A. et al. (2011) ‘Quantification of endocannabinoids in biological systems by chromatography and mass spectrometry: a comprehensive review from an analytical and biological perspective’, Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids, 1811(11), 706-723.Google Scholar

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  • The Endocannabinoids
  • Steven James, University of California, San Diego
  • Book: A Clinician's Guide to Cannabinoid Science
  • Online publication: 12 October 2020
  • Chapter DOI: https://doi.org/10.1017/9781108583336.004
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  • The Endocannabinoids
  • Steven James, University of California, San Diego
  • Book: A Clinician's Guide to Cannabinoid Science
  • Online publication: 12 October 2020
  • Chapter DOI: https://doi.org/10.1017/9781108583336.004
Available formats
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  • The Endocannabinoids
  • Steven James, University of California, San Diego
  • Book: A Clinician's Guide to Cannabinoid Science
  • Online publication: 12 October 2020
  • Chapter DOI: https://doi.org/10.1017/9781108583336.004
Available formats
×