Skip to main content
SpringerLink
Log in

An Historical Introduction to the Endocannabinoid and Endovanilloid Systems

  • Chapter
Cannabinoids and the Brain

Cannabis and chili pepper have been used for medical, gastronomical and recreational purposes for at least 8,000 years. Nevertheless, it was discovered only eight years ago that the cloned neuronal targets of their active principles, delta9-tetrahydrocannabinol (Δ9-THC) and capsaicin are related to each other, as they all can be activated by some arachidonic acid-derivative endogenous ligands. Here, we will summarize the history of man's relationship with cannabis and capsaicin, and we will detail the most important scientific keystones in the evolution of cannabinoid and vanilloid research, featuring the list of cannabinoid and capsaicin effects, the discovery of endogenous ligands and the cloning of receptors, namely, the CB1 and the CB2 cannabinoid receptor as well as the TRPV1 vanilloid receptor, where the endogenous and the plant-derived substances act upon. This chapter serves, therefore, as an introduction to Cannabinoids and the Brain, the book which will extensively describe the neuronal and, to some extent, the peripheral cannabinoid and vanilloid systems in molecular, pharmacological, physiological, pathological and neuropsychiatric viewpoints.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Acs G, Palkovits M, Blumberg PM (1996) Specific binding of [3H]resiniferatoxin by human and rat preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus membrane preparations. Life Sci 59:1899–1908.

    Article  CAS  PubMed  Google Scholar 

  • Bevan S, Hothi S, Hughes G, James IF, Rang HP, Shah K, Walpole CS, Yeats JC (1992) Capsazepine: a competitive antagonist of the sensory neuron excitant capsaicin. Br J Pharmacol 107:544–552.

    CAS  PubMed  Google Scholar 

  • Bleakman D, Brorson, JR, Miller RJ (1990) The effect of capsaicin on voltage-gated calcium currents and calcium signals in cultured dorsal root ganglion cells. Br J Pharmacol 101:423–431.

    CAS  PubMed  Google Scholar 

  • Buckley NE, McCoy KL, Mezey E, Bonner T, Zimmer A, Felder CC, Glass M, Zimmer A (2000) Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor. Eur J Pharmacol 396:141–149.

    Article  CAS  PubMed  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824.Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313.

    Google Scholar 

  • Charrua A, Cruz CD, Cruz F, Avelino A (2007) Transient receptor potential vanilloid subfamily 1 is essential for the generation of noxious bladder input and bladder overactivity in cystitis. J Urol 177:1537–1541.

    Article  CAS  PubMed  Google Scholar 

  • Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4, 5) P2-mediated inhibition. Nature 411:957–962.

    Article  CAS  PubMed  Google Scholar 

  • Comeau P (2006) Cut to marijuana research sends strong message. CMAJ 175:1507–1508.

    PubMed  Google Scholar 

  • Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187.

    Article  CAS  PubMed  Google Scholar 

  • Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Dickenson AH, Dray A (1991) Selective antagonism of capsaicin by capsazepine: evidence for a spinal receptor site in capsaicin-induced antinociception. Br J Pharmacol 104:1045–1049.

    CAS  PubMed  Google Scholar 

  • Dinis P, Charrua A, Avelino A, Yaqoob M, Bevan S, Nagy I, Cruz F (2004) Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 24:11253–11263.

    Article  CAS  PubMed  Google Scholar 

  • Dubois JM (1982) Capsaicin blocks one class of K+ channels in the frog node of Ranvier. Brain Res 245:372–375.

    Article  CAS  PubMed  Google Scholar 

  • Erdelyi L, Such G, Jancso G (1987) Intracellular and voltage clamp studies of capsaicin-induced effects on a sensory neuron model. Acta Physiol Hung 69:481–492.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Gerard C, Mollereau C, Vassart G, Parmentier M (1990) Nucleotide sequence of a human cannabinoid receptor cDNA. Nucleic Acids Res 18:7142.

    Article  CAS  PubMed  Google Scholar 

  • Gerard CM, Mollereau C, Vassart G, Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279:129–134.

    CAS  PubMed  Google Scholar 

  • Gill EW, Paton WDM, Pertwee RG (1970) Preliminary experiments on the chemistry and pharmacology of cannabis. Nature 228:134–136.

    Article  CAS  PubMed  Google Scholar 

  • Haagen-Smit AJ, Wawra CZ, Koepfli JB, Alles GA, Feigen GA, Prater AN (1940) A physiologically active principle from Cannabis sativa (marihuana). Science 91:602–603.

    Article  CAS  PubMed  Google Scholar 

  • Hayry M (2004) Prescribing cannabis: freedom, autonomy, and values. J Med Ethics 30:333–336.

    Article  CAS  PubMed  Google Scholar 

  • Herkenham M, Lynn AB, Johnson MR, Melvin LS, De Costa BR, Rice KC (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11:563–583.

    CAS  PubMed  Google Scholar 

  • Heyman I, Rang HP (1985) Depolarizing responses to capsaicin in a subpopulation of rat dorsal root ganglion cells. Neurosci Lett 56:69–75.

    Article  CAS  PubMed  Google Scholar 

  • Hillard CJ, Harris RA, Bloom AS (1985) Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: fluorescence studies. J Pharmacol Exp Ther 232:579–588.

    CAS  PubMed  Google Scholar 

  • Howlett AC, Fleming RM (1984) Cannabinoid inhibition of adenylate-cyclase: pharmacology of the response in neuroblastoma cell membranes. Mol Pharmacol 26:532–538.Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ (2004) Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 47 Suppl 1:345–358.

    Google Scholar 

  • Jancso G, Kiraly E, Jancso-Gabo A (1977) Pharmacologically induced selective degeneration of chemosensitive primary sensory neurons. Nature 270:741–743.

    Article  CAS  PubMed  Google Scholar 

  • Jancso-Gabor A, Szolcsanyi J, Jancso N (1970) Stimulation and desensitization of the hypothalamic heat-sensitive structures by capsaicin in rats. J Physiol 208:449–459.

    CAS  PubMed  Google Scholar 

  • Lawrence DK, Gill EW (1975) The effects of L9-tetrahydrocannabinol and other cannabinoids on spin-labeled liposomes and their relationship to mechanisms of general anesthesia. Mol Pharmacol 11:595–602.

    CAS  PubMed  Google Scholar 

  • Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Bohme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283:401–404.

    Article  CAS  PubMed  Google Scholar 

  • Loewe (1946) Studies on the pharmacology and acute toxicity of compounds with marihuana activity. J Pharmacol Exp Ther 88:154–161.

    CAS  Google Scholar 

  • Marsh SJ, Stansfeld CE, Brown DA, Davey R, McCarthy D (1987) The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro. Neuroscience 23:275–289.

    Article  CAS  PubMed  Google Scholar 

  • Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutierrez SO, van der Stelt M, Lopez-Rodriguez ML, Casanova E, Schutz G, Zieglgansberger W, Di Marzo V, Behl C, Lutz B (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88.

    Article  CAS  PubMed  Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564.

    Article  CAS  PubMed  Google Scholar 

  • Mechoulam R, Hanus L (2000) A historical overview of chemical research on cannabinoids. Chem Phys Lipids 108:1–13.

    Article  CAS  PubMed  Google Scholar 

  • Mechoulam R, Shvo Y (1963) The structure of cannabidiol. Tetrahedron 19:2073–2078.

    Article  CAS  Google Scholar 

  • Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90.

    Article  CAS  PubMed  Google Scholar 

  • Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Nagy I, Santha P, Jancso G, Urban L (2004) The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology. Eur J Pharmacol 500:351–369.

    Article  CAS  PubMed  Google Scholar 

  • Nelson EK (1919) The constitution of capsaicin—the pungent principle of capsicum. J Am Chem Soc 41:1115–1117.

    Article  CAS  Google Scholar 

  • Nilius B, Mahieu F, Karashima Y, Voets T (2007) Regulation of TRP channels: a voltage-lipid connection. Biochem Soc Trans 35:105–108.

    Article  CAS  PubMed  Google Scholar 

  • Paton WDM, Pertwee RG (1973). The pharmacology of cannabis in animals. In: Marijuana, Chemistry, Pharmacology, Metabolism and Clinical Effects. Mechoulam R, ed. New York: Academic Press, pp. 191–285.

    Google Scholar 

  • Perkins MN, Campbell EA (1992) Capsazepine reversal of the antinociceptive action of capsaicin in vivo. Br J Pharmacol 107:329–333.

    CAS  PubMed  Google Scholar 

  • Perry L, Dickau R, Zarrillo S, Holst I, Pearsall DM, Piperno DR, Berman MJ, Cooke RG, Rademaker K, Ranere AJ, Raymond JS, Sandweiss DH, Scaramelli F, Tarble K, Zeidler JA (2007) Starch fossils and the domestication and dispersal of chili peppers (Capsicum spp. L.) in the Americas. Science 315:986–988.

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG (2006) Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147:S163–S171.

    Article  CAS  PubMed  Google Scholar 

  • Porszasz J, Jancso N (1959) Studies on the action potentials of sensory nerves in animals desensitized with capsaicine. Acta Physiol Acad Sci Hung 16:299–306.

    CAS  PubMed  Google Scholar 

  • Rinaldi-Carmona M, Barth F, Heaulme M, Shire D, Calandra B, Congy C, Martinez S, Maruani J, Neliat G, Caput D, Ferrara P, Soubrié P, Brelière J-C, Fur GL (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350:240–244.

    Article  CAS  PubMed  Google Scholar 

  • Singh Tahim A, Santha P, Nagy I (2005) Inflammatory mediators convert anandamide into a potent activator of the vanilloid type 1 transient receptor potential receptor in nociceptive primary sensory neurons. Neuroscience 136:539–548.

    Article  CAS  PubMed  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97.

    Article  CAS  PubMed  Google Scholar 

  • Szallasi A, Blumberg, PM (1989) Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper. Neuroscience 30:515–520.

    Article  CAS  PubMed  Google Scholar 

  • Szallasi A, Blumberg PM (1990) Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes. Brain Res 524:106–111.

    Article  CAS  PubMed  Google Scholar 

  • Szallasi A, Blumberg PM (1999) Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51:159–212.

    CAS  PubMed  Google Scholar 

  • Szallasi A, Nilsson S, Farkas-Szallasi T, Blumberg PM, Hokfelt T. Lundberg JM (1995) Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment. Brain Res 703:175–183.

    Article  CAS  PubMed  Google Scholar 

  • Thresh LT (1846) Isolation of capsaicin. Pharm J 6:941.

    Google Scholar 

  • Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543.

    Article  CAS  PubMed  Google Scholar 

  • Wall J, Davis S, Ridgway S (2001) Cannabis: its therapeutic use. Nurs Stand 16:39–44.

    CAS  PubMed  Google Scholar 

  • Winter J, Dray A, Wood JN, Yeats JC, Bevan S (1990) Cellular mechanism of action of resiniferatoxin: a potent sensory neuron excitotoxin. Brain Res 520:131–140.

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka K, Kigoshi S, Muramatsu I (1984) Conduction-block induced by capsaicin in crayfish giant axon. Brain Res 300:113–119.

    Article  CAS  PubMed  Google Scholar 

  • Zimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI (1999) Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 96:5780–5785.

    Article  CAS  PubMed  Google Scholar 

  • Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D, Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK

    Istvan Nagy

Authors
  1. Istvan Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John P. M. White
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cleoper C. Paule
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Attila Köfalvi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurosciences of Coimbra, University of Coimbra, Coimbra, 3000-045, Portugal

    Attila Köfalvi (Faculty of Medicine) (Faculty of Medicine)

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer

About this chapter

Cite this chapter

Nagy, I., White, J.P.M., Paule, C.C., Köfalvi, A. (2008). An Historical Introduction to the Endocannabinoid and Endovanilloid Systems. In: Köfalvi, A. (eds) Cannabinoids and the Brain. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-74349-3_1

Download citation

Publish with us

Policies and ethics

Search

Navigation