Skip to main content
SpringerLink
Log in

The Endocannabinoid System

  • Reference work entry
Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

The endocannabinoid system is composed of cannabinoid receptors, their endogenous ligands, the endocannabinoids, and the enzymes that produce and inactivate them. Endocannabinoids are a new family of lipid mediators, which includes amides, esters, and ethers of long-chain polyunsaturated fatty acids. Endocannabinoids engage the cell surface receptors that are targeted by Δ9-tetrahydrocannabinol (Δ9-THC), the active principle of Cannabis sativa preparations like hashish and marijuana. The pathways leading to the synthesis and release of endocannabinoids from neuronal and nonneuronal cells are still rather uncertain. Instead, they are synthesized on demand through cleavage of membrane precursors and are involved in various short-range signaling processes. In the brain, they combine with CB1 cannabinoid receptors (CB1Rs) on axon terminals to regulate ion channel activity and neurotransmitter release. The endocannabinoid system is shown to be involved in an increasing number of pathological conditions. Their ability to modulate synaptic efficacy has a wide range of functional consequences and provides unique therapeutic possibilities. In this chapter, we aim to provide recent progress in our understanding of the endocannabinoid system in the brain. First, the structure, anatomical distribution, and signal transduction mechanism of cannabinoid receptors are described. The synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. Finally, the possible role of the endocannabinoid system in the central nervous system is discussed in relation to neurotransmitter release, synaptic plasticity, and the therapeutic role in various disease conditions including alcohol abuse.

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 299.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
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

Abbreviations

AA:

arachidonic acid

AC:

adenylyl cyclase

ACEA:

arachidonyl-2′-chloroethylamide/(all Z)-N-(2-cycloethyl)-5,8,11,14-eicosatetraenamide

AD:

Alzheimer's disease

A:

β-amyloid

AM251:

N-(piperin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide

AM404:

N-(4-hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide

AMT:

anandamide membrane transporter

APE:

N-arachidonoyl phosphatidylethanolamide

BAPTA-AM:

1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester

cAMP-Kin:

cAMP-dependent protein kinase

CB1 or CB2 :

cannabinoid 1 or 2

CBD:

cannabidiol

CDTA:

calcium-dependent transacylase

CGA:

chorionic gonadotropin

CNS:

central nervous system

CP-55,940:

(1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol

cPLA2:

cytoplasmic phospholipase A2

CPP:

conditioned place preference

Cpu:

caudate putamen

DA:

dopamine

DAG:

diacylglycerol

Δ9-THC:

Δ9-tetrahydrocannabinol

DHPG:

(S)-3,5-dihydroxyphenylglycine

DSI:

depolarization-induced suppression of inhibition

EP:

entopeduncular nucleus

EPSC:

excitatory postsynaptic currents

FAAH:

fatty acid amide hydrolase

FAK:

focal adhesion kinase

5-HT:

5-hydroxytryptamine (serotonin)

Fyn:

src-family kinases p59

GABA:

gamma-aminobutyric acid

GPCR:

G protein-coupled receptor

GP:

globus pallidus

GPe or GPi:

external or internal globus pallidus

GPe or GPi:

external or internal globus pallidus

GTPS:

guanosine 5′-O-(3-thio)triphosphate

HD:

Huntington's disease

HU-210:

Δ8-tetrahydrocannabinol dimethyl heptyl

HD:

Huntington's disease

HU-211:

dexanabinol; N-methyl-D-aspartate receptor

HU-211:

dexanabinol

IPSC:

inhibitory postsynaptic currents

JNK:

c-Jun N-terminal kinase

LTD:

long-term depression

LTP:

long-term potentiation

MAPK:

mitogen activated protein kinase

MetAEA:

R-(+)-methanandamide

MGL:

monoacylglyceride lipase

mGluRs:

metabotropic glutamate receptors

MS:

multiple sclerosis

NAc:

nucleus accumbens

NADA:

N-arachidonyl-dopamine; PLD, phospholiapse D

N-ArPE:

N-arachidonylphosphatidylethanolamine

NMDA receptor:

N-methyl-D-aspartate receptor

PD:

Parkinson's disease

PEA:

palmitoylethanolamide

PE:

phosphatidylethanolamine

PI3K:

phosphatidylinositol-3 kinase; PP2, Src tyrosine kinase inhibitor

PKA:

cAMP-dependent protein kinase

PLA1:

phospholipase A1

PLC:

Phospholipase C

PL:

phospholipase

RFLP:

restriction fragment length polymorphism

SNR:

substantia nigra pars reticulata

SR141716:

N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (rimonabant)

SR144528:

N-((1S)-endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide)

SSRP:

simple sequence repeat polymorphism

TTX:

tetrodotoxin

2-AG:

2-arachidonoylglycerol

UCM707:

N-(3-furanylmethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide

URB597:

cyclohexyl carbamic acid 3′-carbamoyl-biphenyl-3-yl ester

VMN:

ventromedial nucleus of the hypothalamus

VTA:

ventral tegamental area

VTA:

ventral tegmental area

WIN 55,212-2:

R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate

References

  • Abel EL. 1970. Marijuana and memory. Nature 227: 1151–1152.

    CAS  PubMed  Google Scholar 

  • Abood ME, Ditto KE, Noel MA, Showalter VM, Tao Q. 1997. Isolation and expression of a mouse CB1 cannabinoid receptor gene. Comparison of binding properties with those of native CB1 receptors in mouse brain and N18TG2 neuroblastoma cells. Biochem Pharmacol 53: 207–214.

    CAS  PubMed  Google Scholar 

  • Adams IB, Compton DR, Martin BR. 1998. Assessment of anandamide interaction with the cannabinoid brain receptor: SR 141716A antagonism studies in mice and autoradiographic analysis of receptor binding in rat brain. J Pharmacol Exp Ther 284: 1209–1217.

    CAS  PubMed  Google Scholar 

  • Akinshola BE, Chakrabarti A, Onaivi ES. 1999a. In-vitro and in-vivo action of cannabinoids. Neurochem Res 24: 1233–1240.

    CAS  Google Scholar 

  • Akinshola BE, Taylor RE, Ogunseitan AB, Onaivi ES. 1999b. Anandamide inhibition of recombinant AMPA receptor subunits in xenopus oocytes is increased by forskolin and 8-bromo-cyclic AMP. Naunyn Schmiedebergs Arch Pharmacol 360: 242–248.

    CAS  Google Scholar 

  • Aldrich MA. 1971.A brief legal history of marijuana. Presented to the Western Institute of Drug Problems Marijuana Conference, Portland Oregon, August 7, 14.

    Google Scholar 

  • Alger BE. 2002. Retrograde signaling in the regulation of synaptic transmission: Focus on endocannabinoids. Prog Neurobiol 68: 247–286.

    CAS  PubMed  Google Scholar 

  • Alger BE, Pitler TA, Wagner JJ, Martin LA, Morishita W, et al. 1996. Retrograde signalling in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells. J Physiol 496: 197–209.

    CAS  PubMed  Google Scholar 

  • Ameri A. 1999. The effects of cannabinoids on the brain. Prog Neurobiol 58: 315–348.

    CAS  PubMed  Google Scholar 

  • Anwyl R. 1999. Metabotropic glutamate receptors: Electrophysiological properties and role in plasticity. Brain Res Rev 29: 83–120.

    CAS  PubMed  Google Scholar 

  • Arnold JC, Topple AN, Mallet PE, Hunt GE, McGregor IS. 2001. The distribution of cannabinoid-induced Fos expression in rat brain: Differences between the Lewis and Wistar strain. Brain Res 921: 240–255.

    CAS  PubMed  Google Scholar 

  • Arnone M, Maruani J, Chaperon F, Thiebot M, Poncelet M, et al. 1997. Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology 132: 104–106.

    CAS  PubMed  Google Scholar 

  • Auclair N, Otani S, Soubrie P, Crepel F. 2000. Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons. J Neurophysiol 83: 3287–3293.

    CAS  PubMed  Google Scholar 

  • Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, et al. 2001. Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J 15: 300–302.

    CAS  PubMed  Google Scholar 

  • Basavarajappa BS. 2005. Endocannabinoid system in the development of tolerance to alcohol. Klinik and Forschung (J Clin Res) 11: 16–19.

    Google Scholar 

  • Basavarajappa BS. 2006. Endocannabinoid signaling and alcohol addiction. In “New Research on Alcoholism” Douglas Baye, editor. New York: Nova Science Publishers, Inc USA (In press).

    Google Scholar 

  • Basavarajappa BS, Hungund BL. 1999a. Chronic Ethanol Increases the Cannabinoid Receptor Agonist, Anandamide and its Precursor N-Arachidonylphosphatidyl ethanolamine in SK-N-SH Cells. J Neurochem 72: 522–528.

    CAS  Google Scholar 

  • Basavarajappa BS, Hungund BL. 1999b. Down-regulation of cannabinoid receptor agonist-stimulated [35S] GTPγS binding in synaptic plasma membrane from chronic ethanol exposed mouse. Brain Res 815: 89–97.

    CAS  Google Scholar 

  • Basavarajappa BS, Hungund BL. 2001. Cannabinoid receptor agonist-stimulated [35S] guanosine triphosphateγS binding in the brain of C57BL/6 and DBA/2 mice. J Neurosci Res 64: 429–436.

    CAS  PubMed  Google Scholar 

  • Basavarajappa BS, Hungund BL. 2002. Neuromodulatory role of the endocannabinoid signaling system in alcoholism: An overview. Prostaglandins Leukot Essent Fatty Acids 66: 287–299.

    CAS  PubMed  Google Scholar 

  • Basavarajappa BS, Hungund BL. 2005. Role of the endocannabinoid system in the development of tolerance to alcohol. Alcohol 40: 15–24.

    CAS  Google Scholar 

  • Basavarajappa BS, Cooper TB, Hungund BL. 1998. Chronic ethanol administration down-regulates cannabinoid receptors in mouse brain synaptic plasma membrane. Brain Res 793: 212–218.

    CAS  PubMed  Google Scholar 

  • Basavarajappa BS, Saito M, Cooper TB, Hungund BL. 2000. Stimulation of cannabinoid receptor agonist 2-arachidonylglycerol by chronic ethanol and its modulation by specific neuromodulators in cerebellar granule neurons. Biochim Biophys Acta 1535: 78–86.

    CAS  PubMed  Google Scholar 

  • Basavarajappa BS, Saito M, Cooper TB, Hungund BL. 2003. Chronic ethanol inhibits the anandamide transport and increases extracellular anandamide levels in cerebellar granule neurons. Eur J Pharmacol 466: 73–83.

    CAS  PubMed  Google Scholar 

  • Beltramo M, Piomelli D. 2000. Carrier-mediated transport and enzymatic hydrolysis of the endogenous cannabinoid 2-arachidonylglycerol. Neuroreport 11: 1231–1235.

    CAS  PubMed  Google Scholar 

  • Beltramo M, Stella N, Calignano A, Lin SY, Makriyannis A, et al. 1997. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 277: 1094–1097.

    CAS  PubMed  Google Scholar 

  • Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, et al. 1998. An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol 353: 23–31.

    CAS  PubMed  Google Scholar 

  • Biegon A, Kerman IA. 2001. Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain. NeuroImage 14: 1463–1468.

    CAS  PubMed  Google Scholar 

  • Bisogno T, Sepe N, De Petrocellis L, Di Marzo V. 1997a. Biosynthesis of 2-arachidonoyl-glycerol, a novel cannabimimetic eicosanoid, in mouse neuroblastoma cells. Adv Exp Med Biol 433: 201–204.

    CAS  Google Scholar 

  • Bisogno T, Berrendero F, Ambrosino G, Cebeira M, Ramos JA, et al. 1999. Brain regional distribution of endocannabinoids: Implications for their biosynthesis and biological function. Biochem Biophys Res Commun 256: 377–380.

    CAS  PubMed  Google Scholar 

  • Bisogno T, MacCarrone M, De Petrocellis L, Jarrahian A, Finazzi-Agro A, et al. 2001. The uptake by cells of 2-arachidonoylglycerol, an endogenous agonist of cannabinoid receptors. Biochem Biophys Res Commun 256: 377–380.

    Google Scholar 

  • Bisogno T, Sepe N, Melck D, Maurelli S, De Petrocellis L, et al. 1997b. Biosynthesis, release and degradation of the novel endogenous cannabimimetic metabolite 2-arachidonoylglycerol in mouse neuroblastoma cells. Biochem J 322: 671–677.

    CAS  Google Scholar 

  • Bohme GA, Laville M, Ledent C, Parmentier M, Imperato A. 2000. Enhanced long-term potentiation in mice lacking cannabinoid CB1 receptors. Neuroscience 95: 5–7.

    CAS  PubMed  Google Scholar 

  • Bouaboula M, Bianchini L, McKenzie FR, Pouyssegur J, Casellas P. 1999b. Cannabinoid receptor CB1 activates the Na+/H+ exchanger NHE-1 isoform via Gi-mediated mitogen activated protein kinase signaling transduction pathways. FEBS Lett 449: 61–65.

    CAS  Google Scholar 

  • Bouaboula M, Desnoyer N, Carayon P, Combes T, Casellas P. 1999a. Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2: Implication for intracellular signalization cross-regulation. Mol Pharmacol 55: 473–480.

    CAS  Google Scholar 

  • Bouaboula M, Bourrie B, Rinaldi-Carmona M, Shire D, Le Fur G, et al. 1995a. Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. J Biol Chem 270: 13973–13980.

    CAS  Google Scholar 

  • Bouaboula M, Perrachon S, Milligan L, Canat X, Rinaldi- Carmona M, et al. 1997. A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions. J Biol Chem 272: 22330–22339.

    CAS  PubMed  Google Scholar 

  • Bouaboula M, Poinot-Chazel C, Bourrie B, Canat X, Calandra B, et al. 1995b. Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CBI. Biochem J 312: 637–641.

    CAS  Google Scholar 

  • Bracey MH, Hanson MA, Masuda KR, Stevens RC, Cravatt BF, 2002. Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling. Science 298: 1793–1796.

    CAS  PubMed  Google Scholar 

  • Breivogel CS, Sim LJ, Childers SR. 1997. Regional differences in cannabinoid receptor/G-protein coupling in rat brain. J Pharmacol Exp Ther 282: 1632–1642.

    CAS  PubMed  Google Scholar 

  • Breivogel CS, Griffin G, Di Marzo V, Martin BR. 2001. Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 60: 155–163.

    CAS  PubMed  Google Scholar 

  • Brocher S, Artola A, Singer W. 1992. Agonists of cholinergic and noradrenergic receptors facilitate synergistically the induction of long-term potentiation in slices of rat visual cortex. Brain Res 573: 27–36.

    CAS  PubMed  Google Scholar 

  • Bruinsma K, Taren DL. 1999. Chocolate: Food or drug? J Am Diet Assoc 99: 1249–1256.

    CAS  PubMed  Google Scholar 

  • Buck KJ. 1998. Recent progress toward the identification of genes related to risk for alcoholism. Mamm Genome 9: 927–928.

    CAS  PubMed  Google Scholar 

  • Buck KJ, Metten P, Belknap JK, Crabbe JC. 1997. Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J Neurosci 17: 3946–3955.

    CAS  PubMed  Google Scholar 

  • Buckley NE, McCoy KL, Mezey E, Bonner T, Zimmer A, et al. 2000. Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB(2) receptor. Eur J Pharmacol 396: 141–149.

    CAS  PubMed  Google Scholar 

  • Buckley NE, Mezey E, Bonner T, Zimmer A, Felder CC, et al. 1997. Development of a CB2 knockout mouse. In: Proceedings of the Symposium on the Cannabinoids. Vermont, Berlington: International Cannabinoid Research Society.

    Google Scholar 

  • Cabral GA, Dove Pettit DA. 1998. Drugs and immunity: Cannabinoids and their role in decreased resistance to infectious disease. J Neuroimmunol 83: 116–123.

    CAS  PubMed  Google Scholar 

  • Cadas H, di Tomaso E, Piomelli D. 1997. Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. J Neurosci 17: 1226–1242.

    CAS  PubMed  Google Scholar 

  • Caenazzo MR, Hoehe W-T, Hsieh WH, Berrettini TI, Bonner. et al. 1991. HindIII identifies a two allele DNA polymorphism of the human cannabinoid receptor gene (CNR). Nucleic Acids Res 19: 4798.

    CAS  PubMed  Google Scholar 

  • Calandra B, Portier M, Kerneis A, Delpech M, Carillon C, et al. 1999. Dual intracellular signaling pathways mediated by the human cannabinoid CB1 receptor. Eur J Pharmacol 374: 445–455.

    CAS  PubMed  Google Scholar 

  • Cao Q, Martinez M, Zhang J, Sanders AR, Badner JA, et al. 1997. Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics 43: 1–8.

    CAS  PubMed  Google Scholar 

  • Cartmell J, Schoepp DD. 2000. Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem 75: 889–907.

    CAS  PubMed  Google Scholar 

  • Caulfield MP, Brown DA. 1992. Cannabinoid receptor agonists inhibit Ca current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br J Pharmacol 106: 231–232.

    CAS  PubMed  Google Scholar 

  • Caulfield MP, Robbins J, Brown DA. 1992. Neurotransmitters inhibit the omega-conotoxin-sensitive component of Ca current in neuroblastoma x glioma hybrid (NG 108-15) cells, not the nifedipine-sensitive component. Pflugers Arch 420: 486–492.

    CAS  PubMed  Google Scholar 

  • Chakrabarti A, Onaivi ES, Chaudhuri G. 1995. Cloning and sequencing of a cDNA encoding the mouse brain-type cannabinoid receptor protein. DNA Seq 6: 385–388.

    Google Scholar 

  • Chaperon F, Thiebot MH. 1999. Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol 13: 243–281.

    CAS  PubMed  Google Scholar 

  • Chester JA, Blose AM, Froehlich JC. 2003. Further evidence of an inverse genetic relationship between innate differences in alcohol preference and alcohol withdrawal magnitude in multiple selectively bred rat lines. Alcohol Clin Exp Res 27: 377–387.

    PubMed  Google Scholar 

  • Chester JA, Risinger FO, Cunningham CL. 1998. Ethanol reward and aversion in mice bred for sensitivity to ethanol withdrawal. Alcohol Clin Exp Res 22: 468–473.

    CAS  PubMed  Google Scholar 

  • Childers SR, Deadwyler SA. 1996. Role of cyclic AMP in the actions of cannabinoid receptors. Biochem Pharmacol 52: 819–827.

    CAS  PubMed  Google Scholar 

  • Childers SR, Sexton T, Roy MB. 1994. Effects of anandamide on cannabinoid receptors in rat brain membranes. Biochem Pharmacol 47: 711–715.

    CAS  PubMed  Google Scholar 

  • Christison R. 1848. in A Dispensatory or Commentary on the Pharmacopoeias of Great Britain (and the United States). Philadelphia: Lea and Blanchard; pp 971–974.

    Google Scholar 

  • Clement AB, Hawkins EG, Lichtman AH, Cravatt BF. 2003. Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. J Neurosci 23: 3916–3923.

    CAS  PubMed  Google Scholar 

  • Cohen C, Perrault G, Voltz C, Steinberg R, Soubrie P. 2002. SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol 13: 451–463.

    CAS  PubMed  Google Scholar 

  • Colombo G, Agabio R, Fa M, Guano L, Lobina C, et al. 1998. Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the cannabinoid antagonist SR-141716. Alcohol 33: 126–130.

    CAS  Google Scholar 

  • Colombo G, Serra S, Brunetti G, Gomez R, Melis S, et al. 2002. Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats. Psychopharmacology (Berl) 159: 181–187.

    CAS  Google Scholar 

  • Comings DE, Muhleman D, Gade R, Johnson JP, Verde R, et al. 1997. Cannabinoid receptor gene (CNR1): Association with i.v. drug use. Mol Psychiatry 2: 161–168.

    CAS  PubMed  Google Scholar 

  • Conn PJ, Pin JP. 1997. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37: 205–237.

    CAS  PubMed  Google Scholar 

  • Crabbe JC, Gallaher ES, Phillips TJ, Belknap JK. 1994. Genetic determinants of sensitivity to ethanol in inbred mice. Behav Neurosci 108: 186–195.

    CAS  PubMed  Google Scholar 

  • Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, et al. 2001. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98: 9371–9376.

    CAS  PubMed  Google Scholar 

  • Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, et al. 1996. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384: 83–87.

    CAS  PubMed  Google Scholar 

  • Cravatt BF, Prospero-Garcia O, Siuzdak G, Gilula NB, Henriksen SJ, et al. 1995. Chemical characterization of a family of brain lipids that induce sleep. Science 268: 1506–1509.

    CAS  PubMed  Google Scholar 

  • Dawson E. 1995. Identification of a polymorphic triplet marker for the brain cannabinoid receptor gene: Use in linkage and association studies of schizophrenia. Psychiatr Genet 5: S50.

    Google Scholar 

  • Day TA, Rakhshan F, Deutsch DG, Barker EL. 2001. Role of fatty acid amide hydrolase in the transport of the endogenous cannabinoid anandamide. Mol Pharmacol 59: 1369–1375.

    CAS  PubMed  Google Scholar 

  • De Petrocellis L, Melck D, Bisogno T, Milone A, Di Marzo V. 1999. Finding of the endocannabinoid signalling system in Hydra, a very primitive organism: Possible role in the feeding response. Neuroscience 92: 377–387.

    CAS  PubMed  Google Scholar 

  • De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, et al. 1998. The endogeneous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc Natl Acad Sci USA 95: 8375–8380.

    CAS  PubMed  Google Scholar 

  • Dean B, Sundram S, Bradbury R, Scarr E, Copolov D. 2001. Studies on [3H]CP-55940 binding in the human central nervous system: Regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience 103: 9–15.

    CAS  PubMed  Google Scholar 

  • Denovan-Wright EM, Robertson HA. 2000. Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington's disease mice. Neuroscience 98: 705–713.

    CAS  PubMed  Google Scholar 

  • Derkinderen P, Toutant M, Burgaya F, Le Bert M, Siciliano JC, et al. 1996. Regulation of a neuronal form of focal adhesion kinase by anandamide. Science 273: 1719–1722.

    CAS  PubMed  Google Scholar 

  • Derkinderen P, Toutant M, Kadare G, Ledent C, Parmentier M, et al. 2001. Dual role of Fyn in the regulation of FAK+6,7 by cannabinoids in hippocampus. J Biol Chem 276: 38289–38296.

    CAS  PubMed  Google Scholar 

  • Deutsch DG, Chin SA. 1993. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem Pharmacol 46: 791–796.

    CAS  PubMed  Google Scholar 

  • Deutsch DG, Glaser ST, Howell JM, Kunz JS, Puffenbarger RA, et al. 2001. The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase. J Biol Chem 276: 6967–6973.

    CAS  PubMed  Google Scholar 

  • Devane WA, Dysarz FAI, 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, et al. 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258: 1946–1949.

    CAS  PubMed  Google Scholar 

  • Dewey WL. 1986. Cannabinoid pharmacology. Pharmacol Rev 38: 151–178.

    CAS  PubMed  Google Scholar 

  • Di Chiara G, Imperato A. 1988. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85: 5274–5278.

    CAS  PubMed  Google Scholar 

  • Di Marzo V. 1998. ‘Endocannabinoids’ and other fatty acid derivatives with cannabimimetic properties: biochemistry and possible. Biochim Biophys Acta 1392: 153–175.

    CAS  PubMed  Google Scholar 

  • Di Marzo V, Bisogno T, De Petrocellis L. 2000a. Endocannabinoids: New targets for drug development. Curr Pharm Des 6: 1361–1380.

    CAS  Google Scholar 

  • Di Marzo V, De Petrocellis L, Bisogno T, Melck D. 1999. Metabolism of anandamide and 2-arachidonoylglycerol: An historical overview and some recent developments. Lipids 34(Suppl): S319–325.

    CAS  PubMed  Google Scholar 

  • Di Marzo V, De Petrocellis L, Sepe N, Buono A. 1996. Biosynthesis of anandamide and related acylethanolamides in mouse J774 macrophages and N18 neuroblastoma cells. Biochem J 316: 977–984.

    CAS  PubMed  Google Scholar 

  • Di Marzo V, Bisogno T, Sugiura T, Melck D, De Petrocellis L. 1998a. The novel endogenous cannabinoid 2-arachidonoylglycerol is inactivated by neuronal- and basophil-like cells: Connections with anandamide. Biochem J 331: 15–19.

    CAS  Google Scholar 

  • Di Marzo V, Hill MP, Bisogno T, Crossman AR, Brotchie JM. 2000b. Enhanced levels of endogenous cannabinoids in the globus pallidus are associated with a reduction in movement in an animal model of Parkinson's disease. FASEB J 14: 1432–1438.

    CAS  Google Scholar 

  • Di Marzo V, Bisogno T, Melck D, Ross R, Brockie H, et al. 1998c. Interactions between synthetic vanilloids and the endogenous cannabinoid system. FEBS Lett 436: 449–454.

    CAS  Google Scholar 

  • Di Marzo V, Breivogel CS, Tao Q, Bridgen DT, Razdan RK, et al. 2000c. Levels, metabolism, and pharmacological activity of anandamide in CB(1) cannabinoid receptor knockout mice: Evidence for non-CB(1), non-CB(2) receptor-mediated actions of anandamide in mouse brain. J Neurochem 75: 2434–2444.

    CAS  Google Scholar 

  • Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, et al. 1994. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372: 686–691.

    CAS  PubMed  Google Scholar 

  • Di Marzo V, Sepe N, De Petrocellis L, Berger A, Crozier G, et al. 1998b. Trick or treat from food endocannabinoids? Nature 396: 636–637.

    CAS  Google Scholar 

  • di Tomaso E, Beltramo M, Piomelli D. 1996. Brain cannabinoids in chocolate. Nature 382: 677–678.

    CAS  PubMed  Google Scholar 

  • Diana MA, Levenes C, Mackie K, Marty A. 2002. Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids. J Neurosci 22: 200–208.

    CAS  PubMed  Google Scholar 

  • Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, et al. 2002. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99: 10819–10824.

    CAS  PubMed  Google Scholar 

  • Doherty J, Dingledine R. 2003. Functional interactions between cannabinoid and metabotropic glutamate receptors in the central nervous system. Curr Opin Pharmacol 3: 46–53.

    CAS  PubMed  Google Scholar 

  • Drysdale AJ, Platt B. 2003. Cannabinoids: Mechanisms and therapeutic applications in the CNS. Curr Med Chem 10: 2719–2732.

    CAS  PubMed  Google Scholar 

  • Egertova M, Elphick MR. 2000. Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CB. J Comp Neurol 422: 159–171.

    CAS  PubMed  Google Scholar 

  • Egertova M, Cravatt BF, Elphick MR. 2003. Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: Evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Neuroscience 119: 481–496.

    CAS  PubMed  Google Scholar 

  • Egertova M, Giang DK, Cravatt BF, Elphick MR. 1998. A new perspective on cannabinoid signalling: Complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain. Proc R Soc Lond B Biol Sci 265: 2081–2085.

    CAS  Google Scholar 

  • Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, et al. 1995. Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci USA 92: 3376–3380.

    CAS  PubMed  Google Scholar 

  • Farooqui AA, Taylor WA, Horrocks LA. 1986. Characterization and solubilization of membrane bound diacylglycerol lipases from bovine brain. Int J Biochem 18: 991–997.

    CAS  PubMed  Google Scholar 

  • Felder C, Nielsen A, Briley E, Palkovits M, Priller J, et al. 1996. Isolation and measurement of the endogenous cannabinoid receptor agonist, anandamide, in brain and peripheral tissues of human and rat. FEBS Lett 393: 231–235.

    CAS  PubMed  Google Scholar 

  • Felder CC, Briley EM, Axelrod J, Simpson JT, Mackie K, et al. 1993. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc Natl Acad Sci USA 90: 7656–7660.

    CAS  PubMed  Google Scholar 

  • Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, et al. 1995. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 48: 443–450.

    CAS  PubMed  Google Scholar 

  • Ferrer B, Asbrock N, Kathuria S, Piomelli D, Giuffrida A. 2003. Effects of levodopa on endocannabinoid levels in rat basal ganglia: Implications for the treatment of levodopa-induced dyskinesias. Eur J Neurosci 18: 1607–1614.

    PubMed  Google Scholar 

  • Fowler CJ, Nilsson O, Andersson M, Disney G, Jacobsson SO, et al. 2001. Pharmacological properties of cannabinoid receptors in the avian brain: Similarity of fat and chicken cannabinoidl receptor recognition sites and expression of cannabinoid2 receptor-like immunoreactivity in the embryonic chick brain. Pharmacol Toxicol 88: 213–222.

    CAS  PubMed  Google Scholar 

  • Frazier J. 1974. The Marijuana Farmers, Hemp Cults and Cultures. New Orleans, LA: Solar Age Press; p. 133.

    Google Scholar 

  • Freedland CS, Sharpe AL, Samson HH, Porrino LJ. 2001. Effects of SR141716A on ethanol and sucrose self-administration. Alcohol Clin Exp Res 25: 277–282.

    CAS  PubMed  Google Scholar 

  • Freund TF, Katona I, Piomelli D. 2003. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83: 1017–1066.

    CAS  PubMed  Google Scholar 

  • Fritzsche M. 2000. Are cannabinoid receptor knockout mice animal models of schizophrenia. Med Hypotheses 56: 638–643.

    Google Scholar 

  • Gadzicki D, Muller-Vahl K, Stuhrmann M. 1999. A frequent polymorphism in the coding exon of the human cannabinoid receptor (CNR1) gene. Mol Cell Probes 13: 321–323.

    CAS  PubMed  Google Scholar 

  • Gallate JE, McGregor IS. 1999. The motivation for beer in rats: Effects of ritanserin, naloxone and SR 141716. Psychopharmacology 142: 302–308.

    CAS  PubMed  Google Scholar 

  • Gallate JE, Saharov T, Mallet PE, McGregor IS. 1999. Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist. Eur J Pharmacol 370: 233–240.

    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.

    CAS  Google Scholar 

  • Gebremedhin D, Lange AR, Campbell WB, Hillard CJ, Harder DR. 1999. Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type Ca2+ channel current. Am J Physiol 276: H2085–2093.

    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 

  • Gerdeman G, Lovinger DM. 2001. CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. J Neurophysiol 85: 468–471.

    CAS  PubMed  Google Scholar 

  • Gerdeman GL, Ronesi J, Lovinger DM. 2002. Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci 5: 446–451.

    CAS  PubMed  Google Scholar 

  • Gessa GL, Melis M, Muntoni AL, Diana M. 1998. Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. Eur J Pharmacol 341: 39–44.

    CAS  PubMed  Google Scholar 

  • Giuffrida A, Beltramo M, Piomelli D. 2001. Mechanisms of endocannabinoid inactivation: Biochemistry and pharmacology. J Pharmacol Exp Ther 298: 7–14.

    CAS  PubMed  Google Scholar 

  • Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, et al. 1999. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2: 358–363.

    CAS  PubMed  Google Scholar 

  • Glaser ST, Abumrad NA, Fatade F, Kaczocha M, Studholme KM, et al. 2003. Evidence against the presence of an anandamide transporter. Proc Natl Acad Sci USA 100: 4269–4274.

    CAS  PubMed  Google Scholar 

  • Glass M. 2001. The role of cannabinoids in neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 25: 743–765.

    CAS  PubMed  Google Scholar 

  • Glass M, Felder CC. 1997. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: Evidence for a Gs linkage to the CB1 receptor. J Neurosci 17: 5327–5333.

    CAS  PubMed  Google Scholar 

  • Glass M, Dragunow M, Faull RL. 1997. Cannabinoid receptors in the human brain: A detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 77: 299–318.

    CAS  PubMed  Google Scholar 

  • Glass M, Dragunow M, Faull RL. 2000. The pattern of neurodegeneration in Huntington's disease: A comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 97: 505–519.

    CAS  PubMed  Google Scholar 

  • Glass M, van Dellen A, Blakemore C, Hannan AJ, Faull RL. 2004. Delayed onset of huntington's disease in mice in an enriched environment correlates with delayed loss of cannabinoid CB1 receptors. Neuroscience 123: 207–212.

    CAS  PubMed  Google Scholar 

  • Godwin H. 1967. Pollen Analytic Evidence for the Cultivation of Cannabis in England. Rev Paleobotany Palnyol 4: 71–80.

    Google Scholar 

  • Gomez del Pulgar T, Velasco G, Guzman M. 2000. The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt. Biochem J 347: 369–373.

    CAS  PubMed  Google Scholar 

  • Gonzalez S, Grazia Cascio M, Fernandez-Ruiz J, Fezza F, Di Marzo V, et al. 2002. Changes in endocannabinoid contents in the brain of rats chronically exposed to nicotine, ethanol or cocaine. Brain Res 954: 73.

    CAS  PubMed  Google Scholar 

  • Goparaju SK, Ueda N, Yamaguchi H, Yamamoto S. 1998. Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand. FEBS Lett 422: 69–73.

    CAS  PubMed  Google Scholar 

  • Griffin G, Tao Q, Abood ME. 2000. Cloning and pharmacological characterization of the rat CB(2) cannabinoid receptor. J Pharmacol Exp Ther 292: 886–894.

    CAS  PubMed  Google Scholar 

  • Guzman M, Sanchez C. 1999. Effects of cannabinoids on energy metabolism. Life Sci 65: 657–664.

    CAS  PubMed  Google Scholar 

  • Guzman M, Galve-Roperh I, Sanchez C. 2001. Ceramide: A new second messenger of cannabinoid action. Trends Pharmacol Sci 22: 19–22.

    CAS  PubMed  Google Scholar 

  • Hajos N, Ledent C, Freund TF. 2001. Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience 106: 1–4.

    CAS  PubMed  Google Scholar 

  • Hajos N, Katona I, Naiem SS, Mac Kie K, Ledent C, et al. 2000. Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations. Eur J Neurosci 12: 3239–3249.

    CAS  PubMed  Google Scholar 

  • Hampson RE, Mu J, Deadwyler SA. 2000. Cannabinoid and kappa opioid receptors reduce potassium K current via activation of G(s) proteins in cultured hippocampal neurons. J Neurophysiol 84: 2356–2364.

    CAS  PubMed  Google Scholar 

  • Hansen HH, Hansen SH, Schousboe A, Hansen HS. 2000. Determination of the phospholipid precursor of anandamide and other N-acylethanolamine phospholipids before and after sodium azide-induced toxicity in cultured neocortical neurons. J Neurochem 75: 861–871.

    CAS  PubMed  Google Scholar 

  • Hanus L, Gopher A, Almog S, Mechoulam R. 1993. Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J Med Chem 36: 3032–3034.

    CAS  PubMed  Google Scholar 

  • Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, et al. 2001. 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98: 3662–3665.

    CAS  PubMed  Google Scholar 

  • Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, et al. 1990. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87: 1932–1936.

    CAS  PubMed  Google Scholar 

  • Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Cost BR, et al. 1991. Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. J Neurosci 16: 8057–8066.

    Google Scholar 

  • Hillard CJ, Jarrahian A. 2000. The movement of N-arachidonoylethanolamine (anandamide) across cellular membranes. Chem Phys Lipids 108: 123–134.

    CAS  PubMed  Google Scholar 

  • Hillard CJ, Jarrahian A. 2003. Cellular accumulation of anandamide: Consensus and controversy. Br J Pharmacol 140: 802–808.

    CAS  PubMed  Google Scholar 

  • Hillard CJ, Edgemond WS, Jarrahian A, Campbell WB. 1997. Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule cells occurs via facilitated diffusion. J Neurochem 69: 631–638.

    CAS  PubMed  Google Scholar 

  • Ho BY, Uezono Y, Takada S, Takase I, Izumi F. 1999. Coupling of the expressed cannabinoid CB1 and CB2 receptors to phospholipase C and G protein-coupled inwardly rectifying K+ channels. Receptors Channels 6: 363–374.

    CAS  PubMed  Google Scholar 

  • Hoehe MR, Caenazzo L, Martinez MM, Hsieh WT, Modi WS, et al. 1991. Genetic and physical mapping of the human cannabinoid receptor gene to chromosome 6q14-q15. New Biol 3: 880–885.

    CAS  PubMed  Google Scholar 

  • Hoffman AF, Lupica CR. 2000. Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J Neurosci 20: 2470–2479.

    CAS  PubMed  Google Scholar 

  • Hollister LE. 1986. Health aspects of cannabis. Pharmacol Rev 38: 1–20.

    CAS  PubMed  Google Scholar 

  • Hollister LE. 2001. Marijuana (Cannabis) as medicine. J Cnnabis Ther 1: 5–27.

    Google Scholar 

  • Howlett AC, Mukhopadhyay S. 2000. Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chem Phys Lipids 108: 53–70.

    CAS  PubMed  Google Scholar 

  • Howlett AC, Johnson MR, Melvin LS, Milne GM. 1988. Nonclassical cannabinoid analgetics inhibit adenylate cyclase: Development of a cannabinoid receptor model. Mol Pharmacol 33: 297–302.

    CAS  PubMed  Google Scholar 

  • Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, et al. 2002. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54: 161–202.

    CAS  PubMed  Google Scholar 

  • Huang CC, Lo SW, Hsu KS. 2001. Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons. J Physiol 532(Pt3): 731–748.

    CAS  PubMed  Google Scholar 

  • Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, et al. 2002. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99: 8400–8405.

    CAS  PubMed  Google Scholar 

  • Hungund BL, Basavarajappa BS. 2000a. Are anandamide and cannabinoid receptors involved in ethanol tolerance? A review of the evidence. Alcohol 35: 126–133.

    CAS  Google Scholar 

  • Hungund BL, Basavarajappa BS. 2000b. Role of brain's own marijuana, anandamide and its cannabinoid receptors (CB1) in alcoholism. Recent Research Development in Neurochemistry. Vol.3 S.G. Pandalai R.S. editor. Research Signpost, India: Trivandrum; pp. 9–26.

    Google Scholar 

  • Hungund BL, Basavarajappa BS. 2000c. Distinct differences in the cannabinoid receptor binding in the brain of C57BL/6 and DBA/2 mice, selected for their differences in voluntary ethanol consumption. J Neurosci Res 60: 122–128.

    CAS  Google Scholar 

  • Hungund BL, Basavarajappa BS. 2004. Role of endocannabinoids and cannabinoid CB1 receptors in alcohol-related behaviours. Ann N Y Acad Sci 1025: 1–14.

    Google Scholar 

  • Hungund BL, Szakall I, Adam A, Basavarajappa BS, Vadasz C. 2003. Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens. J Neurochem 84: 698–704.

    CAS  PubMed  Google Scholar 

  • Hungund BL, Basavarajappa BS, Vadasz C, Kunos G, Rodriguez de, et al. 2002. Ethanol, endocannabinoids and cannabinoidergic signaling system. Alcohol Clin Exp Res 26: 565–574.

    CAS  PubMed  Google Scholar 

  • Hungund BL, Vinod KY, Kassir SA, Basavarajappa BS, Yalamanchili R, et al. (2004). Upregulation of CB1 receptors and agonist-stimulated [35S]GTPgammaS binding in the prefrontal cortex of depressed suicide victims. Mol Psychiatry 9: 184–190.

    CAS  PubMed  Google Scholar 

  • Jarai Z, Wagner JA, Varga K, Lake KD, Compton DR, et al. 1999. Cannabinoidinduced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci USA 96: 14136–14141.

    CAS  PubMed  Google Scholar 

  • Jarrahian A, Manna S, Edgemond W, Campbell W, Hillard C. 2000. Structure—activity relationships among N-Arachidonylethanolamine (Anandamide) head group analogues for the anandamide transporter. J Neurochem 74: 2597–2606.

    CAS  PubMed  Google Scholar 

  • Johnson JP, Muhleman D, MacMurray J, Gade R, Verde R, et al. 1997. Association between the cannabinoid receptor gene (CNR1) and the P300 event-related potential. Mol Psychiatry 2: 169–171.

    CAS  PubMed  Google Scholar 

  • Kabelik J, Krejci Z, Santavy F. 1960. Cannabis as a Medicant. Bull Narc 12: 5–23.

    Google Scholar 

  • Katayama K, Ueda N, Katoh I, Yamamoto S. 1999. Equilibrium in the hydrolysis and synthesis of cannabimimetic anandamide demonstrated by a purified enzyme. Biochim Biophys Acta 1440: 205–214.

    CAS  PubMed  Google Scholar 

  • Kathmann M, Haug K, Heils A, Nothen MM, Schlicker E. 2000. Exchange of three amino acids in the cannabinoid CB1 receptor (CNR1) of an epilepsy patient. Proceedings of the Symposium on the Cannabinoids, Vermont, Burlington: ICRS; p. 18.

    Google Scholar 

  • Katona I, Rancz EA, Acsady L, Ledent C, Mackie K, et al. 2001. Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. J Neurosci 21: 9506–9518.

    CAS  PubMed  Google Scholar 

  • Katona I, Sperlagh B, Sik A, Kafalvi A, Vizi ES, et al. 1999. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 19: 4544–4558.

    CAS  PubMed  Google Scholar 

  • Katsuki H, Izumi Y, Zorumski CF. 1997. Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region. J Neurophysiol 77: 3013–3020.

    CAS  PubMed  Google Scholar 

  • Kearn CS, Greenberg MJ, DiCamelli R, Kurzawa K, Hillard CJ. 1999. Relationships between ligand affinities for the cerebellar cannabinoid receptor CB1 and the induction of GDP/GTP exchange. J Neurochem 72: 2379–2387.

    CAS  PubMed  Google Scholar 

  • Kim J, Isokawa M, Ledent C, Alger BE. 2002. Activation of muscarinic acetylcholine receptors enhances the release of endogenous cannabinoids in the hippocampus. J Neurosci 22: 10182–10191.

    CAS  PubMed  Google Scholar 

  • Kobayashi M, Ohno M, Shibata S, Yamamoto T, Watanabe S. 1997. Concurrent blockade of beta-adrenergic and muscarinic receptors suppresses synergistically long-term potentiation of population spikes in the rat hippocampal CA1 region. Brain Res 777: 242–246.

    CAS  PubMed  Google Scholar 

  • Kondo S, Kondo H, Nakane S, Kodaka T, Tokumura A, et al. 1998. 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: Identification as one of the major species of monoacylglycerols in various rat tissues, and evidence for its generation through CA2+-dependent and -independent mechanisms. FEBS Lett 429: 152–156.

    CAS  PubMed  Google Scholar 

  • Konrad RJ, Major CD, Wolf BA. 1994. Diacylglycerol hydrolysis to arachidonic acid is necessary for insulin secretion from isolated pancreatic islets: Sequential actions of diacylglycerol and monoacylglycerol lipases. Biochemistry 33: 13284–13294.

    CAS  PubMed  Google Scholar 

  • Kosobud A, Bodor AS, Crabbe JC. 1988. Voluntary consumption of ethanol in WSP, WSC and WSR selectively bred mouse lines. Pharmacol Biochem Behav 29: 601–607.

    CAS  PubMed  Google Scholar 

  • Kreitzer AC, Regehr WG. 2001a. Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. J Neurosci 21: RC174.

    CAS  Google Scholar 

  • Kreitzer AC, Regehr WG. 2001b. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 29: 717–727.

    CAS  Google Scholar 

  • Kumar RN, Chambers WA, Pertwee RG. 2001. Pharmacological actions and therapeutic uses of cannabis and cannabinoids. Anaesthesia 56: 1059–1068.

    CAS  PubMed  Google Scholar 

  • Kurahashi Y, Ueda N, Suzuki H, Suzuki M, Yamamoto S. 1997. Reversible hydrolysis and synthesis of anandamide demonstrated by recombinant rat fatty-acid amide hydrolase. Biochem Biophys Res Commun 237: 512–515.

    CAS  PubMed  Google Scholar 

  • Lallemand F, Soubrie PH, De Witte PH. 2001. Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic ethanol administration. Alcohol Clin Exp Res 25: 1317–1323.

    CAS  PubMed  Google Scholar 

  • Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, et al. 1999. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283: 401–404.

    CAS  PubMed  Google Scholar 

  • Leweke FM, Schneider U, Thies M, Munte TF, Emrich HM. 1999. Effects of synthetic Delta(9)-tetrahydrocannabinol on binocular depth inversion of natural and artificial objects in man. Psychopharmacology 142: 230–235.

    CAS  PubMed  Google Scholar 

  • Li T, Liu X, Zhu ZH, Zhao J, Hu X, et al. 2000. No association between (AAT)n repeats in the cannabinoid receptor gene (CNR1) and heroin abuse in a Chinese population. Mol Psychiatry 5: 128–130.

    PubMed  Google Scholar 

  • Lichtman AH, Hawkins EG, Griffin G, Cravatt BF. (2002). Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo. J Pharmacol Exp Ther 302: 73–79.

    CAS  PubMed  Google Scholar 

  • Liu J, Gao B, Mirshahi F, Sanyal AJ, Khanolkar AD, et al. 2000. Functional CB1 cannabinoid receptors in human vascular endothelial cells. Biochem J Mar 15; 346 Pt 3: 835–40.

    CAS  PubMed  Google Scholar 

  • Llano I, Leresche N, Marty A. 1991. Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron 6: 565–574.

    CAS  PubMed  Google Scholar 

  • Loewe S. 1950. Cannabiswiswirkstoffe and Parmakologie der Cannabinole (Active constituent of cannabis and pharmacology of the cannabinoids.) (in German.). Arciv Fur Experimentelle pathologie und pharmakogie 175-193.

    Google Scholar 

  • Maccarrone M, Bari M, Menichelli A, Del Principe D, Agro AF. 1999. Anandamide activates human platelets through a pathway independent of the arachidonate cascade. FEBS Lett 447: 277–282.

    CAS  PubMed  Google Scholar 

  • Maccarrone M, Attina M, Bari M, Cartoni A, Ledent C, et al. 2001. Anandamide degradation and N-acylethanolamines level in wild-type and CB1 cannabinoid receptor knockout mice of different ages. J Neurochem 78: 339–348.

    CAS  PubMed  Google Scholar 

  • Maccarrone M, Bari M, Lorenzon T, Bisogno T, Di Marzo V, 2000b. Anandamide uptake by human endothelial cells and its regulation by nitric oxide. J Biol Chem 275: 13484–13492.

    CAS  Google Scholar 

  • Maccarrone M, Fiorucci L, Erba F, Bari M, Finazzi-Agro A, et al. 2000a. Human mast cells take up and hydrolyze anandamide under the control of 5-lipoxygenase and do not express cannabinoid receptors. FEBS Lett 468: 176–180.

    CAS  Google Scholar 

  • Maccarrone M, van der Stelt M, Rossi A, Veldink GA, Vliegenthart JF, et al. 1998. Anandamide hydrolysis by human cells in culture and brain. J Biol Chem 273: 32332–32339.

    CAS  PubMed  Google Scholar 

  • Mackie K, Hille B. 1992. Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 89: 3825–3829.

    CAS  PubMed  Google Scholar 

  • Maejima T, Ohno-Shosaku T, Kano M. 2001. Endogenous cannabinoid as a retrograde messenger from depolarized postsynaptic neurons to presynaptic terminals. Neurosci Res 40: 205–210.

    CAS  PubMed  Google Scholar 

  • Mailleux P, Verslype M, Preud'homme X, Vanderhaeghen JJ. 1994. Activation of multiple transcription factor genes by tetrahydrocannabinol in rat forebrain. Neuroreport 5: 1265–1268.

    CAS  PubMed  Google Scholar 

  • Maneuf YP, Nash JE, Crossman AR, Brotchie JM. 1996. Activation of the cannabinoid receptor by delta 9-tetrahydrocannabinol reduces gamma-aminobutyric acid uptake in the globus pallidus. Eur J Pharmacol 308: 161–164.

    CAS  PubMed  Google Scholar 

  • Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, et al. 2002. The endogenous cannabinoid system controls extinction of aversive memories. Nature 418: 530–534.

    CAS  PubMed  Google Scholar 

  • Martinez M, Goldin LR, Cao Q, Zhang J, Sanders AR, et al. 1999. Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q. Am J Med Genet 88: 337–343.

    CAS  PubMed  Google Scholar 

  • Mascia MS, Obinu MC, Ledent C, Parmentier M, Bohme GA, et al. 1999. Lack of morphine-induced dopamine release in the nucleus accumbens of cannabinoid CB(1) receptor knockout mice. Eur J Pharmacol 383: R1–2.

    CAS  PubMed  Google Scholar 

  • Mato S, Pazos A, Valdizan EM. 2002. Cannabinoid receptor antagonism and inverse agonism in response to SR141716A on cAMP production in human and rat brain. Eur J Pharmacol 443: 43–46.

    CAS  PubMed  Google Scholar 

  • Matsuda LA. 1997. Molecular aspects of cannabinoid receptors. Crit Rev Neurobiol 11: 143–166.

    CAS  PubMed  Google Scholar 

  • Matsuda LA, Bonner TI, Lolait SJ. 1993. Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol 327: 535–550.

    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.

    CAS  PubMed  Google Scholar 

  • Mazzola C, Micale V, Drago F. 2003. Amnesia induced by beta-amyloid fragments is counteracted by cannabinoid CB1 receptor blockade. Eur J Pharmacol 477: 219–225.

    CAS  PubMed  Google Scholar 

  • McGregor IS, Arnold JC, Weber MF, Topple AN, Hunt GE. 1998. A comparison of delta 9-THC and anandamide induced c-fos expression in the rat forebrain. Brain Res 802: 19–26.

    CAS  PubMed  Google Scholar 

  • Mechoulam R, Fride E, Di Marzo V. 1998. Endocannabinoids. Eur J Pharmacol 359: 1–18.

    CAS  PubMed  Google Scholar 

  • Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, et al. 1995. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50: 83–90.

    CAS  PubMed  Google Scholar 

  • Melck D, Bisogno T, De Petrocellis L, Chuang H, Julius D, et al. 1999. Unsaturated long-chain N-acyl-vanillyl-amides (N-AVAMs): Vanilloid receptor ligands that inhibit anandamide-facilitated transport and bind to CB1 cannabinoid receptors. Biochem Biophys Res Commun 262: 275–284.

    CAS  PubMed  Google Scholar 

  • Melis M, Pistis M, Perra S, Muntoni AL, Pillolla G, et al. 2004. Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in rat ventral tegmental area dopamine neurons through activation of CB1 receptors. J Neurosci 24: 53–62.

    CAS  PubMed  Google Scholar 

  • Meschler JP, Kraichely DM, Wilken GH, Howlett AC. 2000. Inverse agonist properties of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HC1 (SR141716A) and 1-(2-chlorophenyl)-4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxyl ic acid phenylamide (CP-272871) for the CB(1) cannabinoid receptor. Biochem Pharmacol 60: 1315–1323.

    CAS  PubMed  Google Scholar 

  • Metten P, Phillips TJ, Crabbe JC, Tarantino LM, McClearn GE, et al. 1998. High genetic susceptibility to ethanol withdrawal predicts low ethanol consumption. Mamm Genome 9: 983–990.

    CAS  PubMed  Google Scholar 

  • Mikuriya TH. 1970. Cannabis substitution. An adjunctive therapeutic tool in the treatment of alcoholism. Med Times 98: 187–191.

    CAS  PubMed  Google Scholar 

  • Morishita W, Alger BE. 2000. Differential effects of the group II mGluR agonist, DCG-IV, on depolarization-induced suppression of inhibition in hippocampal CA1 and CA3 neurons. Hippocampus 10: 261–268.

    CAS  PubMed  Google Scholar 

  • Morishita W, Alger BE. 2001. Direct depolarization and antidromic action potentials transiently suppress dendritic IPSPs in hippocampal CA1 pyramidal cells. J Neurophysiol 85: 480–484.

    CAS  PubMed  Google Scholar 

  • Morisset V, Urban L. 2001. Cannabinoid-induced presynaptic inhibition of glutamatergic EPSCs in substantia gelatinosa neurons of the rat spinal cord. J Neurophysiol 86: 40–48.

    CAS  PubMed  Google Scholar 

  • Mu J, Zhuang SY, Kirby MT, Hampson RE, Deadwyler SA. 1999. Cannabinoid receptors differentially modulate potassium A and D currents in hippocampal neurons in culture. J Pharmacol Exp Ther 291: 893–902.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Musty RE, Deyo RA, Baer JL, Darrow SM, Coleman B. 2000. Effects of SR141716 on animal models of schizophrenia. Symposium on the cannabinoids, International Cannabinoid Research Society. Vermont: Burlington.

    Google Scholar 

  • Naassila M, Pierrefiche O, Ledent C, Daoust M. 2004. Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice. Neuropharmacology 46: 243–253.

    CAS  PubMed  Google Scholar 

  • Natarajan V, Reddy PV, Schmid PC, Schmid HH. 1981. On the biosynthesis and metabolism of N-acylethanolamine phospholipids in infarcted dog heart. Biochim Biophys Acta 664: 445–448.

    CAS  PubMed  Google Scholar 

  • Netzeband JG, Conroy SM, Parsons KL, Gruol DL. 1999. Cannabinoids enhance NMDA-elicited Ca2+ signals in cerebellar granule neurons in culture. J Neurosci 19: 8765–8777.

    CAS  PubMed  Google Scholar 

  • Nocerino E, Amato M, Izzo AA. 2000. Cannabis and cannabinoid receptors. Fitoterapia 71: S6–12.

    CAS  PubMed  Google Scholar 

  • Ohno-Shosaku T, Maejima T, Kano M. 2001. Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminal. Neuron 29: 729–738.

    CAS  PubMed  Google Scholar 

  • Ohno-Shosaku T, Sawada S, Kano M. 2000. Heterosynaptic expression of depolarization-induced suppression of inhibition (DSI) in rat hippocampal cultures. Neurosci Res 36: 67–71.

    CAS  PubMed  Google Scholar 

  • Ohno-Shosaku T, Sawada S, Yamamoto C. 1998. Properties of depolarization-induced suppression of inhibitory transmission in cultured rat hippocampal neurons. Pflugers Arch 435: 273–279.

    CAS  PubMed  Google Scholar 

  • Ohno-Shosaku T, Tsubokawa H, Mizushima I, Yoneda N, Zimmer A, et al. 2002. Presynaptic cannabinoid sensitivity is a major determinant of depolarization-induced retrograde suppression at hippocampal synapses. J Neurosci 22: 3864–3872.

    CAS  PubMed  Google Scholar 

  • Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N. 2004. Molecular characterization of a phospholipase D generating anandamide and its congeners. J Biol Chem 279: 5298–5305.

    CAS  PubMed  Google Scholar 

  • Onaivi ES, Chakrabarti A, Chaudhuri G. 1996. Cannabinoid receptor genes. Prog Neurobiol 48: 275–305.

    CAS  PubMed  Google Scholar 

  • Onaivi ES, Leonard CM, Ishiguro H, Zhang PW, Lin Z, et al. 2002. Endocannabinoids and cannabinoid receptor genetics. Prog Neurobiol 66: 307–344.

    CAS  PubMed  Google Scholar 

  • Onaivi ES, Stubbs A, Chakrabarti L, Chittenden DP, Hurst BE, et al. 1998. Murine Cannabinoid receptor genetics. FASEB J 124: A194.

    Google Scholar 

  • Ortiz S, Oliva JM, Perez S, Palomo T, Manzanares J. 2004a. Chronic ethanol consumption regulates cannabinoid CB1 receptor gene expression in selected regions of rat brain. Alcohol 39: 88–92.

    CAS  Google Scholar 

  • Ortiz S, Oliva JM, Perez-Rial S, Palomo T, Manzanares J. 2004b. Differences in basal cannabinoid CB1 receptor function in selective brain areas and vulnerability to voluntary alcohol consumption in Fawn Hooded and Wistar rats. Alcohol 39: 297–302.

    CAS  Google Scholar 

  • Palmer SL, Khanolkar AD, Makriyannis A. 2000. Natural and synthetic endocannabinoids and their structure -activity relationships. Curr Pharm Des 6: 1381–1397.

    CAS  PubMed  Google Scholar 

  • Pan X, Ikeda SR, Lewis DL. 1996. Rat brain cannabinoid receptor modulates N-type Ca2+ channels in a neuronal expression system. Mol Pharmacol 49: 707–714.

    CAS  PubMed  Google Scholar 

  • Pan X, Ikeda SR, Lewis DL. 1998. SR 141716A acts as an inverse agonist to increase neuronal voltage-dependent Ca2+ currents by reversal of tonic CB1 cannabinoid receptor activity. Mol Pharmacol 54: 1064–1072.

    CAS  PubMed  Google Scholar 

  • Paria BC, Dey SK. 2000. Ligand–receptor signaling with endocannabinoids in preimplatation embryo development and implantation. Chem Phys Lipids 108: 211–220.

    CAS  PubMed  Google Scholar 

  • Patricelli MP, Lovato MA, Cravatt BF. 1999. Chemical and mutagenic investigations of fatty acid amide hydrolase: Evidence for a family of serine hydrolases with distinct catalytic properties. Biochemistry 38: 9804–9812.

    CAS  PubMed  Google Scholar 

  • Pertwee RG. 1997. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 74: 129–180.

    CAS  PubMed  Google Scholar 

  • Pettit DA, Harrison MP, Olson JM, Spencer RF, Cabral GA. 1998. Immunohistochemical localization of the neural cannabinoid receptor in rat brain. J Neurosci Res 51: 391–402.

    CAS  PubMed  Google Scholar 

  • Pfister-Genskow M, Weesner GD, Hayes H, Eggen A, Bishop MD. 1997. Physical and genetic localization of the bovine cannabinoid receptor (CNR1) gene to bovine hromosome 9. Mamm Genome 8: 301–302.

    CAS  PubMed  Google Scholar 

  • Pinto JC, Potie F, Rice KC, Boring D, Johnson MR, et al. 1994. Cannabinoid receptor binding and agonist activity of amides and esters of arachidonic acid. Mol Pharmacol 46: 516–522.

    CAS  PubMed  Google Scholar 

  • Piomelli D. 2003. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 4: 873–884.

    CAS  PubMed  Google Scholar 

  • Piomelli D, Beltramo M, Glasnapp S, Lin SY, Goutopoulos A, et al. 1999. Structural determinants for recognition and translocation by the anandamide transporter. Proc Natl Acad Sci USA 96: 5802–5807.

    CAS  PubMed  Google Scholar 

  • Pitler TA, Alger BE. 1990. Activation of the pharmacologically defined M3 muscarinic receptor depolarizes hippocampal pyramidal cells. Brain Res 534: 257–262.

    CAS  PubMed  Google Scholar 

  • Pitler TA, Alger BE. 1992. Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells. J Neurosci 12: 4122–4132.

    CAS  PubMed  Google Scholar 

  • Pitler TA, Alger BE. 1994. Depolarization-induced suppression of GABAergic inhibition in rat hippocampal pyramidal cells: G protein involvement in a presynaptic mechanism. Neuron 13: 1447–1455.

    CAS  PubMed  Google Scholar 

  • Poncelet M, Maruani J, Calassi R, Soubrie P. 2003. Overeating, alcohol and sucrose consumption decrease in CB1 receptor deleted mice. Neurosci Lett 343: 216–218.

    CAS  PubMed  Google Scholar 

  • Porter AC, Felder CC. 2001. The endocannabinoid nervous system: Unique opportunities for therapeutic intervention. Pharmacol Ther 90: 45–60.

    CAS  PubMed  Google Scholar 

  • Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, et al. 2002. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301: 1020–1024.

    CAS  PubMed  Google Scholar 

  • Prescott SM, Majerus PW. 1983. Characterization of 1,2-diacylglycerol hydrolysis in human platelets. Demonstration of an arachidonoyl-monoacylglycerol intermediate. J Biol Chem 258: 764–769.

    CAS  PubMed  Google Scholar 

  • Racz I, Bilkei-Gorzo A, Toth ZE, Michel K, Palkovits M, et al. 2003. A critical role for the cannabinoid CB1 receptors in alcohol dependence and stress-stimulated ethanol drinking. J Neurosci 23: 2453–2458.

    CAS  PubMed  Google Scholar 

  • Rakhshan F, Day TA, Blakely RD, Barker EL. 2000. Carrier-mediated uptake of the endogenous cannabinoid anandamide in RBL-2H3 cells. J Pharmacol Exp Ther 292: 960–967.

    CAS  PubMed  Google Scholar 

  • Ravinet Trillou C, Delgorge C, Menet C, Arnone M, Soubrie P. 2004. CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 28: 640–648.

    CAS  PubMed  Google Scholar 

  • Ravinet Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, et al. 2003. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 284: R345–353.

    PubMed  Google Scholar 

  • Reibaud M, Obinu MC, Ledent C, Parmentier M, Bohme GA, et al. 1999. Enhancement of memory in cannabinoid CB1 receptor knock-out mice. Eur J Pharmacol 379: R1–2.

    CAS  PubMed  Google Scholar 

  • Rhee MH, Bayewitch M, Avidor-Reiss T, Levy R, Vogel Z. 1998. Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J Neurochem 71: 1525–1534.

    CAS  PubMed  Google Scholar 

  • Rimondini R, Arlinde C, Sommer W, Heilig M. 2002. Long-lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol. FASEB J 16: 27–35.

    CAS  PubMed  Google Scholar 

  • Robbe D, Kopf M, Remaury A, Bockaert J, Manzoni OJ. 2002. Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. Proc Natl Acad Sci USA 99: 8384–8388.

    CAS  PubMed  Google Scholar 

  • Robbins TW, Everitt BJ. 1996. Neurobehavioural mechanisms of reward and motivation. Curr Opin Neurobiol 6: 228–236.

    CAS  PubMed  Google Scholar 

  • Rodriguez de Fonseca F, Roberts AJ, Bilbao A, Koob GF, Navarro M. 1999. Cannabinoid receptor antagonist SR 141716A decreases operant ethanol self administration in rats exposed to ethanol-vapor chambers. Acta Pharmacol Sin 20: 1109–1114.

    CAS  Google Scholar 

  • Rosenberg CM. 1979. Alcoholics anonymous as treatment and as ideology; comments on the article by R. E. Tournier. J Stud Alcohol 40: 330–333.

    CAS  PubMed  Google Scholar 

  • Rosenberg CM, Gerrein JR, Schnell C. 1978. Cannabis in the treatment of alcoholism. J Stud Alcohol 39: 1955–1958.

    CAS  PubMed  Google Scholar 

  • Rowland RS. 2002. Using X-ray crystallography in drug discovery. Curr Opin Drug Discov Devel 5: 613–619.

    CAS  PubMed  Google Scholar 

  • Rueda D, Galve-Roperh I, Haro A, Guzman M. 2000. The CB(1) cannabinoid receptor is coupled to the activation of c-Jun N-terminal kinase. Mol Pharmacol 58: 814–820.

    CAS  PubMed  Google Scholar 

  • Ryan WJ, Banner WK, Wiley JL, Martin BR, Razdan RK. 1997. Potent anandamide analogs: The effect of changing the length and branching of the end pentyl chain. J Med Chem 40: 3617–3625.

    CAS  PubMed  Google Scholar 

  • Ryberg E, Vu HK, Larsson N, Groblewski T, Hjorth S, et al. 2005. Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett 579: 259–264.

    CAS  PubMed  Google Scholar 

  • Salzet M, Breton C, Bisogno T, Di Marzo V. 2000. Comparative biology of the endocannabinoid system. Possible role in the immune response. Eur J Biochem 267: 4917–4927.

    CAS  PubMed  Google Scholar 

  • Sanchez C, Galve-Roperh I, Rueda D, Guzman M. 1998. Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the delta9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. Mol Pharmacol 54: 834–843.

    CAS  PubMed  Google Scholar 

  • Sanchez C, Rueda D, Segui B, Galve-Roperh I, Levade T, et al. 2001. The CB(1) cannabinoid receptor of astrocytes is coupled to sphingomyelin hydrolysis through the adaptor protein fan. Mol Pharmacol 59: 955–959.

    CAS  PubMed  Google Scholar 

  • Schabitz WR, Giuffrida A, Berger C, Aschoff A, Schwaninger M, et al. 2002. Release of fatty acid amides in a patient with hemispheric stroke: A microdialysis study. Stroke 33: 2112–2114.

    CAS  PubMed  Google Scholar 

  • Schmid PC, Reddy PV, Natarajan V, Schmid HH. 1983. Metabolism of N-acylethanolamine phospholipids by a mammalian phosphodiesterase of the phospholipase D type. J Biol Chem 258: 9302–9306.

    CAS  PubMed  Google Scholar 

  • Schultes RE. 1967. Man and marijuana. Nat Hist 82: 59–63, 80, 82.

    Google Scholar 

  • Schweitzer P. 2000. Cannabinoids decrease the K(+) M-current in hippocampal CA1 neurons. J Neurosci 20: 51–58.

    CAS  PubMed  Google Scholar 

  • Self DW. 1999. Anandamide: A candidate neurotransmitter heads for the big leagues. Nat Neurosci 2: 303–304.

    CAS  PubMed  Google Scholar 

  • Seltzman HH, Fleming DN, Thomas BF, Gilliam AF, McCallion DS, et al. 1997. Synthesis and pharmacological comparison of dimethylheptyl and pentyl analogs of anandamide. J Med Chem 40: 3626–3634.

    CAS  PubMed  Google Scholar 

  • Serra S, Brunetti G, Pani M, Vacca G, Carai MA, et al. 2002. Blockade by the cannabinoid CB(1) receptor antagonist, SR 141716, of alcohol deprivation effect in alcohol-preferring rats. Eur J Pharmacol 443: 95–97.

    CAS  PubMed  Google Scholar 

  • Shen M, Thayer SA. 1998. The cannabinoid agonist Win55, 212-2 inhibits calcium channels by receptor-mediated and direct pathways in cultured rat hippocampal neurons. Brain Res 783: 77–84.

    CAS  PubMed  Google Scholar 

  • Sim-Selley LJ, Martin BR. 2002. Effect of chronic administration of R-(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate (WIN55, 212-2) or delta (9)-tetrahydrocannabinol on cannabinoid receptor adaptation in mice. J Pharmacol Exp Ther 303: 36–44.

    CAS  PubMed  Google Scholar 

  • Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF. 2002. A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci USA 99: 8394–8399.

    CAS  PubMed  Google Scholar 

  • Soderstrom K, Johnson F. 2000. CB1 cannabinoid receptor expression in brain regions associated with zebra finch song control. Brain Res 857: 151–157.

    CAS  PubMed  Google Scholar 

  • Stanton PK, Sarvey JM. 1985. Depletion of norepinephrine, but not serotonin, reduces long-term potentiation in the dentate gyrus of rat hippocampal slices. J Neurosci 5: 2169–2176.

    CAS  PubMed  Google Scholar 

  • Stefano GB, Salzet B, Salzet M. 1997. Identification and characterization of the leech CNS cannabinoid receptor: Coupling to nitric oxide release. Brain Res 753: 219–224.

    CAS  PubMed  Google Scholar 

  • Steiner H, Bonner TI, Zimmer AM, Kitai ST, Zimmer A. 1999. Altered gene expression in striatal projection neurons in CB1 cannabinoid receptor knockout mice. Proc Natl Acad Sci USA 96: 5786–5790.

    CAS  PubMed  Google Scholar 

  • Stella N, Piomelli D. 2001. Receptor-dependent formation of endogenous cannabinoids in cortical neurons. Eur J Pharmacol 425: 189–196.

    CAS  PubMed  Google Scholar 

  • Stella N, Schweitzer P, Piomelli D. 1997. A second endogenous cannabinoid that modulates long-term potentiation. Nature 388: 773–778.

    CAS  PubMed  Google Scholar 

  • Stubbs L, Chittenden L, Chakrabarti A, Onaivi E. 1996. The gene encoding the central cannabinoid receptor is located in proximal mouse Chromosome 4. Mamm Genome 7: 165–166.

    CAS  PubMed  Google Scholar 

  • Sugiura T, Kobayashi Y, Oka S, Waku K. 2002. Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot Essent Fatty Acids 66: 173–192.

    CAS  PubMed  Google Scholar 

  • Sugiura T, Yoshinaga N, Kondo S, Waku K, Ishima Y. 2000. Generation of 2-arachidonoylglycerol, and endogenous cannabinoid receptor ligand, in picrotoxinin-administered rat brain. Biochem Biophys Res Commun 271: 654–658.

    CAS  PubMed  Google Scholar 

  • Sugiura T, Kodaka T, Kondo S, Nakane S, Kondo H, et al. 1997. Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor? Structural requirements for triggering a Ca2+ transient in NG108–15 cells. J Biochem (Tokyo) 122: 890–895.

    CAS  Google Scholar 

  • Sugiura T, Kodaka T, Nakane S, Kishimoto S, Kondo S, et al. 1998. Detection of an endogenous cannabimimetic molecule, 2-arachidonoylglycerol, and cannabinoid CB1 receptor mRNA in human vascular cells: Is 2-arachidonoylglycerol a possible vasomodulator? Biochem Biophys Res Commun 243: 838–843.

    CAS  PubMed  Google Scholar 

  • Sugiura T, Kodaka T, Nakane S, Miyashita T, Kondo S, et al. 1999. Evidence that the cannabinoid CB1 receptor is a 2-arachidonylglycerol receptor. J Biol Chem 274: 2794–2801.

    CAS  PubMed  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, et al. 1995. 2-Arachidonoylglycerol: A possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215: 89–97.

    CAS  PubMed  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, et al. 1996a. N-arachidonoylethanolamine (anandamide), an endogenous cannabinoid receptor ligand, and related lipid molecules in the nervous tissues. J Lipid Mediat Cell Signal 14: 51–56.

    CAS  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, et al. 1996b. Enzymatic synthesis of anandamide, an endogenous cannabinoid receptor ligand, through N-acylphosphatidylethanolamine pathway in testis: Involvement of Ca(2+)-dependent transacylase and phosphodiesterase activities. Biochem Biophys Res Commun 218: 113–117.

    CAS  Google Scholar 

  • Sugiura T, Kodaka T, Kondo S, Tonegawa T, Nakane S, et al. 1996c. 2-Arachidonoylglycerol, a putative endogenous cannabinoid receptor ligand, induces rapid, transient elevation of intracellular free Ca2+ in neuroblastoma x glioma hybrid NG108–15 cells. Biochem Biophys Res Commun 229: 58–64.

    CAS  Google Scholar 

  • Sullivan JM. 2000. Cellular and molecular mechanisms underlying learning and memory impairments produced by cannabinoids. Learn Mem 7: 132–139.

    CAS  PubMed  Google Scholar 

  • Szabo B, Muller T, Koch H. 1999. Effects of cannabinoids on dopamine release in the corpus striatum and the nucleus accumbens in vitro. J Neurochem 73: 1084–1089.

    CAS  PubMed  Google Scholar 

  • Szabo B, Wallmichrath I, Mathonia P, Pfreundtner C. 2000. Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata. Neuroscience 97: 89–97.

    CAS  PubMed  Google Scholar 

  • Szabo B, Dorner L, Pfreundtner C, Norenberg W, Starke K. 1998. Inhibition of GABAergic inhibitory postsynaptic currents by cannabinoids in rat corpus striatum. Neuroscience 85: 395–403.

    CAS  PubMed  Google Scholar 

  • Takahashi KA, Linden DJ. 2000. Cannabinoid receptor modulation of synapses received by cerebellar Purkinje cells. J Neurophysiol 83: 1167–1180.

    CAS  PubMed  Google Scholar 

  • Tanda G, Pontieri FE, Di Chiara G. 1997. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mul opioid receptor mechanism. Science 276: 2048–2050.

    CAS  PubMed  Google Scholar 

  • Tart CT. 1970. Marijuana intoxication common experiences. Nature 226: 701–704.

    CAS  PubMed  Google Scholar 

  • Thomas BF, Adams IB, Mascarella SW, Martin BR, Razdan RK. 1996. Structure-activity analysis of anandamide analogs: Relationship to a cannabinoid pharmacophore. J Med Chem 39: 471–479.

    CAS  PubMed  Google Scholar 

  • Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM. 1998a. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83: 393–411.

    CAS  Google Scholar 

  • Tsou K, Nogueron MI, Muthian S, Sanudo-Pena MC, Hillard CJ, et al. 1998b. Fatty acid amide hydrolase is located preferentially in large neurons in the rat central nervous system as revealed by immunohistochemistry. Neurosci Lett 254: 137–140.

    CAS  Google Scholar 

  • Twitchell W, Brown S, Mackie K. 1997. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol 78: 43–50.

    CAS  PubMed  Google Scholar 

  • Ueda N, Kurahashi Y, Yamamoto S, Tokunaga T. 1995. Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide. J Biol Chem 270: 23823–23827.

    CAS  PubMed  Google Scholar 

  • Ueda N, Puffenbarger RA, Yamamoto S, Deutsch DG. 2000. The fatty acid amide hydrolase (FAAH). Chem Phys Lipids 108: 107–121.

    CAS  PubMed  Google Scholar 

  • Valjent E, Pages C, Rogard M, Besson MJ, Maldonado R, et al. 2001. Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission. Eur J Neurosci 14: 342–352.

    CAS  PubMed  Google Scholar 

  • Valk PJ, Hol S, Vankan Y, Ihle JN, Askew D, et al. 1997. The genes encoding the peripheral cannabinoid receptor and alpha-L-fucosidase are located near a newly identified common virus integration site, evill. J Virol 71: 6796–6804.

    CAS  PubMed  Google Scholar 

  • Valverde O, Noble F, Beslot F, Dauge V, Fournie-Zaluski MC, et al. 2001. Delta 9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: Reduction in morphine withdrawal syndrome without change in rewarding effect. Eur J Neurosci 13: 1816–1824.

    CAS  PubMed  Google Scholar 

  • Varma N, Carlson GC, Ledent C, Alger BE. 2001. Metabotropic glutamate receptors drive the endocannabinoid system in hippocampus. J Neurosci 21: RC188.

    CAS  PubMed  Google Scholar 

  • Vaughan CW, McGregor IS, Christie MJ. 1999. Cannabinoid receptor activation inhibits GABAergic neurotransmission in rostral ventromedial medulla neurons in vitro. Br J Pharmacol 127: 935–940.

    CAS  PubMed  Google Scholar 

  • Vaughan CW, Connor M, Bagley EE, Christie MJ. 2000. Actions of cannabinoids on membrane properties and synaptic transmission in rat periaqueductal gray neurons in vitro. Mol Pharmacol 57: 288–295.

    CAS  PubMed  Google Scholar 

  • Vincent P, Marty A. 1993. Neighboring cerebellar Purkinje cells communicate via retrograde inhibition of common presynaptic interneurons. Neuron 11: 885–893.

    CAS  PubMed  Google Scholar 

  • Vincent P, Marty A. 1996. Fluctuations of inhibitory postsynaptic currents in Purkinje cells from rat cerebellar slices. J Physiol 494 (Pt 1): 183–199.

    CAS  PubMed  Google Scholar 

  • Vincent P, Armstrong CM, Marty A. 1992. Inhibitory synaptic currents in rat cerebellar Purkinje cells: Modulation by postsynaptic depolarization. J Physiol 456: 453–471.

    CAS  PubMed  Google Scholar 

  • Wagner JA, Varga K, Jarai Z, Kunos G. 1999. Mesenteric vasodilation mediated by endothelial anandamide receptors. Hypertension 33: 429–434.

    CAS  PubMed  Google Scholar 

  • Walker JM, Huang SM. 2002. Endocannabinoids in pain modulation. Prostaglandins Leukot Essent Fatty Acids 66: 235–242.

    CAS  PubMed  Google Scholar 

  • Wallmichrath I, Szabo B. 2002. Cannabinoids inhibit striatonigral GABAergic neurotransmission in the mouse. Neuroscience 113: 671–682.

    CAS  PubMed  Google Scholar 

  • Wang L, Liu J, Harvey-white J, Zimmer A, Kunos G. 2003. Endocannabinoid signaling via CB1 receptors is involved in ethanol preference and its age-dependent decline in mice. Proc Natl Acad Sci USA 100: 1393–1398.

    CAS  PubMed  Google Scholar 

  • Wartmann M, Campbell D, Subramanian A, Burstein SH, Davis RJ. 1995. The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide. FEBS Lett 2-3: 133–136.

    Google Scholar 

  • Willoughby KA, Moore SF, Martin BR, Ellis EF. 1997. The biodisposition and metabolism of anandamide in mice. J Pharmacol Exp Ther 282: 243–247.

    CAS  PubMed  Google Scholar 

  • Wilson RI, Nicoll RA. 2001. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410: 588–592.

    CAS  PubMed  Google Scholar 

  • Wilson RI, Nicoll RA. 2002. Endocannabinoid Signaling in the Brain. Science 296: 678–682.

    CAS  PubMed  Google Scholar 

  • Wilson RI, Kunos G, Nicoll RA. 2001. Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 31: 453–462.

    CAS  PubMed  Google Scholar 

  • Wise RA. 1996. Addictive drugs and brain stimulation reward. Annu Rev Neurosci 19: 319–340.

    CAS  PubMed  Google Scholar 

  • Wise RA, Bozarth MA. 1987. A psychomotor stimulant theory of addiction. Psychol Rev 94: 469–492.

    CAS  PubMed  Google Scholar 

  • Yamaguchi F, Macrae AD, Brenner S. 1996. Molecular cloning of two cannabinoid type 1-like receptor genes from the puffer fish Fugu rubripes. Genomics 35: 603–605.

    CAS  PubMed  Google Scholar 

  • Yang HY, Karoum F, Felder C, Badger H, Wang TC, et al. 1999. GC/MS analysis of anandamide and quantification of N-arachidonoylphosphatidylethanolamides in various brain regions, spinal cord, testis, and spleen of the rat. J Neurochem 72: 1959–1968.

    CAS  PubMed  Google Scholar 

  • Yoshida T, Hashimoto K, Zimmer A, Maejima T, Araishi K, et al. 2002. The cannabinoid CB1 receptor mediates retrograde signals for depolarization-induced suppression of inhibition in cerebellar Purkinje Cells. J Neurosci 22: 1690–1697.

    CAS  PubMed  Google Scholar 

  • Zhang PW, Ishiguro H, Ohtsuki T, Hess J, Carillo F, et al. 2004. Human cannabinoid receptor 1:5′exons, candidate regulatory regions, polymorphisms, haplotypes and association with polysubstance abuse. Mol Psychiatry 9: 916–931.

    CAS  PubMed  Google Scholar 

  • Zilberter Y. 2000. Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurons in rat neocortex. J Physiol 528 (Pt 3): 489–496.

    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.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors acknowledge support in part by grants from NIH AA11031 (BSB) and AA13003 (BLH). We thank Dr. Emmanuel S Onaivi for providing permission to reproduce CB1 gene structure.

Authors
  1. B. S. Basavarajappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Yalamanchili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. B. Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. L. Hungund
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Institute of Experimental Medicine, Hungarian Academy of Sciences, 43, H-1083 Budapest, Szigony, Hungary

    E. Sylvester Vizi

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this entry

Cite this entry

Basavarajappa, B.S., Yalamanchili, R., Cooper, T.B., Hungund, B.L. (2008). The Endocannabinoid System. In: Lajtha, A., Vizi, E.S. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30382-6_14

Download citation

Publish with us

Policies and ethics

Search

Navigation