Cannabinoid receptors: Introduction

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. » Email us


Historically, cannabinoid receptors were defined as those receptors that respond to cannabinoid drugs, such as Δ9-tetrahydrocannabinol (THC) derived from Cannabis sativa [14,18,38] and its biologically active synthetic analogues (see PHARMACOLOGY section below). This is because there was no known endogenous agonist when the first of these receptors was discovered in the late 1980's. Subsequently, it was found that mammalian tissues do synthesize and release compounds that can activate cannabinoid receptors. The most widely investigated of these ‘endocannabinoids’ are N-arachidonoylethanolamine (anandamide) and 2-arachidonoyl glycerol [12,41,72], both of which are synthesized on demand in response to elevations of intracellular calcium [13]. Other compounds that may serve as endocannabinoids include N-dihomo-γ-linolenoylethanolamine, N-docosatetraenoylethanolamine, O-arachidonoylethanolamine (virodhamine), oleamide, N-arachidonoyl dopamine and N-oleoyl dopamine [52]. Endocannabinoids and their receptors constitute the ‘endocannabinoid system’. Because it is not yet clear whether these are the only endogenous agonists, the subcommittee continues to call the receptors 'cannabinoid receptors' rather than naming them after the endogenous agonists as recommended by NC-IUPHAR (see Revised NC-IUPHAR Recommendations for Nomenclature of Receptors, this edition and [52]).

Cannabinoid Receptors

The cannabinoid receptor family is denoted by the abbreviation 'CB' and receptors are numbered by their order of discovery, denoted by a numerical subscript (e.g. CB1, CB2). Two cannabinoid receptors have been described to date.

The CB1 cannabinoid receptor has been cloned from rat [40], mouse [10] and human [20] tissues (97-99% amino acid (aa) sequence identity across species). Its structure is that of a seven-transmembrane domain (7TM) receptor [40] consistent with biochemical and cellular determinations of signal transduction via G proteins [11,31,34,44,62,67]. The CB1 receptor mRNA and protein are found primarily in brain and nervous tissue [25,32,36,40].

The CB2 cannabinoid receptor was discovered in a human leukemia HL60 library as a cDNA fragment that exhibited 68% homology with the CB1 cannabinoid receptor, and mRNA is found primarily in immune tissue [42]. Expressed CB2 receptor protein was shown to bind cannabinoid and aminoalkylindole compounds and to signal a response through the inhibition of adenylate cyclase [7,15,42,66,70]. The mouse [64] and rat [23] CB2 receptors have been cloned and exhibit 82% and 81% sequence identity, respectively to the human CB2 receptor.

Cannabinoid CB1 and CB2 receptors are phylogenetically restricted to the chordate branch of the animal kingdom [52]. Among other established G protein-coupled receptors (GPCRs), those most closely related to CB1/CB2-type receptors are the lysophospholipid receptors S1P1, S1P2, S1P3, S1P4, S1P5, LPA1, LPA2 and LPA3. These receptors for endocannabinoids or lysophospholipid-like molecules have evolved independently in different branches of the GPCR superfamily but CB1 and CB2 are the only bona fide ‘cannabinoid receptors’ that have been identified to-date.

Molecular Biology

The coding sequence of the CB1 receptor is contained in a single exon (see, for example, the human gene sequence Genbank accession U73304). However, an alternatively spliced form of the human receptor has been reported in which a 167 base portion of this exon is spliced out of the human mRNA leading to the predicted substitution of a different 28 residue sequence for the first 90aa [65]. This shorter mRNA appears to be relatively rare (< 20% of message by RT-PCR analysis), and the short isoform is likely to be inefficiently translated since it initiates at the second AUG of the mRNA and has a T rather than the highly preferred A or G at the critical -3 position of the Kozak consensus sequence. In both the rat and mouse genes, the invariant GT of the human splice donor site exists as a GA, which implies that this alternative splicing should not occur in these species. If the splice variant protein were expressed, the NC-IUPHAR guidelines dictate that the major, larger isoform should be termed CB1(a) and the short isoform be referred to as CB1(b). To date the short isoform has been referred to as CB1A.

Functional characteristics of the CB1 receptor

The CB1 cannabinoid receptor has been extensively characterized for biological responses (see references [2,27] for review). Nervous system responses to Δ9-THC and other cannabinoid receptor agonists include therapeutically beneficial effects of analgesia, attenuation of the nausea and vomiting in cancer chemotherapy, appetite stimulation in wasting syndromes, and decreased intestinal motility. Untoward side effects accompanying these therapeutic responses include alterations in cognition and memory, dysphoria/euphoria and sedation. Animal models that distinguish cannabinoid receptor activity include drug discrimination paradigms in rodents, pigeons and primates, a typical static ataxia in dogs, and a tetrad of responses in rodents (hypothermia, analgesia, hypoactivity and catalepsy) [39]. Nerve-muscle tissue preparations (mouse vas deferens, mouse and guinea-pig ileum) respond to cannabinoid receptor agonists with an inhibition of contraction, believed to be the result of diminished release of neurotransmitter [54,60,76]. Indeed, it is now generally accepted that most CB1 receptors are located at central or peripheral nerve terminals and that their main function is to mediate inhibition of on-going release of certain excitatory and inhibitory neurotransmitters [29,53,73]. These receptors are also expressed by some non-neuronal cells, for example immune cells [29].

CB1 cannabinoid receptors are coupled to pertussis toxin (PTX)-sensitive Gi/Go proteins in a manner that leads to the inhibition of adenylate cyclase activity [31,44], regulatation of L-, N- and P- or Q-type Ca2+ channels [19,34-35,74], and G protein-regulated A-type and inwardly rectifying K+ channels [11,24,35,52], an initiation of intracellular Ca2+ transients [71], a stimulation of mitogen-activated protein (MAP) kinase [71] and an induction of immediate early gene expression [6]. CB1 receptors can also signal through Gs proteins [9,21,33,37].

In addition to orthosteric site(s), CB1 receptors possess one or more allosteric sites with which some ligands can interact to enhance or inhibit CB1 receptor activation by direct agonists [3,28,43,55]. There is also evidence that some CB1 receptors form heteromers with dopamine D2 receptors, μ-opioid receptors and orexin-1 receptors and that this heteromerization can affect CB1 receptor activation by agonists [52]. These ‘CB-X receptor heteromers’ conform to the proposed conventions for structurally associated pairs in which the functional interactions influence ligand selectivity or relative intrinsic activity.

Functional characteristics of the CB2 receptor

Most CB2 receptors are expressed by immune cells located either outside or within the brain. When activated these receptors can modulate immune cell migration and cytokine release [8,29,48]. Cannabinoid CB2 receptor mRNA can be found in spleen, tonsils, bone marrow, pancreas, splenic macrophage / monocyte preparations, peripheral blood leukocytes, and in a variety of cultured immune cell models including the myeloid cell line U937 and undifferentiated and differentiated granulocyte-like or macrophage-like HL60 cells [17,42]. CB2 receptors may also be expressed by certain central and peripheral neurons [4-5,22,59,69,75,77]. However, the role of these putative neuronal receptors has yet to be established.

Signal transduction by the CB2 receptor includes PTX-sensitive inhibition of cAMP production in transfected host CHO cells [15,23,70], MAP kinase activation and immediate early gene expression [7]. No modulation of ion channels or alterations of intracellular Ca2+ were observed in host cells expressing CB2 receptors [15,70].


Ki values derived from various ligand-binding assays and EC50 values for a series of in vitro and in vivo activities have been compiled in several reviews [30,45-46,51-52,56,63].

Some cannabinoid receptor agonists activate CB1 and CB2 receptors with similar potency, although not always with similar intrinsic activity. These CB1/CB2 receptor agonists fall into one or other of four main chemical groups that have been named classical, nonclassical, aminoalkylindole and eicosanoid [29,46,48-52]. The classical group consists of dibenzopyran derivatives, two prominent members of which are (–)-Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive constituent of cannabis, and (–)-11-hydroxy-Δ8-tetrahydrocannabinol-dimethylheptyl (HU-210), a synthetic analogue of (–)-Δ8-tetrahydrocannabinol. The nonclassical group contains bicyclic and tricyclic analogues of Δ9-THC that lack a pyran ring, a well-known member of this group being CP55940. The best known member of the aminoalkylindole group of CB1/CB2 receptor agonists is R-(+)-WIN55212, whilst two particularly notable members of the eicosanoid group are the endocannabinoids, anandamide and 2-arachidonoyl glycerol. Aminoalkylindoles and eicosanoids have structures that are markedly different both from each other and from classical and nonclassical cannabinoid receptor agonists.

Compounds that display markedly greater potency at activating CB1 receptors than at activating CB2 receptors have also been developed. The most notable of these CB1-selective agonists are all synthetic analogues of anandamide: R-(+)-methanandamide, arachidonyl-2’-chloroethylamide (ACEA) and arachidonylcyclopropylamide (ACPA) [1,26]. Important CB2-selective agonists include the classical cannabinoid, JWH-133, the nonclassical cannabinoid, HU-308, and the aminoalkylindoles, JWH-015 and AM1241 [29,46,48-49,51-52].

Several cannabinoid CB1 and CB2 receptor competitive antagonists have also been developed [16,29,46,49,51-52]. Antagonists that display significant CB1-selectivity include rimonabant (SR141716A), AM251, AM281, LY320135 and taranabant. Importantly, these five compounds all behave as cannabinoid receptor inverse agonists as indicated by their ability to elicit responses in some CB1 receptor-containing tissues that are opposite in direction from those induced by a CB1 receptor agonist [16,47]. CB1-selective competitive antagonists that lack any detectable ability to induce signs of inverse agonism at the CB1 receptor when administered alone, thus behaving as ‘neutral’ antagonists, have also been discovered. These include NESS O327 and AM4113, both of which are structural analogues of rimonabant [61,68].

As to CB2-selective competitive antagonists, those most often used as experimental tools are 6-iodopravadoline (AM630) and SR144528 [29,46,48-49,51-52]. Both these compounds behave as CB2 receptor inverse agonists [57-58]. A neutral antagonist that selectively targets the CB2 receptor has yet to be developed.

Non-CB1/NON-CB2 Receptor-mediated effects of Cannabinoid receptor ligands

It is now generally accepted that some endocannabinoids, including anandamide, 2-arachidonoyl glycerol and N-arachidonoyl dopamine, as well as Δ9-THC and a number of synthetic CB1/CB2 receptor agonists and antagonists can activate or block established non-CB1, non-CB2 GPCRs, ligand-gated ion channels, ion channels and/or nuclear receptors (PPAR receptors) [51-52]. Importantly, some cannabinoids seem to target these channels or receptors with potencies that differ little from those with which they activate or block CB1 and/or CB2 receptors. Anandamide, such example, displays such potency at T-type voltage-gated calcium channels, voltage-gated KV3.1 and KV4.3 potassium channels, calcium-activated potassium (BK) channels, NMDA receptors, glycine receptors, and allosteric sites on 5-HT3 and nicotinic acetylcholine receptors [52].

Findings such as these strengthen the need to address the question of whether any known mammalian channel or non-CB1, non-CB2 receptor should be classified as a novel cannabinoid ‘CB3’ receptor or channel. It is noteworthy, therefore, that the NC-IUPHAR cannabinoid receptor subcommittee has proposed five criteria that should be met by any such receptor or channel and come to the conclusion that, according to these five criteria, no channel, non-CB1, non-CB2 established receptor or deorphanized receptor should currently be classified or reclassified as a novel cannabinoid receptor [52]. However, it also considers that since the TRPV1 channel does appear to meet three of these criteria, at least in part, it may eventually come to be regarded as being either an ‘ionotropic cannabinoid CB3 receptor’ or a dual TRPV1/CB3 receptor that functions as a cannabinoid receptor when anandamide and/or other endocannabinoids are released onto it in high amounts under pathological conditions [52].


Show »

1. Abadji V, Lin S, Taha G, Griffin G, Stevenson LA, Pertwee RG, Makriyannis A. (1994) (R)-methanandamide: a chiral novel anandamide possessing higher potency and metabolic stability. J. Med. Chem.37 (12): 1889-93. [PMID:8021930]

2. Abood ME, Martin BR. (1992) Neurobiology of marijuana abuse. Trends Pharmacol. Sci.13: 201-206. [PMID:1604713]

3. Adam L, Salois D, Rihakova L, Lapointe S, St-Onge S, Labrecque J, Payza K. (2007) Positive allosteric modulators of CB1 receptors. in 17th Annual Symposium of the Cannabinoids, St-Sauveur, Canada International Cannabinoid Research Society. 86

4. Baek JH, Zheng Y, Darlington CL, Smith PF. (2008) Cannabinoid CB2 receptor expression in the rat brainstem cochlear and vestibular nuclei. Acta Otolaryngol.128 (9): 961-7. [PMID:19086305]

5. Beltramo M, Bernardini N, Bertorelli R, Campanella M, Nicolussi E, Fredduzzi S, Reggiani A. (2006) CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. Eur. J. Neurosci.23 (6): 1530-8. [PMID:16553616]

6. Bouaboula M, Bourrié B, Rinaldi-Carmona M, Shire D, Le Fur G, Casellas P. (1995) Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. J. Biol. Chem.270 (23): 13973-80. [PMID:7775459]

7. Bouaboula M, Poinot-Chazel C, Marchand J, Canat X, Bourrie B, Rinaldi-Carmona M, Calandra B, Le Fur G, Casellas P. (1996) Signalling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinases and induction of Krox-24 expression. Eur. J. Biochem.237: 704-711. [PMID:8647116]

8. Cabral GA, Staab A. (2005) Effects on the immune system. Handb Exp Pharmacol,  (168): 385-423. [PMID:16596782]

9. Calandra B, Portier M, Kernéis A, Delpech M, Carillon C, Le Fur G, Ferrara P, Shire D. (1999) Dual intracellular signaling pathways mediated by the human cannabinoid CB1 receptor. Eur. J. Pharmacol.374 (3): 445-55. [PMID:10422789]

10. Chakrabarti A, Onaivi ES, Chaudhuri G. (1995) Cloning and sequencing of a cDNA encoding the mouse brain-type cannabinoid receptor protein. DNA Seq.5: 385-388. [PMID:8777318]

11. Childers SR, Deadwyler SA. (1996) Role of cyclic AMP in the actions of cannabinoid receptors. Biochem. Pharmacol.52: 819-827. [PMID:8781498]

12. 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. Science258: 1946-1949. [PMID:1470919]

13. Di Marzo V, De Petrocellis L, Bisogno T. (2005) The biosynthesis, fate and pharmacological properties of endocannabinoids. Handb Exp Pharmacol,  (168): 147-85. [PMID:16596774]

14. Edery H, Grunfeld Y, Ben-Zvi Z, Mechoulam R. (1971) Structural requirements for cannabinoid activity. Ann. N.Y. Acad. Sci.191: 40-53.

15. Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL, Mitchell RL. (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol. Pharmacol.48: 443-450. [PMID:7565624]

16. Fong TM, Guan XM, Marsh DJ, Shen CP, Stribling DS, Rosko KM, Lao J, Yu H, Feng Y, Xiao JC et al.. (2007) Antiobesity efficacy of a novel cannabinoid-1 receptor inverse agonist, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364), in rodents. J. Pharmacol. Exp. Ther.321 (3): 1013-22. [PMID:17327489]

17. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P. (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur. J. Biochem.232: 54-61. [PMID:7556170]

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

19. 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: 2085-2093. [PMID:10362691]

20. Gerard C, Mollereau C, Vassart G, Parmentier M. (1990) Nucleotide sequence of a human cannabinoid receptor cDNA. Nucleic Acids Res.18: 7142---. [PMID:2263478]

21. 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. [PMID:9204917]

22. Gong JP, Onaivi ES, Ishiguro H, Liu QR, Tagliaferro PA, Brusco A, Uhl GR. (2006) Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res.1071 (1): 10-23. [PMID:16472786]

23. Griffin G, Tao Q, Abood ME. (2000) Cloning and pharmacological characterization of the rat CB2 cannabinoid receptor. J. Pharmacol. Exp. Ther.292: 886-894. [PMID:10688601]

24. Henry DJ, Chavkin C. (1995) Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors inXenopusoocytes. Neurosci. Lett.186: 91-94. [PMID:7777206]

25. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. (1990) Cannabinoid receptor localization in brain. Proc. Natl. Acad. Sci. U.S.A.87: 1932-1936. [PMID:2308954]

26. Hillard CJ, Manna S, Greenberg MJ, DiCamelli R, Ross RA, Stevenson LA, Murphy V, Pertwee RG, Campbell WB. (1999) Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1). J. Pharmacol. Exp. Ther.289: 1427-1433. [PMID:10336536]

27. Hollister LE. (1986) Health aspects of cannabis. Pharmacol. Rev.38: 1-20. [PMID:3520605]

28. Horswill JG, Bali U, Shaaban S, Keily JF, Jeevaratnam P, Babbs AJ, Reynet C, Wong Kai In P. (2007) PSNCBAM-1, a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats. Br. J. Pharmacol.152 (5): 805-14. [PMID:17592509]

29. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG. (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev.54: 161-202. [PMID:12037135]

30. Howlett AC, Berglund BA, Melvin LS. (1995) Cannabinoid receptor agonists and antagonists. Curr. Pharm. Des.1: 343-354.

31. Howlett AC, Qualy JM, Khachatrian LL. (1986) Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. Mol. Pharmacol.29: 307-313. [PMID:2869405]

32. Jansen EM, Haycock DA, Ward SJ, Seybold VS. (1992) Distribution of cannabinoid receptors in rat brain determined with aminoalkylindoles. Brain Res.575: 93-102. [PMID:1504787]

33. Jarrahian A, Watts VJ, Barker EL. (2004) D2 dopamine receptors modulate Galpha-subunit coupling of the CB1 cannabinoid receptor. J. Pharmacol. Exp. Ther.308 (3): 880-6. [PMID:14634050]

34. Mackie K, Hille B. (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc. Natl. Acad. Sci. U.S.A.89: 3825-3829. [PMID:1315042]

35. Mackie K, Lai Y, Westenbroek R, Mitchell R. (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J. Neurosci.15: 6552-6561. [PMID:7472417]

36. Mailleux P, Parmentier M, Vanderhaeghen JJ. (1992) Distribution of cannabinoid receptor messenger RNA in the human brain: an in situ hybridization histochemistry with oligonucleotides. Neurosci. Lett.143: 200-204. [PMID:1436667]

37. Maneuf YP, Brotchie JM. (1997) Paradoxical action of the cannabinoid WIN 55,212-2 in stimulated and basal cyclic AMP accumulation in rat globus pallidus slices. Br. J. Pharmacol.120 (8): 1397-8. [PMID:9113356]

38. Martin BR, Balster RL, Razdan RK, Harris LS, Dewey WL. (1981) Behavioral comparisons of the stereoisomers of tetrahydrocannabinols. Life Sci.29: 565-574. [PMID:6268916]

39. Martin BR, Compton DR, Thomas BF, Prescott WR, Little PJ, Razdan RK, Johnson MR, Melvin LS, Mechoulam R, Ward SJ. (1991) Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol. Biochem. Behav.40: 471-478. [PMID:1666911]

40. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature346: 561-564. [PMID:2165569]

41. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR et al.. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol.50: 83-90. [PMID:7605349]

42. Munro S, Thomas KL, Abu-Shaar M. (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature365: 61-65. [PMID:7689702]

43. Navarro HA, Howard JL, Pollard GT, Carroll FI. (2009) Positive allosteric modulation of the human cannabinoid (CB) receptor by RTI-371, a selective inhibitor of the dopamine transporter. Br. J. Pharmacol.156 (7): 1178-84. [PMID:19226282]

44. Pacheco M, Childers SR, Arnold R, Casiano F, Ward SJ. (1991) Aminoalkylindoles: actions on specific G-protein-linked receptors. J. Pharmacol. Exp. Ther.257: 170-183. [PMID:1902257]

45. Pertwee RG. (1997) Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther.74: 129-180. [PMID:9336020]

46. Pertwee RG. (1999) Pharmacology of cannabinoid receptor ligands. Curr. Med. Chem.6: 635-664. [PMID:10469884]

47. Pertwee RG. (2005) Inverse agonism and neutral antagonism at cannabinoid CB1 receptors. Life Sci.76 (12): 1307-24. [PMID:15670612]

48. Pertwee RG. (2005) Pharmacological actions of cannabinoids. Handb Exp Pharmacol,  (168): 1-51. [PMID:16596770]

49. Pertwee RG. (2008) Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addict Biol13 (2): 147-59. [PMID:18482430]

50. Pertwee RG. (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br. J. Pharmacol.153 (2): 199-215. [PMID:17828291]

51. Pertwee RG. (2010) Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr. Med. Chem.17 (14): 1360-81. [PMID:20166927]

52. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K et al.. (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol. Rev.62 (4): 588-631. [PMID:21079038]

53. Pertwee RG, Ross RA. (2002) Cannabinoid receptors and their ligands. Prostaglandins Leukot. Essent. Fatty Acids66 (2-3): 101-21. [PMID:12052030]

54. Pertwee RG, Stevenson LA, Elrick DB, Mechoulam R, Corbett AD. (1992) Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea-pig small intestine. Br. J. Pharmacol.105: 980-984. [PMID:1324060]

55. Price MR, Baillie GL, Thomas A, Stevenson LA, Easson M, Goodwin R, McLean A, McIntosh L, Goodwin G, Walker G et al.. (2005) Allosteric modulation of the cannabinoid CB1 receptor. Mol. Pharmacol.68 (5): 1484-95. [PMID:16113085]

56. Razdan RK. (1986) Structure-activity relationships in cannabinoids. Pharmacol. Rev.38: 75-149. [PMID:3018800]

57. Rinaldi-Carmona M, Barth F, Millan J, Derocq JM, Casellas P, Congy C, Oustric D, Sarran M, Bouaboula M, Calandra B, Portier M, Shire D, Breliere JC, Le Fur GL. (1998) SR144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J. Pharmacol. Exp. Ther.284: 644-650. [PMID:9454810]

58. Ross RA, Brockie HC, Stevenson LA, Murphy VL, Templeton F, Makriyannis A, Pertwee RG. (1999) Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656 and AM630. Br. J. Pharmacol.126: 665-672. [PMID:10188977]

59. Ross RA, Coutts AA, McFarlane SM, Anavi-Goffer S, Irving AJ, Pertwee RG, MacEwan DJ, Scott RH. (2001) Actions of cannabinoid receptor ligands on rat cultured sensory neurones: implications for antinociception. Neuropharmacology40 (2): 221-32. [PMID:11114401]

60. Roth SH. (1978) Stereospecific presynaptic inhibitory effect of Δ9-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig. Can. J. Physiol. Pharmacol.56: 968-975. [PMID:217512]

61. Ruiu S, Pinna GA, Marchese G, Mussinu JM, Saba P, Tambaro S, Casti P, Vargiu R, Pani L. (2003) Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor. J. Pharmacol. Exp. Ther.306 (1): 363-70. [PMID:12663689]

62. Selley DE, Stark S, Childers SR. (1996) Cannabinoid receptor stimulation of [35S]GTPγS binding in rat brain membranes. Life Sci.59: 659-668. [PMID:8761016]

63. Sheskin T, Hanus L, Slager J, Vogel Z, Mechoulam R. (1997) Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor. J. Med. Chem.40: 659-667. [PMID:9057852]

64. Shire D, Calandra B, Rinaldi-Carmona M, Oustric D, Pessegue B, Bonnin-Cabanne O, Le Fur G, Caput D, Ferrara P. (1996) Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. Biochim. Biophys. Acta1307: 132-136. [PMID:8679694]

65. Shire D, Carillon C, Kaghad M, Calandra B, Rinaldi-Carmona M, Le Fur G, Caput D, Ferrara P. (1995) An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. J. Biol. Chem.270: 3726-3731. [PMID:7876112]

66. Showalter VM, Compton DR, Martin BR, Abood ME. (1996) Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): Identification of cannabinoid receptor subtype selective ligands. J. Pharmacol. Exp. Ther.278: 989-999. [PMID:8819477]

67. Sim LJ, Selley DE, Childers SR. (1995) In vitro autoradiography of receptor-activated G proteins in rat brain by agonist-stimulated guanylyl 5'-[γ[35S]thio]-triphosphate binding. Proc. Natl. Acad. Sci. U.S.A.92: 7242-7246. [PMID:7638174]

68. Sink KS, McLaughlin PJ, Wood JA, Brown C, Fan P, Vemuri VK, Peng Y, Pang Y, Olszewska T, Olzewska T et al.. (2008) The novel cannabinoid CB1 receptor neutral antagonist AM4113 suppresses food intake and food-reinforced behavior but does not induce signs of nausea in rats. Neuropsychopharmacology33 (4): 946-55. [PMID:17581535]

69. Skaper SD, Buriani A, Dal Toso R, Petrelli L, Romanello S, Facci L, Leon A. (1996) The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proc. Natl. Acad. Sci. U.S.A.93 (9): 3984-9. [PMID:8633002]

70. Slipetz DM, O'Neill GP, Favreau L, Dufresne C, Gallant M, Gareau Y, Guay D, Labelle M, Metters KM. (1995) Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase. Mol. Pharmacol.48: 352-361. [PMID:7651369]

71. Sugiura T, Kodaka T, Kondo S, Tonegawa T, Nakane S, Kishimoto S, Yamashita A, Waku K. (1996) 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. [PMID:8954083]

72. 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. [PMID:7575630]

73. Szabo B, Schlicker E. (2005) Effects of cannabinoids on neurotransmission. Handb Exp Pharmacol,  (168): 327-65. [PMID:16596780]

74. 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. [PMID:9242259]

75. Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS et al.. (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science310 (5746): 329-32. [PMID:16224028]

76. Ward SJ, Mastriani D, Casiano F, Arnold R. (1990) Pravadoline: profile in isolated tissue preparations. J. Pharmacol. Exp. Ther.255: 1230-1239. [PMID:2175798]

77. Wotherspoon G, Fox A, McIntyre P, Colley S, Bevan S, Winter J. (2005) Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons. Neuroscience135 (1): 235-45. [PMID:16084654]

How to cite this page

To cite this family introduction, please use the following:

Roger G. Pertwee, Allyn C. Howlett, Mary Abood, Francis Barth, Tom I. Bonner, Guy Cabral, Pierre Casellas, Ben F. Cravatt, William A. Devane, Maurice R. Elphick, Christian C. Felder, Miles Herkenham, George Kunos, Ken Mackie, Raphael Mechoulam.
Cannabinoid receptors, introduction. Last modified on 10/08/2015. Accessed on 24/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY,