More information on this family may be found on the IUPHAR-DB family and introduction pages.
Cannabinoid receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on Cannabinoid Receptors; [17]) are activated by endogenous ligands that include N-arachidonoylethanolamine (anandamide), N-homo-γ-linolenoylethanolamine, N-docosatetra-7,10,13,16-enoylethanolamine and 2-arachidonoylglycerol. Potency determinations of endogenous agonists at these receptors are complicated by the possibility of differential susceptibility of endogenous ligands to enzymatic conversion [1].
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Alexander, SP; Kendall, DA. (2007) The complications of promiscuity: endocannabinoid action and metabolism. Br. J. Pharmacol., 152 (5): 602-23. [PMID:17876303]
Bosier, B; Muccioli, GG; Hermans, E; Lambert, DM. (2010) Functionally selective cannabinoid receptor signalling: therapeutic implications and opportunities. Biochem. Pharmacol., 80 (1): 1-12. [PMID:20206137]
Bradshaw, HB; Lee, SH; McHugh, D. (2009) Orphan endogenous lipids and orphan GPCRs: a good match. Prostaglandins Other Lipid Mediat., 89 (3-4): 131-4. [PMID:19379823]
Centonze, D; Finazzi-Agrò, A; Bernardi, G; Maccarrone, M. (2007) The endocannabinoid system in targeting inflammatory neurodegenerative diseases. Trends Pharmacol. Sci., 28 (4): 180-7. [PMID:17350694]
Di Marzo, V; Bisogno, T; De Petrocellis, L. (2007) Endocannabinoids and related compounds: walking back and forth between plant natural products and animal physiology. Chem. Biol., 14 (7): 741-56. [PMID:17656311]
Di Marzo, V; Petrocellis, LD. (2006) Plant, synthetic, and endogenous cannabinoids in medicine. Annu. Rev. Med., 57: 553-74. [PMID:16409166]
Di Marzo, V; Petrosino, S. (2007) Endocannabinoids and the regulation of their levels in health and disease. Curr. Opin. Lipidol., 18 (2): 129-40. [PMID:17353660]
Fernández-Ruiz, J; Romero, J; Velasco, G; Tolón, RM; Ramos, JA; Guzmán, M. (2007) Cannabinoid CB2 receptor: a new target for controlling neural cell survival?. Trends Pharmacol. Sci., 28 (1): 39-45. [PMID:17141334]
Godlewski, G; Offertáler, L; Wagner, JA; Kunos, G. (2009) Receptors for acylethanolamides-GPR55 and GPR119. Prostaglandins Other Lipid Mediat., 89 (3-4): 105-11. [PMID:19615459]
Hansen, HS; Diep, TA. (2009) N-acylethanolamines, anandamide and food intake. Biochem. Pharmacol., 78 (6): 553-60. [PMID:19413995]
Howlett, AC; Reggio, PH; Childers, SR; Hampson, RE; Ulloa, NM; Deutsch, DG. (2011) Endocannabinoid tone versus constitutive activity of cannabinoid receptors. Br. J. Pharmacol., 163 (7): 1329-43. [PMID:21545414]
Izzo, AA; Sharkey, KA. (2010) Cannabinoids and the gut: new developments and emerging concepts. Pharmacol. Ther., 126 (1): 21-38. [PMID:20117132]
Maccarrone, M; Gasperi, V; Catani, MV; Diep, TA; Dainese, E; Hansen, HS; Avigliano, L. (2010) The endocannabinoid system and its relevance for nutrition. Annu. Rev. Nutr., 30: 423-40. [PMID:20645854]
McPartland, JM; Glass, M; Pertwee, RG. (2007) Meta-analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences. Br. J. Pharmacol., 152 (5): 583-93. [PMID:17641667]
O'Sullivan, SE. (2007) Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br. J. Pharmacol., 152 (5): 576-82. [PMID:17704824]
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]
Ross, RA. (2011) L-α-lysophosphatidylinositol meets GPR55: a deadly relationship. Trends Pharmacol. Sci., 32 (5): 265-9. [PMID:21367464]
Sharir, H; Abood, ME. (2010) Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol. Ther., 126 (3): 301-13. [PMID:20298715]
Ueda, N; Tsuboi, K; Uyama, T. (2010) Enzymological studies on the biosynthesis of N-acylethanolamines. Biochim. Biophys. Acta, 1801 (12): 1274-85. [PMID:20736084]
1. Alexander, SP; Kendall, DA. (2007) The complications of promiscuity: endocannabinoid action and metabolism. Br. J. Pharmacol., 152 (5): 602-23. [PMID:17876303]
2. Breivogel, C. S., Sim, L. J. and Childers, S. R. (1997) Regional differences in cannabinoid receptor/G-protein coupling in rat brain. J. Pharmacol. Exp. Ther., 282: 1632-1642. [PMID:9316881]
3. Di Marzo, V., Bisogno, T., De Petrocellis, L., Brandi, I., Jefferson, R. G., Winckler, R. L., Davis, J. B., Dasse, O., Mahadevan, A., Razdan, R. K. and Martin, B. R. (2001) Highly selective CB1 cannabinoid receptor ligands and novel CB1/VR1 vanilloid receptor "hybrid" ligands. Biochem. Biophys. Res. Commun., 281: 444-451. [PMID:11181068]
4. Felder, C. C., Joyce, K. E., Briley, E. M., Glass, M., Mackie, K. P., Fahey, K. J., Cullinan, G. J., Hunden, D. C., Johnson, D. W., Chaney, M. O., Koppel, G. A. and Brownstein, M. (1998) LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation. J. Pharmacol. Exp. Ther., 284: 291-297. [PMID:9435190]
5. Felder, C. C., Joyce, K. E., Briley, E. M., Mansouri, J., Mackie, K., Blond, O., Lai, Y., Ma, A. L and Mitchell, R. L. (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol. Pharmacol., 48: 443-450. [PMID:7565624]
6. Gareau, Y., Dufresne, C., Gallant, M., Rochette, C., Sawyer, N., Slipetz, D. M., Tremblay, N., Weech, P.K., Metters, K.M. and Labelle, M. (1996) Structure activity relationships of tetrahydrocannabinol analogues on human cannabinoid receptors. Bioorg. Med. Chem. Lett., 6: 189-194.
7. Hanus, L., Breuer, A., Tchilibon, S., Shiloah, S., Goldenberg, D., Horowitz, M., Pertwee, R.G., Ross, R.A., Mechoulam, R. and Fride, E. (1999) HU-308: a specific agonist for CB2, a peripheral cannabinoid receptor. Proc. Natl. Acad. Sci. USA, 96: 14228-14233. [PMID:10588688]
8. Hillard, C. J., Manna, S., Greenberg, M. J., DiCamelli, R., Ross, R. A., Stevenson, L. A., Murphy, V., Pertwee, R. G. and Campbell, W. B. (1999) Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1). J. Pharmacol. Exp. Ther., 289: 1427-1433. [PMID:10336536]
9. Hirst, R. A., Almond, S. L. and Lambert, D. G. (1996) Characterisation of the rat cerebella CB1 receptor using SR141716A, a central cannabinoid receptor antagonist. Neurosci. Lett., 220: 101-104. [PMID:8981483]
10. Huffman, J. W., Liddle, J., Yu, S., Aung, M. M., Abood, M. E., Wiley, J. L. and Martin, B. R. (1999) 3-(1',1'-dimethylbutyl)-1-deoxy-Δ8-THC and related compounds: synthesis of selective ligands for the CB2 receptor. Bioorg. Med. Chem., 7: 2905-2914. [PMID:10658595]
11. Jung, M., Calassi, R., Rinaldi Carmona, M., Chardenot, P., Le Fur, G., Soubrie, P. and Oury-Donat, F. (1997) Characterization of CB1 receptors on rat neuronal cell cultures: binding and functional studies using the selective receptor antagonist SR 141716A. J. Neurochem., 68: 402-409. [PMID:8978752]
12. Khanolkar, AD; Abadji, V; Lin, S; Hill, WA; Taha, G; Abouzid, K; Meng, Z; Fan, P; Makriyannis, A. (1996) Head group analogs of arachidonylethanolamide, the endogenous cannabinoid ligand. J. Med. Chem., 39 (22): 4515-9. [PMID:8893848]
13. Lan, R., Gatley, J., Lu, Q., Fan, P., Fernando, S. R., Volkow, N. D., Pertwee, R. and Makriyannis, A. (1999) Design and synthesis of the CB1 selective cannabinoid antagonist AM281: a potential human SPECT ligand. AAPS Pharmsci., 1: E4-null. [PMID:11741201]
14. Lan, R; Liu, Q; Fan, P; Lin, S; Fernando, SR; McCallion, D; Pertwee, R; Makriyannis, A. (1999) Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J. Med. Chem., 42 (4): 769-76. [PMID:10052983]
15. O'Sullivan, SE. (2007) Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br. J. Pharmacol., 152 (5): 576-82. [PMID:17704824]
16. Pertwee, RG. (2000) Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development. Expert Opin Investig Drugs, 9 (7): 1553-71. [PMID:11060760]
17. 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]
18. Petitet, F., Marin, L. and Doble, A. (1996) Biochemical and pharmacological characterization of cannabinoid binding sites using [3H]SR141716A. Neuroreport, 7: 789-792. [PMID:8733746]
19. 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]
20. Rinaldi-Carmona, M., Barth, F., Heaulme, M., Shire, D., Calandra, B., Congy, C., Martinez, S., Maruani, J., Neliat, G., Caput, D. et al.. (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett., 350: 240-244. [PMID:8070571]
21. Rinaldi-Carmona, M., Barth, F., Millan, J., Derocq, J. M., Casellas, P., Congy, C., Oustric, D., Sarran, M., Bouaboula, M., Calandra, B., Portier, M., Shire, D., Breliere, J. C. and Le Fur, G. L. (1998) SR144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J. Pharmacol. Exp. Ther., 284: 644-650. [PMID:9454810]
22. Rinaldi-Carmona, M., Pialot, F., Congy, C., Redon, E., Barth, F., Bachy, A., Breliere, J. C., Soubrie, P. and Le Fur, G. (1996) Characterization and distribution of binding sites for [3H]-SR 141716A, a selective brain (CB1) cannabinoid receptor antagonist, in rodent brain. Life Sci., 58: 1239-1247. [PMID:8614277]
23. Ross, R. A., Brockie, H. C., Fernando, S. R., Saha, B., Razdan, R. K. and Pertwee, R. G. (1998) Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine. Br. J. Pharmacol., 125: 1345-1351. [PMID:9863666]
24. Ross, R. A., Brockie, H. C., Stevenson, L. A., Murphy, V. L., Templeton, F., Makriyannis, A. and Pertwee, R. G. (1999) Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656 and AM630. Br. J. Pharmacol., 126: 665-672. [PMID:10188977]
25. Showalter, V. M., Compton, D. R., Martin, B. R. and Abood, M. E. (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]
26. Sim, L. J., Hampson, R. E., Deadwyler, S. A. and Childers, S. R. (1996) Effects of chronic treatment with Δ9-tetrahydrocannabinol on cannabinoid-stimulated [35S]GTPγS autoradiography in rat brain. J. Neurosci., 16: 8057-8066. [PMID:8987831]
27. Slipetz, D. M., O'Neill, G. P., Favreau, L., Dufresne, C., Gallant, M., Gareau, Y., Guay, D., Labelle, M. and Metters, K. M. (1995) Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase. Mol. Pharmacol., 48: 352-361. [PMID:7651369]
28. Song, Z. H. and Bonner, T. I. (1996) A lysine residue of the cannabinoid receptor is critical for receptor recognition by several agonists but not WIN55212-2. . Mol. Pharmacol., 49: 891-896. [PMID:8622639]
29. Thomas, B. F., Gilliam, A. F., Burch, D. F., Roche, M. J. and Seltzman, H. H. (1998) Comparative receptor binding analyses of cannabinoid agonists and antagonists. J. Pharmacol. Exp. Ther., 285: 285-292. [PMID:9536023]
30. Yao, BB; Mukherjee, S; Fan, Y; Garrison, TR; Daza, AV; Grayson, GK; Hooker, BA; Dart, MJ; Sullivan, JP; Meyer, MD. (2006) In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor?. Br. J. Pharmacol., 149 (2): 145-54. [PMID:16894349]
31. Zygmunt, P. M., Petersson, J., Andersson, D. A., Chuang, H., Sorgard, M., Di Marzo, V., Julius, D. and Hogestatt, E. D. (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature, 400: 452-457. [PMID:10440374]
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Both CB1 and CB2 receptors may be labelled with [3H]CP55940 (0.6 nM; [25]) and [3H]WIN55212-2(2–12 nM; [27-28]). anandamide is also an agonist at vanilloid receptors (TRPV1) and PPARs [15,31]. There is evidence for an allosteric site on the CB1 receptor [19]. All of the compounds listed as antagonists behave as inverse agonists in some bioassay systems [17]. For some cannabinoid receptor ligands, additional pharmacological targets that include GPR55 and GPR119 have been identified [17]. Moreover, GPR18, GPR55 and GPR119, although showing little structural similarity to CB1 and CB2 receptors, respond to endogenous agents that are structurally similar to the endogenous cannabinoid ligands [17].