Cannabinoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Cannabinoid Receptors [26]) 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].

There are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB₁ and CB₂ receptors [25]. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are nabilone (Cesamet®), a synthetic CB₁/CB₂ receptor agonist, and synthetic Δ⁹-tetrahydrocannabinol (Marinol®; dronabinol), which can also be used as an appetite stimulant. The third medicine, Sativex®, contains mainly Δ⁹-tetrahydrocannabinol and cannabidiol, both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain.

Both CB₁ and CB₂ receptors may be labelled with [³H]CP55940 (0.5 nM; [38]) and [³H]WIN55212-2 (2–2.4 nM; [40-41]). Anandamide is also an agonist at vanilloid receptors (TRPV1) and PPARs [23,45]. There is evidence for an allosteric site on the CB₁ receptor [29]. All of the compounds listed as antagonists behave as inverse agonists in some bioassay systems [26]. For some cannabinoid receptor ligands, additional pharmacological targets that include GPR55 and GPR119 have been identified [26]. 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 [26].

* Key recommended reading is highlighted with an asterisk

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Subcommittee members: Roger G. Pertwee (Chairperson) School of Medical Sciences Institute of Medical Sciences University of Aberdeen Foresterhill Aberdeen AB25 2ZD UK Allyn C. Howlett (Past chairperson) Neuroscience of Drug Abuse Research Program Julius L. Chambers Biomedical/Biotechnology Research Institute North Carolina Central University 700 George Street Durham NC 27707 USA Mary Abood California Pacific Med Ctr San Francisco CA 94115 USA Stephen P.H. Alexander Associate Professor in Molecular Pharmacology Life Sciences E Floor University of Nottingham Medical School Nottingham NG7 2UH UK Heather Bradshaw Psychological and Brain Sciences Indiana University 1101 East 10th Street Bloomington, IN 47405 USA Guy Cabral Microbiology and Immunology Department Medical College of Virginia Room 6040 1101 E. Marshall Street Richmond VA 23219 USA Vincenzo Di Marzo Via Campi Flegrei 34, Fabbr. 70 Pozzuoli Napoli 80078 Italy Maurice R. Elphick Queen Mary University London London E1 4NS UK Peter Greasley Department of Molecular Pharmacology AstraZeneca R&D Mölndal S-431 83 Mölndal Sweden George Kunos Lab. Physiol. Studies NIAAA NIH Bethesda MD 20892 USA Ken Mackie Dept. Anesthesiology University of Washington Seattle WA 98195 USA Raphael Mechoulam Department of Natural Products Faculty of Medicine of Hebrew University Jerusalem 91120 Israel

Other contributors: Francis Barth Sanofi Synthelabo Recherche Montpellier 34184 France Tom I. Bonner Special Volunteer Office of Science Director NIMH Bethesda MD USA Pierre Casellas Sanofi Recherche Centre de Montpellier 371 rue du Professeur Joseph-Blayac Montpellier 34184 France Ben F. Cravatt Skaggs Institute for Chemical Biology Scripps Research Institute La Jolla CA 92037 USA William A. Devane Department of Pharmacology and Toxicology Medical College of Virginia Box 613 MCV Station Richmond VA 23298-0613 USA Christian C. Felder Lilly Research Laboratories Lilly Corporate Center Drop 0510 Indianapolis IN 46285 USA Miles Herkenham Section of Functional Neuroanatomy National Institute of Mental Health Building 36 Room 2D15 36 Convent Drive Bethesda MD 20892-4070 USA Ruth A. Ross University of Toronto Department of Pharmacology & Toxicology Medical Sciences Building, Room 4207 1 King's College Circle Toronto, Ontario M5S 1A8 Canada