cannabinoid receptors


Summary: A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. They also bind a structurally distinct class of endogenous factors referred to as ENDOCANNABINOIDS. The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES.

Top Publications

  1. Despres J, Golay A, Sjöström L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353:2121-34 pubmed
  2. Korzh A, Keren O, Gafni M, Bar Josef H, Sarne Y. Modulation of extracellular signal-regulated kinase (ERK) by opioid and cannabinoid receptors that are expressed in the same cell. Brain Res. 2008;1189:23-32 pubmed
    ..phosphorylation of ERK by a similar mechanism that involved activation of delta-opioid receptors or CB1 cannabinoid receptors coupled to Gi/Go proteins, matrix metalloproteases, vascular endothelial growth factor (VEGF) receptors ..
  3. Kempf K, Hector J, Strate T, Schwarzloh B, Rose B, Herder C, et al. Immune-mediated activation of the endocannabinoid system in visceral adipose tissue in obesity. Horm Metab Res. 2007;39:596-600 pubmed
    ..Our data show a strong association between adipose tissue inflammation and ECS activation in obesity, and indicate that a pro-inflammatory state may directly activate the ECS. ..
  4. Gratzke C, Christ G, Stief C, Andersson K, Hedlund P. Localization and function of cannabinoid receptors in the corpus cavernosum: basis for modulation of nitric oxide synthase nerve activity. Eur Urol. 2010;57:342-8 pubmed publisher
    ..However, no information is available on the distribution of CB-receptors or effects by anandamide in CC from primates or humans...
  5. Ross R. The enigmatic pharmacology of GPR55. Trends Pharmacol Sci. 2009;30:156-63 pubmed publisher
    ..Here, I review the recent literature in an effort to glean the key controversies and outstanding questions surrounding the interaction between cannabinoids and this orphan receptor. ..
  6. Gary Bobo M, Elachouri G, Gallas J, Janiak P, Marini P, Ravinet Trillou C, et al. Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. Hepatology. 2007;46:122-9 pubmed
  7. McPartland J. The endocannabinoid system: an osteopathic perspective. J Am Osteopath Assoc. 2008;108:586-600 pubmed
    ..The endocannabinoid system consists of cannabinoid receptors, endogenous ligands, and ligand-metabolizing enzymes...
  8. Durdagi S, Papadopoulos M, Zoumpoulakis P, Koukoulitsa C, Mavromoustakos T. A computational study on cannabinoid receptors and potent bioactive cannabinoid ligands: homology modeling, docking, de novo drug design and molecular dynamics analysis. Mol Divers. 2010;14:257-76 pubmed publisher
    ..The re-obtained models confirmed the ligand-binding pockets that were derived based on rhodopsin. ..
  9. Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson N, Leonova J, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007;152:1092-101 pubmed
    ..These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s). ..

More Information


  1. Brown A. Novel cannabinoid receptors. Br J Pharmacol. 2007;152:567-75 pubmed
    ..However, there remain several examples where these classical cannabinoid receptors do not explain observed pharmacology...
  2. De Petrocellis L, Di Marzo V. An introduction to the endocannabinoid system: from the early to the latest concepts. Best Pract Res Clin Endocrinol Metab. 2009;23:1-15 pubmed publisher
    ..The complexity of the endocannabinoid system and of its physiological and pathological function is outlined in this introductory chapter, for a better understanding of the subsequent chapters in this special issue. ..
  3. Di Marzo V. The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacol Res. 2009;60:77-84 pubmed publisher
    ..Compounds that selectively manipulate the action and levels of endocannabinoids at their targets have been and are being developed, and represent templates for potential new therapeutic drugs. ..
  4. Athanasiou A, Clarke A, Turner A, Kumaran N, Vakilpour S, Smith P, et al. Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death. Biochem Biophys Res Commun. 2007;364:131-7 pubmed
    ..These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors.
  5. Reggio P. Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown. Curr Med Chem. 2010;17:1468-86 pubmed
    ..g., the serotonin and dopamine receptors), the cannabinoid receptors have neutral, highly lipophilic ligands derived from the fatty acid, arachidonic acid...
  6. Jesudason D, Wittert G. Endocannabinoid system in food intake and metabolic regulation. Curr Opin Lipidol. 2008;19:344-8 pubmed publisher
    ..The ubiquitous role of the endocannabinoid system in food intake and energy metabolism is now established. Drugs that manipulate different aspects of this system may benefit subjects with the metabolic and cachectic syndromes. ..
  7. Korte G, Dreiseitel A, Schreier P, Oehme A, Locher S, Geiger S, et al. Tea catechins' affinity for human cannabinoid receptors. Phytomedicine. 2010;17:19-22 pubmed publisher
    ..Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33...
  8. Bennetzen M, Nielsen T, Paulsen S, Bendix J, Fisker S, Jessen N, et al. Reduced cannabinoid receptor 1 protein in subcutaneous adipose tissue of obese. Eur J Clin Invest. 2010;40:121-6 pubmed publisher
    ..Our present findings do not indicate that cannabinoid receptor 1 is directly involved in the endocannabinoid system over-activity in adipose tissue in obesity. ..
  9. Alexander S, Kendall D. The complications of promiscuity: endocannabinoid action and metabolism. Br J Pharmacol. 2007;152:602-23 pubmed
    ..We highlight the complexity of the endocannabinoid system, based on the promiscuous nature of ECLs and their metabolites, as well as the synthetic modulators of the endocannabinoid system. ..
  10. Fichna J, Schicho R, Andrews C, Bashashati M, Klompus M, McKay D, et al. Salvinorin A inhibits colonic transit and neurogenic ion transport in mice by activating kappa-opioid and cannabinoid receptors. Neurogastroenterol Motil. 2009;21:1326-e128 pubmed publisher
    ..Due to its specific regional action, SA or its derivatives may be useful drugs in the treatment of lower GI disorders associated with increased GI transit and diarrhoea. ..
  11. Jourdan T, Djaouti L, Demizieux L, Gresti J, Verges B, Degrace P. CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice. Diabetes. 2010;59:926-34 pubmed publisher
    ..We examined the impact of CB1 antagonism on liver and adipose tissue lipid metabolism in a mouse model of diet-induced obesity...
  12. Van Gaal L, Pi Sunyer X, Despres J, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care. 2008;31 Suppl 2:S229-40 pubmed publisher
    ..Rimonabant was generally well tolerated, with more frequently reported adverse events being gastrointestinal, neurological, and psychiatric in nature. ..
  13. Lauckner J, Jensen J, Chen H, Lu H, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A. 2008;105:2699-704 pubmed publisher
    ..GPR55 activation also inhibits M current. These results establish GPR55 as a cannabinoid receptor with signaling distinct from CB(1) and CB(2). ..
  14. Onaivi E. Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications. Int Rev Neurobiol. 2009;88:335-69 pubmed publisher
    ..Thus, understanding the ECS in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease. ..
  15. Mechoulam R, Peters M, Murillo Rodriguez E, Hanus L. Cannabidiol--recent advances. Chem Biodivers. 2007;4:1678-92 pubmed
    ..The plethora of positive pharmacological effects observed with CBD make this compound a highly attractive therapeutic entity. ..
  16. Massa F, Storr M, Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med (Berl). 2005;83:944-54 pubmed
  17. Endoh T. Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius. Br J Pharmacol. 2006;147:391-401 pubmed
    1. The profile of opioid and cannabinoid receptors in neurons of the nucleus tractus solitarius (NTS) has been studied using the whole-cell configuration of the patch clamp technique. 2...
  18. Karanian D, Bahr B. Cannabinoid drugs and enhancement of endocannabinoid responses: strategies for a wide array of disease states. Curr Mol Med. 2006;6:677-84 pubmed
    ..The endocannabinoid system is comprised of three primary components: (i) cannabinoid receptors, (ii) endocannabinoid transport system, and (iii) hydrolysis enzymes that break down the endogenous ..
  19. Mackie K, Stella N. Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J. 2006;8:E298-306 pubmed
  20. Davis S. Contemporary strategies for managing cardiometabolic risk factors. J Manag Care Pharm. 2006;12:S4-9 pubmed
    ..It has led to significant weight loss, reduced central fat, and improved glycemic and lipid profiles. ..
  21. Milman G, Maor Y, Abu Lafi S, Horowitz M, Gallily R, Batkai S, et al. N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties. Proc Natl Acad Sci U S A. 2006;103:2428-33 pubmed
    ..Many of these effects parallel those reported for abnormal cannabidiol (Abn-CBD), a synthetic agonist of a putative novel cannabinoid-type receptor. Hence, ARA-S may represent an endogenous agonist for this receptor. ..
  22. Juan Pico P, Fuentes E, Bermúdez Silva F, Javier Díaz Molina F, Ripoll C, Rodriguez de Fonseca F, et al. Cannabinoid receptors regulate Ca(2+) signals and insulin secretion in pancreatic beta-cell. Cell Calcium. 2006;39:155-62 pubmed
    ..This effect may be a new component involved in the orexigenic effect of endocannabinoids and constitutes a potential target for pharmacologic manipulation of the energy balance. ..
  23. Scheen A, Van Gaal L, Despres J, Pi Sunyer X, Golay A, Hanotin C. [Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: overview of RIO studies]. Rev Med Suisse. 2006;2:1916-23 pubmed
    ..Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant. ..
  24. Schuel H. Tuning the oviduct to the anandamide tone. J Clin Invest. 2006;116:2087-90 pubmed
    ..Anandamide (N-arachidonoylethanolamide) is a lipid signal molecule that was the first endogenous agonist for cannabinoid receptors to be discovered...
  25. Gobbi G, Bambico F, Mangieri R, Bortolato M, Campolongo P, Solinas M, et al. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci U S A. 2005;102:18620-5 pubmed
    ..The active constituent of cannabis, delta9-tetrahydrocannabinol, acts by binding to brain CB1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous ..
  26. Mestre L, Correa F, Docagne F, Clemente D, Ortega Gutierrez S, Arevalo Martin A, et al. [Cannabinoid system and neuroinflammation:therapeutic perspectives in multiple sclerosis]. Rev Neurol. 2006;43:541-8 pubmed
    The endocannabinoid system consists of cannabinoid receptors, endogenous ligands and the enzymatic elements involved in their synthesis and breakdown...
  27. Duncan M, Davison J, Sharkey K. Review article: endocannabinoids and their receptors in the enteric nervous system. Aliment Pharmacol Ther. 2005;22:667-83 pubmed
    ..In the last 25 years this area of research has grown exponentially with the discovery of specific cannabinoid receptors and endogenous ligands...
  28. Whiteside G, Gottshall S, Boulet J, Chaffer S, Harrison J, Pearson M, et al. A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833. Eur J Pharmacol. 2005;528:65-72 pubmed
    ..Furthermore, these data suggest that the mechanism of action for GW405833 does not depend on the release of endogenous opioids. ..
  29. Zaniewska M, McCreary A, Przegalinski E, Filip M. Evaluation of the role of nicotinic acetylcholine receptor subtypes and cannabinoid system in the discriminative stimulus effects of nicotine in rats. Eur J Pharmacol. 2006;540:96-106 pubmed
    ..Furthermore, we excluded the involvement of either cannabinoid CB1 and CB2 receptors or increases in the endocannabinoid tone in the nicotine discrimination. ..
  30. Shapiro H, Singer P. Rimonabant in obese patients with type 2 diabetes. Lancet. 2007;369:553-4; author reply 554-5 pubmed
  31. Mitrirattanakul S, Ramakul N, Guerrero A, Matsuka Y, Ono T, Iwase H, et al. Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain. Pain. 2006;126:102-14 pubmed
  32. Pertwee R. The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes (Lond). 2006;30 Suppl 1:S13-8 pubmed
    ..Endogenous agonists for cannabinoid receptors also exist, and are all eicosanoids...
  33. Mackie K. Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol. 2006;46:101-22 pubmed
    CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids)...
  34. Koch M, Dehghani F, Habazettl I, Schomerus C, Korf H. Cannabinoids attenuate norepinephrine-induced melatonin biosynthesis in the rat pineal gland by reducing arylalkylamine N-acetyltransferase activity without involvement of cannabinoid receptors. J Neurochem. 2006;98:267-78 pubmed
    Cannabinoids modulate neuronal and neuroendocrine circuits by binding to cannabinoid receptors acting upon cAMP/Ca(2+)-mediated intracellular signaling cascades...
  35. Pi Sunyer F, Aronne L, Heshmati H, Devin J, Rosenstock J. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 2006;295:761-75 pubmed
    ..However, the trial was limited by a high drop-out rate and longer-term effects of the drug require further study. Clinical Trials Registration Identifier: NCT00029861. ..
  36. Pertwee R. The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids. AAPS J. 2005;7:E625-54 pubmed
    ..Endogenous agonists for cannabinoid receptors also exist...
  37. Laviolette S, Grace A. The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction. Cell Mol Life Sci. 2006;63:1597-613 pubmed
  38. Wright K, Rooney N, Feeney M, Tate J, Robertson D, Welham M, et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology. 2005;129:437-53 pubmed
    Two G-protein-coupled cannabinoid receptors, termed CB1 and CB2, have been identified and several mammalian enteric nervous systems express CB1 receptors and produce endocannabinoids...
  39. Baker D, Pryce G, Davies W, Hiley C. In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol Sci. 2006;27:1-4 pubmed
    ..This receptor is reported to be expressed in several tissues and might function in lipid or vascular biology. Thus, GPR55 might represent a new cannabinoid receptor. ..
  40. Wang H, Xie H, Guo Y, Zhang H, Takahashi T, Kingsley P, et al. Fatty acid amide hydrolase deficiency limits early pregnancy events. J Clin Invest. 2006;116:2122-31 pubmed
    ..This study uncovers what we believe to be a novel regulation of preimplantation processes, which could be clinically relevant for fertility regulation in women. ..
  41. Marchalant Y, Rosi S, Wenk G. Anti-inflammatory property of the cannabinoid agonist WIN-55212-2 in a rodent model of chronic brain inflammation. Neuroscience. 2007;144:1516-22 pubmed
    b>Cannabinoid receptors (CBr) stimulation induces numerous central and peripheral effects...
  42. Pavon F, Bilbao A, Hernandez Folgado L, Cippitelli A, Jagerovic N, Abellán G, et al. Antiobesity effects of the novel in vivo neutral cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole--LH 21. Neuropharmacology. 2006;51:358-66 pubmed
  43. Sarfaraz S, Afaq F, Adhami V, Malik A, Mukhtar H. Cannabinoid receptor agonist-induced apoptosis of human prostate cancer cells LNCaP proceeds through sustained activation of ERK1/2 leading to G1 cell cycle arrest. J Biol Chem. 2006;281:39480-91 pubmed
    We have recently shown that the expression levels of both cannabinoid receptors CB(1) and CB(2) are higher in human prostate cancer cells than in normal prostate epithelial cells, and treatment of LNCaP cells with WIN-55,212-2 (a mixed ..
  44. Guzman M, Duarte M, Blazquez C, Ravina J, Rosa M, Galve Roperh I, et al. A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer. 2006;95:197-203 pubmed
  45. Di Marzo V, Izzo A. Endocannabinoid overactivity and intestinal inflammation. Gut. 2006;55:1373-6 pubmed
    b>Cannabinoid receptors of type 1 and 2 (CB(1) and CB(2)), endogenous ligands that activate them (endocannabinoids), and mechanisms for endocannabinoid biosynthesis and inactivation have been identified in the gastrointestinal system...
  46. Jia W, Hegde V, Singh N, Sisco D, Grant S, Nagarkatti M, et al. Delta9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria. Mol Cancer Res. 2006;4:549-62 pubmed
    ..Together, these data suggested that Raf-1/MEK/ERK/RSK-mediated Bad translocation played a critical role in THC-induced apoptosis in Jurkat cells. ..
  47. Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev. 2006;27:73-100 pubmed
    ..b>Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic ..
  48. Yanovski S. Pharmacotherapy for obesity--promise and uncertainty. N Engl J Med. 2005;353:2187-9 pubmed
  49. Scheen A, Finer N, Hollander P, Jensen M, Van Gaal L. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 2006;368:1660-72 pubmed
  50. Bowling A. Cannabinoids in MS--are we any closer to knowing how best to use them?. Mult Scler. 2006;12:523-5 pubmed
  51. Leichsenring A, Andriske M, Bäcker I, Stichel C, Lübbert H. Analgesic and antiinflammatory effects of cannabinoid receptor agonists in a rat model of neuropathic pain. Naunyn Schmiedebergs Arch Pharmacol. 2009;379:627-36 pubmed publisher
    ..Our results emphasize the therapeutic efficacy of cannabinoid receptor agonists and their inhibitory effects on the formation of gliosis. ..
  52. Golay A. [Rimonabant helps in overweight patients with multiple cardiovascular risk factors such as type 2 diabetes]. Rev Med Suisse. 2008;4:1828 pubmed
  53. Petko J, Tranchina T, Patel G, Levenson R, Justice Bitner S. Identifying novel members of the Wntless interactome through genetic and candidate gene approaches. Brain Res Bull. 2018;138:96-105 pubmed publisher
    ..we show that among a variety of protein, Wls interacts with the dopamine transporter (target of cocaine), cannabinoid receptors (target of THC), Adenosine A2A receptor (target of caffeine), and SGIP1 (endocytic regulator of ..