AM 251

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Cat.No. 1117 - AM 251 | C22H21Cl2IN4O | CAS No. 183232-66-8
Description: Potent CB1 antagonist; also GPR55 agonist
Chemical Name: N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
Purity: ≥99% (HPLC)
Datasheet
Citations (114)
Literature

Biological Activity

Potent CB1 receptor antagonist (IC50 = 8 nM, Ki = 7.49 nM) that displays 306-fold selectivity over CB2 receptors. Also potent GPR55 agonist (EC50 = 39 nM). Also available in a fluorescent form (Cat. No. 2540).

Technical Data

M. Wt 555.24
Formula C22H21Cl2IN4O
Storage Store at RT
Purity ≥99% (HPLC)
CAS Number 183232-66-8
PubChem ID 2125
InChI Key BUZAJRPLUGXRAB-UHFFFAOYSA-N
Smiles CC1=C(N(N=C1C(=O)NN1CCCCC1)C1=C(Cl)C=C(Cl)C=C1)C1=CC=C(I)C=C1

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

All Tocris products are intended for laboratory research use only.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 55.52 100
ethanol 13.88 25

Preparing Stock Solutions

The following data is based on the product molecular weight 555.24. Batch specific molecular weights may vary from batch to batch due to solvent of hydration, which will affect the solvent volumes required to prepare stock solutions.

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Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.8 mL 9.01 mL 18.01 mL
5 mM 0.36 mL 1.8 mL 3.6 mL
10 mM 0.18 mL 0.9 mL 1.8 mL
50 mM 0.04 mL 0.18 mL 0.36 mL

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Product Datasheets

Certificate of Analysis / Product Datasheet
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Safety Datasheet

References

References are publications that support the products' biological activity.

Gatley et al (1996) 125I-labeled AM 251: a radioiodinated ligand which binds in vivo to mouse brain cannabinoid CB1 receptors. Eur.J.Pharmacol. 307 331 PMID: 8836622

Lan et al (1999) Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J.Med.Chem. 42 769 PMID: 10052983

Pertwee (2005) Inverse agonism and neutral antagonism at cannabinoid CB1 receptors. Life Sci. 76 1307 PMID: 15670612

Gatley et al (1997) Binding of the non-classical cannabinoid CP 55,940, and the diarylpyrazole AM251 to rodent brain cannabinoid receptors. Life Sci. 61 191 PMID: 9335234

Ryberg et al (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br.J.Pharmacol. 152 1092 PMID: 17876302


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Keywords: Potent CB1 antagonist GPR55 agonist cannabinoid receptors AM251 cb1r CB1 Receptors

114 Citations for AM 251

Citations are publications that use Tocris products. Selected citations for AM 251 include:

Han (2017) Cannabinoid receptor 1 contributes to sprouted innervation in endometrial ectopic growth through mitogen-activated protein kinase activation. Brain Res 1663 132 PMID: 28322749

King-Himmelreich (2017) AMPK contributes to aerobic exercise-induced antinociception downstream of endocannabinoids. Neuropharmacology 124 134 PMID: 28479394

Shang et al (2016) Δ 9-Tetrahydrocannabinol Reverses TNFα-induced Increase in Airway Epithelial Cell Permeability through CB 2 Receptors Biochemical Pharmacology PMID: 27641813

Malek et al (2015) Anandamide, Acting via CB2 Receptors, Alleviates LPS-Induced Neuroinflammation in Rat Primary Microglial Cultures. Neural Plast 2015 130639 PMID: 26090232

Zhang et al (2015) Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex. PLoS One 10 e0142160 PMID: 26558388

Yang et al (2015) Cannabinoid receptor CB2 is involved in tetrahydrocannabinol-induced anti-inflammation against lipopolysaccharide in MG-63 cells. Sci Rep 2015 362126 PMID: 25653478

Liu et al (2015) Involvement of GluR2 up-regulation in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptor in mice. Nutr Diabetes 5 9490 PMID: 25830356

Vähätalo et al (2015) Role of the endocannabinoid system in obesity induced by neuropeptide Y overexpression in noradrenergic neurons. Mol Cell Neurosci 5 e151 PMID: 25915740

Zhou et al (2015) Regional effects of endocannabinoid, BDNF and FGF receptor signalling on neuroblast motility and guidance along the rostral migratory stream. Nat Commun 64 32 PMID: 25481343

Dincheva et al (2015) FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nat Commun 6 6395 PMID: 25731744

Lenkey et al (2015) Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals. Sci Rep 6 6557 PMID: 25891347

Smith et al (2015) The Effects of the Endocannabinoids Anandamide and 2-Arachidonoylglycerol on Human Osteoblast Proliferation and Differentiation. Proc Natl Acad Sci U S A 10 e0136546 PMID: 26414859

Bowles et al (2015) A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome. Mol Pharmacol 112 285 PMID: 25535367

Stanley et al (2015) Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation. Front Cell Neurosci 107 568 PMID: 26092099

Martin et al (2015) Endocannabinoids Mediate Muscarinic Acetylcholine Receptor-Dependent Long-Term Depression in the Adult Medial Prefrontal Cortex. Br J Pharmacol 9 457 PMID: 26648844

Parvathy and Masocha (2015) Coadministration of indomethacin and minocycline attenuates established paclitaxel-induced neuropathic thermal hyperalgesia: Involvement of cannabinoid CB1 receptors. J Neurosci 5 10541 PMID: 26085115

Krishnan and Chatterjee (2015) Differential immune mechanism to HIV-1 Tat variants and its regulation by AEA [corrected]. PLoS One 5 9887 PMID: 25943894

Szabó et al (2014) Presynaptic calcium channel inhibition underlies CB1 cannabinoid receptor-mediated suppression of GABA release. Mediators Inflamm 34 7958 PMID: 24899717

Alpár et al (2014) Endocannabinoids modulate cortical development by configuring Slit2/Robo1 signalling. J Neurosci 5 4421 PMID: 25030704

Tortoriello et al (2014) Miswiring the brain: △9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. Proc Natl Acad Sci U S A 33 668 PMID: 24469251

Hassanzadeh and Rostami (2014) CB1 cannabinoid receptors are involved in neuroleptic-induced enhancement of brain neurotensin. J Neurosci 17 181 PMID: 24847420

Sreevalsan and Safe (2013) The cannabinoid WIN 55,212-2 decreases specificity protein transcription factors and the oncogenic cap protein eIF4E in colon cancer cells. Mol Cancer Ther 12 2483 PMID: 24030632

Wargent et al (2013) The cannabinoid δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutr Diabetes 3 e68 PMID: 23712280

Chanda et al (2013) Hepatic cannabinoid receptor type 1 mediates alcohol-induced regulation of bile acid enzyme genes expression via CREBH. PLoS One 8 e68845 PMID: 23894352

Benz et al (2013) Expression and functional relevance of cannabinoid receptor 1 in Hodgkin lymphoma. PLoS One 8 e81675 PMID: 24349109

Malenczyk et al (2013) CB1 cannabinoid receptors couple to focal adhesion kinase to control insulin release. J Biol Chem 288 32685 PMID: 24089517

Abush and Akirav (2013) Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory. Neuropsychopharmacology 38 1521 PMID: 23426383

Cao et al (2013) Cannabinoid HU210 protects isolated rat stomach against impairment caused by serum of rats with experimental acute pancreatitis. PLoS One 7 e52921 PMID: 23285225

Keimpema et al (2013) Diacylglycerol lipase α manipulation reveals developmental roles for intercellular endocannabinoid signaling. Nat Commun 3 2093 PMID: 23806960

Stern et al (2012) On disruption of fear memory by reconsolidation blockade: evidence from cannabidiol treatment. Neuropsychopharmacology 37 2132 PMID: 22549120

Tumati et al (2012) Repeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist. J Neuroimmunol 244 23 PMID: 22285397

Laricchiuta et al (2012) CB1 receptor autoradiographic characterization of the individual differences in approach and avoidance motivation. PLoS One 7 e42111 PMID: 22848724

Brents et al (2012) Monohydroxylated metabolites of the K2 synthetic cannabinoid JWH-073 retain intermediate to high cannabinoid 1 receptor (CB1R) affinity and exhibit neutral antagonist to partial agonist activity. Biochem Pharmacol 83 952 PMID: 22266354

Liu et al (2012) Betulinic acid targets YY1 and ErbB2 through cannabinoid receptor-dependent disruption of microRNA-27a:ZBTB10 in breast cancer. Mol Cancer Ther 11 1421 PMID: 22553354

Guida et al (2012) Salvinorin A reduces mechanical allodynia and spinal neuronal hyperexcitability induced by peripheral formalin injection. Mol Pain 8 60 PMID: 22913292

Ganon-Elazar and Akirav (2012) Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress. Neuropsychopharmacology 37 456 PMID: 21918506

Tozzi et al (2012) A2A adenosine receptor antagonism enhances synaptic and motor effects of cocaine via CB1 cannabinoid receptor activation. PLoS One 7 e38312 PMID: 22715379

Caiati et al (2012) Developmental regulation of CB1-mediated spike-time dependent depression at immature mossy fiber-CA3 synapses. Sci Rep 2 285 PMID: 22368777

Chanda et al (2012) Activation of cannabinoid receptor type 1 (Cb1r) disrupts hepatic insulin receptor signaling via cyclic AMP-response element-binding protein H (Crebh)-mediated induction of Lipin1 gene. Br J Pharmacol 287 38041 PMID: 22989885

Gonzalez-Islas et al (2012) Tonic and transient endocannabinoid regulation of AMPAergic miniature postsynaptic currents and homeostatic plasticity in embryonic motor networks. Sci Rep 32 13597 PMID: 23015449

Casarotto et al (2012) Opposing roles for cannabinoid receptor type-1 (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Pain 37 478 PMID: 21937980

Niu et al (2012) Effects of gonadal hormones on the peripheral cannabinoid receptor 1 (CB1R) system under a myositis condition in rats. J Pharmacol Exp Ther 153 2283 PMID: 22940464

Brents et al (2011) Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity. PLoS One 6 e21917 PMID: 21755008

Crespillo et al (2011) Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade. Biochem J 433 175 PMID: 20955176

Li and Burrell (2011) Associative, bidirectional changes in neural signaling utilizing NMDA receptor- and endocannabinoid-dependent mechanisms. Learn Mem 18 545 PMID: 21844187

Pan et al (2011) Alterations of endocannabinoid signaling, synaptic plasticity, learning, and memory in monoacylglycerol lipase knock-out mice. J Cell Biol 31 13420 PMID: 21940435

Hassanzadeh and Hassanzadeh (2011) The Role of the Endocannabinoids in Suppression of the Hypothalamic-pituitary-adrenal Axis Activity by Doxepin. J Leukoc Biol 14 414 PMID: 23493814

Buznikov et al (2010) A putative 'pre-nervous' endocannabinoid system in early echinoderm development. Dev Neurosci 32 1 PMID: 19907129

Mair et al (2010) Interaction between anandamide and sphingosine-1-phosphate in mediating vasorelaxation in rat coronary artery. Br J Pharmacol 161 176 PMID: 20718749

Jiang et al (2010) The maturation of GABAergic transmission in visual cortex requires endocannabinoid-mediated LTD of inhibitory inputs during a critical period. Neuron 66 248 PMID: 20435001

Yuan and Burrell (2010) Endocannabinoid-dependent LTD in a nociceptive synapse requires activation of a presynaptic TRPV-like receptor. J Neurophysiol 104 2766 PMID: 20884761

Atkinson et al (2010) Regulation of the hypothalamic-pituitary-adrenal axis circadian rhythm by endocannabinoids is sexually diergic. Endocrinology 151 3720 PMID: 20534730

Schlosburg et al (2010) Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci 13 1113 PMID: 20729846

Henstridge et al (2010) GPR55 ligands promote receptor coupling to multiple signalling pathways. Br J Pharmacol 160 604 PMID: 20136841

Curto-Reyes et al (2010) Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain. Br J Pharmacol 160 561 PMID: 20233215

Jones et al (2010) Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. Cereb Cortex 332 569 PMID: 19906779

Ho et al (2010) Endocannabinoid modulation of hyperaemia evoked by physiologically relevant stimuli in the rat primary somatosensory cortex. Neuropsychopharmacology 160 736 PMID: 20590576

Hao et al (2010) The cannabinoid WIN55,212-2 protects against oxidized LDL-induced inflammatory response in murine macrophages. Iran J Basic Med Sci 51 2181 PMID: 20305287

Acuna-Goycolea et al (2010) Cannabinoids excite circadian clock neurons. J Neurosci 30 10061 PMID: 20668190

Farkas et al (2010) Retrograde endocannabinoid signaling reduces GABAergic synaptic transmission to gonadotropin-releasing hormone neurons. J Biol Chem 151 5818 PMID: 20926585

Bhaskaran and Smith (2010) Effects of TRPV1 activation on synaptic excitation in the dentate gyrus of a mouse model of temporal lobe epilepsy. Endocrinology 223 529 PMID: 20144892

Garzón et al (2009) Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine. Mol Pain 5 11 PMID: 19284549

Tjen-A-Looi et al (2009) Processing cardiovascular information in the vlPAG during electroacupuncture in rats: roles of endocannabinoids and GABA. J Appl Physiol (1985) 106 1793 PMID: 19325030

Mendiguren and Pineda (2009) Effect of the CB(1) receptor antagonists rimonabant and AM251 on the firing rate of dorsal raphe nucleus neurons in rat brain slices. Br J Pharmacol 158 1579 PMID: 19845674

Meuth et al (2009) The neuroprotective impact of the leak potassium channel TASK1 on stroke development in mice. Exp Neurol 33 42675 PMID: 18930826

Fraga et al (2009) Endogenous cannabinoids induce fever through the activation of CB1 receptors. Neuropsychopharmacology 157 1494 PMID: 19681872

Wallace et al (2009) PKCε regulates behavioral sensitivity, binding and tolerance to the CB1 receptor agonist WIN55,212-2. Iran J Basic Med Sci 34 1733 PMID: 19158669

Ho and Gardiner (2009) Acute hypertension reveals depressor and vasodilator effects of cannabinoids in conscious rats. Br J Pharmacol 156 94 PMID: 19133994

Shen et al (2008) Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321 848 PMID: 18687967

Gibson et al (2008) TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron 57 746 PMID: 18341994

Potenzieri et al (2008) The cannabinoid receptor agonist, WIN 55, 212-2, attenuates tumor-evoked hyperalgesia through peripheral mechanisms. Brain Res 1215 69 PMID: 18486111

Melis et al (2008) Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors. J Neurosci 28 13985 PMID: 19091987

Giannini et al (2008) Activation of cannabinoid receptors prevents antigen-induced asthma-like reaction in guinea pigs. Br J Pharmacol 12 2381 PMID: 18266975

Desroches et al (2008) Modulation of the anti-nociceptive effects of 2-arachidonoyl glycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model. Eur J Neurosci 155 913 PMID: 18695638

Börner et al (2008) Analysis of promoter regions regulating basal and interleukin-4-inducible expression of the human CB1 receptor gene in T lymphocytes. Eur J Pharmacol 73 1013 PMID: 18156315

Georgieva et al (2008) Unique agonist-bound cannabinoid CB1 receptor conformations indicate agonist specificity in signaling. Br J Pharmacol 581 19 PMID: 18162180

Crozier et al (2007) Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex. Proc Natl Acad Sci U S A 104 1383 PMID: 17227847

Huang et al (2007) Cannabinoids excite hypothalamic melanin-concentrating hormone but inhibit hypocretin/orexin neurons: implications for cannabinoid actions on food intake and cognitive arousal. J Neurosci 27 4870 PMID: 17475795

Czesnik et al (2007) Cannabinoid action in the olfactory epithelium. Proc Natl Acad Sci U S A 104 2967 PMID: 17301239

Bátkai et al (2007) Endocannabinoids acting at CB1 receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats. Br J Pharmacol 293 H1689 PMID: 17557913

Kelm et al (2007) Calcium release from presynaptic internal stores is required for ethanol to increase spontaneous γ-aminobutyric acid release onto cerebellum Purkinje neurons. PLoS One 323 356 PMID: 17652632

Rajesh et al (2007) Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis. Cardiovasc Res 82 1382 PMID: 17652447

Ghasemi et al (2007) Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats. EMBO J 151 591 PMID: 17486141

Saitoh et al (2007) The differential contractile responses to capsaicin and anandamide in muscle strips isolated from the rat urinary bladder. J Neurosci 570 182 PMID: 17586490

Fortin and Levine (2007) Differential effects of endocannabinoids on glutamatergic and GABAergic inputs to layer 5 pyramidal neurons. J Biol Chem 17 163 PMID: 16467564

Bender et al (2006) Two coincidence detectors for spike timing-dependent plasticity in somatosensory cortex. J Neurosci 26 4166 PMID: 16624937

Cenni et al (2006) Differential effect of cannabinoid agonists and endocannabinoids on histamine release from distinct regions of the rat brain. Eur J Neurosci 24 1633 PMID: 17004927

Wang et al (2006) Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Neuron 50 443 PMID: 16675398

Moezi et al (2006) Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. J Neurosci 149 898 PMID: 17043671

Derbenev et al (2006) Vanilloid-mediated heterosynaptic facilitation of inhibitory synaptic input to neurons of the rat dorsal motor nucleus of the vagus. PLoS One 26 9666 PMID: 16988037

Kurihara et al (2006) Effects of peripheral cannabinoid receptor ligands on motility and polarization in neutrophil-like HL60 cells and human neutrophils. Br J Pharmacol 281 12908 PMID: 16513651

Jayamanne et al (2006) Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. J Neurosci 147 281 PMID: 16331291

Safo and Regehr (2005) Endocannabinoids control the induction of cerebellar LTD. Neuron 48 647 PMID: 16301180

Berghuis et al (2005) Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Neurobiol Dis 102 19115 PMID: 16357196

Gaskari et al (2005) Role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Sci Rep 146 315 PMID: 16025138

Hoffman et al (2005) Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus. Am J Physiol Heart Circ Physiol 22 2387 PMID: 16262678

Pacher et al (2005) Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase. J Lipid Res 289 H533 PMID: 15821037

Price et al (2004) Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on trigeminal sensory neurons. Br J Pharmacol 142 257 PMID: 15155534

Mathison et al (2004) Effects of cannabinoid receptor-2 activation on accelerated gastrointestinal transit in lipopolysaccharide-treated rats. Br J Pharmacol 142 1247 PMID: 15249429

Melyan et al (2004) Metabotropic regulation of intrinsic excitability by synaptic activation of kainate receptors. J Neurosci 24 4530 PMID: 15140923

Akerman et al (2004) Anandamide acts as a vasodilator of dural blood vessels in vivo by activating TRPV1 receptors. Br J Pharmacol 142 1354 PMID: 15277315

Chevaleyre and Castillo (2004) Endocannabinoid-mediated metaplasticity in the hippocampus. Neuron 43 871 PMID: 15363397

Scorticati et al (2004) The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen. Mol Pharmacol 101 11891 PMID: 15280536

Jin et al (2004) Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. Am J Physiol Heart Circ Physiol 66 204 PMID: 15266010

Harkany et al (2004) Endocannabinoid-independent retrograde signaling at inhibitory synapses in layer 2/3 of neocortex: involvement of vesicular glutamate transporter 3. Circulation 24 4978 PMID: 15163690

Bátkai et al (2004) Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Eur J Pharmacol 110 1996 PMID: 15451779

Galarreta et al (2004) Electrical coupling among irregular-spiking GABAergic interneurons expressing cannabinoid receptors. J Pharmacol Exp Ther 24 9770 PMID: 15525762

Savinainen et al (2003) An optimized approach to study endocannabinoid signaling: evidence against constitutive activity of rat brain adenosine A1 and cannabinoid CB1 receptors. Br J Pharmacol 140 1451 PMID: 14623770

Williams et al (2003) The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response. J Cell Mol Med 160 481 PMID: 12578907

Savinainen et al (2001) Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB(1) receptor-dependent G-protein activation in rat cerebellar membranes. Br J Pharmacol 134 664 PMID: 11588122

Lafourcade et al Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex. PLoS One 2 e709 PMID: 17684555

Jiang et al Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells. PLoS One 2 e641 PMID: 17653268

Kola et al The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system. Br J Pharmacol 3 e1797 PMID: 18335063

Sinnayah et al Feeding induced by cannabinoids is mediated independently of the melanocortin system. Proc Natl Acad Sci U S A 3 e2202 PMID: 18493584


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