Skip to main content
SpringerLink
Log in

The Effects of Cannabinoids on Immune Cells, Responses and Diseases

  • Chapter
  • First Online:
Nerve-Driven Immunity

  • 1062 Accesses

Abstract

Cannabinoids (CB) are a group of molecules that act upon cannabinoid receptors (CBR) and are divided in three categories: phytocannabinoids (natural terpenophenolic compounds derived from the Cannabis plant species), endocannabinoids (endogenous) and synthetic cannabinoids.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agudelo M, Newton C, Widen R et al (2008) Cannabinoid receptor 2 (CB2) mediates immunoglobulin class switching from IgM to IgE in cultures of murine-purified B lymphocytes. J Neuroimmune Pharmacol 3:35–42

    PubMed  Google Scholar 

  • Alexander SP, Kendall DA (2007) The complications of promiscuity: endocannabinoid action and metabolism. Br J Pharmacol 152:602–623

    PubMed  CAS  Google Scholar 

  • Ashton JC, Wright JL, McPartland JM et al (2008) Cannabinoid CB1 and CB2 receptor ligand specificity and the development of CB2-selective agonists. Curr Med Chem 15:1428–1443

    PubMed  CAS  Google Scholar 

  • Athanasiou A, Clarke AB, Turner AE et al (2007a) Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death. Biochem Biophys Res Commun 364:131–137

    PubMed  CAS  Google Scholar 

  • Athanasiou A, Smith PA, Vakilpour S et al (2007b) Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: how vanilloids cause non-vanilloid receptor mediated cell death. Biochem Biophys Res Commun 354:50–55

    PubMed  CAS  Google Scholar 

  • Bacci A, Huguenard JR, Prince DA (2004) Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 431:312–316

    PubMed  CAS  Google Scholar 

  • Baker D, Jackson SJ, Pryce G (2007) Cannabinoid control of neuroinflammation related to multiple sclerosis. Br J Pharmacol 152:649–654

    PubMed  CAS  Google Scholar 

  • Bari M, Battista N, Fezza F et al (2005) Lipid rafts control signaling of type-1 cannabinoid receptors in neuronal cells. Implications for anandamide-induced apoptosis. J Biol Chem 280:12212–12220

    PubMed  CAS  Google Scholar 

  • Bayewitch M, Rhee MH, Avidor-Reiss T et al (1996) (−)Δ9-Tetrahydrocannabinol antagonizes the peripheral cannabinoid receptor-mediated inhibition of adenylyl cyclase. J Biol Chem 271:9902–9905

    PubMed  CAS  Google Scholar 

  • Beltramo M, Stella N, Calignano A et al (1997) Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 277:1094–1097

    PubMed  CAS  Google Scholar 

  • Beltramo M, Bernardini N, Bertorelli R et al (2006) CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. Eur J Neurosci 23:1530–1538

    PubMed  CAS  Google Scholar 

  • Benito C, Nunez E, Tolon RM et al (2003) Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23:11136–11141

    PubMed  CAS  Google Scholar 

  • Benito C, Romero JP, Tolón RM et al (2007) Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. J Neurosci 27:2396–2402

    PubMed  CAS  Google Scholar 

  • Ben-Shabat S, Fride E, Sheskin T et al (1998) An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol 353:23–31

    PubMed  CAS  Google Scholar 

  • Berdyshev EV (2000) Cannabinoid receptors and the regulation of immune response. Chem Phys Lipids 108:169–190

    PubMed  CAS  Google Scholar 

  • Berdyshev EV, Schmid PC, Krebsbach RJ et al (2001) Role of N-acylethanolamines in cell signaling. World Rev Nutr Diet 88:207–214

    PubMed  CAS  Google Scholar 

  • Bisogno T, Maurelli S, Melck D et al (1997) Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes. J Biol Chem 272:3315–3323

    PubMed  CAS  Google Scholar 

  • Biswas KK, Sarker KP, Abeyama K et al (2003) Membrane cholesterol but not putative receptors mediates anandamide-induced hepatocyte apoptosis. Hepatology 38:1167–1177

    PubMed  CAS  Google Scholar 

  • Bjarnadottir TK, Fredriksson R, Hoglund PJ et al (2004) The human and mouse repertoire of the adhesion family of G-protein-coupled receptors. Genomics 84:23–33

    PubMed  CAS  Google Scholar 

  • Blake DR, Robson P, Ho M et al (2006) Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology 45:50–52

    PubMed  CAS  Google Scholar 

  • Blankman JL, Simon GM, Cravatt BF (2007) A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 14:1347–1356

    PubMed  CAS  Google Scholar 

  • Bodor ÁL, Katona I, Nyíri G et al (2005) Endocannabinoid signaling in rat somatosensory cortex: laminar differences and involvement of specific interneuron types. J Neurosci 25:6845–6856

    PubMed  CAS  Google Scholar 

  • Booth M (2005) Cannabis: a history. Picador, St.Martin's Press, New York

    Google Scholar 

  • Börner C, Höllt V, Kraus J (2007a) Activation of human T cells induces upregulation of cannabinoid receptor type 1 transcription. Neuroimmunomodulation 14:281–286

    PubMed  Google Scholar 

  • Börner C, Höllt V, Sebald W et al (2007b) Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids. J Leukoc Biol 81:336–343

    PubMed  Google Scholar 

  • Börner C, Bedini A, Höllt V et al (2008) Analysis of promoter regions regulating basal and interleukin-4-inducible expression of the human CB1 receptor gene in T lymphocytes. Mol Pharmacol 73:1013–1019

    PubMed  Google Scholar 

  • Börner C, Smida M, Hollt V, Schraven B, Kraus J (2009) Cannabinoid receptor type 1- and 2-mediated increase in cyclic AMP inhibits T cell receptor-triggered signaling. J Biol Chem 284 (51):35450–35460

    Google Scholar 

  • Breivogel CS, Griffin G, Di Marzo V et al (2001) Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 60:155–163

    PubMed  CAS  Google Scholar 

  • Buccellato E, Carretta D, Utan A et al (2011) Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis. J Ethnopharmacol 133:1033–1038

    PubMed  CAS  Google Scholar 

  • Buchweitz JP, Karmaus PWF, Williams KJ et al (2008) Targeted deletion of cannabinoid receptors CB1 and CB2produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of Δ9-tetrahydrocannabinol. J Leukoc Biol 83:785–796

    PubMed  CAS  Google Scholar 

  • Buckley NE, McCoy KL, Mezey E et al (2000) Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor. Eur J Pharmacol 396:141–149

    PubMed  CAS  Google Scholar 

  • Bueb JL, Lambert DM, Tschirhart EJ (2001) Receptor-independent effects of natural cannabinoids in rat peritoneal mast cells in vitro. Biochim Biophys Acta 1538:252–259

    PubMed  CAS  Google Scholar 

  • Caberlotto L, Rimondini R, Hansson A et al (2004) Corticotropin-releasing hormone (CRH) mRNA expression in rat central amygdala in cannabinoid tolerance and withdrawal: evidence for an allostatic shift? Neuropsychopharmacology 29:15–22

    PubMed  CAS  Google Scholar 

  • Cabral G, Dove Pettit D (1998) Drugs and immunity: cannabinoids and their role in decreased resistance to infectious diseases. J Neuroimmunol 83:116–123

    PubMed  CAS  Google Scholar 

  • Cabral GA, Staab A (2005) Effects on the immune system. Handb Exp Pharmacol 168:385–423

    PubMed  CAS  Google Scholar 

  • Cabral GA, Toney DM, Fischer-Stenger K et al (1995) Anandamide inhibits macrophage-mediated killing of tumor necrosis factor-sensitive cells. Life Sci 56:2065–2072

    PubMed  CAS  Google Scholar 

  • Cabral GA, Raborn ES, Griffin L et al (2008) CB2 receptors in the brain: role in central immune function. Br J Pharmacol 153:240–251

    PubMed  CAS  Google Scholar 

  • Calignano A, La Rana G, Giuffrida A et al (1998) Control of pain initiation by endogenous cannabinoids. Nature 394:277–281

    PubMed  CAS  Google Scholar 

  • Carlisle SJ, Marciano-Cabral F, Staab A et al (2002) Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation. Int Immunopharmacol 2:69–82

    PubMed  CAS  Google Scholar 

  • Carracedo A, Lorente M, Egia A et al (2006) The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell 9:301–312

    PubMed  CAS  Google Scholar 

  • Carrier EJ, Kearn CS, Barkmeier AJ et al (2004) Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol 65:999–1007

    PubMed  CAS  Google Scholar 

  • Carrier EJ, Patel S, Hillard CJ (2005) Endocannabinoids in neuroimmunology and stress. Curr Drug Targets CNS Neurol Disord 4:657–665

    PubMed  CAS  Google Scholar 

  • Cavuoto P, McAinch AJ, Hatzinikolas G et al (2007) The expression of receptors for endocannabinoids in human and rodent skeletal muscle. Biochem Biophys Res Commun 364:105–110

    PubMed  CAS  Google Scholar 

  • Cencioni MT, Chiurchiu V, Catanzaro G et al (2010) Anandamide suppresses proliferation and cytokine release from primary human T-lymphocytes mainly via CB2 receptors. PLoS One 5:e8688

    PubMed  Google Scholar 

  • Chanda PK, Gao Y, Mark L et al (2010) Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system. Mol Pharmacol 78:996–1003

    PubMed  CAS  Google Scholar 

  • Chang YH, Lee ST, Lin WW (2001) Effects of cannabinoids on LPS-stimulated inflammatory mediator release from macrophages: involvement of eicosanoids. J Cell Biochem 81:715–723

    PubMed  CAS  Google Scholar 

  • Chapman KD (2000) Emerging physiological roles for N-acylphosphatidylethanolamine metabolism in plants: signal transduction and membrane protection. Chem Phys Lipids 108:221–229

    PubMed  CAS  Google Scholar 

  • Chen Y, Buck J (2000) Cannabinoids protect cells from oxidative cell death: a receptor- independent mechanism. J Pharmacol Exp Ther 293:807–812

    PubMed  CAS  Google Scholar 

  • Chevaleyre V, Takahashi KA, Castillo PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29:37–76

    PubMed  CAS  Google Scholar 

  • Condie R, Herring A, Koh WS et al (1996) Cannabinoid inhibition of adenylate cyclase-mediated signal transduction and interleukin 2 (IL-2) expression in the murine T-cell line, EL4.IL-2. J Biol Chem 271:13175–13183

    PubMed  CAS  Google Scholar 

  • Correa F, Docagne F, Mestre L et al (2009) A role for CB2 receptors in anandamide signalling pathways involved in the regulation of IL-12 and IL-23 in microglial cells. Biochem Pharmacol 77:86–100

    PubMed  CAS  Google Scholar 

  • Correa F, Hernangomez M, Mestre L et al (2010) Anandamide enhances IL-10 production in activated microglia by targeting CB(2) receptors: roles of ERK1/2, JNK, and NF-kappaB. GLIA 58:135–147

    PubMed  Google Scholar 

  • Cota D (2008) The role of the endocannabinoid system in the regulation of hypothalamic-pituitary-adrenal axis activity. J Neuroendocrinol 20:35–38

    PubMed  CAS  Google Scholar 

  • Craddock D, Thomas A (2006) Cytokines and late-life depression. Essent Psychopharmacol 7:42–52

    PubMed  Google Scholar 

  • Cravatt BF, Giang DK, Mayfield SP et al (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384:83–87

    PubMed  CAS  Google Scholar 

  • Croxford JL (2003) Therapeutic potential of cannabinoids in CNS disease. CNS Drugs 17:179–202

    PubMed  CAS  Google Scholar 

  • Croxford JL, Miller SD (2003) Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R(+)WIN55,212. J Clin Invest 111:1231–1240

    PubMed  CAS  Google Scholar 

  • Croxford JL, Yamamura T (2005) Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J Neuroimmunol 166:3–18

    PubMed  CAS  Google Scholar 

  • Croxford JL, Pryce G, Jackson SJ et al (2008) Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J Neuroimmunol 193:120–129

    PubMed  CAS  Google Scholar 

  • Daaka Y, Friedman H, Klein TW (1996) Cannabinoid receptor proteins are increased in Jurkat, human T-cell line after mitogen activation. J Pharmacol Exp Ther 276:776–783

    PubMed  CAS  Google Scholar 

  • D'Argenio G, Valenti M, Scaglione G et al (2006) Up-regulation of anandamide levels as an endogenous mechanism and a pharmacological strategy to limit colon inflammation. FASEB J 20:568–570

    PubMed  Google Scholar 

  • De Filippis D, D’Amico A, Iuvone T (2008a) Cannabinomimetic control of mast cell mediator release: new perspective in chronic inflammation. J Neuroendocrinol 20:20–25

    PubMed  Google Scholar 

  • De Filippis D, Russo A, D’Amico A et al (2008b) Cannabinoids reduce granuloma-associated angiogenesis in rats by controlling transcription and expression of mast cell protease-5. Br J Pharmacol 154:1672–1679

    PubMed  Google Scholar 

  • De Filippis D, Iuvone T, D'Amico A et al (2008c) Effect of cannabidiol on sepsis-induced motility disturbances in mice: involvement of CB1 receptors and fatty acid amide hydrolase. Neurogastroenterol Motil 20:919–927

    PubMed  Google Scholar 

  • De Filippis D, Esposito G, Cipriano M, Scuderi C, De Man J, Iuvone T (2009) Canabidiol controls intestinal inflammation through modulation of enteric glial cells. In: International cannabinoid research society 19th symposium, St. Charles, 7–12 July 2009

    Google Scholar 

  • De Petrocellis L, Di Marzo V (2009) An introduction to the endocannabinoid system: from the early to the latest concepts. Best Pract Res Clin Endocrinol Metab 23:1–15

    PubMed  Google Scholar 

  • De Winter BY, De Man JG (2010) Interplay between inflammation, immune system and neuronal pathways: effect on gastrointestinal motility. World J Gastroenterol 16:5523–5535

    PubMed  Google Scholar 

  • Derocq JM, Bouaboula M, Marchand J et al (1998) The endogenous cannabinoid anandamide is a lipid messenger activating cell growth via a cannabinoid receptor-independent pathway in hematopoietic cell lines. FEBS Lett 425:419–425

    PubMed  CAS  Google Scholar 

  • Deusch E, Kraft B, Nahlik G et al (2003) No evidence for direct modulatory effects of Δ9- tetrahydrocannabinol on human polymorphonuclear leukocytes. J Neuroimmunol 141:99–103

    PubMed  CAS  Google Scholar 

  • Devane WA, Dysarz Iii FA, Johnson MR et al (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613

    PubMed  CAS  Google Scholar 

  • Devane WA, Hanus L, Breuer A et al (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949

    PubMed  CAS  Google Scholar 

  • Di Filippo C, Rossi F, Rossi S et al (2004) Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN. J Leukoc Biol 75:453–459

    PubMed  Google Scholar 

  • Di Marzo V (2006) A brief history of cannabinoid and endocannabinoid pharmacology as inspired by the work of British scientists. Trends Pharmacol Sci 27:134–140

    PubMed  Google Scholar 

  • Di Marzo V, De Petrocellis L (2010) Endocannabinoids as regulators of transient receptor potential (TRP) channels: a further opportunity to develop new endocannabinoid-based therapeutic drugs. Curr Med Chem 17:1430–1449

    PubMed  Google Scholar 

  • Di Marzo V, De Petrocellis L, Sepe N et al (1996) Biosynthesis of anandamide and related acylethanolamides in mouse J774 macrophages and N18 neuroblastoma cells. Biochem J 316:977–984

    PubMed  Google Scholar 

  • Di Marzo V, De Petrocellis L, Bisogno T (2005) The biosynthesis, fate and pharmacological properties of endocannabinoids. Handb Exp Pharmacol 168:147–185

    PubMed  Google Scholar 

  • Dinh TP, Carpenter D, Leslie FM et al (2002) Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99:10819–10824

    PubMed  CAS  Google Scholar 

  • Do Y, McKallip RJ, Nagarkatti M et al (2004) Activation through cannabinoid receptors 1 and 2 on dendritic cells triggers NF-kappaB-dependent apoptosis: novel role for endogenous and exogenous cannabinoids in immunoregulation. J Immunol 173:2373–2382

    PubMed  CAS  Google Scholar 

  • Dol-Gleizes F, Paumelle R, Visentin V et al (2009) Rimonabant, a selective cannabinoid CB1 receptor antagonist, inhibits atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 29:12–18

    PubMed  CAS  Google Scholar 

  • Downer EJ, Fogarty MP, Campbell VA (2003) Tetrahydrocannabinol-induced neurotoxicity depends on CB1 receptor-mediated c-Jun N-terminal kinase activation in cultured cortical neurons. Br J Pharmacol 140:547–557

    PubMed  CAS  Google Scholar 

  • Dunn AJ (2000) Cytokine activation of the HPA axis. Ann NY Acad Sci 917:608–617

    PubMed  CAS  Google Scholar 

  • Eisenstein TK, Meissler JJ, Wilson Q et al (2007) Anandamide and Delta9-tetrahydrocannabinol directly inhibit cells of the immune system via CB2 receptors. J Neuroimmunol 189:17–22

    PubMed  CAS  Google Scholar 

  • El-Gohary M, Eid MA (2004) Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students. Hum Exp Toxicol 23:149–156

    PubMed  CAS  Google Scholar 

  • Eljaschewitsch E, Witting A, Mawrin C et al (2006) The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. Neuron 49:67–79

    PubMed  CAS  Google Scholar 

  • Elphick MR, Egertova M (2001) The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond B Biol Sci 356:381–408

    PubMed  CAS  Google Scholar 

  • Facci L, Dal Toso R, Romanello S et al (1995) Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci USA 92:3376–3380

    PubMed  CAS  Google Scholar 

  • Fernández-Ruiz J, Romero J, Velasco G et al (2007) Cannabinoid CB2 receptor: a new target for controlling neural cell survival? Trends Pharmacol Sci 28:39–45

    PubMed  Google Scholar 

  • Ferre S, Baler R, Bouvier M et al (2009) Building a new conceptual framework for receptor heteromers. Nat Chem Biol 5:131–134

    PubMed  CAS  Google Scholar 

  • Fezza F, Battista N, Bari M et al (2006) Methods to assay anandamide hydrolysis and transport in synaptosomes. Methods Mol Med 123:163–168

    PubMed  CAS  Google Scholar 

  • Finn DP (2010) Endocannabinoid-mediated modulation of stress responses: physiological and pathophysiological significance. Immunobiology 215:629–646

    PubMed  CAS  Google Scholar 

  • Fischer-Stenger K, Updegrove AW, Cabral GA (1992) Δ9-Tetrahydrocannabinol decreases cytotoxic T lymphocyte activity to herpes simplex virus Type 1-infected cells. Proc Soc Exp Biol Med 200:422–430

    PubMed  CAS  Google Scholar 

  • Fowler CJ, Holt S, Tiger G (2003) Acidic nonsteroidal anti-inflammatory drugs inhibit rat brain fatty acid amide hydrolase in a pH-dependent manner. J Enzyme Inhib Med Chem 18:55–58

    PubMed  CAS  Google Scholar 

  • Fredriksson R, Lagerstrom MC, Lundin LG et al (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63:1256–1272

    PubMed  CAS  Google Scholar 

  • Freeman-Anderson NE, Pickle TG, Netherland CD et al (2008) Cannabinoid (CB2) receptor deficiency reduces the susceptibility of macrophages to oxidized LDL/oxysterol-induced apoptosis. J Lipid Res 49:2338–2346

    PubMed  CAS  Google Scholar 

  • Galiegue S, Mary S, Marchand J et al (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Garcia Mdel C, Adler-Graschinsky E, Celuch SM (2009) Enhancement of the hypotensive effects of intrathecally injected endocannabinoids by the entourage compound palmitoylethanolamide. Eur J Pharmacol 610:75–80

    PubMed  Google Scholar 

  • Gardner B, Zu LX, Sharma S et al (2002) Autocrine and paracrine regulation of lymphocyte CB2 receptor expression by TGF-β. Biochem Biophys Res Comm 290:91–96

    PubMed  CAS  Google Scholar 

  • George KL, Saltman LH, Stein GS et al (2008) Ajulemic acid, a nonpsychoactive cannabinoid acid, suppresses osteoclastogenesis in mononuclear precursor cells and induces apoptosis in mature osteoclast-like cells. J Cell Physiol 214:714–720

    PubMed  CAS  Google Scholar 

  • Giudice ED, Rinaldi L, Passarotto M et al (2007) Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2 H3 mast cells. J Leukoc Biol 81:1512–1522

    PubMed  Google Scholar 

  • Glass M, Northup JK (1999) Agonist selective regulation of G proteins by cannabinoid CB1 and CB2 receptors. Mol Pharmacol 56:1362–1369

    PubMed  CAS  Google Scholar 

  • Graham ES, Angel CE, Schwarcz LE et al (2010) Detailed characterisation of CB2 receptor protein expression in peripheral blood immune cells from healthy human volunteers using flow cytometry. Int J Immunopathol Pharmacol 23:25–34

    PubMed  CAS  Google Scholar 

  • Griebel G, Stemmelin J, Scatton B (2005) Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents. Biological Psychiatry 57:261–267

    PubMed  CAS  Google Scholar 

  • Griffin G, Fernando SR, Ross RA et al (1997) Evidence for the presence of CB2-1ike cannabinoid receptors on peripheral nerve terminals. Eur J Pharmacol 339:53–61

    PubMed  CAS  Google Scholar 

  • Guzman M, Sanchez C (1999) Effects of cannabinoids on energy metabolism. Life Sci 65:657–664

    PubMed  CAS  Google Scholar 

  • Halttunen T, Maki M (1999) Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. Gastroenterology 116:566–572

    PubMed  CAS  Google Scholar 

  • Hanus LO, Mechoulam R (2010) Novel natural and synthetic ligands of the endocannabinoid system. Curr Med Chem 17:1341–1359

    PubMed  CAS  Google Scholar 

  • Hashimotodani Y, Ohno-Shosaku T, Kano M (2007) Endocannabinoids and synaptic function in the CNS. Neuroscientist 13:127–137

    PubMed  CAS  Google Scholar 

  • He F, Qiao ZH, Cai J et al (2007) Involvement of the 90-kDa heat shock protein (Hsp-90) in CB2 cannabinoid receptor-mediated cell migration: a new role of Hsp-90 in migration signaling of a G protein-coupled receptor. Mol Pharmacol 72:1289–1300

    PubMed  CAS  Google Scholar 

  • Hegde VL, Hegde S, Cravatt BF et al (2008) Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells. Mol Pharmacol 74:20–33

    PubMed  CAS  Google Scholar 

  • Henquet C, Di Forti M, Morrison P et al (2008) Gene-environment interplay between cannabis and psychosis. Schizophr Bull 34:1111–1121

    PubMed  Google Scholar 

  • Herring AC, Kaminski NE (1999) Cannabinol-mediated inhibition of nuclear factor-[kappa]B, cAMP response element-binding protein, and interleukin-2 secretion by activated thymocytes. J Pharmacol Exp Ther 291:1156–1163

    PubMed  CAS  Google Scholar 

  • Herring AC, Koh WS, Kaminski NE (1998) Inhibition of the cyclic AMP signaling cascade and nuclear factor binding to CRE and κB elements by cannabinol, a minimally CNS-active cannabinoid. Biochem Pharmacol 55:1013–1023

    PubMed  CAS  Google Scholar 

  • Hill MN, McLaughlin RJ, Morrish AC et al (2009) Suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology 34:2733–2745

    PubMed  CAS  Google Scholar 

  • Hill MN, McLaughlin RJ, Bingham B et al (2010) Endogenous cannabinoid signaling is essential for stress adaptation. Proc Natl Acad Sci USA 107:9406–9411

    PubMed  CAS  Google Scholar 

  • Hollister LE (1986) Health aspects of cannabis. Pharmacol Rev 38:1–20

    PubMed  CAS  Google Scholar 

  • Howlett AC, Mukhopadhyay S (2000) Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chem Phys Lipids 108:53–70

    PubMed  CAS  Google Scholar 

  • Howlett AC, Barth F, Bonner TI et al (2002) International union of pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202

    PubMed  CAS  Google Scholar 

  • Howlett AC, Blume LC, Dalton GD (2010) CB1 cannabinoid receptors and their associated proteins. Curr Med Chem 17:1382–1393

    PubMed  CAS  Google Scholar 

  • Huang C, Hepler JR, Chen LT et al (1997) Organization of G proteins and adenylyl cyclase at the plasma membrane. Mol Biol Cell 8:2365–2378

    PubMed  CAS  Google Scholar 

  • Ignatowska-Jankowska B, Jankowski M, Glac W et al (2009) Cannabidiol-induced lymphopenia does not involve NKT and NK cells. J Physiol Pharmacol 60(Suppl 3):99–103

    PubMed  Google Scholar 

  • Ihenetu K, Molleman A, Parsons ME et al (2003) Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids. Eur J Pharmacol 458:207–215

    PubMed  CAS  Google Scholar 

  • Izzo AA, Camilleri M (2008) Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects. Gut 57:1140–1155

    PubMed  CAS  Google Scholar 

  • Izzo AA, Camilleri M (2009) Cannabinoids in intestinal inflammation and cancer. Pharmacol Res 60:117–125

    PubMed  CAS  Google Scholar 

  • Izzo AA, Sharkey KA (2010) Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther 126:21–38

    PubMed  CAS  Google Scholar 

  • Jan TR, Su ST, Wu HY et al (2007) Suppressive effects of cannabidiol on antigen-specific antibody production and functional activity of splenocytes in ovalbumin-sensitized BALB/c mice. Int Immunopharmacol 7:773–780

    PubMed  CAS  Google Scholar 

  • Jara LJ, Navarro C, Medina G et al (2006) Immune-neuroendocrine interactions and autoimmune diseases. Clin Dev Immunol 13:109–123

    PubMed  CAS  Google Scholar 

  • Jean-Gilles L, Feng S, Tench CR et al (2009) Plasma endocannabinoid levels in multiple sclerosis. J Neurol Sci 287:212–215

    PubMed  CAS  Google Scholar 

  • Jean-Gilles L, Gran B, Constantinescu CS (2010) Interaction between cytokines, cannabinoids and the nervous system. Immunobiology 215:606–610

    PubMed  CAS  Google Scholar 

  • Jeon YJ, Yang KH, Pulaski JT et al (1996) Attenuation of inducible nitric oxide synthase gene expression by Δ9- tetrahydrocannabinol is mediated through the inhibition of NF- κB/Rel activation. Mol Pharmacol 50:334–341

    PubMed  CAS  Google Scholar 

  • Jhaveri MD, Richardson D, Robinson I et al (2008) Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain. Neuropharmacology 55:85–93

    PubMed  CAS  Google Scholar 

  • Jiang S, Zagozdzon R, Jorda MA et al (2010) Endocannabinoids are expressed in bone marrow stromal niches and play a role in interactions of hematopoietic stem and progenitor cells with the bone marrow microenvironment. J Biol Chem 285:35471–35478

    PubMed  CAS  Google Scholar 

  • Jiang S, Alberich-Jorda M, Zagozdzon R et al (2011) Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization. Blood 117:827–838

    PubMed  CAS  Google Scholar 

  • Jonsson KO, Vandevoorde S, Lambert DM et al (2001) Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide. Br J Pharmacol 133:1263–1275

    PubMed  CAS  Google Scholar 

  • Jonsson KO, Holt S, Fowler CJ (2006a) The endocannabinoid system: current pharmacological research and therapeutic possibilities. Basic Clin Pharmacol Toxicol 98:124–134

    PubMed  CAS  Google Scholar 

  • Jonsson KO, Persson E, Fowler CJ (2006b) The cannabinoid CB2 receptor selective agonist JWH133 reduces mast cell oedema in response to compound 48/80 in vivo but not the release of beta-hexosaminidase from skin slices in vitro. Life Sci 78:598–606

    PubMed  CAS  Google Scholar 

  • Jordà MA, Verbakel SE, Valk PJM et al (2002) Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol. Blood 99:2786–2793

    PubMed  Google Scholar 

  • Jordà MA, Rayman N, Tas M et al (2004) The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner. Blood 104:526–534

    Google Scholar 

  • Kaczocha M, Glaser ST, Chae J et al (2010) Lipid droplets are novel sites of N-acylethanolamine inactivation by fatty acid amide hydrolase-2. J Biol Chem 285:2796–2806

    PubMed  CAS  Google Scholar 

  • Kaminski NE, Abood ME, Kessler FK et al (1992) Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation. Mol Pharmacol 42:736–742

    PubMed  CAS  Google Scholar 

  • Kaminski NE, Koh WS, Yang KH et al (1994) Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism. Biochem Pharmacol 48:1899–1908

    PubMed  CAS  Google Scholar 

  • Kano M, Ohno-Shosaku T, Hashimotodani Y et al (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380

    PubMed  CAS  Google Scholar 

  • Kaplan BLF, Springs AEB, Kaminski NE (2008) The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT). Biochem Pharmacol 76:726–737

    PubMed  CAS  Google Scholar 

  • Kaufmann I, Schelling G, Eisner C et al (2008) Anandamide and neutrophil function in patients with fibromyalgia. Psychoneuroendocrinology 33:676–685

    PubMed  CAS  Google Scholar 

  • Kenakin T (2001) Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J 15:598–611

    PubMed  CAS  Google Scholar 

  • Klein TW (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74:486–496

    PubMed  CAS  Google Scholar 

  • Klein TW (2005) Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol 5:400–411

    PubMed  CAS  Google Scholar 

  • Klein TW, Cabral GA (2006) Cannabinoid-induced immune suppression and modulation of antigen-presenting cells. J Neuroimmune Pharmacol 1:50–64

    PubMed  Google Scholar 

  • Klein TW, Kawakami Y, Newton C et al (1991) Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo. J Toxicol Environ Heal 32:465–477

    CAS  Google Scholar 

  • Klein TW, Newton C, Widen R et al (1993) Δ9Tetrahydrocannabinol injection induces cytokine-mediated mortality of mice infected with L pneumophila. J Pharm Exp Ther 267:635–640

    CAS  Google Scholar 

  • Klein T, Newton C, Friedman H (1998) Cannabinoid receptors and immunity. Immunol Today 19:373–381

    PubMed  CAS  Google Scholar 

  • Klein TW, Lane B, Newton CA et al (2000) The cannabinoid system and cytokine network. Proc Soc Exp Biol Med 225:1–8

    PubMed  CAS  Google Scholar 

  • Kobayashi Y, Arai S, Waku K et al (2001) Activation by 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, of p42/44 mitogen-activated protein kinase in HL-60 cells. J Biochem 129:665–669

    PubMed  CAS  Google Scholar 

  • Koh WS, Jeon YJ, Herring AC et al (1997) Transient CRE- and κB site-binding is cross-regulated by cAMP-dependent protein kinase and a protein phosphatase in mouse splenocytes. Life Sci 60:425–432

    PubMed  CAS  Google Scholar 

  • Kraft B, Wintersberger W, Kress HG (2004) Cannabinoid receptor-independent suppression of the superoxide generation of human neutrophils (PMN) by CP55 940, but not by anandamide. Life Sci 75:969–977

    PubMed  CAS  Google Scholar 

  • Kubajewska I, Constantinescu CS (2010) Cannabinoids and experimental models of multiple sclerosis. Immunobiology 215:647–657

    PubMed  CAS  Google Scholar 

  • Lastres-Becker I, Fernández-Ruiz J (2006) An overview of Parkinson’s disease and the cannabinoid system and possible benefits of cannabinoid-based treatments. Curr Med Chem 13:3705–3718

    PubMed  CAS  Google Scholar 

  • Lau RJ, Tubergen DG, Barr M Jr (1976) Phytohemagglutinin induced lymphocyte transformation in humans receiving Δ9 tetrahydrocannabinol. Science 192:805–807

    PubMed  CAS  Google Scholar 

  • Lee M, Kyu Hwan Y, Kaminski NE (1995) Effects of putative cannabinoid receptor ligands, anandamide and 2- arachidonyl-glycerol, on immune function in B6C3F1 mouse splenocytes. J Pharmacol ExpTher 275:529–536

    CAS  Google Scholar 

  • Lee SF, Newton C, Widen R et al (2001) Differential expression of cannabinoid CB2 receptor mRNA in mouse immune cell subpopulations and following B cell stimulation. Eur J Pharmacol 423:235–241

    PubMed  CAS  Google Scholar 

  • Leonard BE (2006) HPA and immune axes in stress: involvement of the serotonergic system. Neuroimmunomodulation 13:268–276

    PubMed  CAS  Google Scholar 

  • Levite M (2008) Neurotransmitters activate T-cells and elicit crucial functions via neurotransmitter receptors. Curr Opin Pharmacol 8:460–471

    PubMed  CAS  Google Scholar 

  • Li X, Kaminski NE, Fischer LJ (2001) Examination of the immunosuppressive effect of Δ9tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes. Int Immunopharmacol 1:699–712

    PubMed  CAS  Google Scholar 

  • Lim G, Sung B, Ji RR et al (2003) Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats. Pain 105:275–283

    PubMed  CAS  Google Scholar 

  • Liu J, Wang L, Harvey-White J et al (2006) A biosynthetic pathway for anandamide. Proc Natl Acad Sci USA 103:13345–13350

    PubMed  CAS  Google Scholar 

  • Loría F, Petrosino S, Mestre L et al (2008) Study of the regulation of the endocannabinoid system in a virus model of MS reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci 28:633–641

    PubMed  Google Scholar 

  • Loría F, Petrosino S, Hernangómez M et al (2010) An endocannabinoid tone limits excitotoxicity in vitro and in a model of multiple sclerosis. Neurobiol Dis 37:166–176

    PubMed  Google Scholar 

  • Lu Q, Straiker A, Maguire G (2000) Expression of CB2 cannabinoid receptor mRNA in adult rat retina. Vis Neurosci 17:91–95

    PubMed  CAS  Google Scholar 

  • Lu T, Newton C, Perkins I et al (2006) Cannabinoid treatment suppresses the T-helper cell-polarizing function of mouse dendritic cells stimulated with Legionella pneumophila infection. J Pharmacol Exp Ther 319:269–276

    PubMed  CAS  Google Scholar 

  • Lunn CA, Fine JS, Rojas-Triana A et al (2006) A novel cannabinoid peripheral cannabinoid receptor-selective inverse agonist blocks leukocyte recruitment in vivo. J Pharmacol Exp Ther 316:780–788

    PubMed  CAS  Google Scholar 

  • Lynn AB, Herkenham M (1994) Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: implications for receptor-mediated immune modulation by cannabinoids. J Pharmacol Exp Ther 268:1612–1623

    PubMed  CAS  Google Scholar 

  • Maccarrone M, Valensise H, Bari M et al (2001a) Progesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines and implications for fertility. J Immunol 166:7183–7189

    PubMed  CAS  Google Scholar 

  • Maccarrone M, De Petrocellis L, Bari M et al (2001b) Lipopolysaccharide downregulates fatty acid amide hydrolase expression and increases anandamide levels in human peripheral lymphocytes. Arch Biochem Biophys 393:321–328

    PubMed  CAS  Google Scholar 

  • Maccarrone M, Dainese E, Oddi S (2010a) Intracellular trafficking of anandamide: new concepts for signaling. Trends Biochem Sci 35:601–608

    PubMed  CAS  Google Scholar 

  • Maccarrone M, Gasperi V, Catani MV et al (2010b) The endocannabinoid system and its relevance for nutrition. Annu Rev Nutr 30:423–440

    PubMed  CAS  Google Scholar 

  • Mach F, Steffens S (2008) The role of the endocannabinoid system in atherosclerosis. J Neuroendocrinol 20:53–57

    PubMed  CAS  Google Scholar 

  • Mackie K (2005a) Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol 168:299–325

    PubMed  CAS  Google Scholar 

  • Mackie K (2005b) Cannabinoid receptor homo- and heterodimerization. Life Sci 77:1667–1673

    PubMed  CAS  Google Scholar 

  • Mackie K (2008) Cannabinoid receptors: where they are and what they do. J Neuroendocrinol 20:10–14

    PubMed  CAS  Google Scholar 

  • Maestroni GJ (2004) The endogenous cannabinoid 2-arachidonoyl glycerol as in vivo chemoattractant for dendritic cells and adjuvant for Th1 response to a soluble protein. FASEB J 18:1914–1916

    PubMed  CAS  Google Scholar 

  • Mageed RA, Adams G, Woodrow D et al (1998) Prevention of collagen-induced arthritis by gene delivery of soluble p75 tumour necrosis factor receptor. Gene Ther 5:1584–1592

    PubMed  CAS  Google Scholar 

  • Malfait AM, Gallily R, Sumariwalla PF et al (2000) The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA 97:9561–9566

    PubMed  CAS  Google Scholar 

  • Mallat A, Teixeira-Clerc F, Deveaux V et al (2007) Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases. Expert Opin Ther Targets 11:403–409

    PubMed  Google Scholar 

  • Maresz K, Carrier EJ, Ponomarev ED et al (2005) Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 95:437–445

    PubMed  CAS  Google Scholar 

  • Massa F, Marsicano G, Hermana H et al (2004) The endogenous cannabinoid system protects against colonic inflammation. J Clin Investig 113:1202–1209

    PubMed  CAS  Google Scholar 

  • Massi P, Patrini G, Rubino T et al (1997) Changes in rat spleen cannabinoid receptors after chronic CP-55,940: an autoradiographic study. Pharmacol Biochem Behav 58:73–78

    PubMed  CAS  Google Scholar 

  • Massi P, Sacerdote P, Ponti W et al (1998) Immune function alterations in mice tolerant to Δ9 tetrahydrocannabinol: functional and biochemical parameters. J Neuroimmunol 92:60–66

    PubMed  CAS  Google Scholar 

  • Massi P, Vaccani A, Parolaro D (2006) Cannabinoids, immune system and cytokine network. Curr Pharm Des 12:3135–3146

    PubMed  CAS  Google Scholar 

  • Mastorakos G, Ilias I (2006) Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. Ann NY Acad Sci 1088:373–381

    PubMed  CAS  Google Scholar 

  • Matias I (2002) Presence and regulation of the endocannabinoid system in human dendritic cells. Eur J Biochem 269:3771–3778

    PubMed  CAS  Google Scholar 

  • Matias I, Pochard P, Orlando P et al (2002) Presence and regulation of the endocannabinoid system in human dendritic cells. Eur J Biochem 269:3771–3778

    PubMed  CAS  Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein MJ et al (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

    PubMed  CAS  Google Scholar 

  • McDougall JJ, Yu V, Thomson J (2008) In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee joints. Br J Pharmacol 153:358–366

    PubMed  CAS  Google Scholar 

  • Mechoulam R, Ben-Shabat S, Hanus L et al (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90

    PubMed  CAS  Google Scholar 

  • Melamede R (2005) Harm reduction – the cannabis paradox. Harm Reduct J 2:17

    PubMed  Google Scholar 

  • Michalik L, Auwerx J, Berger JP et al (2006) International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 58:726–741

    PubMed  CAS  Google Scholar 

  • Miller AM, Stella N (2008) CB2 receptor-mediated migration of immune cells: it can go either way. Br J Pharmacol 153:299–308

    PubMed  CAS  Google Scholar 

  • Milligan G (2004) G protein-coupled receptor dimerization: function and ligand pharmacology. Mol Pharmacol 66:1–7

    PubMed  CAS  Google Scholar 

  • Molina-Holgado E, Vela JM, Arévalo-Martín A et al (2002) Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 22:9742–9753

    PubMed  CAS  Google Scholar 

  • Montecucco F, Matias I, Lenglet S et al (2009) Regulation and possible role of endocannabinoids and related mediators in hypercholesterolemic mice with atherosclerosis. Atherosclerosis 205:433–441

    PubMed  CAS  Google Scholar 

  • Moser B, Wolf M, Walz A et al (2004) Chemokines: multiple levels of leukocyte migration control. Trends Immunol 25:75–84

    PubMed  CAS  Google Scholar 

  • Muccioli GG (2010) Endocannabinoid biosynthesis and inactivation, from simple to complex. Drug Discov Today 15:474–483

    PubMed  CAS  Google Scholar 

  • Muccioli GG, Stella N (2008) Microglia produce and hydrolyze palmitoylethanolamide. Neuropharmacology 54:16–22

    PubMed  CAS  Google Scholar 

  • Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65

    PubMed  CAS  Google Scholar 

  • Nagarkatti M, Rieder SA, Hegde VL et al (2010) Do cannabinoids have a therapeutic role in transplantation? Trends Pharmacol Sci 31:345–350

    PubMed  CAS  Google Scholar 

  • Nagayama T, Sinor AD, Simon RP et al (1999) Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci 19:2987–2995

    PubMed  CAS  Google Scholar 

  • Nahas GG, Osserman EF (1991) Altered serum immunoglobulin concentration in chronic marijuana smokers. Adv Exp Med Biol 288:25–32

    PubMed  CAS  Google Scholar 

  • Nahas GG, Morishima A, Desoize B (1977) Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Fed Proc 36:1748–1752

    PubMed  CAS  Google Scholar 

  • Newton CA, Chou PJ, Perkins I et al (2009) CB(1) and CB(2) cannabinoid receptors mediate different aspects of delta-9-tetrahydrocannabinol (THC)-induced T helper cell shift following immune activation by Legionella pneumophila infection. J Neuroimmune Pharmacol 4:92–102

    PubMed  Google Scholar 

  • Ni X, Geller EB, Eppihimer MJ et al (2004) Win 55212-2, a cannabinoid receptor agonist, attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model. Mult Scler 10:158–164

    PubMed  CAS  Google Scholar 

  • Nong L, Newton C, Cheng Q et al (2002) Altered cannabinoid receptor mRNA expression in peripheral blood mononuclear cells from marijuana smokers. J Neuroimmunol 127:169–176

    PubMed  CAS  Google Scholar 

  • Norrod AG, Puffenbarger RA (2007) Genetic polymorphisms of the endocannabinoid system. Chem Biodivers 4:1926–1932

    PubMed  CAS  Google Scholar 

  • Nunn AVW, Guy GW, Bell JD (2010) Endocannabinoids, FOXO and the metabolic syndrome: redox, function and tipping point – the view from two systems. Immunobiology 215:617–628

    PubMed  CAS  Google Scholar 

  • Nyíri G, Cserép C, Szabadits E et al (2005) CB1 cannabinoid receptors are enriched in the perisynaptic annulus and on preterminal segments of hippocampal GABAergic axons. Neuroscience 136:811–822

    PubMed  Google Scholar 

  • Oddi S, Spagnuolo P, Bari M et al (2007) Differential modulation of type 1 and type 2 cannabinoid receptors along the neuroimmune axis. Int Rev Neurobiol 82:327–337

    PubMed  CAS  Google Scholar 

  • Ofek O, Karsak M, Leclerc N et al (2006) Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci USA 103:696–701

    PubMed  CAS  Google Scholar 

  • Onaivi ES, Ishiguro H, Gong JP et al (2006a) Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann NY Acad Sci 1074:514–536

    PubMed  CAS  Google Scholar 

  • Onaivi ES, Ishiguro H, Sejal P et al (2006b) Methods to study the behavioral effects and expression of CB2 cannabinoid receptor and its gene transcripts in the chronic mild stress model of depression. Methods Mol Med 123:291–298

    PubMed  CAS  Google Scholar 

  • Onaivi ES, Ishiguro H, Gong JP et al (2008) Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLoS One 3:e1640

    PubMed  Google Scholar 

  • Oz M (2006) Receptor-independent effects of endocannabinoids on ion channels. Curr Pharm Des 12:227–239

    PubMed  CAS  Google Scholar 

  • Palazuelos J, Aguado T, Egia A et al (2006) Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation. FASEB J 20:2405–2407

    PubMed  CAS  Google Scholar 

  • Pandey R, Mousawy K, Nagarkatti M et al (2009) Endocannabinoids and immune regulation. Pharmacol Res 60:85–92

    PubMed  CAS  Google Scholar 

  • Parker LA, Kwiatkowska M, Burton P et al (2004) Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew). Psychopharmacology 171:156–161

    PubMed  CAS  Google Scholar 

  • Parker J, Atez F, Rossetti RG et al (2008) Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid. Rheumatol Int 28:631–635

    PubMed  CAS  Google Scholar 

  • Patel S, Hillard CJ (2006) Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J Pharmacol Exp Ther 318:304–311

    PubMed  CAS  Google Scholar 

  • Patel S, Roelke CT, Rademacher DJ et al (2004) Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology 145:5431–5438

    PubMed  CAS  Google Scholar 

  • Patinkin D, Milman G, Breuer A et al (2008) Endocannabinoids as positive or negative factors in hematopoietic cell migration and differentiation. Eur J Pharmacol 595:1–6

    PubMed  CAS  Google Scholar 

  • Patrini G, Sacerdote P, Fuzio D et al (1997) Regulation of immune functions in rat splenocytes after acute and chronic in vivo treatment with CP-55,940, a synthetic cannabinoid compound. J Neuroimmunol 80:143–148

    PubMed  CAS  Google Scholar 

  • Pereira JP, An J, Xu Y et al (2009) Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nat Immunol 10:403–411

    PubMed  CAS  Google Scholar 

  • Pertwee RG (2005) Pharmacological actions of cannabinoids. Handb Exp Pharmacol 168:1–51

    PubMed  CAS  Google Scholar 

  • Pertwee RG (2006) The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes (Lond) 30(Suppl 1):S13–S18

    CAS  Google Scholar 

  • Pertwee RG (2008a) Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addict Biol 13:147–159

    PubMed  CAS  Google Scholar 

  • Pertwee RG (2008b) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215

    PubMed  CAS  Google Scholar 

  • Pertwee RG (2010) Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr Med Chem 17:1360–1381

    PubMed  CAS  Google Scholar 

  • Pertwee RG, Howlett AC, Abood ME et al (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB. Pharmacol Rev 62:588–631

    PubMed  CAS  Google Scholar 

  • Pestonjamasp VK, Burstein SH (1998) Anandamide synthesis is induced by arachidonate mobilizing agonists in cells of the immune system. Biochim Biophys Acta 1394:249–260

    PubMed  CAS  Google Scholar 

  • Porter AC, Sauer JM, Knierman MD et al (2002) Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301:1020–1024

    PubMed  CAS  Google Scholar 

  • Pulvirenti N, Nasca MR, Micali G (2007) Topical adelmidrol 2% emulsion, a novel aliamide, in the treatment of mild atopic dermatitis in pediatric subjects: a pilot study. Acta Dermatovenerol Croat 15:80–83

    PubMed  CAS  Google Scholar 

  • Raborn ES, Marciano-Cabral F, Buckley NE et al (2008) The cannabinoid delta-9-tetrahydrocannabinol mediates inhibition of macrophage chemotaxis to RANTES/CCL5: linkage to the CB2 receptor. J NeuroImmune Pharmacol 3:117–129

    PubMed  Google Scholar 

  • Rachelefsky GS, Opelz G, Mickey MR (1976) Intact humoral and cell mediated immunity in chronic marijuana smoking. J Allergy Clin Immunol 58:483–490

    PubMed  CAS  Google Scholar 

  • Racke MK, Dhib-Jalbut S, Cannella B et al (1991) Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-β1. J Immunol 146:3012–3017

    PubMed  CAS  Google Scholar 

  • Racz I, Nadal X, Alferink J et al (2008) Interferon-γ is a critical modulator of CB2 cannabinoid receptor signaling during neuropathic pain. J Neurosci 28:12136–12145

    PubMed  CAS  Google Scholar 

  • Raduner S, Majewska A, Chen JZ et al (2006) Alkylamides from Echinacea are a new class of cannabinomimetics: cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J Biol Chem 281:14192–14206

    PubMed  CAS  Google Scholar 

  • Ramirez BG, Blazquez C, Gomez del Pulgar T et al (2005) Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 25:1904–1913

    PubMed  CAS  Google Scholar 

  • Randall MD (2007) Endocannabinoids and the haematological system. Br J Pharmacol 152:671–675

    PubMed  CAS  Google Scholar 

  • Reggio PH (2002) Endocannabinoid structure-activity relationships for interaction at the cannabinoid receptors. Prostaglandins Leukot Essent Fatty Acids 66:143–160

    PubMed  CAS  Google Scholar 

  • Ribeiro A, Ferraz-de-Paula V, Pinheiro ML et al (2010) Anandamide prior to sensitization increases cell-mediated immunity in mice. Int Immunopharmacol 10:431–439

    PubMed  CAS  Google Scholar 

  • Richardson D, Pearson RG, Kurian N et al (2008) Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 10:R43

    PubMed  Google Scholar 

  • Rieder SA, Chauhan A, Singh U et al (2010) Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology 215:598–605

    PubMed  CAS  Google Scholar 

  • Roche M, Diamond M, Kelly JP et al (2006) In vivo modulation of LPS-induced alterations in brain and peripheral cytokines and HPA axis activity by cannabinoids. J Neuroimmunol 181:57–67

    PubMed  CAS  Google Scholar 

  • Roche M, Kelly JP, O'Driscoll M et al (2008) Augmentation of endogenous cannabinoid tone modulates lipopolysaccharide- induced alterations in circulating cytokine levels in rats. Immunology 125:263–271

    PubMed  CAS  Google Scholar 

  • Rossi S, Bernardi G, Centonze D (2010) The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis. Exp Neurol 224:92–102

    PubMed  CAS  Google Scholar 

  • Roth MD, Baldwin GC, Tashkin DP (2002) Effects of delta-9-tetrahydrocannabinol on human immune function and host defense. Chem Phys Lipids 121:229–239

    PubMed  CAS  Google Scholar 

  • Ryan D, Drysdale AJ, Lafourcade C et al (2009) Cannabidiol targets mitochondria to regulate intracellular ca2+ levels. J Neurosci 29:2053–2063

    PubMed  CAS  Google Scholar 

  • Ryberg E, Larsson N, Sjögren S et al (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101

    PubMed  CAS  Google Scholar 

  • Sacerdote P, Martucci C, Vaccani A et al (2005) The nonpsychoactive component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both in vivo and in vitro. J Neuroimmunol 159:97–105

    PubMed  CAS  Google Scholar 

  • Salzet M, Breton C, Bisogno T et al (2000) Comparative biology of the endocannabinoid system possible role in the immune response. Eur J Biochem 267:4917–4927

    PubMed  CAS  Google Scholar 

  • Schuelert N, McDougall JJ (2008) Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum 58:145–153

    PubMed  CAS  Google Scholar 

  • Schwarz H, Blanco FJ, Lotz M (1994) Anadamide, an endogenous cannabinoid receptor agonist inhibits lymphocyte proliferation and induces apoptosis. J Neuroimmunol 55:107–115

    PubMed  CAS  Google Scholar 

  • Scotter EL, Abood ME, Glass M (2010) The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol 160:480–498

    PubMed  CAS  Google Scholar 

  • Shay AH, Choi R, Whittaker K et al (2003) Impairment of antimicrobial activity and NO production in alveolar macrophages from smokers of marijuana and cocaine. J Infect Dis 187:700–704

    PubMed  CAS  Google Scholar 

  • Sherwood TA, Nong L, Agudelo M et al (2009) Identification of transcription start sites and preferential expression of select CB2 transcripts in mouse and human B lymphocytes. J NeuroImmune Pharmacol 4:476–488

    PubMed  Google Scholar 

  • Shoemaker JL, Ruckle MB, Mayeux PR et al (2005) Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors. J Pharmacol Exp Ther 315:828–838

    PubMed  CAS  Google Scholar 

  • Shohami E, Gallily R, Mechoulam R et al (1997) Cytokine production in the brain following closed head injury: dexanabinol (HU-211) is a novel TNF-α inhibitor and an effective neuroprotectant. J Neuroimmunol 72:169–177

    PubMed  CAS  Google Scholar 

  • Sidney S, Beck JE, Tekawa IS et al (1997) Marijuana use and mortality. Am J Pub Health 87:585–590

    CAS  Google Scholar 

  • Sinha D, Bonner TI, Bhat NR et al (1998) Expression of the CB1 cannabinoid receptor in macrophage-like cells from brain tissue: immunochemical characterization by fusion protein antibodies. J Neuroimmunol 82:13–21

    PubMed  CAS  Google Scholar 

  • Smid SD (2008) Gastrointestinal endocannabinoid system: multifaceted roles in the healthy and inflamed intestine. Clin Exp Pharmacol Physiol 35:1383–1387

    PubMed  CAS  Google Scholar 

  • Smith SR, Terminelli C, Denhardt G (2000) Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice. J Pharmacol Exp Ther 293:136–150

    PubMed  CAS  Google Scholar 

  • Smith SR, Terminelli C, Denhardt G (2001) Modulation of cytokine responses in Corynebacterium parvum-primed endotoxemic mice by centrally administered cannabinoid ligands. Eur J Pharmacol 425:73–83

    PubMed  CAS  Google Scholar 

  • Song ZH, Zhong M (2000) CB1 cannabinoid receptor-mediated cell migration. J Pharmacol Exp Ther 294:204–209

    PubMed  CAS  Google Scholar 

  • Specter SC, Klein TW, Newton C et al (1986) Marijuana effects on immunity: suppression of human natural killer cell activity of delta-9-tetrahydrocannabinol. Int J Immunopharmacol 8:741–745

    PubMed  CAS  Google Scholar 

  • Springs AE, Karmaus PW, Crawford RB et al (2008) Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by Delta9-tetrahydrocannabinol. J Leukoc Biol 84:1574–1584

    PubMed  CAS  Google Scholar 

  • Stefano GB, Liu Y, Goligorsky MS (1996) Cannabinoid receptors are coupled to nitric oxide release in invertebrate immunocytes, microglia, and human monocytes. J Biol Chem 271:19238–19242

    PubMed  CAS  Google Scholar 

  • Steffens S, Veillard NR, Arnaud C et al (2005) Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 434:782–786

    PubMed  CAS  Google Scholar 

  • Stella N (2004) Cannabinoid signaling in glial cells. GLIA 48:267–277

    PubMed  Google Scholar 

  • Stella N (2009) Endocannabinoid signaling in microglial cells. Neuropharmacology 56:244–253

    PubMed  CAS  Google Scholar 

  • Storr MA, Keenan CM, Emmerdinger D et al (2008) Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors. J Mol Med 86:925–936

    PubMed  CAS  Google Scholar 

  • Storr M, Emmerdinger D, Diegelmann J et al (2009) The role of fatty acid hydrolase gene variants in inflammatory bowel disease. Aliment Pharmacol Ther 29:542–551

    PubMed  CAS  Google Scholar 

  • Sugamura K, Sugiyama S, Nozaki T et al (2009) Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages. Circulation 119:28–36

    PubMed  CAS  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A et al (1995) 2-arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Comm 215:89–97

    PubMed  CAS  Google Scholar 

  • Sugiura T, Kishimoto S, Oka S et al (2006) Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Prog Lipid Res 45:405–446

    PubMed  CAS  Google Scholar 

  • Szabo I, Chen XH, Xin L et al (2002) Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain. Proc Natl Acad Sci USA 99:10276–10281

    PubMed  CAS  Google Scholar 

  • Szallasi A, Di Marzo V (2000) New perspectives on enigmatic vanilloid receptors. Trends Neurosci 23:491–497

    PubMed  CAS  Google Scholar 

  • Tanasescu R, Constantinescu CS (2010) Cannabinoids and the immune system: an overview. Immunobiology 215:588–597

    PubMed  CAS  Google Scholar 

  • Tanikawa T, Kurohane K, Imai Y (2007) Induction of preferential chemotaxis of unstimulated B-lymphocytes by 2-arachidonoylglycerol in immunized mice. Microbiol Immunol 51:1013–1019

    PubMed  CAS  Google Scholar 

  • Tashkin DP, Baldwin GC, Sarafian T et al (2002) Respiratory and immunologic consequences of marijuana smoking. J Clin Pharmacol 42:71S–81S

    PubMed  CAS  Google Scholar 

  • Tasker J (2004) Endogenous cannabinoids take the edge off neuroendocrine responses to stress. Endocrinology 145:5429–5430

    PubMed  CAS  Google Scholar 

  • Terabe M, Berzofsky JA (2007) NKT cells in immunoregulation of tumor immunity: a new immunoregulatory axis. Trends Immunol 28:491–496

    PubMed  CAS  Google Scholar 

  • Toth CC, Jedrzejewski NM, Ellis CL et al (2010) Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Mol Pain 6:16

    PubMed  Google Scholar 

  • Triantaphyllopoulos KA, Williams RO, Tailor H et al (1999) Amelioration of collagen-induced arthritis and suppression of interferon-γ interleukin-12, and tumor necrosis factor α production by interferon-β gene therapy. Arthritis Rheum 42:90–99

    PubMed  CAS  Google Scholar 

  • Tsuboi K, Zhao LY, Okamoto Y et al (2007) Predominant expression of lysosomal N-acylethanolamine-hydrolyzing acid amidase in macrophages revealed by immunochemical studies. Biochim Biophys Acta 1771:623–632

    PubMed  CAS  Google Scholar 

  • Valk P, Verbakel S, Vankan Y et al (1997) Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells. Blood 90:1448–1457

    PubMed  CAS  Google Scholar 

  • Van Diepen H, Schlicker E, Michel MC (2008) Prejunctional and peripheral effects of the cannabinoid CB1 receptor inverse agonist rimonabant (SR 141716). Naunyn-Schmiedebergs Arch Pharmacol 378:345–369

    PubMed  Google Scholar 

  • Van Sickle MD, Duncan M, Kingsley PJ et al (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332

    PubMed  Google Scholar 

  • Vannacci A, Giannini L, Passani MB et al (2004) The endocannabinoid 2-arachidonylglycerol decreases the immunological activation of Guinea pig mast cells: involvement of nitric oxide and eicosanoids. J Pharmacol Exp Ther 311:256–264

    PubMed  CAS  Google Scholar 

  • Varga K, Wagner JA, Bridgen DT et al (1998) Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB J 12:1035–1044

    PubMed  CAS  Google Scholar 

  • Vogt AB, Spindeldreher S, Kropshofer H (2002) Clustering of MHC-peptide complexes prior to their engagement in the immunological synapse: lipid raft and tetraspan microdomains. Immunol Rev 189:136–151

    PubMed  CAS  Google Scholar 

  • Wacnik PW, Luhr KM, Hill RH et al (2008) Cannabinoids affect dendritic cell (DC) potassium channel function and modulate DC T cell stimulatory capacity. J Immunol 181:3057–3066

    PubMed  CAS  Google Scholar 

  • Wager-Miller J, Westenbroek R, Mackie K (2002) Dimerization of G protein-coupled receptors: CB1 cannabinoid receptors as an example. Chem Phys Lipids 121:83–89

    PubMed  CAS  Google Scholar 

  • Walsh SK, Hepburn CY, Kane KA et al (2010) Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion. Br J Pharmacol 160:1234–1242

    PubMed  CAS  Google Scholar 

  • Walter L, Franklin A, Witting A et al (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23:1398–1405

    PubMed  CAS  Google Scholar 

  • Wang J, Zhao LY, Uyama T et al (2008) Amino acid residues crucial in pH regulation and proteolytic activation of N-acylethanolamine-hydrolyzing acid amidase. Biochim Biophys Acta 1781:710–717

    PubMed  CAS  Google Scholar 

  • Wei BQ, Mikkelsen TS, McKinney MK et al (2006) A second fatty acid amide hydrolase with variable distribution among placental mammals. J Biol Chem 281:36569–36578

    PubMed  CAS  Google Scholar 

  • Weibel GL, Joshi MR, Alexander ET et al (2009) Overexpression of human 15(S)-lipoxygenase-1 in RAW macrophages leads to increased cholesterol mobilization and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 29:837–842

    PubMed  CAS  Google Scholar 

  • White SC, Brin SC, Janicki BW (1975) Mitogen induced blastogenic responses of lymphocytes from marihuana smokers. Science 188:71–72

    PubMed  CAS  Google Scholar 

  • Woelkart K, Marth E, Suter A et al (2006) Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system. Int J Clin Pharmacol Ther 44:401–408

    PubMed  CAS  Google Scholar 

  • Woelkart K, Salo-Ahen OM, Bauer R (2008) CB receptor ligands from plants. Curr Top Med Chem 8:173–186

    PubMed  CAS  Google Scholar 

  • Wolf SA, Ullrich O (2008a) Endocannabinoids and the brain immune system: new neurones at the horizon? J Neuroendocrinol 20:15–19

    PubMed  CAS  Google Scholar 

  • Wolf SA, Ullrich O (2008b) Endocannabinoids and the brain immune system: new neurones at the horizon? J Neuroendocrinol 20(Suppl 1):15–19

    PubMed  CAS  Google Scholar 

  • Wotherspoon G, Fox A, McIntyre P et al (2005) Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons. Neuroscience 135:235–245

    PubMed  CAS  Google Scholar 

  • Wright K, Rooney N, Feeney M et al (2005) Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology 129:437–453

    PubMed  Google Scholar 

  • Wright KL, Duncan M, Sharkey KA (2008) Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. Br J Pharmacol 153:263–270

    PubMed  CAS  Google Scholar 

  • Yang HYT, Karoum F, Felder C et al (1999) GC/MS analysis of anandamide and quantification of N- arachidonoylphosphatidylethanolamides in various brain regions, spinal cord, testis, and spleen of the rat. J Neurochem 72:1959–1968

    PubMed  CAS  Google Scholar 

  • Yao BB, Mukherjee S, Fan Y et al (2006) In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor? Br J Pharmacol 149:145–154

    PubMed  CAS  Google Scholar 

  • Yea SS, Yang KH, Kaminski NE (2000) Role of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T- cells. J Pharmacol Exp Ther 292:597–605

    PubMed  CAS  Google Scholar 

  • Yuan M (2002) [Delta]9-Tetrahydrocannabinol regulates TH1/TH2 cytokine balance in activated human T cells. J Neuroimmunol 133:124–131

    PubMed  CAS  Google Scholar 

  • Yuan M, Kiertscher SM, Cheng Q et al (2002) Δ9Tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells. J Neuroimmunol 133:124–131

    PubMed  CAS  Google Scholar 

  • Zhang ZF, Morgenstern H, Spitz MR et al (1999) Marijuana use and increased risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomark Prev 8:1071–1078

    CAS  Google Scholar 

  • Zhao LY, Tsuboi K, Okamoto Y et al (2007) Proteolytic activation and glycosylation of N-acylethanolamine-hydrolyzing acid amidase, a lysosomal enzyme involved in the endocannabinoid metabolism. Biochim Biophys Acta 1771:1397–1405

    PubMed  CAS  Google Scholar 

  • Zhao P, Leonoudakis D, Abood ME et al (2010) Cannabinoid receptor activation reduces TNFα-Induced surface localization of AMPAR-type glutamate receptors and excitotoxicity. Neuropharmacology 58:551–558

    PubMed  CAS  Google Scholar 

  • Ziring D, Wei B, Velazquez P et al (2006) Formation of B and T cell subsets require the cannabinoid receptor CB2. Immunogenetics 58:714–725

    PubMed  CAS  Google Scholar 

  • Zoppi S, Pérez Nievas BG, Madrigal JL, Manzanares J, Leza JC, García-Bueno B (2011) Regulatory role of cannabinoid receptor 1 in stress-induced excitotoxicity and neuroinflammation. Neuropsychopharmacology 36(4):805–18

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Academic Division of Clinical Neurology, University of Nottingham, C Floor, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    Cris S. Constantinescu

  2. Department of Neurology, Colentina Hospital, Carol Davila University of Medicine and Pharmacy, Av. Stefan cel Mare 19-21, Sector 2, Bucharest, Romania

    Radu Tanasescu

Authors
  1. Cris S. Constantinescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Radu Tanasescu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cris S. Constantinescu .

Editor information

Editors and Affiliations

  1. School of Behavioral Sciences, The Academic College of TLV Yaffo, Rabenu Yeruham Street 29, Yaffo, 61083, Israel

    Mia Levite

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag/Wien

About this chapter

Cite this chapter

Constantinescu, C.S., Tanasescu, R. (2012). The Effects of Cannabinoids on Immune Cells, Responses and Diseases. In: Levite, M. (eds) Nerve-Driven Immunity. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0888-8_11

Download citation

Publish with us

Policies and ethics

Search

Navigation