Skip to main content

Cannabinoid CB2 Receptor Mechanism of Cannabis sativa L.

Abstract

Cannabinoids and many other compounds are constituents in Cannabis sativa L., (cannabaceae) and endocannabinoids (eCBs) are the endogenous marijuana-like substances found in animals and humans. Endocannabinoids, phytocannabinoids and marijuana use activate two cannabinoid receptors (CBRs), CB1Rs and CB2Rs that are encoded in human chromosomes 6 and 1 respectively. New understanding in the science of cannabis botany along with medical and biotechnological advances demonstrate that phytocannabinoids and eCBs acting on CBRs are important regulators of various aspects of physiological, behavioral, immunological and metabolic functions. CB2Rs were previously thought to be predominantly expressed in immune cells in the periphery and were traditionally referred to as peripheral CB2Rs. The neuronal and functional expression of CB2Rs in the brain had been controversial and have been less well characterized in comparison with the expression of the ubiquitous CB1Rs. We and others have now demonstrated the expression of CB2Rs in neuronal, glial and endothelial cells in the brain, and this warrants a re-evaluation of the CNS effects of CB2Rs. In this chapter we focused on the neurobiology of CB2Rs and describe its gene structure, regulation, variation, CNS distribution and its emerging role in immuno-endocannabinoid interactions with novel knowledge and deeper insight from the genetic and epigenetic manipulation of CB2Rs. With the rapidly shifting landscape on recreational, medicalization, and legalization of marijuana use, further research will certainly provide the scientific basis to unravel the mode of action of marijuana use and its implication on its neurological and psychiatric effects in human health and disease. We conclude that CB2 cannabinoid receptor signaling plays an important role in neuro-immuno-cannabinoid activity and beyond with potential therapeutic targets in neurological and mental diseases.

Keywords

  • Anorexia Nervosa
  • Neuropsychiatric Disorder
  • Chronic Mild Stress
  • Central Nervous System Effect
  • CNR2 Gene

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-319-54564-6_10
  • Chapter length: 21 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   219.00
Price excludes VAT (USA)
  • ISBN: 978-3-319-54564-6
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   279.99
Price excludes VAT (USA)
Hardcover Book
USD   279.99
Price excludes VAT (USA)
Fig. 10.1
Fig. 10.2
Fig. 10.3

References

  • Abood ME (2005) Molecular biology of cannabinoid receptors. HandB Exp Pharmacol 81–115

    Google Scholar 

  • Albayram O, Alferink J, Pitsch J, Piyanova A, Neitzert K, Poppensieke K, Mauer D, Michel K, Legler A, Becker A, Monory K, Lutz B, Zimmer A, Bilkei-Gorzo A (2011) Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging. PNAS 108:11256–11261

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Aso E, Ferrer I (2014) Cannabinoids for treatment of Alzheimers’s disease: moving toward the clinic. Front Pharmacol 5:37

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Atwood BK, Mackie K (2010) CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol 160:467–479

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Basu S, Dittel BN (2011) Unraveling the complexities of cannabinoid receptor 2 (CB2) immune regulation in health and disease. Immunol Res 51:26–38

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Benito C, Tolon RM, Pazos MR, Nunez E, Castillo AI, Romero J (2008) Cannabinoid CB2 receptors in human brain inflammation. Br J Pharmacol 153:277–285

    CAS  CrossRef  PubMed  Google Scholar 

  • Borrman E, Zajkowska Z, Ahmed R, Pariante CM, Zunszain PA (2016) Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression. Psychopharmacology 233:1591–1604

    CrossRef  Google Scholar 

  • Brown SM, Wager-Miller J, Mackie K (2002) Cloning and molecular characterization of the rat CB2 cannabinoid receptor. Biochim Biophys Act 1576:255–264

    CAS  CrossRef  Google Scholar 

  • Buchmann AF, Hohm E, Witt SH, Blomeyer D, Jennen-Steinmetz C, Schmidt MH, Esser G, Banaschewski T, Brandeis D, Laucht M (2014) Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents. J Neural Transm 122:455–463

    CrossRef  PubMed  Google Scholar 

  • Buckley NE, McCoy KL, Mezey E, Bonner T, Zimmer A, Felder CC, Glass M, Zimmer A (2000) Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor. Eur J Pharmacol 396:141–149

    CAS  CrossRef  PubMed  Google Scholar 

  • Callen L, Moreno E, Barroso-Chinea P, Moreno-Delgado Cortes A, Mallol J, Casado V, Lanciego JL, Franco R, Lluis C, Canela EL, McCormic PJ (2012) Cannabinoid receptors CB1 and CB2 form functional heteromers in brain. J Biol Chem 287:20851–20865

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Chiarlone A, Bellocchio L, Blazquez C, Resel E, Soria-Gomez E, Cannich A, Ferrero JJ, Sagredo O, Benito C, Romero J, Sanchez-Prieto J, Lutz B, Fernandez-Ruiz J, Galve-Roperh I, Guzman M (2014) A restricted population of CB1 cannabinoid receptors with neuroprotective activity. PNAS 111:8257–8262

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Corbille A-G, Valjent E, Marsicano G, Ledent C, Lutz B, Herve D, Girault J-A (2007) Role of cannabinoid type 1 receptors in locomotor activity and striatal signaling in response to psychostimulants. J Neuroscience 27:6937–6947

    CAS  CrossRef  PubMed  Google Scholar 

  • Ehlers CL, Slutske WS, Lind P, Wilhelmsen KC (2007) Association between single nucleotide polymorphisms in the cannabinoid receptor gene (CNR1) and impulsivity in South West California Indians. Twin Res Hum Gen 10:805–811

    CrossRef  Google Scholar 

  • ElSholy MA, Slade D (2005) Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 78:539–548

    CrossRef  Google Scholar 

  • Fagan SG, Campbell VA (2012) The influence of cannabinoids on generic traits of neurodegeneration. Br J Pharmacol 171:1347–1360

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Fernandez-Ruiz J, Romero J, Velasco G, Tolon RM, Ramos JA, Guzman M (2006) Cannabinoid CB2 receptor: a new target for controlling neural cell survival. Trends Pharmacol Sci 28:39–45

    CrossRef  PubMed  Google Scholar 

  • Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire S, Le Fur F, Casellas P (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61

    CAS  CrossRef  PubMed  Google Scholar 

  • García-Gutiérrez MS, Ortega-Álvaro A, Busquets-García A, Pérez-Ortiz JM, Caltana L, Ricatti MJ, Brusco A, Maldonado R, Manzanares J (2013) Synaptic plasticity alterations associated with memory impairment induced by deletion of CB2 cannabinoid receptors. Neuropharmacology 73:388–396

    CrossRef  PubMed  Google Scholar 

  • Ghose H (2009) Cannabinoid controversy. http://www.the-scientist.com/news/display/55969/

  • Golech SA, McCarron RM, Chen Y, Bembry J, Lenz F, Mechoulam R, Shohami E, Spatz M (2004) Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors. Mol Brain Res 132:87–92

    CAS  CrossRef  PubMed  Google Scholar 

  • Gong J-P, Onaivi ES, Ishiguro H, Liu Q-R, Tagliaferro PA, Brusco A, Uhl GR (2006) Cannabinoid CB2 receptors: immunohistochemically localization in rat brain. Brain Res 1071:10–23

    CAS  CrossRef  PubMed  Google Scholar 

  • Griffin G, Wray EJ, Tao Q, McAllister SD, Rorrer WK, Aung MM, Martin BR, Abood ME (1999) Evaluation of the cannabinoid CB2 receptor-selective antagonist, SR144528: further evidence for CB2 receptor absence in the rat central nervous system. Eur J Pharmacol 377:117–125

    CAS  CrossRef  PubMed  Google Scholar 

  • Grimsey NL, Goodfellow CE, Scotter EL, Dowie MJ, Glass M, Graham ES (2008) Specific detection of CB1 receptors; cannabinoid CB1 receptor antibodies are not all created equal. J Neurosci Methods 171:78–86

    CAS  CrossRef  PubMed  Google Scholar 

  • Hillard CJ, Weinlander KM, Stuhr KL (2012) Contributions of endocannabinoid signaling to psychiatric disorders in humans: genetic and biochemical evidence. Neuroscience 204:207–229

    CAS  CrossRef  PubMed  Google Scholar 

  • Horev G, Ellegood J, Lerch JP, Son YE, Muthuswamy L, Vogel H, Krieger AM, Buja A, Henkelman RM, Wigler M, Mills AA (2011) Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism. Proc Natl Acad Sci 108:17076–17081

    Google Scholar 

  • Ishiguro H, Iwasaki S, Teasenfitz L, Higuchi S, Horiuchi Y, Saito T, Arinami T, Onaivi ES (2007) Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans. Pharmacogenomics J 7:380–385

    CAS  CrossRef  PubMed  Google Scholar 

  • Ishiguro H, Carpio O, Horiuchi Y, Shu A, Higuchi S, Schanz N, Benno R, Arinami T, Onaivi ES (2010a) A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands. Synapse 64:92–96

    CAS  CrossRef  PubMed  Google Scholar 

  • Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, Morikawa M, Inada T, Watanabe Y, Takahashi M, Someya T, Ujike H, Iwata N, Ozaki N, Onaivi ES, Kunugi H, Sasaki T, Itokawa M, Arai M, Niizato K, Iritani S, Naka I, Ohashi J, Kakita A, Takahashi H, Nawa H, Arinami T (2010b) Brain cannabinoid CB2 receptor in schizophrenia. Biol Psychiatry 67:974–982

    CAS  CrossRef  PubMed  Google Scholar 

  • Jean-Gilles L, Braitch M, Latif ML, Aram J, Fahey AJ, Edwards LJ, Robins RA, Tanasescu R, Tighe PJ, Gran B, Showe LC, Alexander SP, Chapman V, Kendall DA, Constantinescu CS (2015) Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells. Acta Physiol 214:63–74

    Google Scholar 

  • Jesudason D, Wittert G (2008) Endocannabinoid system in food intake and metabolic regulation. Curr Opin Lipidol 19:344–348

    CAS  CrossRef  PubMed  Google Scholar 

  • Kannan G, Sawa A, Pletnikov MV (2013) Mouse models of gene-environment interactions in schizophrenia. Neurobiol Dis 57:5–11

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Karsak M, Cohen-Solal M, Freudenberg J, Ostertag A, Morieux C, Kornak U, Essig J, Erxlebe E, Bab I, Kubisch C, de Vernejoul MC, Zimmer A (2005) The cannabinoid receptor type 2 (CNR2) gene is associated with human osteoporosis. Hum Mol Genet 14:3389–3396

    CAS  CrossRef  PubMed  Google Scholar 

  • Koch M, Habazetti I, Dehghani F, Korf HW (2008) The rat pineal gland comprises an endocannabinoid system. J Pineal Res 45:351–360

    CAS  CrossRef  PubMed  Google Scholar 

  • Kong W, Li H, Tuma RF, Ganea D (2014) Selective CB2 receptor activation ameliorates EAE by reducing TH17 differentiation and immune cell accumulation in the CNS. Cellular Immunol 287:1–17

    CAS  CrossRef  Google Scholar 

  • Lanciego JL, Barroso-Chinea P, Rico AJ, Conte-Perales L, Callen L, Roda E, Gomez-Bautista V, Lopez IP, Lluis C, Labandeira-Garcia JL, Franco R (2011) Expression of mRNA coding the cannabinoid receptor 2 in the pallidal complex of Macaca fascicularis. J Psychopharmacol 25:97–104

    CAS  CrossRef  PubMed  Google Scholar 

  • Lehmann C, Burkovskiy I, Kuethe J, Zhou J, Caldwell C, Kelly MEM (2014) Inhibition of cannabinoid 2 receptor in CNS-injury induced immunodeficiency syndrome. Med Hypothesis 82:736–739

    CAS  CrossRef  Google Scholar 

  • Liu Q-R, Pan C-H, Hishimoto A, Li C-Y, Xi Z-X, Llorente Berzal A, Viveros MA, Ishiguro H, Arinami T, Onaivi ES, Uhl GR (2009) Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression, and regulation by cannabinoid receptor ligands. Genes Brain Behav 8:519–530

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Lovinger DM (2008) Presynaptic modulation by endocannabinoids. Handb Exp Pharmacol 184:435–477

    CAS  CrossRef  Google Scholar 

  • Malfitano AM, Basu S, Bifulco M, Dittel BN (2014) What we know and do not know about the cannabinoid receptor 2. Semin Immunol 26:369–379

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutiérrez SO, van der Stelt M, Lopez-Rodriguez ML, Casanova E, Schutz G, Zieglgansberger W, Di Marzo V, Behl C, Lutz B (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88

    CAS  CrossRef  PubMed  Google Scholar 

  • Minocci D, Massei J, Martino A, Milianti M, Piz L, Di Bello D, Sbrana A, Martinotti E, Rossi AM, Nieri P (2011) Genetic association between bipolar disorder and 524A > C (Leu133Ile) polymorphism of CNR2 gene, encoding for CB2 cannabinoid receptor. J Affect Disord 134:427–430

    CAS  CrossRef  PubMed  Google Scholar 

  • Monory K, Massa F, Egertova M, Eder M, Blaudzun H, Westenbroek R, Kelsch W, Jacob W, Marsch R, Ekker M, Long J, Rubenstein JL, Goebbels S, Nave K-A, During M, Klugmann M, Woflel B, Dodt H-U, Zieglgansberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B (2006) The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 51:455–466

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

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

    CAS  CrossRef  PubMed  Google Scholar 

  • Nagarkatti P, Pandey R, Rieder SA, Hedge VL, Nagarkatti M (2010) Cannabinoids as novel anti-inflammatory drugs. Future Med Chem 1:1333–1349

    CrossRef  Google Scholar 

  • Navarrete F, Pérez-Ortiz JM, Manzanares J (2012) Cannabinoid CB2 receptor-mediated regulation of impulsivelike behaviour in DBA/2 mice. Br J Pharmacol 165:260–273

    Google Scholar 

  • Navarrete F, Rodríguez-Arias M, Martín-García E, Navarro D, García-Gutiérrez MS, Aguilar MA, Aracil-Fernández A, Berbel P, Miñarro J, Maldonado R, Manzanares J (2013) Role of CB2 cannabinoid receptors in the rewarding, reinforcing and physical effects of nicotine. Neuropsychopharmacology 38:2515–2524

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Ndong C, O’Donnell D, Ahmad S, Groblewski T (2011) Cloning and pharmacological characterization of the dog cannabinoid CB2 receptor. Eur J Pharmacol 669:24–31

    Google Scholar 

  • Nunez E, Benito C, Pazos MR, Barbachano A, Fajardo O, Gonzalez S, Tolon RM, Romero J (2004) Cannabinoid CB2 receptors are expressed by perivascular microglia cells in the human brain: an immunohistochemical study. Synapse 53:208–213

    CAS  CrossRef  PubMed  Google Scholar 

  • Onaivi ES (2006) Preface. In: Onaivi ES (ed) Marijuana and cannabinoid research, methods and protocols. Humana Press, Totowa, pp vii

    Google Scholar 

  • Onaivi ES (2009) Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications. Int Rev Neurobiol 88:335–369

    CAS  CrossRef  PubMed  Google Scholar 

  • Onaivi ES (2011) Commentary: functional neuronal CB2 cannabinoid receptors in the CNS. Curr Neuropharmacol 9:205–208

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Onaivi ES, Leonard CM, Ishiguro H, Zhang PW, Lin Z, Akinshola BE, Uhl GR (2002) Endocannabinoids and cannabinoid receptor genetics. Prog Neurobiol 66:307–344

    Google Scholar 

  • Onaivi ES, Sugiura T, Di Marzo V (eds) (2006) Endocannabinoids: the brain and body’s marijuana and beyond. CRC Press, Taylor and Francis Group, Boca Raton

    Google Scholar 

  • Onaivi ES, Carpio O, Ishiguro H, Schanz N, Uhl GR, Benno R (2008a) Behavioral effects of CB2 cannabinoid receptor activation and its influence on food and alcohol consumption. Ann N Y Acad Sci 1139:426–433

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Onaivi ES, Ishiguro H, Gong J-P, Patel S, Meozzi PA, Myers L, Perchuk A, Mora Z, Tagliaferro PA, Gardner E, Brusco A, Akinshola BE, Hope B, Lujilde J, Inada T, Iwasaki S, Macharia D, Teasenfitz L, Arinami T, Uhl GR (2008b) Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: From mice to human subjects. PLoS ONE 3:e1640

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Onaivi ES, Ishiguro H, Gu S, Liu Q-R (2012) CNS effects of CB2 cannabinoid receptors: beyond neuro-immuno-cannabinoid activity. J Psychopharmacol 26:92–103

    CAS  CrossRef  PubMed  Google Scholar 

  • Onaivi ES, Ishiguro H, Sgro S, Leonard CM (2013) Cannabinoid receptor gene variations in drug addiction and neuropsychiatric disorders. J Drug Alcohol Res 2, ID235714

    Google Scholar 

  • Onaivi ES, Ishiguro H, Liu QR (2015) In: Fattore L (ed) Cannabinoids in neurologic and mental disease, Elsevier Inc. Future perspectives: Cannabinoid CB2 receptor ligands and their therapeutic potential in mental diseases. Chapter 18: 425–444

    Google Scholar 

  • Paldy E, Bereczki E, Santha M, Wenger T, Borsodi A, Zimmer A, Benhyhe S (2008) CB2 cannabinoid receptor antagonist SR144528 decreases mu-opioid receptor expression and activation in mouse brainstem: role of CB2 receptor in pain. Neurochem Int 53:309–316

    CAS  CrossRef  PubMed  Google Scholar 

  • Paldyova E, Bereczki E, Santha M, Wenger T, Borsodi A, Benyhe S (2008) Oladin ether, a putative endocannabinoid, inhibits mu-opoid receptor activation via CB2 cannabinoid receptors. Neurochem Int 52:321–328

    CAS  CrossRef  PubMed  Google Scholar 

  • Palomo T, Kostrzewa RM, Beninger RJ, Archer T (2007) Genetic variation and shared biological susceptibility underlying comorbidity in neuropsychiatry. Neurotox Res 12:29–42

    CAS  CrossRef  PubMed  Google Scholar 

  • Pazos MR, Nunez E, Benito C, Tolon RM, Romero J (2004) Role of the endocannabinoid system in Alzheimer’s disease: new perspectives. Life Sci 75:1907–1915

    CAS  CrossRef  PubMed  Google Scholar 

  • Reinhard W, Stark K, Neureuther K, Sedlacek K, Fischer M, Baessler A, Weber S, Kaess B, Wiedmann S, Erdmann J, Lieb W, Jeron A, Riegger G, Hengstenberg C (2008) Common polymorphisms in the cannabinoid CB2 gene (CNR2) are not associated with myocardial infarction and cardiovascular risk factors. Int J Mole Med 22:165–174

    CAS  Google Scholar 

  • Rogers N (2015) Cannabinoid receptor with an “identity crisis” gets a second look. Nat Med 21:967

    Google Scholar 

  • Shire D, Calandra B, Rinaldi-Carmona M, Oustric D, Pessegue B, Bonnin-Cabanne O, Le Fur G, Caput D, Ferrara P (1996) Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. Biochim Biophys Act 1307:132–136

    CrossRef  Google Scholar 

  • Sipe JC, Arbour N, Gerber A, Beutler E (2005) Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders. J Leukoc Biol 78:231–238

    CAS  CrossRef  PubMed  Google Scholar 

  • Steiner MA, Marsicano G, Wotjak CA, Lutz B (2008) Conditional cannabinoid receptor type 1 mutants reveal neuron subpopulation-specific effects on behavioral and neuroendocrine stress responses. Psychoneuroendocrinology 33:1165–1170

    CAS  CrossRef  PubMed  Google Scholar 

  • Stempel AV, Stumpf A, Zhang H-Y, Ozdogan T, Pannasch U, Theis A-K, Otte D-M, Wojtalla A, Racz I, Ponomarenko A, Xi Z-X, Zimmer A, Schmitz D (2016) Cannabinoid type 2 receptors mediate a cell type-specific plasticity in the hippocampus. Neuron 90:1–15

    CrossRef  Google Scholar 

  • Suarez J, Bermudez-Silva FJ, Mackie K, Ledent C, Zimmer A, Cravatt BF, de Fonseca FR (2008) Immunohistochemical description of the endogenous cannabinoid system in the rat cerebellum and functionally related nuclei. J Comp Neurol 509:400–421

    CAS  CrossRef  PubMed  Google Scholar 

  • Suarez J, Llorente R, Romero-Zerbo SY, Mateos B, Bermudez-Silva FJ, de Fonseca FR, Viveros MP (2009) Early maternal deprivation induces gender-dependent changes on the expression of hippocampla CB1 and CB2 cannabinoid receptors of neonatal rats. Hippocampus 19:623–632

    CAS  CrossRef  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  • Tyndale RF (2003) Genetics of alcohol and tobacco use in humans. Ann Med 35:94–121

    CAS  CrossRef  PubMed  Google Scholar 

  • Uhl GR, Ishiguro H, Onaivi ES, Zhang PW, Akinshola BE, Lin Z, Hope B, Leonard CM, Liu Q-R (2006) Molecular neurobiological methods in marijuana-cannabinoid research. In: Onaivi ES (ed) Marijuana and cannabinoid research: methods and protocols. Totowa, Humana press Inc pp 1–17

    Google Scholar 

  • Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332

    CrossRef  PubMed  Google Scholar 

  • Viscomi MT, Oddi S, Latini L, Pasquariello N, Florenzano F, Bernardi G, Molinari M, Maccarrone M (2009) Selective CB2 receptor agonism protects central neurons from remote axotomy-induced apoptosis through the PI3K/Akt pathway. J Neurosci 29(14):4564–4570

    Google Scholar 

  • Vlachou S, Panagis G (2014) Regulation of brain reward by the endocannabinoid system: a critical review of behavioral studies in animals. Curr Pharm Des 20:2072–2088

    CAS  CrossRef  PubMed  Google Scholar 

  • Yamada Y, Ando F, Shimkata H (2007) Association of candidate gene polymorphisms with bone mineral density in community-dwelling Japanese women and men. Int J Mole Med 19:791–801

    CAS  Google Scholar 

  • Zhang HY, Bi GH, Li X, Li J, Qu H, Zhang SJ, Li CY, Onaivi ES, Gardner EL, Xi ZX, Liu QR (2015) Species differences in cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats. Neuropsychopharmacology 40:1037–1051

    CAS  CrossRef  PubMed  Google Scholar 

  • Zhang P-W, Ishiguro H, Ohtsuki T, Hess J, Carillo F, Walther D, Onaivi ES, Arinami T, Uhl GR (2004) Human cannabinoid receptor 1:5’ exons, candidate regulatory regions, polymorphisms, haplotypes and association with polysubstance abuse. Mol Psychiatry 9:916–931

    CAS  CrossRef  PubMed  Google Scholar 

  • Zimmer A (2015) Genetic manipulation of the endocannabinoid system. In: Pertwee (ed) Endocannabinoids, Handbook of Experimental Pharmacology. Switzerland

    Google Scholar 

Download references

Acknowledgements

We would like to thank the Dean, Dr. Wolf for student worker fund to support the maintenance of animals in our research. ESO is supported by NIH grant DA032890. This is also in remembrance of Dorcas Omope Dimowo who passed away during the preparation of this chapter.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Emmanuel S. Onaivi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Onaivi, E.S., Ishiguro, H., Liu, QR. (2017). Cannabinoid CB2 Receptor Mechanism of Cannabis sativa L.. In: Chandra, S., Lata, H., ElSohly, M. (eds) Cannabis sativa L. - Botany and Biotechnology. Springer, Cham. https://doi.org/10.1007/978-3-319-54564-6_10

Download citation