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An overview of cannabinoid receptor 1 (CB1) and therapeutic approaches-II

Year 2012, Volume: 2 Issue: 1, 1 - 8, 31.01.2014

Abstract

Cannabinoid receptor 1 (CB1) is highly important in the pathophysiology of several diseases due to their regulatory roles in central nervous system and peripheral tissues. Direct use of cannabinoids is limited mostly because of their psychoactive properties; therefore augmenting endocannabinoids by inhibiting the enzymes responsible for their degradation (e.g. FAAH, MAGL) appears as a valuable therapeutic strategy. Furthermore, peripherally restricted CB1 agonists and antagonists emerge as novel therapeutics. While activation of CB1 receptors can be used for the treatment of pain, anxiety, depression, PTSD, post-menopausal osteoporosis, cancer and neurodegenerative disorders; inhibition of this system can be used for the treatment of obesity, diabetes, liver and cardiometabolic disorders, post-menopausal osteoporosis and addiction. Here we summarized the therapeutical considerations for the cannabinoid system.

Key words: Cannabinoids, CB1 receptor, FAAH, MAGL, CNS disorders, metabolic disorders

References

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Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-II

Year 2012, Volume: 2 Issue: 1, 1 - 8, 31.01.2014

Abstract

Kannabinoid tip 1 (CB1) reseptörleri merkezi sinir sistemi ve periferik organlardaki düzenleyici rollerinden dolayı pek çok hastalığın patofizyolojisinde önemli rol oynarlar. Kannabinoidlerin psikotrop etkileri nedeniyle kullanımları kısıtlandığından endokannabinoidleri metabolize eden enzimlerin (FAAH, MAGL) inhibisyonuyla endokannabinoidlerin arttırılması daha avantajlı bir tedavi stratejisi olabilir. Ayrıca kan-beyin engelini geçmeyen antagonistler ve agonistler de periferik CB1 reseptörlerini hedefleyerek terapötik amaçlı kullanılabilirler. Genel olarak CB1 reseptör aktivasyonu ağrı, anksiyete, depresyon, travma sonrası stres bozukluğu, postmenopozal osteoporoz, kanser ve nörodejeneratif hastalıkların tedavisinde, inhibisyonu ise obezite, diyabet, karaciğer hastalıkları, kardiyometabolik komplikasyonlar, alkol ve ilaç bağımlılığı ve postmenopozal osteoporoz tedavisinde terapötik amaçlı kullanılabilirler. Derlememizin bu kısmında kannabinoid reseptörlerin tedavi potansiyelleri özetlenmiştir.

Anahtar Kelimeler : Kannabinoidler, Kannabinoid tip-1 reseptör, FAAH, MAGL, Santral sinir sistemi hastalıkları, metabolik hastalıklar 

References

  • Çınar R, Gündüz Çınar Ö. Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-1. MÜSBED 2011;1(2):149-154.
  • Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993;262(5134):689-695.
  • Lutz B. On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem Pharmacol 2004;68(9):1691-1698.
  • Marsicano G, Lutz B. Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 1999;11(12):4213-4225.
  • Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003;83(3):1017-1066.
  • Cabral GA, Toney DM, Fischer-Stenger K, Harrison MP, Marciano- Cabral F. Anandamide inhibits macrophage-mediated killing of tumor necrosis factor-sensitive cells. Life sciences 1995;56(23- 24):2065-2072.
  • Mechoulam R. Discovery of endocannabinoids and some random thoughts on their possible roles in neuroprotection and aggression. Prostaglandins Leukot Essent Fatty Acids 2002 F;66(2-3):93-99.
  • Emrich HM, Leweke FM, Schneider U. Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system. Pharmacol Biochem Behav 1997;56(4):803-807.
  • Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport 1999;10(8): 1665-1669.
  • Schwarz E, Guest PC, Rahmoune H, Harris LW, Wang L, Leweke FM, Rothermundt M, Bogerts B, Koethe D, Kranaster L, Ohrmann P, Suslow T, McAllister G, Spain M, Barnes A, van Beveren NJ, Baron-Cohen S, Steiner J, Torrey FE, Yolken RH, Bahn S. Identification of a biological signature for schizophrenia in serum. Mol Psyc. 2011. DOI 10.1038/ mp.2011.42
  • Dean B, Sundram S, Bradbury R, Scarr E, Copolov D. Studies on [3H] CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neurosci 2001;103(1):9-15.
  • Tsai SJ, Wang YC, Hong CJ. Association study of a cannabinoid receptor gene (CNR1) polymorphism and schizophrenia. Psychiatr Genet 2000;10(3):149-151.
  • Ujike H, Takaki M, Nakata K, Tanaka Y, Takeda T, Kodama M, Fujiwara Y, Sakai A, Kuroda S. CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia. Mol Psychiatr 2002;7(5):515-518.
  • Hamdani N, Tabeze JP, Ramoz N, Ades J, Hamon M, Sarfati Y, Boni C, Gorwood P. The CNR1 gene as a pharmacogenetic factor for antipsychotics rather than a susceptibility gene for schizophrenia. Euro Neuropsychopharmacol 2008;18(1):34-40.
  • Seillier A, Advani T, Cassano T, Hensler JG, Giuffrida A. Inhibition of fatty-acid amide hydrolase and CB1 receptor antagonism differentially affect behavioural responses in normal and PCP-treated rats. Neuropsychopharmacologicum 2010;13(3):373-386.
  • McGregor IS, Issakidis CN, Prior G. Aversive effects of the synthetic cannabinoid CP 55,940 in rats. Pharmacology, biochemistry, and behavior 1996;53(3):657-664.
  • Arevalo C, de Miguel R, Hernandez-Tristan R. Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters. Pharmacol Biochem Behav 2001;70(1):123-131.
  • Haller J, Bakos N, Szirmay M, Ledent C, Freund TF. The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety. Eur J Neurosci 2002;16(7):1395-1398.
  • Moreira FA, Crippa JA. The psychiatric side-effects of rimonabant. Revista brasileira de psiquiatria 2009;31(2):145-153.
  • Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, Lutz B. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002;418(6897):530-534.
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  • Chhatwal JP, Davis M, Maguschak KA, Ressler KJ. Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacol 2005;30(3):516-524.
  • Lu AT, Ogdie MN, Jarvelin MR, Moilanen IK, Loo SK, McCracken JT, McGough JJ, Yang MH, Peltonen L, Nelson SF, Cantor RM, Smalley SL. Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder. American journal of medical genetics Part B, Neuropsychiatric genetics 2008;147B(8):1488-1494.
  • Hariri AR, Gorka A, Hyde LW, Kimak M, Halder I, Ducci F, Ferrell RE, Goldman D, Manuck SB. Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function. Biol Psychiat 2009;66(1):9-16.
  • Calhoun PS, Sampson WS, Bosworth HB, Feldman ME, Kirby AC, Hertzberg MA, Wampler TP, Tate-Williams F, Moore SD, Beckham JC. Drug use and validity of substance use self-reports in veterans seeking help for posttraumatic stress disorder. J Consult Clin Psychol 2000;68(5):923-927.
  • Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 1992;13(5):177-184.
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  • Melis M, Pistis M, Perra S, Muntoni AL, Pillolla G, Gessa GL. Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in rat ventral tegmental area dopamine neurons through activation of CB1 receptors. J Neurosci 2004 ;24(1):53-62.
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There are 79 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Özge Çınar This is me

Reşat Çınar This is me

Publication Date January 31, 2014
Submission Date November 7, 2013
Published in Issue Year 2012 Volume: 2 Issue: 1

Cite

APA Çınar, Ö., & Çınar, R. (2014). Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-II. Clinical and Experimental Health Sciences, 2(1), 1-8.
AMA Çınar Ö, Çınar R. Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-II. Clinical and Experimental Health Sciences. January 2014;2(1):1-8.
Chicago Çınar, Özge, and Reşat Çınar. “Kannabinoid Tip 1 reseptör (CB1) Ve terapötik yaklaşımlara Genel bakış-II”. Clinical and Experimental Health Sciences 2, no. 1 (January 2014): 1-8.
EndNote Çınar Ö, Çınar R (January 1, 2014) Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-II. Clinical and Experimental Health Sciences 2 1 1–8.
IEEE Ö. Çınar and R. Çınar, “Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-II”, Clinical and Experimental Health Sciences, vol. 2, no. 1, pp. 1–8, 2014.
ISNAD Çınar, Özge - Çınar, Reşat. “Kannabinoid Tip 1 reseptör (CB1) Ve terapötik yaklaşımlara Genel bakış-II”. Clinical and Experimental Health Sciences 2/1 (January 2014), 1-8.
JAMA Çınar Ö, Çınar R. Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-II. Clinical and Experimental Health Sciences. 2014;2:1–8.
MLA Çınar, Özge and Reşat Çınar. “Kannabinoid Tip 1 reseptör (CB1) Ve terapötik yaklaşımlara Genel bakış-II”. Clinical and Experimental Health Sciences, vol. 2, no. 1, 2014, pp. 1-8.
Vancouver Çınar Ö, Çınar R. Kannabinoid tip 1 reseptör (CB1) ve terapötik yaklaşımlara genel bakış-II. Clinical and Experimental Health Sciences. 2014;2(1):1-8.

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