Kanabinoid Sistem ve Epilepsi

Hatice Aygün; Serdar Savaş Gül

Derleme

Kanabinoid Sistem ve Epilepsi

Yıl 2017, Cilt: 9 Sayı: 4, 222 - 234, 01.12.2017

Hatice Aygün Serdar Savaş Gül

Öz

Epilepsi
tekrarlayan nöbetlerle karakterize olan en yaygın nörolojik hastalıklardan
biridir. Kanabinoidlerin epilepside önemli rolü olduğu yapılan deneysel
çalışmalarda gösterilmiştir. Kanabinoidlerin birçok fizyolojik süreçte
düzenleyici rol oynadığı bilinmektedir ve son yıllarda, hastalıkların
tedavisinde kullanılması konusunda artan bir ilgi söz konusudur. Kanabinoid
sistemde CB1 ve CB2 olmak üzere iki tip reseptör bulunur. Esrarın psikoaktif
bileşeni olan Δ9-Tetrahydrocannabinol (THC), kimyasal olarak üretilen sentetik
kanabinoidler ve insan ve hayvanlarda doğal olarak üretilen dokanabinoidler,
kanabinoid reseptörlerine bağlanarak etki gösterirler. Kanabinoidler, beyinde
aynı anda birden fazla kanal ve reseptör sistemi üzerinde etkili maddeler
olduğundan, epilepsi üzerine olan etkisinin hangi sistem üzerinden
gerçekleştiğinin ortaya konulması zordur. Bu yazıda kanabinoid sistem ve
epilepsiyle olan ilişkisi özetlenmiştir.

Anahtar Kelimeler

Kanabinoid sietem, epilepsi, Kanabinoid, CB1, CB2

Kaynakça

1. Zupec-Kania BA, Spellman E. An overview of the ketogenic diet for pediatric epilepsy. Nutr Clin Pract. 2009;23(6):589-596.
2. Engelborghs S, D’Hooge R, De Deny PP. Pathophysiology of epilepsy. Acta Neurol Belg. 2000;100(4): 201-213.
3. Marangoz C. Deneysel epilepsi modelleri. O.M.Ü. Tıp Dergisi 1997;14:147-186.
4. Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, Russo E, Whalley BJ, DiMarzo V, Stephens GJ. Non psychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: Potential for thetreatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014;5(11):1131-1141.
5. Gaoni Y, Mechoulam R. The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. J Am Chem Soc. 1971;93:217-224.
6. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946- 1949.
7. Felder CC, Veluz JS, Williams HL, Briley EM, Matsuda LA. Cannabinoid agonists stimulate both receptor- and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clones. Mol Pharmacol. 1992;42:838-845.
8. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346:561-564.
9. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365:61-65.
10. Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptoragonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci. 2012;367:3353-3363.
11. Agar E. The role of cannabinoids and leptin in neurological diseases. Acta Neurol Scand. 2015;132(6):371-380.
12. Katona I, Freund TF. Multiple functions of endo cannabinoid signaling in the brain. Annu Rev Neurosci. 2012;35:529-558.
13. Katona I. Cannabis and endocannabinoid signaling in epilepsy, in Endocannabinoids, Petwee RG. editor, New York London, Springer. 2015;285-316.
14. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediatedcontrol of synaptic transmission. Physiol Rev. 2009;89:309-380.
15. Ohno-Shosaku T, Tsubokawa H, Mizushima I, Yoneda N, Zimmer A, Kano M. Presynaptic cannabinoid sensitivity is a major determinant of depolarization-induced retrograde suppression at hippocampal synapses. J Neurosci 2002;22: 3864-3872.
16. Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M. The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 2006;26:2991-3001.
17. Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ. The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther. 2003;307:129-137.
18. Wallace MJ, Martin BR, DeLorenzo RJ. Evidencefor a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol. 2002;452:295-301.
19. Pertwee RG, Ross R. Cannabinoid receptors and their ligands. Prostaglandins. 2002; 66(2-3):101-121.
20. Childers SR, Deadwyler SA. Role of cyclic AMP in the actions of cannabinoid receptors. Biochem Pharmacol. 1996;52:819-827.
21. Caulfield MP and Brown, DA. Cannabinoid receptor agonists inhibit Ca2+ current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br. J. Pharmacol. 1992;106, 231-232.
22. Schlicker E, Kathmann M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci. 2001;22:565-572.
23. Irvıng AJ, Rae MG, Couttts AA. Cannabinoids on the brain. Sci W J. 2002;2:632-648.
24. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro auto radiographic study. J Neurosci. 1991;11(2):563-583.
25. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA. 1990;87(5):1932-1936.
26. Noe SN, Newton C, Widen R, Friedman H, Klein TW. Anti-CD40, anti- CD3, and IL-2 stimulation induce contrasting changes in CB1 mRNAexpression in Mouse splenocytes. J Neuroimmunol. 2000;110(1- 2):161-167.
27. Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. HandbExpPharmacol 2005;168:299-325.
28. Mackie K, Stella N. Cannabinoid receptors and endocannabinoids: evidence for new players. Aaps J. 2006;8:298-306.
29. Castillo PE, Younts TJ, Cha ´vez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron. 2012;76:70-81.
30. Katona I, Freund TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 2008;14:923-930.
31. Szaﬂarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy–from receptor stoclinical response. Epilepsy Behav. 2014;41:277-282.
32. Ludanyi A, Eross L, Czirj KS, Vajda J, Halsz P, Watanabe M, Palkovits M, Maglczky Z, Freund TF, Katona I. Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci. 2008;28:2976-2990.
33. Goffin K, Van Paesschen W, Van Laere K. Invivoactivation of endocannabinoidsystem in temporal lobe epilepsy with hippocampal sclerosis. Brain. 2011;134:1033-1040.
34. Russ SA, Larson K, Halfon N. A national proﬁle of childhood epilepsy and seizure disorder. Pediatrics 2012;129:256-264.
35. Hegde M, Santos-Sanchez C, Hess CP, Kabir AA, Garcia PA. Seizure exacerbation in two patients with focal epilepsy following marijuana cessation. Epilepsy Behav. 2012;25:563-566.
36. Braakman HM, vanOostenbrugge RJ, vanKranen-Mastenbroek VH, de Krom MC. Rimonabant induces partial seizures in a patient with a history of generalized epilepsy. Epilepsia. 2009;50:2171-2172.
37. Press CA, Knupp KG, Chapman KE. Parental reporting of responseto oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015;45:49-52.
38. 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 KA, During M, Klugmann M, Wolfel B, Dodt HU, Zieglgansberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B. The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron. 2006;51:455-466.
39. Lutz B. On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem Pharmacol. 2004; 68:1691-1698.
40. Chen K, Neu A, Howard AL et al. Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures. J Neurosci. 2007;27:46-58
41. Echegoyen J, Armstrong C, Morgan RJ, Soltesz I. Singleapplication of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model. Epilepsy Res. 2009;85:123-127.
42. Deshpande LS, Blair RE, Ziobro JM, Sombati S, Martin BR, DeLorenzo RJ. Endocannabinoids block status epilepticus in cultured hippocampal neurons. Eur J Pharmacol 2007a;558:52-59.
43. Rudenko V, Raﬁuddin A, Leheste JR, Friedman LK. Inverse relationship of cannabimimetic (Rþ) WIN 55. 212 on behavior and seizure threshold during the juvenile period. Pharmacol Biochem Behav. 2012;100:474-484.
44. Katona I, Urban GM, Wallace M, Ledent C, Jung KM, Piomelli D, Mackie K, Freund TF. Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci. 2006;26:5628-5637.
45. Hoffman AF, Lupica CR. Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J Neurosci 2000;20:2470-2479.
46. Vinogradova LV, Shatskova AB, vanRijn CM. Pro-epileptic effects of the cannabinoid receptor antagonist SR141716 in a model of audiogenic epilepsy. Epilepsy Res. 2011;96:250-256.
47. Arslan G, Alici, SK, Ayyildiz, M, Agar, E. The role of CB1-receptors in the proconvulsant effect of leptin on penicillin-induced epileptiform activity in rats. CNS Neurosci Ther. 2013;19(4):222-228.
48. Arslan G, Ayyildiz M, Agar E. The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats. Neuropeptides 2014;48:345-352.
49. Kow RL, Jiang K, Naydenov AV, Le JH, Stella N, Nathanson NM. Modulation of pilocarpine-induced seizures by cannabinoid receptor 1. PLoS One. 2014;9:95-92.
50. Van Rijn CM, Perescis MF, Vinogradova L, vanLuijtelaar G. Endocannabinoid system protect sagainst cryptogenic seizures. Pharmacol Rep. 2011;63:165-168.
51. VonRu den EL, Bogdanovic RM, Wotjak CT, Potschka H. Inhibition of monoacyl glycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice. Neurobiol Dis. 2015b;77:238-245.

Cannabinoid System and Epilepsy

Yıl 2017, Cilt: 9 Sayı: 4, 222 - 234, 01.12.2017

Hatice Aygün Serdar Savaş Gül

Öz

Epilepsy is one of the commonest chronic neurological
disease, which is characterized by recurrent spontaneous seizures. Experimental
studies show that cannabinoid system has an important role in epilepsy. The
cannabinoids plays a regulatory role in a number of physiological processes and
over the past decade there has been an increasing interest in using
cannabinoids to in many diseased treatments. The Cannabinoids system comprises
CB1 receptors, and CB2 receptors. Δ9-Tetrahidrokannabinol (THC) the psychoactive
component of marihuana, chemically produced synthetic cannabinoids and
naturally occurring in humans and animals, endocannabinoids bind to cannabinoid
receptor. Cannabinoids are so active substances that effects multiple channel
and receptors systems, simultaneously. Therefore, it is diffucult to reveal in
which system cannabinoids show their effects on epilepsy.The cannabinoid system
and its physiological properties are relation to epilepsy briefly summarized
here.

Anahtar Kelimeler

Canabinoid system, epilepsy, Canabinoid, CB1, CB2

Kaynakça

1. Zupec-Kania BA, Spellman E. An overview of the ketogenic diet for pediatric epilepsy. Nutr Clin Pract. 2009;23(6):589-596.
2. Engelborghs S, D’Hooge R, De Deny PP. Pathophysiology of epilepsy. Acta Neurol Belg. 2000;100(4): 201-213.
3. Marangoz C. Deneysel epilepsi modelleri. O.M.Ü. Tıp Dergisi 1997;14:147-186.
4. Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, Russo E, Whalley BJ, DiMarzo V, Stephens GJ. Non psychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: Potential for thetreatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014;5(11):1131-1141.
5. Gaoni Y, Mechoulam R. The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. J Am Chem Soc. 1971;93:217-224.
6. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946- 1949.
7. Felder CC, Veluz JS, Williams HL, Briley EM, Matsuda LA. Cannabinoid agonists stimulate both receptor- and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clones. Mol Pharmacol. 1992;42:838-845.
8. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346:561-564.
9. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365:61-65.
10. Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptoragonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci. 2012;367:3353-3363.
11. Agar E. The role of cannabinoids and leptin in neurological diseases. Acta Neurol Scand. 2015;132(6):371-380.
12. Katona I, Freund TF. Multiple functions of endo cannabinoid signaling in the brain. Annu Rev Neurosci. 2012;35:529-558.
13. Katona I. Cannabis and endocannabinoid signaling in epilepsy, in Endocannabinoids, Petwee RG. editor, New York London, Springer. 2015;285-316.
14. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediatedcontrol of synaptic transmission. Physiol Rev. 2009;89:309-380.
15. Ohno-Shosaku T, Tsubokawa H, Mizushima I, Yoneda N, Zimmer A, Kano M. Presynaptic cannabinoid sensitivity is a major determinant of depolarization-induced retrograde suppression at hippocampal synapses. J Neurosci 2002;22: 3864-3872.
16. Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M. The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 2006;26:2991-3001.
17. Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ. The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther. 2003;307:129-137.
18. Wallace MJ, Martin BR, DeLorenzo RJ. Evidencefor a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol. 2002;452:295-301.
19. Pertwee RG, Ross R. Cannabinoid receptors and their ligands. Prostaglandins. 2002; 66(2-3):101-121.
20. Childers SR, Deadwyler SA. Role of cyclic AMP in the actions of cannabinoid receptors. Biochem Pharmacol. 1996;52:819-827.
21. Caulfield MP and Brown, DA. Cannabinoid receptor agonists inhibit Ca2+ current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br. J. Pharmacol. 1992;106, 231-232.
22. Schlicker E, Kathmann M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci. 2001;22:565-572.
23. Irvıng AJ, Rae MG, Couttts AA. Cannabinoids on the brain. Sci W J. 2002;2:632-648.
24. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro auto radiographic study. J Neurosci. 1991;11(2):563-583.
25. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA. 1990;87(5):1932-1936.
26. Noe SN, Newton C, Widen R, Friedman H, Klein TW. Anti-CD40, anti- CD3, and IL-2 stimulation induce contrasting changes in CB1 mRNAexpression in Mouse splenocytes. J Neuroimmunol. 2000;110(1- 2):161-167.
27. Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. HandbExpPharmacol 2005;168:299-325.
28. Mackie K, Stella N. Cannabinoid receptors and endocannabinoids: evidence for new players. Aaps J. 2006;8:298-306.
29. Castillo PE, Younts TJ, Cha ´vez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron. 2012;76:70-81.
30. Katona I, Freund TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 2008;14:923-930.
31. Szaﬂarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy–from receptor stoclinical response. Epilepsy Behav. 2014;41:277-282.
32. Ludanyi A, Eross L, Czirj KS, Vajda J, Halsz P, Watanabe M, Palkovits M, Maglczky Z, Freund TF, Katona I. Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci. 2008;28:2976-2990.
33. Goffin K, Van Paesschen W, Van Laere K. Invivoactivation of endocannabinoidsystem in temporal lobe epilepsy with hippocampal sclerosis. Brain. 2011;134:1033-1040.
34. Russ SA, Larson K, Halfon N. A national proﬁle of childhood epilepsy and seizure disorder. Pediatrics 2012;129:256-264.
35. Hegde M, Santos-Sanchez C, Hess CP, Kabir AA, Garcia PA. Seizure exacerbation in two patients with focal epilepsy following marijuana cessation. Epilepsy Behav. 2012;25:563-566.
36. Braakman HM, vanOostenbrugge RJ, vanKranen-Mastenbroek VH, de Krom MC. Rimonabant induces partial seizures in a patient with a history of generalized epilepsy. Epilepsia. 2009;50:2171-2172.
37. Press CA, Knupp KG, Chapman KE. Parental reporting of responseto oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015;45:49-52.
38. 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 KA, During M, Klugmann M, Wolfel B, Dodt HU, Zieglgansberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B. The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron. 2006;51:455-466.
39. Lutz B. On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem Pharmacol. 2004; 68:1691-1698.
40. Chen K, Neu A, Howard AL et al. Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures. J Neurosci. 2007;27:46-58
41. Echegoyen J, Armstrong C, Morgan RJ, Soltesz I. Singleapplication of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model. Epilepsy Res. 2009;85:123-127.
42. Deshpande LS, Blair RE, Ziobro JM, Sombati S, Martin BR, DeLorenzo RJ. Endocannabinoids block status epilepticus in cultured hippocampal neurons. Eur J Pharmacol 2007a;558:52-59.
43. Rudenko V, Raﬁuddin A, Leheste JR, Friedman LK. Inverse relationship of cannabimimetic (Rþ) WIN 55. 212 on behavior and seizure threshold during the juvenile period. Pharmacol Biochem Behav. 2012;100:474-484.
44. Katona I, Urban GM, Wallace M, Ledent C, Jung KM, Piomelli D, Mackie K, Freund TF. Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci. 2006;26:5628-5637.
45. Hoffman AF, Lupica CR. Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J Neurosci 2000;20:2470-2479.
46. Vinogradova LV, Shatskova AB, vanRijn CM. Pro-epileptic effects of the cannabinoid receptor antagonist SR141716 in a model of audiogenic epilepsy. Epilepsy Res. 2011;96:250-256.
47. Arslan G, Alici, SK, Ayyildiz, M, Agar, E. The role of CB1-receptors in the proconvulsant effect of leptin on penicillin-induced epileptiform activity in rats. CNS Neurosci Ther. 2013;19(4):222-228.
48. Arslan G, Ayyildiz M, Agar E. The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats. Neuropeptides 2014;48:345-352.
49. Kow RL, Jiang K, Naydenov AV, Le JH, Stella N, Nathanson NM. Modulation of pilocarpine-induced seizures by cannabinoid receptor 1. PLoS One. 2014;9:95-92.
50. Van Rijn CM, Perescis MF, Vinogradova L, vanLuijtelaar G. Endocannabinoid system protect sagainst cryptogenic seizures. Pharmacol Rep. 2011;63:165-168.
51. VonRu den EL, Bogdanovic RM, Wotjak CT, Potschka H. Inhibition of monoacyl glycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice. Neurobiol Dis. 2015b;77:238-245.

Toplam 51 adet kaynakça vardır.

Ayrıntılar

Birincil Dil	Türkçe
Konular	Klinik Tıp Bilimleri
Bölüm	Derleme
Yazarlar	Hatice Aygün Bu kişi benim Serdar Savaş Gül
Yayımlanma Tarihi	1 Aralık 2017
Yayımlandığı Sayı	Yıl 2017 Cilt: 9 Sayı: 4

Kaynak Göster

APA	Aygün, H., & Gül, S. S. (2017). Kanabinoid Sistem ve Epilepsi. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi, 9(4), 222-234.
AMA	Aygün H, Gül SS. Kanabinoid Sistem ve Epilepsi. Gaziosmanpaşa Tıp Dergisi. Aralık 2017;9(4):222-234.
Chicago	Aygün, Hatice, ve Serdar Savaş Gül. “Kanabinoid Sistem Ve Epilepsi”. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi 9, sy. 4 (Aralık 2017): 222-34.
EndNote	Aygün H, Gül SS (01 Aralık 2017) Kanabinoid Sistem ve Epilepsi. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi 9 4 222–234.
IEEE	H. Aygün ve S. S. Gül, “Kanabinoid Sistem ve Epilepsi”, Gaziosmanpaşa Tıp Dergisi, c. 9, sy. 4, ss. 222–234, 2017.
ISNAD	Aygün, Hatice - Gül, Serdar Savaş. “Kanabinoid Sistem Ve Epilepsi”. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi 9/4 (Aralık 2017), 222-234.
JAMA	Aygün H, Gül SS. Kanabinoid Sistem ve Epilepsi. Gaziosmanpaşa Tıp Dergisi. 2017;9:222–234.
MLA	Aygün, Hatice ve Serdar Savaş Gül. “Kanabinoid Sistem Ve Epilepsi”. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi, c. 9, sy. 4, 2017, ss. 222-34.
Vancouver	Aygün H, Gül SS. Kanabinoid Sistem ve Epilepsi. Gaziosmanpaşa Tıp Dergisi. 2017;9(4):222-34.

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