Skip to main content
SpringerLink
Log in

Do Cannabinoids Represent a Good Therapeutic Strategy for Epilepsy?

  • Protocol
  • First Online:
Antiepileptic Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

  • 666 Accesses

Abstract

The medical use of cannabinoids has been proposed for the control of epilepsy. At present, several studies have focused on investigating how cannabinoids can regulate the expression of epileptic seizures as well as the epileptogenesis process. Some of them suggest that cannabinoids may represent a therapeutic approach for different types of epilepsy. However, experimental evidence indicates that the effects of cannabinoids depend on several experimental and pathological conditions. In this chapter, we provide an overview of these preclinical and clinical research.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

  1. Abel EL (1980) Marihuana: the first twelve thousand years. Plenum, New York

    Book  Google Scholar 

  2. Kmietowicz Z (2010) Cannabis based drug is licensed for spasticity in patients with MS. BMJ 340:c3363

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Mechoulam R, Hanus L (2000) A historical overview of chemical research on cannabinoids. Chem Phys Lipids 108:1–13

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Adams R, Pease DC, Clark JH (1940) Isolation of cannabinol, cannabidiol, and quebrachitol from red oil of Minnesota wild hemp. J Am Chem Soc 62:2194–2196

    Article  CAS  Google Scholar 

  7. Michoulam R, Shvo Y, Hashish I (1963) The structure of cannabidiol. Tetrahedron 19:2073–2078

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Mechoulam R, Shani A, Edery H et al (1970) Chemical basis of hashish activity. Science 169:611–612

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. 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

    Article  CAS  PubMed  Google Scholar 

  13. 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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Benbadis SR, Sanchez-Ramos J, Bozorg A et al (2014) Medical marijuana in neurology. Expert Rev Neurother 14(12):1453–1465

    Article  CAS  PubMed  Google Scholar 

  16. Mechoulam R, Parker LA (2013) The endocannabinoid system and the brain. Annu Rev Psychol 64:21–47

    Article  PubMed  Google Scholar 

  17. Tabatadze N, Huang G, May RM et al (2015) Sex differences in molecular signaling at inhibitory synapses in the hippocampus. J Neurosci 35(32):11252–11265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pertwee RG, Howlett AC, Abood ME et al (2010) International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 62:588–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kreitzer AC, Regehr WG (2001) Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 29:717–727

    Article  CAS  PubMed  Google Scholar 

  20. Wilson RI, Kunos G, Nicoll RA (2001) Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 31:453–462

    Article  CAS  PubMed  Google Scholar 

  21. Okamoto Y, Morishita J, Tsuboi K et al (2004) Molecular characterization of a phospholipase D generating anandamide and its congeners. J Biol Chem 279:5298–5305

    Article  CAS  PubMed  Google Scholar 

  22. Bisogno T, Howell F, Williams G et al (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol 163:463–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. McKinney MK, Cravatt BF (2005) Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 74:411–432

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Marrs WR, Blankman JL, Horne EA et al (2010) The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nat Neurosci 13:951–957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Di Marzo V, Fontana A, Cadas H et al (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686–691

    Article  PubMed  Google Scholar 

  28. Hillard CJ, Edgemond WS, Jarrahian A, Campbell WB (1997) Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule cells occurs via facilitated diffusion. J Neurochem 69:631–638

    Article  CAS  PubMed  Google Scholar 

  29. Piomelli D, Beltramo M, Glasnapp S et al (1999) Structural determinants for recognition and translocation by the anandamide transporter. Proc Natl Acad Sci U S A 96:5802–5807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Deutsch DG, Ueda N, Yamamoto S (2002) The fatty acid amide hydrolase (FAAH). Prostaglandins Leukot Essent Fatty Acids 66:201–210

    Article  CAS  PubMed  Google Scholar 

  31. Yates ML, Barker EL (2009) Inactivation and biotransformation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol. Mol Pharmacol 76:11–17

    Article  CAS  PubMed  Google Scholar 

  32. Di Marzo V, Deutsch DG (1998) Biochemistry of the endogenous ligands of cannabinoid receptors. Neurobiol Dis 5:386–404

    Article  PubMed  Google Scholar 

  33. Ohno-Shosaku T, Maejima T, Kano M (2001) Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 29(3):729–738

    Article  CAS  PubMed  Google Scholar 

  34. Wilson RI, Nicoll RA (2001) Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410:588–592

    Article  CAS  PubMed  Google Scholar 

  35. Wallmichrath I, Szabo B (2002) Cannabinoids inhibit striatonigral GABAergic neurotransmission in the mouse. Neuroscience 113:671–682

    Article  CAS  PubMed  Google Scholar 

  36. Kim J, Alger BE (2004) Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus. Nat Neurosci 7:697–698

    Article  CAS  PubMed  Google Scholar 

  37. Szabo B, Urbanski MJ, Bisogno T et al (2006) Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol. J Physiol (Lond) 577:263–280

    Article  CAS  Google Scholar 

  38. Maejima T, Hashimoto K, Yoshida T et al (2001) Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors. Neuron 31:463–475

    Article  CAS  PubMed  Google Scholar 

  39. Galante M, Diana MA (2004) Group I metabotropic glutamate receptors inhibit GABA release at interneuron–Purkinje cell synapses through endocannabinoid production. J Neurosci 24:4865–4874

    Article  CAS  PubMed  Google Scholar 

  40. Straiker A, Mackie K (2007) Metabotropic suppression of excitation in murine autaptic hippocampal neurons. J Physiol (Lond) 578:773–785

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Min R, Di Marzo V, Mansvelder HD (2010) DAG lipase involvement in depolarization induced suppression of inhibition: does endocannabinoid biosynthesis always meet the demand? Neuroscientist 16:608–613

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  44. Hampson RE, Evans GJ, Mu J (1995) Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium “A-current” in cultured rat hippocampal neurons. Life Sci 56:2081–2088

    Article  CAS  PubMed  Google Scholar 

  45. Mackie K, Lai Y, Westenbroek R et al (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in Att20 cells transfected with rat-brain cannabinoid receptor. J Neurosci 15:6552–6561

    CAS  PubMed  Google Scholar 

  46. Twitchell W, Brown S, Mackie K (1997) Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol 78:43–50

    CAS  PubMed  Google Scholar 

  47. Schweitzer P (2000) Cannabinoids decrease the K(+) M-current in hippocampal CA1 neurons. J Neurosci 20:51–58

    CAS  PubMed  Google Scholar 

  48. Wilson RI, Nicoll RA (2002) Endocannabinoid signaling in the brain. Science 296(5568):678–682

    Article  CAS  PubMed  Google Scholar 

  49. Huang CC, Lo SW, Hsu KS (2001) Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons. J Physiol 532:731–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Robbe D, Alonso G, Duchamp F et al (2001) Localization and mechanisms of action of cannabinoid receptors at the glutamatergic synapses of the mouse nucleus accumbens. J Neurosci 21:109–116

    CAS  PubMed  Google Scholar 

  51. Azad SC, Eder M, Marsicano G et al (2003) Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse. Learn Mem 10:116–128

    Article  PubMed  PubMed Central  Google Scholar 

  52. Brown SP, Safo PK, Regehr WG (2004) Endocannabinoids inhibit transmission at granule cell to Purkinje cell synapses by modulating three types of presynaptic calcium channels. J Neurosci 24:5623–5631

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  54. Li Y, Krogh KA, Thayer SA (2012) Epileptic stimulus increases Homer 1a expression to modulate endocannabinoid signaling in cultured hippocampal neurons. Neuropharmacology 63:1140–1149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Katona I, Freund TF (2012) Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 35:529–558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Glass M, Felder CC (1997) Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci 17:5327–5333

    CAS  PubMed  Google Scholar 

  57. Mackie K, Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci U S A 89:3825–3829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Szabo GG, Lenkey N, Holderith N et al (2014) Presynaptic calcium channel inhibition underlies CB(1) cannabinoid receptor-mediated suppression of GABA release. J Neurosci 34:7958–7963

    Article  CAS  PubMed  Google Scholar 

  59. Deadwyler SA, Hampson RE, Mu J et al (1995) Cannabinoids modulate voltage sensitive potassium A-current in hippocampal neurons via a cAMP dependent process. J Pharmacol Exp Ther 273:734–743

    CAS  PubMed  Google Scholar 

  60. Mu J, Zhuang SY, Hampson RE et al (2000) Protein kinase-dependent phosphorylation and cannabinoid receptor modulation of potassium A current (IA) in cultured rat hippocampal neurons. Pflugers Arch 439:541–546

    CAS  PubMed  Google Scholar 

  61. Henry DJ, Chavkin C (1995) Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. Neurosci Lett 186:91–94

    Article  CAS  PubMed  Google Scholar 

  62. McAllister SD, Griffin G, Satin LS et al (1999) Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a xenopus oocyte expression system. J Pharmacol Exp Ther 291:618–626

    CAS  PubMed  Google Scholar 

  63. Photowala H, Blackmer T, Schwartz E et al (2006) G protein beta gamma-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties. Proc Natl Acad Sci U S A 103:4281–4286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lauckner JE, Jensen JB, Chen HY et al (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A 105:2699–2704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Oka S, Nakajima K, Yamashita A et al (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun 362:928–934

    Article  CAS  PubMed  Google Scholar 

  67. Sylantyev S, Jensen TP, Ross RA et al (2013) Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci U S A 110:5193–5198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Qin N, Neeper MP, Liu Y et al (2008) TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 28:6231–6238

    Article  CAS  PubMed  Google Scholar 

  69. De Petrocellis L, Vellani V, Schiano-Moriello A et al (2008) Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther 325:1007–1015

    Article  PubMed  CAS  Google Scholar 

  70. De Petrocellis L, Ligresti A, Moriello AS et al (2011) Effects of cannabinoids and cannabinoid enriched Cannabis extracts on TRP channel s and endocannabinoid metabolic enzymes. Br J Pharmacol 163:1479–1494

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Thomas BF, Gilliam AF, Burch DF et al (1998) Comparative receptor binding analyses of cannabinoid agonists and antagonists. J Pharmacol Exp Ther 285:285–292

    CAS  PubMed  Google Scholar 

  72. Bisogno T, Hanus L, De Petrocellis L et al (2001) Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 134:845–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Russo EB, Burnett A, Hall B et al (2005) Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res 30:1037–1043

    Article  CAS  PubMed  Google Scholar 

  74. Ahrens J, Demir R, Leuwer M et al (2009) The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function. Pharmacology 83:217–222

    Article  CAS  PubMed  Google Scholar 

  75. Ross HR, Napier I, Connor M (2008) Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol. J Biol Chem 283:16124–16134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ross RA (2009) The enigmatic pharmacology of GPR55. Trends Pharmacol Sci 30:156–163

    Article  CAS  PubMed  Google Scholar 

  77. Drysdale AJ, Ryan D, Pertwee RG et al (2006) Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells. Neuropharmacology 50:621–631

    Article  CAS  PubMed  Google Scholar 

  78. Ryan D, Drysdale AJ, Lafourcade C et al (2009) Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci 29:2053–2063

    Article  CAS  PubMed  Google Scholar 

  79. De Petrocellis L, Di Marzo V (2010) Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels. J Neuroimmune Pharmacol 5:103–121

    Article  PubMed  Google Scholar 

  80. Karniol IG, Carlini EA (1973) Pharmacological interaction between cannabidiol and delta9-tetrahydrocannabinol. Psychopharmacologia 33:53–70

    Article  CAS  PubMed  Google Scholar 

  81. Russo E, Guy GW (2006) A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 66:234–246

    Article  CAS  PubMed  Google Scholar 

  82. Englund A, Morrison PD, Nottage J et al (2013) Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol 27:19–27

    Article  CAS  PubMed  Google Scholar 

  83. Schubart CD, Sommer IE, van Gastel WA et al (2011) Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr Res 130:216–221

    Article  PubMed  Google Scholar 

  84. Kozan R, Ayyildiz M, Agar E (2009) The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats. Epilepsia 50(7):1760–1767

    Article  CAS  PubMed  Google Scholar 

  85. Wallace MJ, Wiley JL, Martin BR et al (2001) Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. Eur J Pharmacol 428:51–57

    Article  CAS  PubMed  Google Scholar 

  86. Wallace MJ, Martin BR, DeLorenzo RJ (2002) Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol 452:295–301

    Article  CAS  PubMed  Google Scholar 

  87. Ameri A, Wilhelm A, Simmet T (1999) Effects of the endogeneous cannabinoid, anandamide, on neuronal activity in rat hippocampal slices. Br J Pharmacol 126(8):1831–1839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ameri A, Simmet T (2000) Effects of 2-arachidonylglycerol, an endogenous cannabinoid, on neuronal activity in rat hippocampal slices. Naunyn Schmiedebergs Arch Pharmacol 361(3):265–272

    Article  CAS  PubMed  Google Scholar 

  89. Deshpande LS, Blair RE, Ziobro JM et al (2007) Endocannabinoids block status epilepticus in cultured hippocampal neurons. Eur J Pharmacol 558:52–59

    Article  CAS  PubMed  Google Scholar 

  90. Mason R, Cheer JF (2009) Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus. Front Int Neurosci 3:1–6

    Google Scholar 

  91. Wallace MJ, Blair RE, Falenski KW et al (2003) The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 307:129–137

    Article  CAS  PubMed  Google Scholar 

  92. Di Maio R, Cannon JR, Greenamyre JT (2015) Post-status epilepticus treatment with the cannabinoid agonist WIN 55,212-2 prevents chronic epileptic hippocampal damage in rats. Neurobiol Dis 73:356–365

    Article  PubMed  CAS  Google Scholar 

  93. Wendt H, Soerensen J, Wotjak CT et al (2011) Targeting the endocannabinoid system in the amygdala kindling model of temporal lobe epilepsy in mice. Epilepsia 52(7):e62–e65

    Article  PubMed  Google Scholar 

  94. von Rüden EL, Jafari M, Bogdanovic RM et al (2015) Analysis in conditional cannabinoid 1 receptor-knockout mice reveals neuronal subpopulation-specific effects on epileptogenesis in the kindling paradigm. Neurobiol Dis 73:334–347

    Article  CAS  Google Scholar 

  95. Navarrete M, Araque A (2008) Endocannabinoids mediate neuron-astrocyte communication. Neuron 57:883–893

    Article  CAS  PubMed  Google Scholar 

  96. Navarrete M, Araque A (2010) Endocannabinoids potentiate synaptic transmission through stimulation of astrocytes. Neuron 68:113–126

    Article  CAS  PubMed  Google Scholar 

  97. Coiret G, Ster J, Grewe B et al (2012) Neuron to astrocyte communication via cannabinoid receptors is necessary for sustained epileptiform activity in rat hippocampus. PLoS One 7(5):e37320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Shafaroodi H, Samini M, Moezi L et al (2004) The interaction of cannabinoids and opioids on pentylenetetrazole-induced seizure threshold in mice. Neuropharmacology 47:390–400

    Article  CAS  PubMed  Google Scholar 

  99. Bahremand A, Shafaroodi H, Ghasemi M et al (2008) The cannabinoid anticonvulsant effect on pentylenetetrazole-induced seizure is potentiated by ultra-low dose naltrexone in mice. Epilepsy Res 81:44–51

    Article  CAS  PubMed  Google Scholar 

  100. Monory K, Massa F, Egertová M et al (2006) The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 51(4):455–466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bhaskaran MD, Smith BN (2010) Cannabinoid mediated inhibition of recurrent excitatory circuitry in the dentate gyrus in a mouse model of temporal lobe epilepsy. PLoS One 5:e10683

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Vilela LR, Medeiros DC, Rezende GH et al (2013) Effects of cannabinoids and endocannabinoid hydrolysis inhibition on pentylenetetrazole-induced seizure and electroencephalographic activity in rats. Epilepsy Res 104(3):195–202

    Article  CAS  PubMed  Google Scholar 

  103. Naydenov AV, Horne EA, Cheah CS et al (2014) ABHD6 blockade exerts antiepileptic activity in PTZ-induced seizures and in spontaneous seizures in R6/2 mice. Neuron 83(2):361–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. von Rüden EL, Bogdanovic RM, Wotjak CT et al (2015) Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice. Neurobiol Dis 77:238–245

    Article  CAS  Google Scholar 

  105. Shubina L, Aliev R, Kitchigina V (2015) Attenuation of kainic acid-induced status epilepticus by inhibition of endocannabinoid transport and degradation in guinea pigs. Epilepsy Res 111:33–44

    Article  CAS  PubMed  Google Scholar 

  106. Citraro R, Russo E, Ngomba RT et al (2013) CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations. Epilepsy Res 106(1-2):74–82

    Article  CAS  PubMed  Google Scholar 

  107. Marsicano G, Goodenough S, Monory K et al (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88

    Article  CAS  PubMed  Google Scholar 

  108. Fezza F, Marrone MC, Avvisati R et al (2014) Distinct modulation of the endocannabinoid system upon kainic acid-induced in vivo seizures and in vitro epileptiform bursting. Mol Cell Neurosci 62:1–9

    Article  CAS  PubMed  Google Scholar 

  109. Karlócai MR, Tóth K, Watanabe M et al (2011) Redistribution of CB1 cannabinoid receptors in the acute and chronic phases of pilocarpine-induced epilepsy. PLoS One 6(11):e27196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Bojnik E, Turunç E, Armağan G et al (2012) Changes in the cannabinoid (CB1) receptor expression level and G-protein activation in kainic acid induced seizures. Epilepsy Res 99(1–2):64–68

    Article  CAS  PubMed  Google Scholar 

  111. Falenski KW, Carter DS, Harrison AJ et al (2009) Temporal characterization of changes in hippocampal cannabinoid CB(1) receptor expression following pilocarpine-induced status epilepticus. Brain Res 1262:64–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Wyeth MS, Zhang N, Mody I et al (2010) Selective reduction of cholecystokinin-positive basket cell innervation in a model of temporal lobe epilepsy. J Neurosci 30(26):8993–9006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Falenski KW, Blair RE, Sim-Selley LJ et al (2007) Status epilepticus causes a long-lasting redistribution of hippocampal cannabinoid type 1 receptor expression and function in the rat pilocarpine model of acquired epilepsy. Neuroscience 146(3):1232–1244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gesell FK, Zoerner AA, Brauer C et al (2013) Alterations of endocannabinoids in cerebrospinal fluid of dogs with epileptic seizure disorder. BMC Vet Res 9:262

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Romigi A, Bari M, Placidi F et al (2010) Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Epilepsia 51:768–772

    Article  CAS  PubMed  Google Scholar 

  116. Goffin K, Van Paesschen W, Van Laere K (2011) In vivo activation of endocannabinoid system in temporal lobe epilepsy with hippocampal sclerosis. Brain 134(Pt 4):1033–1040

    Article  PubMed  Google Scholar 

  117. Ludányi A, Eross L, Czirják S et al (2008) Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci 28:2976–2990

    Article  PubMed  CAS  Google Scholar 

  118. Maglóczky Z, Tóth K, Karlócai R et al (2010) Dynamic changes of CB1-receptor expression in hippocampi of epileptic mice and humans. Epilepsia 51(Suppl 3):115–120

    Article  PubMed  PubMed Central  Google Scholar 

  119. Sun FJ, Guo W, Zheng DH et al (2013) Increased expression of TRPV1 in the cortex and hippocampus from patients with mesial temporal lobe epilepsy. J Mol Neurosci 49(1):182–193

    Article  CAS  PubMed  Google Scholar 

  120. Izquierdo I, Tannhauser M (1973) Letter: the effect of cannabidiol on maximal electroshock seizures in rats. J Pharm Pharmacol 25:916–917

    Article  CAS  PubMed  Google Scholar 

  121. Karler R, Turkanis SA (1978) Cannabis and epilepsy. Adv Biosci 22–23:619–641

    PubMed  Google Scholar 

  122. Jones NA, Hill AJ, Smith I et al (2010) Cannabidiol displays anti-epileptiform and anti-seizure properties in vitro and in vivo. J Pharmacol Exp Ther 332:569–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Jones NA, Glyn SE, Akiyama S et al (2012) Cannabidiol exerts anticonvulsant effects in animal models of temporal lobe and partial seizures. Seizure 21:344–352

    Article  PubMed  Google Scholar 

  124. Colasanti BK, Lindamood C III, Craig CR (1982) Effects of marihuana cannabinoids on seizure activity in cobalt-epileptic rats. Pharmacol Biochem Behav 16:573–578

    Article  CAS  PubMed  Google Scholar 

  125. Turkanis SA, Smiley KA, Borys HK et al (1979) An electrophysiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats. Epilepsia 20:351–363

    Article  CAS  PubMed  Google Scholar 

  126. Devinsky O, Cilio MR, Cross H et al (2014) Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55:791–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Hill AJ, Weston SE, Jones NA et al (2010) Delta(9)-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia 51:1522–1532

    Article  CAS  PubMed  Google Scholar 

  128. Hill AJ, Williams CM, Whalley BJ et al (2012) Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 133:79–97

    Article  CAS  PubMed  Google Scholar 

  129. Hill TD, Cascio MG, Romano B et al (2013) Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Br J Pharmacol 170:679–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Amada N, Yamasaki Y, Williams CM et al (2013) Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression. Peer J 1:e214

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Bialer M, Johannessen SI, Levy RH et al (2015) Progress report on new antiepileptic drugs: a summary of the Twelfth Eilat Conference (EILAT XII). Epilepsy Res 111:85–141

    Article  PubMed  Google Scholar 

  132. Maa E, Figi P (2014) The case for medical marijuana in epilepsy. Epilepsia 55:783–786

    Article  PubMed  Google Scholar 

  133. Hussain SA, Zhou R, Jacobson C et al (2015) Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: a potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav 47:138–141

    Article  PubMed  Google Scholar 

  134. Devinsky O, Sullivan J, Friedman D et al (2015) Epidiolex (Cannabidiol) in treatment resistant epilepsy. American Academy of Neurology 67th annual meeting abstract 2015, Washington, DC, USA

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Physiology of the Reticular Formation, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877, Col. La Fama, Tlalpan, Mexico City, 14269, Mexico

    Cecilia Zavala-Tecuapetla

  2. Department of Pharmacobiology, Center for Research and Advanced Studies, Calz. Tenorios 235. Col. Granjas Coapa, Tlalpan, Mexico City, 14330, Mexico

    Luisa Rocha

Authors
  1. Cecilia Zavala-Tecuapetla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luisa Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cecilia Zavala-Tecuapetla .

Editor information

Editors and Affiliations

  1. Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB) Faculty of Exact Sciences, National University of La Plata, La Plata, Buenos Aires, Argentina

    Alan Talevi

  2. Department of Pharmacobiology, Center for Research and Advanced Studies, Mexico City, Mexico

    Luisa Rocha

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Zavala-Tecuapetla, C., Rocha, L. (2016). Do Cannabinoids Represent a Good Therapeutic Strategy for Epilepsy?. In: Talevi, A., Rocha, L. (eds) Antiepileptic Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6355-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6355-3_5

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6353-9

  • Online ISBN: 978-1-4939-6355-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation