Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Neurotherapeutics
Erschienen in: Neurotherapeutics 4/2015

01.10.2015 | Review

Cannabinoids and Epilepsy

verfasst von: Evan C. Rosenberg, Richard W. Tsien, Benjamin J. Whalley, Orrin Devinsky

Erschienen in: Neurotherapeutics | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Fisher RS, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470-472.PubMedCrossRef
2.
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342:314-319.PubMedCrossRef
3.
Kwan P, Brodie MJ. Refractory epilepsy: a progressive, intractable but preventable condition? Seizure 2002;11:77-84.PubMedCrossRef
4.
5.
Nilsson L, et al. Risk factors for sudden unexpected death in epilepsy: a case–control study. Lancet 1999;353:888-893.PubMedCrossRef
6.
Walczak TS, et al. Incidence and risk factors in sudden unexpected death in epilepsy: a prospective cohort study. Neurology 2001;56:519-525.PubMedCrossRef
7.
8.
Jacoby A, Baker GA. Quality-of-life trajectories in epilepsy: a review of the literature. Epilepsy Behav 2008;12:557-571.PubMedCrossRef
9.
Rogawski MA. The intrinsic severity hypothesis of pharmacoresistance to antiepileptic drugs. Epilepsia 2013;54(Suppl. 2):33-40.PubMedCrossRef
10.
Perucca E. Is there a role for therapeutic drug monitoring of new anticonvulsants? Clin Pharmacokinet 2000;38:191-204.PubMedCrossRef
11.
Devinsky O, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 2014;55:791-802.PubMedCrossRefPubMedCentral
12.
Koppel BS, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82:1556-63.PubMedCentralPubMedCrossRef
13.
Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev 2014; 3:CD009270.PubMed
14.
Abel EL. Marihuana: the first twelve thousand years. Plenum Press, New York, 1980.CrossRef
15.
16.
Lozano I. The therapeutic use of Cannabis sativa L. in Arabic medicine. J Cannabis Ther 2001;1:63-70.CrossRef
17.
Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy—from receptors to clinical response. Epilepsy Behav 2014;41:277-282.PubMedCrossRef
18.
O'Shaughnessy WB. On the preparations of the Indian hemp, or Gunjah. Prov Med J Retrosp Med Sci 1843;5:363-369.PubMedCentral
19.
Reynolds JR. Epilepsy: its symptoms, treatment, and relation to other chronic convulsive diseases. J. Churchill (Ed.) London, 1861.
20.
Gowers W. Epilepsy and other chronic convulsive disorders. Churchill (Ed.) London, 1881.
21.
Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964;86:1646-1647.CrossRef
22.
Gaoni Y, Mechoulam R. The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. J Am Chem Soc 1971;9:217-224.CrossRef
23.
Adams R, Pease DC, Clark JH. Isolation of cannabinol, cannabidiol, and quebrachitrol from red oil of Minnesota wild hemp. J Am Chem Soc 1940;62: 2194-2196.CrossRef
24.
Michoulam R, Shvo Y., Hashish, I. The structure of cannabidiol. Tetrahedron 1963; 19:2073-2078.PubMedCrossRef
25.
Matsuda LA, et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346:561-564.PubMedCrossRef
26.
Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993;365:61-65.PubMedCrossRef
27.
28.
Pitler TA, Alger BE. Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells. J Neurosci 1992;12:4122-4132.PubMed
29.
Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 2001;29:717-727.PubMedCrossRef
30.
Kreitzer AC, Regehr WG. Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. J Neurosci 2001;21:RC174.PubMed
31.
Wilson RI, Kunos G, Nicoll RA. Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 2001;31:453-462.PubMedCrossRef
32.
Devane WA, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-1949.PubMedCrossRef
33.
Mechoulam R, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50:83-90.PubMedCrossRef
34.
Sugiura T, et al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 1995;215:89-97.PubMedCrossRef
35.
Alger BE. Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog Neurobiol 2002;68:247-286.PubMedCrossRef
36.
Brown SP, Brenowitz SD, Regehr WG. Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nat Neurosci 2003;6:1048-1057.PubMedCrossRef
37.
Maejima T, Ohno-Shosaku T, Kano M. Endogenous cannabinoid as a retrograde messenger from depolarized postsynaptic neurons to presynaptic terminals. Neurosci Res 2001;40:205-210.PubMedCrossRef
38.
Melis M, et al. Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons. J Neurosci 2004;24:10707-10715.PubMedCrossRef
39.
Katona I, Freund TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med 2008;14:923-930.PubMedCrossRef
40.
Di Marzo V, et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 1994;372:686-691.PubMedCrossRef
41.
Di Marzo V, Deutsch DG. Biochemistry of the endogenous ligands of cannabinoid receptors. Neurobiol Dis 1998;5:386-404.PubMedCrossRef
42.
Di Marzo V, et al. Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 1998;21:521-528.PubMedCrossRef
43.
Sugiura T, et al. Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot Essent Fatty Acids 2002;66:173-192.PubMedCrossRef
44.
Stella N, Schweitzer P, Piomelli D. A second endogenous cannabinoid that modulates long-term potentiation. Nature 1997;388:773-778.PubMedCrossRef
45.
Pertwee RG. Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development. Expert Opin Investig Drugs 2000;9:1553-1571.PubMedCrossRef
46.
Pi-Sunyer F, et al. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients - RIO-North America: A randomized controlled trial. JAMA 2006;295:761-775.PubMedCrossRef
47.
Cahill K, Ussher M. Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Cochrane Database Syst Rev 2007:CD005353.
48.
Glass M,. Felder CC. 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 1997;17:5327-5333.PubMed
49.
50.
Caulfield MP, Brown DA. Cannabinoid receptor agonists inhibit Ca current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br J Pharmacol 1992;106:231-232.PubMedCentralPubMedCrossRef
51.
Twitchell W, Brown S, Mackie K. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol 1997;78:43-50.PubMed
52.
Szabo GG, et al. Presynaptic calcium channel inhibition underlies CB(1) cannabinoid receptor-mediated suppression of GABA release. J Neurosci 2014;34:7958-7963.PubMedCrossRef
53.
Deadwyler SA, et al. Cannabinoids modulate potassium current in cultured hippocampal neurons. Receptors Channels 1993;1:121-134.PubMed
54.
Deadwyler SA, et al. Cannabinoids modulate voltage sensitive potassium A-current in hippocampal neurons via a cAMP-dependent process. J Pharmacol Exp Ther 1995;273:734-743.PubMed
55.
Hampson RE, et al. Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium "A-current" in cultured rat hippocampal neurons. Life Sci 1995;56:2081-2088.PubMedCrossRef
56.
Mu J, et al. Protein kinase-dependent phosphorylation and cannabinoid receptor modulation of potassium A current (IA) in cultured rat hippocampal neurons. Pflugers Arch 2000;439:541-546.PubMed
57.
Henry DJ, Chavkin C. Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. Neurosci Lett 1995;186:91-94.PubMedCrossRef
58.
Mackie K, et al. Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci 1995;15:6552-6561.PubMed
59.
McAllister SD, et al. Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a xenopus oocyte expression system. J Pharmacol Exp Ther 1999;291:618-626.PubMed
60.
Photowala H, et al. G protein betagamma-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties. Proc Natl Acad Sci U S A 2006;103:4281-4286.PubMedCentralPubMedCrossRef
61.
Schlicker E, Kathmann M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 2001;22:565-572.PubMedCrossRef
62.
Chevaleyre V, Takahashi KA, Castillo PE. Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 2006;29:37-76.PubMedCrossRef
63.
Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003;4:873-884.PubMedCrossRef
64.
Katona I, et al. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 1999; 19:4544-4558.PubMed
65.
Marsicano G, Lutz B. Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 1999;11: 4213-4225.PubMedCrossRef
66.
Dudok B, et al. Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling. Nat Neurosci 2015;18:75-86.PubMedCentralPubMedCrossRef
67.
Kawamura Y, et al. The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 2006;26:2991-3001.PubMedCrossRef
68.
69.
70.
Wittmann G, et al. Distribution of type 1 cannabinoid receptor (CB1)-immunoreactive axons in the mouse hypothalamus. J Comp Neurol 2007;503:270-279.PubMedCrossRef
71.
Robbe D, et al. Localization and mechanisms of action of cannabinoid receptors at the glutamatergic synapses of the mouse nucleus accumbens. J Neurosci 2001;21:109-116.PubMed
72.
Elsohly MA, Slade D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 2005;78:539-548.PubMedCrossRef
73.
Joy JE. Marijuana and medicine: assessing the science base. National Academics Press, Washington, DC 1999.
74.
Huestis MA, et al. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry 2001;58:322-328.PubMedCrossRef
75.
Lichtman AH, Martin BR. Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism. Psychopharmacology (Berl) 1996;126: 125-131.CrossRef
76.
Mallet PE, Beninger RJ. The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta9-tetrahydrocannabinol or anandamide. Psychopharmacology (Berl) 1998;140:11-19.CrossRef
77.
Varvel SA, et al. Differential effects of delta 9-THC on spatial reference and working memory in mice. Psychopharmacology (Berl) 2001;157:142-150.CrossRef
78.
Da S, Takahashi RN. SR 141716A prevents delta 9-tetrahydrocannabinol-induced spatial learning deficit in a Morris-type water maze in mice. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:321-325.PubMedCrossRef
79.
Pagotto U, et al. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006;27:73-100.PubMedCrossRef
80.
Abood ME, et al. Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons against excitotoxicity. Neurosci Lett 2001;309:197-201.PubMedCrossRef
81.
van der Stelt M, et al. Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity. J Neurosci 2001;21:6475-6479.PubMed
82.
El-Remessy AB, et al. Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite. Am J Pathol 2003;163:1997-2008.PubMedCentralPubMedCrossRef
83.
Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury: therapeutic implications. Trends Mol Med 2002;8:58-61.PubMedCrossRef
84.
Gilbert GL, et al. Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity. Brain Res 2007;1128:61-69.PubMedCrossRef
85.
Nagayama T, et al. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci 1999;19:2987-2995.PubMed
86.
Zani A, et al. Delta9-tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors. Br J Pharmacol 2007;152:1301-1311.PubMedCentralPubMedCrossRef
87.
88.
Molina-Holgado F, Lledo A, Guaza C. Anandamide suppresses nitric oxide and TNF-alpha responses to Theiler's virus or endotoxin in astrocytes. Neuroreport 1997;8:1929-1933.PubMedCrossRef
89.
Molina-Holgado F, et al. Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide-induced nitric oxide release in astrocyte cultures. J Neurosci Res 2002;67:829-836.PubMedCrossRef
90.
Shohami E, et al. Cytokine production in the brain following closed head injury: dexanabinol (HU-211) is a novel TNF-alpha inhibitor and an effective neuroprotectant. J Neuroimmunol 1997;72:169-177.PubMedCrossRef
91.
Puffenbarger RA, Boothe AC, Cabral GA. Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells. Glia 2000;29:58-69.PubMedCrossRef
92.
Cabral GA, Harmon KN, Carlisle SJ. Cannabinoid-mediated inhibition of inducible nitric oxide production by rat microglial cells: evidence for CB1 receptor participation. Adv Exp Med Biol 2001;493:207-214.PubMedCrossRef
93.
94.
Klein TW, et al. The cannabinoid system and cytokine network. Proc Soc Exp Biol Med 2000;225:1-8.PubMedCrossRef
95.
Molina-Holgado F, et al. Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. J Neurosci 2003;23:6470-6474.PubMed
96.
97.
De Petrocellis L, et al. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther 2008;325:1007-1015.PubMedCrossRef
98.
De Petrocellis L, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol 2011;163:1479-1494.PubMedCentralPubMedCrossRef
99.
Qin N, et al. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 2008;28:6231-6238.PubMedCrossRef
100.
101.
102.
Devinsky O, et al. Glia and epilepsy: excitability and inflammation. Trends Neurosci 2013;36:174-184.PubMedCrossRef
103.
Thomas BF, et al. Comparative receptor binding analyses of cannabinoid agonists and antagonists. J Pharmacol Exp Ther 1998;285:285-292.PubMed
104.
Bisogno T, et al. 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 2001;134:845-852.PubMedCentralPubMedCrossRef
105.
106.
107.
Russo EB, et al. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res 2005;30:1037-1043.PubMedCrossRef
108.
Ahrens J, et al. The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function. Pharmacology 2009;83:217-222.PubMedCrossRef
109.
Ross HR, Napier I, Connor M. Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol. J Biol Chem 2008;283: 16124-16134.PubMedCentralPubMedCrossRef
110.
Drysdale AJ, et al. Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells. Neuropharmacology 2006;50:621-631.PubMedCrossRef
111.
Ryan D, et al. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci 2009;29:2053-2063.PubMedCrossRef
112.
Rimmerman N, et al. The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells. Cell Mol Neurobiol 2011; 31:921-930.PubMedCrossRef
113.
114.
115.
Lauckner JE, et al. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A 2008;105:2699-2704.PubMedCentralPubMedCrossRef
116.
Oka S, et al. Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun 2007;362:928-934.PubMedCrossRef
117.
Sylantyev S, et al. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci U S A 2013;110:5193-5198.PubMedCentralPubMedCrossRef
118.
Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A 2006;103:7895-7900.PubMedCentralPubMedCrossRef
119.
Pandolfo P, et al. Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum. Eur J Pharmacol 2011;655:38-45.PubMedCrossRef
120.
121.
De Petrocellis L, Di Marzo V. 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 2010;5:103-121.PubMedCrossRef
122.
Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med 2011;51:1054-1061.PubMedCentralPubMedCrossRef
123.
Hampson AJ, et al. Neuroprotective antioxidants from marijuana. Ann N Y Acad Sci 2000;899:274-282.PubMedCrossRef
124.
Liou GI, et al. Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. Invest Ophthalmol Vis Sci 2008;49:5526-5531.PubMedCentralPubMedCrossRef
125.
Hayakawa K, et al. Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism. J Neurochem 2007;102:1488-1496.PubMedCrossRef
126.
Hayakawa K, et al. Therapeutic time window of cannabidiol treatment on delayed ischemic damage via high-mobility group box1-inhibiting mechanism. Biol Pharm Bull 2009;32:1538-1544.PubMedCrossRef
127.
Iuvone T, et al. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J Neurochem 2004;89:134-141.PubMedCrossRef
128.
Esposito G, et al. Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett 2006;399:91-95.PubMedCrossRef
129.
Esposito G, et al. Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br J Pharmacol 2007;151:1272-1279.PubMedCentralPubMedCrossRef
130.
Pietr M, et al. Differential changes in GPR55 during microglial cell activation. FEBS Lett 2009;583:2071-2076.PubMedCrossRef
131.
Staton PC, et al. The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 2008;139: 225-236.PubMedCrossRef
132.
Ben-Shabat S, et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol 1998;353: 23-31.PubMedCrossRef
133.
Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 2009;16:97-110.PubMedCrossRef
134.
Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat Prod Rep 1999;16:131-143.PubMedCrossRef
135.
136.
Karniol IG, Carlini EA. Pharmacological interaction between cannabidiol and delta 9-tetrahydrocannabinol. Psychopharmacologia 1973;33:53-70.PubMedCrossRef
137.
Englund A, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol 2013;27:19-27.PubMedCrossRef
138.
Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 2006;66:234-246.PubMedCrossRef
139.
Schubart CD, et al. Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr Res 2011;130:216-221.PubMedCrossRef
140.
Hemaiswarya S, Kruthiventi AK, Doble M. Synergism between natural products and antibiotics against infectious diseases. Phytomedicine 2008;15:639-652.PubMedCrossRef
141.
142.
Hill AJ, et al. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 2012;133:79-97.PubMedCrossRef
143.
Raol YH, Brooks-Kayal AR. Experimental models of seizures and epilepsies. Prog Mol Biol Transl Sci 2012;105:57-82.PubMedCrossRef
144.
Loscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure 2011;20:359-368.PubMedCrossRef
145.
Simonato M, et al. The challenge and promise of anti-epileptic therapy development in animal models. Lancet Neurol 2014;13:949-960.PubMedCrossRef
146.
Marsicano G, et al. CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 2003;302:84-88.PubMedCrossRef
147.
Wallace MJ, et al. The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 2003;307: 129-137.PubMedCrossRef
148.
Karanian DA, et al. Endocannabinoid enhancement protects against kainic acid-induced seizures and associated brain damage. J Pharmacol Exp Ther 2007;322: 1059-1066.PubMedCrossRef
149.
Karanian DA, et al. Dual modulation of endocannabinoid transport and fatty acid amide hydrolase protects against excitotoxicity. J Neurosci 2005;25:7813-7820.PubMedCrossRef
150.
Naidoo V, et al. Equipotent inhibition of fatty acid amide hydrolase and monoacylglycerol lipase—dual targets of the endocannabinoid system to protect against seizure pathology. Neurotherapeutics 2012;9:801-813.PubMedCentralPubMedCrossRef
151.
152.
153.
Guggenhuber S, et al. AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity. PLoS One 2010;5:e15707.PubMedCentralPubMedCrossRef
154.
155.
Falenski KW, et al. 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 2007;146:1232-1244.PubMedCentralPubMedCrossRef
156.
Falenski KW, et al. Temporal characterization of changes in hippocampal cannabinoid CB(1) receptor expression following pilocarpine-induced status epilepticus. Brain Res 2009;1262:64-72.PubMedCentralPubMedCrossRef
157.
Bhaskaran MD, Smith BN. Cannabinoid-mediated inhibition of recurrent excitatory circuitry in the dentate gyrus in a mouse model of temporal lobe epilepsy. PLoS One 2010;5:e10683.PubMedCentralPubMedCrossRef
158.
Sayers KW, et al. Statistical parametric mapping reveals regional alterations in cannabinoid CB1 receptor distribution and G-protein activation in the 3D reconstructed epileptic rat brain. Epilepsia 2012;53:897-907.PubMedCentralPubMedCrossRef
159.
Ludanyi A, et al. Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci 2008;28:2976-2990.PubMedCrossRef
160.
Romigi A, et al. Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Epilepsia 2010;51:768-772.PubMedCrossRef
161.
Wyeth MS, et al. Selective reduction of cholecystokinin-positive basket cell innervation in a model of temporal lobe epilepsy. J Neurosci 2010;30:8993-9006.PubMedCentralPubMedCrossRef
162.
Sun C, et al. Loss of cholecystokinin-containing terminals in temporal lobe epilepsy. Neurobiol Dis 2014;62:44-55.PubMedCrossRef
163.
Karlocai MR, et al. Redistribution of CB1 cannabinoid receptors in the acute and chronic phases of pilocarpine-induced epilepsy. PLoS One 2011;6:e27196.PubMedCentralPubMedCrossRef
164.
165.
Chen K, et al. Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures. Neuron 2003;39:599-611.PubMedCrossRef
166.
Chen K, et al. Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures. J Neurosci 2007;27: 46-58.PubMedCrossRef
167.
Hill AJ, Hill TD, Whalley B. The development of cannabinoid based therapies for epilepsy. In: Murillo-Rodriguez (Ed.) Endocannabinoids: molecular, pharmacological, behavioral and clinical features. bentham science publishers, Oak Park, IL, 2013, pp 164-204.
168.
Manna SS, Umathe SN. Involvement of transient receptor potential vanilloid type 1 channels in the pro-convulsant effect of anandamide in pentylenetetrazole-induced seizures. Epilepsy Res 2012;100:113-124.PubMedCrossRef
169.
Luszczki JJ, et al. Arachidonyl-2'-chloroethylamide, a highly selective cannabinoid CB1 receptor agonist, enhances the anticonvulsant action of valproate in the mouse maximal electroshock-induced seizure model. Eur J Pharmacol 2006;547:65-74.PubMedCrossRef
170.
Luszczki JJ, et al. Effect of arachidonyl-2'-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the protective action of the various antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:18-25.PubMedCrossRef
171.
Luszczki JJ, et al. Synthetic cannabinoid WIN 55,212-2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock-induced seizures in mice. Pharmacol Biochem Behav 2011;98:261-267.PubMedCrossRef
172.
Luszczki JJ, et al. Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1870-1876.PubMedCrossRef
173.
Andres-Mach M, et al. Effect of ACEA--a selective cannabinoid CB1 receptor agonist on the protective action of different antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model. Prog Neuropsychopharmacol Biol Psychiatry 2012;39: 301-309.PubMedCrossRef
174.
Luszczki JJ, et al. Effects of WIN 55,212-2 mesylate on the anticonvulsant action of lamotrigine, oxcarbazepine, pregabalin and topiramate against maximal electroshock-induced seizures in mice. Eur J Pharmacol 2013;720:247-254.PubMedCrossRef
175.
Florek-Luszczki M, et al. Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB 2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model. J Neural Transm 2014;121: 707-715.PubMedCentralPubMedCrossRef
176.
Florek-Luszczki M, Zagaja M, Luszczki JJ. Influence of WIN 55,212-2 on the anticonvulsant and acute neurotoxic potential of clobazam and lacosamide in the maximal electroshock-induced seizure model and chimney test in mice. Epilepsy Res 2014;108:1728-1733.PubMedCrossRef
177.
Florek-Luszczki M, et al. Effects of WIN 55,212-2 (a synthetic cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various novel antiepileptic drugs against 6Hz-induced psychomotor seizures in mice. Pharmacol Biochem Behav 2015; 130:53-58.PubMedCrossRef
178.
Chesher GB, Jackson DM. The effect of withdrawal from cannabis on pentylenetetrazol convulsive threshold in mice. Psychopharmacologia 1974;40: 129-135.PubMedCrossRef
179.
Chesher GB, Jackson DM, Malor RM. Interaction of delta9-tetrahydrocannabinol and cannabidiol with phenobarbitone in protecting mice from electrically induced convulsions. J Pharm Pharmacol 1975;27:608-609.PubMedCrossRef
180.
National Toxicology Program. NTP toxicology and carcinogenesis studies of 1-trans-delta(9)-tetrahydrocannabinol (CAS No. 1972-08-3) in F344 rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser 1996;446:1-317.
181.
182.
Oviedo A, Glowa J, Herkenham M. Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study. Brain Res 1993;616:293-302.PubMedCrossRef
183.
Rodriguez de Fonseca F, et al. Downregulation of rat brain cannabinoid binding sites after chronic delta 9-tetrahydrocannabinol treatment. Pharmacol Biochem Behav 1994;47:33-40.PubMedCrossRef
184.
Sim LJ, et al. Effects of chronic treatment with delta9-tetrahydrocannabinol on cannabinoid-stimulated [35S]GTPgammaS autoradiography in rat brain. J Neurosci 1996;16:8057-8066.PubMed
185.
Fan F, et al. Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice. Brain Res 1996;706:13-20.PubMedCrossRef
186.
Romero J, et al. Effects of chronic exposure to delta9-tetrahydrocannabinol on cannabinoid receptor binding and mRNA levels in several rat brain regions. Brain Res Mol Brain Res 1997;46:100-108.PubMedCrossRef
187.
Romero J, et al. Autoradiographic analysis of cannabinoid receptor binding and cannabinoid agonist-stimulated [35S]GTP gamma S binding in morphine-dependent mice. Drug Alcohol Depend 1998;50:241-249.PubMedCrossRef
188.
Romero J, et al. Cannabinoid receptor and WIN-55,212-2-stimulated [35S]GTP gamma S binding and cannabinoid receptor mRNA levels in the basal ganglia and the cerebellum of adult male rats chronically exposed to delta 9-tetrahydrocannabinol. J Mol Neurosci 1998;11:109-119.PubMedCrossRef
189.
Romero J, et al. Time-course of the cannabinoid receptor down-regulation in the adult rat brain caused by repeated exposure to delta9-tetrahydrocannabinol. Synapse 1998;30:298-308.PubMedCrossRef
190.
Zhuang S, et al. Effects of long-term exposure to delta9-THC on expression of cannabinoid receptor (CB1) mRNA in different rat brain regions. Brain Res Mol Brain Res 1998;62:141-149.PubMedCrossRef
191.
Hsieh C, et al. Internalization and recycling of the CB1 cannabinoid receptor. J Neurochem 1999;73:493-501.PubMedCrossRef
192.
Corchero J, et al. Time-dependent differences of repeated administration with Delta9-tetrahydrocannabinol in proenkephalin and cannabinoid receptor gene expression and G-protein activation by mu-opioid and CB1-cannabinoid receptors in the caudateputamen. Brain Res Mol Brain Res 1999;67:148-157.PubMedCrossRef
193.
Breivogel CS, et al. Chronic delta9-tetrahydrocannabinol treatment produces a time-dependent loss of cannabinoid receptors and cannabinoid receptor-activated G proteins in rat brain. J Neurochem 1999;73:2447-2459.PubMedCrossRef
194.
Breivogel CS, et al. The effects of delta9-tetrahydrocannabinol physical dependence on brain cannabinoid receptors. Eur J Pharmacol 2003;459:139-150.PubMedCrossRef
195.
McKinney DL, et al. Dose-related differences in the regional pattern of cannabinoid receptor adaptation and in vivo tolerance development to delta9-tetrahydrocannabinol. J Pharmacol Exp Ther 2008;324:664-673.PubMedCentralPubMedCrossRef
196.
Sim-Selley LJ, Martin BR. Effect of chronic administration of R-(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxaz inyl]-(1-naphthalenyl)methanone mesylate (WIN55,212-2) or delta(9)-tetrahydrocannabinol on cannabinoid receptor adaptation in mice. J Pharmacol Exp Ther 2002;303:36-44.PubMedCrossRef
197.
Sim-Selley LJ. Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids. Crit Rev Neurobiol 2003;15:91-119.PubMedCrossRef
198.
Sim-Selley LJ, et al. Prolonged recovery rate of CB1 receptor adaptation after cessation of long-term cannabinoid administration. Mol Pharmacol 2006;70:986-996.PubMedCrossRef
199.
Martin BR, Sim-Selley LJ, Selley DE. Signaling pathways involved in the development of cannabinoid tolerance. Trends Pharmacol Sci 2004;25:325-330.PubMedCrossRef
200.
Villares J. Chronic use of marijuana decreases cannabinoid receptor binding and mRNA expression in the human brain. Neuroscience 2007;145:323-334.PubMedCrossRef
201.
Coutts AA, et al. Agonist-induced internalization and trafficking of cannabinoid CB1 receptors in hippocampal neurons. J Neurosci 2001;21:2425-2433.PubMed
202.
Lundberg DJ, Daniel AR, Thayer SA. Delta(9)-Tetrahydrocannabinol-induced desensitization of cannabinoid-mediated inhibition of synaptic transmission between hippocampal neurons in culture. Neuropharmacology 2005;49:1170-1177.PubMedCrossRef
203.
Deshpande LS, Blair RE, DeLorenzo RJ. Prolonged cannabinoid exposure alters GABA(A) receptor mediated synaptic function in cultured hippocampal neurons. Exp Neurol 2011;229:264-273.PubMedCentralPubMedCrossRef
204.
Dewey WL. Cannabinoid pharmacology. Pharmacol Rev 1986;38:151-178.PubMed
205.
Abood ME, et al. Development of behavioral tolerance to delta 9-THC without alteration of cannabinoid receptor binding or mRNA levels in whole brain. Pharmacol Biochem Behav 1993;46:575-579.PubMedCrossRef
206.
Ten Ham M, Loskota WJ, Lomax P. Acute and chronic effects of beta9-tetrahydrocannabinol on seizures in the gerbil. Eur J Pharmacol 1975;31:148-152.PubMedCrossRef
207.
Corcoran ME, McCaughran JA, Jr., Wada JA, Antiepileptic and prophylactic effects of tetrahydrocannabinols in amygdaloid kindled rats. Epilepsia 1978;19: 47-55.PubMedCrossRef
208.
Colasanti BK, Lindamood C, 3rd, Craig CR. Effects of marihuana cannabinoids on seizure activity in cobalt-epileptic rats. Pharmacol Biochem Behav 1982;16: 573-578.PubMedCrossRef
209.
Karler R, Turkanis SA. Subacute cannabinoid treatment: anticonvulsant activity and withdrawal excitability in mice. Br J Pharmacol 1980;68:479-484.PubMedCentralPubMedCrossRef
210.
Blair RE, et al. Prolonged exposure to WIN55,212-2 causes downregulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy. Neuropharmacology 2009;57:208-218.PubMedCentralPubMedCrossRef
211.
Jones RT, Benowitz N, Bachman J. Clinical studies of cannabis tolerance and dependence. Ann N Y Acad Sci 1976;282:221-239.PubMedCrossRef
212.
Jones RT, Benowitz NL, Herning RI. Clinical relevance of cannabis tolerance and dependence. J Clin Pharmacol 1981;21(8-9 Suppl.):143S-152S.PubMedCrossRef
213.
Kirk JM, de Wit H. Responses to oral delta9-tetrahydrocannabinol in frequent and infrequent marijuana users. Pharmacol Biochem Behav 1999;63:137-142.PubMedCrossRef
214.
Hart CL, et al. Comparison of smoked marijuana and oral Delta(9)-tetrahydrocannabinol in humans. Psychopharmacology (Berl) 2002;164:407-415.CrossRef
215.
Babor TF, et al. Marijuana consumption and tolerance to physiological and subjective effects. Arch Gen Psychiatry 1975;32:1548-1552.PubMedCrossRef
216.
Nowlan R, Cohen S. Tolerance to marijuana: heart rate and subjective "high". Clin Pharmacol Ther 1977;22:550-556.PubMedCrossRef
217.
Aceto MD, et al. Cannabinoid precipitated withdrawal by the selective cannabinoid receptor antagonist, SR 141716A. Eur J Pharmacol 1995;282:R1-R2.PubMedCrossRef
218.
Tsou K, Patrick SL, Walker JM. Physical withdrawal in rats tolerant to delta 9-tetrahydrocannabinol precipitated by a cannabinoid receptor antagonist. Eur J Pharmacol 1995;280:R13-R15.PubMedCrossRef
219.
Rodriguez de Fonseca F, et al. Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 1997;276:2050-2054.PubMedCrossRef
220.
Kaymakcalan S. Tolerance to and dependence on cannabis. Bull Narc 1973;25:39–47.
221.
Beardsley PM, Balster RL, Harris LS. Dependence on tetrahydrocannabinol in rhesus monkeys. J Pharmacol Exp Ther 1986;239:311-319.PubMed
222.
Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiatry 2006;19:233-238.PubMedCrossRef
223.
Karler R, et al. Interaction between delta-9-tetrahydrocannabinol and kindling by electrical and chemical stimuli in mice. Neuropharmacology 1984;23:1315-1320.PubMedCrossRef
224.
Karler R, Calder LD, Turkanis SA. Prolonged CNS hyperexcitability in mice after a single exposure to delta-9-tetrahydrocannabinol. Neuropharmacology 1986;25:441-446.PubMedCrossRef
225.
Hegde M, et al. Seizure exacerbation in two patients with focal epilepsy following marijuana cessation. Epilepsy Behav 2012;25:563-566.PubMedCrossRef
226.
Ellison JM, Gelwan E, Ogletree J. Complex partial seizure symptoms affected by marijuana abuse. J Clin Psychiatry 1990;51:439-440.PubMed
227.
Leite JR, Carlini EA. Failure to obtain "cannabis-directed behavior" and abstinence syndrome in rats chronically treated with cannabis sativa extracts. Psychopharmacologia 1974;36:133-145.PubMedCrossRef
228.
Robson P. Abuse potential and psychoactive effects of delta-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Expert Opin Drug Saf 2011;10:675-685.PubMedCrossRef
229.
Wade DT, et al. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler 2004;10:434-441.PubMedCrossRef
230.
Russo EB, Guy GW, Robson PJ. Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine. Chem Biodivers 2007; 4:1729-1743.PubMedCrossRef
231.
Rog DJ, Nurmikko TJ, Young CA. Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther 2007;29: 2068-2079.PubMedCrossRef
232.
Perez J. Combined cannabinoid therapy via an oromucosal spray. Drugs Today (Barc) 2006;42:495-503.CrossRef
233.
Crippa JA, et al. Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. J Clin Pharm Ther 2013;38:162-164.PubMedCrossRef
234.
Allsop DJ, et al. Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA Psychiatry 2014;71:281-291.PubMedCrossRef
235.
Allsop DJ, Lintzeris N, Copeland J, Dunlop A, McGregor IS. Cannabinoid replacement therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal. Clin Pharmacol Ther 2015;97:571-574.PubMedCrossRef
236.
Keeler MH, Reifler CB. Grand mal convulsions subsequent to marijuana use. Case report. Dis Nerv Syst 1967;28:474-475.PubMed
237.
Lapoint J, et al. Severe toxicity following synthetic cannabinoid ingestion. Clin Toxicol (Phila) 2011;49:760-764.CrossRef
238.
Jinwala FN, Gupta M. Synthetic cannabis and respiratory depression. J Child Adolesc Psychopharmacol 2012;22:459-462.PubMedCrossRef
239.
Hermanns-Clausen M, et al. Acute intoxication by synthetic cannabinoids—four case reports. Drug Test Anal 2013;5:790-794.PubMedCrossRef
240.
Hermanns-Clausen M, et al. Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 2013;108: 534-544.PubMedCrossRef
241.
McQuade D, et al. First European case of convulsions related to analytically confirmed use of the synthetic cannabinoid receptor agonist AM-2201. Eur J Clin Pharmacol 2013; 69:373-376.PubMedCrossRef
242.
243.
Tofighi B, Lee JD. Internet highs—seizures after consumption of synthetic cannabinoids purchased online. J Addict Med 2012;6:240-241.PubMedCrossRef
244.
245.
Castaneto MS, et al. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend 2014;144:12-41.PubMedCrossRef
246.
Davis JP, Ramsey HH. Anti-epileptic action of marijuana-active substances. Fed Proc Am Soc Exp Biol 1949;8:284.
247.
Consroe PF, Wood GC, Buchsbaum H. Anticonvulsant nature of marihuana smoking. JAMA 1975;234:306-307.PubMedCrossRef
248.
Lorenz R. On the application of cannabis in paediatrics and epileptology. Neuro Endocrinol Lett 2004;25:40-44.PubMed
249.
Mortati K, Dworetzky B, Devinsky O. Marijuana: an effective antiepileptic treatment in partial epilepsy? A case report and review of the literature. Rev Neurol Dis 2007;4:103-106.PubMed
250.
Gordon E, Devinsky O. Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy. Epilepsia 2001;42:1266-1272.PubMedCrossRef
251.
252.
Corral VJ. Differential effects of medical marijuana based on strain and route of administration: a three-year observational study. J Cannabis Ther 2001;1:43-59.CrossRef
253.
Hamerle M, et al. Cannabis and other illicit drug use in epilepsy patients. Eur J Neurol, 2014;21:167-170.PubMedCrossRef
254.
Gieringer D. Madical use of cannabis: experience in California. Haworth Press, Binghamton, NY, 2001.
255.
Feeney D, Spiker M. Marijuana and epilepsy: activation of symptoms by delta-9-THC. In: C.S and S.RC (Eds.). The therapeutic potential of marihuana. Plenum Press, New York, 1976.
256.
Alldredge BK, Lowenstein DH, Simon RP. Seizures associated with recreational drug abuse. Neurology 1989;39:1037-1039.PubMedCrossRef
257.
Brust JC, et al. Marijuana use and the risk of new onset seizures. Trans Am Clin Climatol Assoc 1992;103:176-181.PubMedCentralPubMed
258.
Gross DW, et al. Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center. Neurology 2004;62:2095-2097.PubMedCrossRef
259.
Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav 2013;29:574-577.PubMedCentralPubMedCrossRef
260.
Press CA, Knupp KG, Chapman KE. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav 2015;45: 49–52.PubMedCrossRef
261.
Mechoulam R, Carlini EA. Toward drugs derived from cannabis. Naturwissenschaften 1978;65:174-179.PubMedCrossRef
262.
Cunha JM, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 1980;21:175-185.PubMedCrossRef
263.
Ames FR, Cridland S. Anticonvulsant effect of cannabidiol. S Afr Med J 1986; 69:14.PubMed
264.
Trembly B, Sherman M. Double-blind clinical study of cannabidiol as a secondary anticonvulsant. In: Marijuana '90 international conference on cannabis and cannabinoids, Kolympari, Crete, 1990.
265.
266.
267.
Mathern GW, Beninsig L, Nehlig A. Fewer specialists support using medical marijuana and CBD in treating epilepsy patients compared with other medical professionals and patients: result of Epilepsia's survey. Epilepsia 2015;56:1-6.PubMedCrossRef
268.
Volkow ND, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med 2014;371:879.PubMed
269.
Morales-Munoz I, et al. Characterizing cannabis-induced psychosis: a study with prepulse inhibition of the startle reflex. Psychiatry Res 2014;220:535-540.PubMedCrossRef
270.
Lynskey M, Hall W. The effects of adolescent cannabis use on educational attainment: a review. Addiction 2000;95:1621-1630.PubMedCrossRef
271.
Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med 2011;5: 1-8.PubMedCentralPubMedCrossRef
272.
Lisdahl KM, et al. Dare to delay? The impacts of adolescent alcohol and marijuana use onset on cognition, brain structure, and function. Front Psychiatry 2013;4:53.PubMedCentralPubMedCrossRef
273.
Crane NA, Schuster RM, Gonzalez R. Preliminary evidence for a sex-specific relationship between amount of cannabis use and neurocognitive performance in young adult cannabis users. J Int Neuropsychol Soc 2013;19:1009-1015.PubMedCentralPubMedCrossRef
274.
Jacobus J, et al. Cortical thickness and neurocognition in adolescent marijuana and alcohol users following 28 days of monitored abstinence. J Stud Alcohol Drugs 2014; 75:729-743.PubMedCentralPubMedCrossRef
275.
Gilman JM, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci 2014;34: 5529-5538.PubMedCentralPubMedCrossRef
276.
Gruber SA, et al. Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity. Psychopharmacology (Berl) 2014;231:1455-1465.CrossRef
277.
Tortoriello G, et al. Miswiring the brain: Delta9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J 2014;33:668-685.PubMedCentralPubMedCrossRef
278.
Raver SM, Haughwout SP, Keller A. Adolescent cannabinoid exposure permanently suppresses cortical oscillations in adult mice. Neuropsychopharmacology 2013;38:2338-2347.PubMedCentralPubMedCrossRef
279.
Raver SM, Keller A. Permanent suppression of cortical oscillations in mice after adolescent exposure to cannabinoids: receptor mechanisms. Neuropharmacology 2014;86:161-173.PubMedPubMedCentralCrossRef
280.
Houck JM, Bryan AD, Feldstein Ewing SW. Functional connectivity and cannabis use in high-risk adolescents. Am J Drug Alcohol Abuse 2013;39:414-423.PubMedCentralPubMedCrossRef
281.
282.
Guy GW, Robson PJ. A phase I, open label, four-way crossover study to compare the pharmacokinetic profiles of a single dose of 20 mg of a cannabis based medicine extract (CBME) administered on 3 different areas of the buccal mucosa and to investigate the pharmacokinetics of CBME per oral in healthy male and female volunteers (GWPK0112). J Cannabis Ther 2003;3:79-120.CrossRef
283.
Hawksworth G, McArdle K. Metabolism and pharmacokinetics of cannabinoids. Pharmaceutical Press, London, 2004.
284.
Bornheim LM, et al. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45:1323-1331.PubMedCrossRef
285.
Yamaori S, et al. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 2011;39:2049-2056.PubMedCrossRef
286.
Jiang R, et al. Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci 2011;89:165-170.PubMedCrossRef
287.
Yamaori S, et al. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci 2011;88:730-736.PubMedCrossRef
288.
Jiang R, et al. Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19. Drug Metab Pharmacokinet 2013;28:332-338.PubMedCrossRef
289.
Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev 2014;46:86-95.PubMedCrossRef
290.
Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol 2003;2: 473-481.PubMedCrossRef
291.
Yamaori S, et al. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem Pharmacol 2010;79:1691-1698.PubMedCrossRef
292.
Friedman D, et al. The effect of Epidiolex (Cannabidiol) on serum levels of concomminant anti-epileptic drugs in children and young adults with treatment-resistant epilepsy in an expanded access program. In: American Epilepsy Society, Seattle, WA, 2014.
293.
294.
295.
Kemeny ME, et al. Placebo response in asthma: a robust and objective phenomenon. J Allergy Clin Immunol 2007;119:1375-1381.PubMedCrossRef
296.
Rheims S, et al. Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy. PLoS Med 2008;5: e166.PubMedCentralPubMedCrossRef
297.
Anon. Double-blind, placebo-controlled evaluation of cinromide in patients with the Lennox-Gastaut Syndrome. The Group for the Evaluation of Cinromide in the Lennox-Gastaut Syndrome. Epilepsia 1989;30:422-429.CrossRef
298.
Rekand T. THC:CBD spray and MS spasticity symptoms: data from latest studies. Eur Neurol 2014;71(Suppl. 1):4-9.PubMedCrossRef
299.
Naderi N, et al. Evaluation of interactions between cannabinoid compounds and diazepam in electroshock-induced seizure model in mice. J Neural Transm 2008;115:1501-1511.PubMedCrossRef
300.
Naderi N, et al. Modulation of anticonvulsant effects of cannabinoid compounds by GABA-A receptor agonist in acute pentylenetetrazole model of seizure in rat. Neurochem Res 2011;36:1520-1525.PubMedCrossRef
301.
Vilela LR, et al. Effects of cannabinoids and endocannabinoid hydrolysis inhibition on pentylenetetrazole-induced seizure and electroencephalographic activity in rats. Epilepsy Res 2013;104:195-202.PubMedCrossRef
302.
Shubina L, Aliev R, Kitchigina V. Attenuation of kainic acid-induced status epilepticus by inhibition of endocannabinoid transport and degradation in guinea pigs. Epilepsy Res 2015;111:33-44.PubMedCrossRef
303.
Wendt H, et al. Targeting the endocannabinoid system in the amygdala kindling model of temporal lobe epilepsy in mice. Epilepsia 2011;52:e62-e65.PubMedCrossRef
304.
Wallace MJ, et al. Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. Eur J Pharmacol 2001;428:51-57.PubMedCrossRef
305.
Payandemehr B, et al. Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2. Prog Neuropsychopharmacol Biol Psychiatry 2015;57:140-145.PubMedCrossRef
306.
van Rijn CM, et al. WAG/Rij rats show a reduced expression of CB(1) receptors in thalamic nuclei and respond to the CB(1) receptor agonist, R(+)WIN55,212-2, with a reduced incidence of spike-wave discharges. Epilepsia 2010;51:1511-1521.PubMedCrossRef
307.
Citraro R, et al. CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations. Epilepsy Res 2013; 106:74-82.PubMedCrossRef
308.
Lambert DM, et al. Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice. Epilepsia 2001;42:321-327.PubMedCrossRef
309.
Sheerin AH, et al. Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid. Epilepsia 2004;45:1184-1188.PubMedCrossRef
310.
Wallace MJ, Martin BR, DeLorenzo RJ. Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol 2002;452:295-301.PubMedCrossRef
311.
Shafaroodi H, et al. The interaction of cannabinoids and opioids on pentylenetetrazole-induced seizure threshold in mice. Neuropharmacology 2004;47:390-400.PubMedCrossRef
312.
Bahremand A, et al. The cannabinoid anticonvulsant effect on pentylenetetrazole-induced seizure is potentiated by ultra-low dose naltrexone in mice. Epilepsy Res 2008;81:44-51.PubMedCrossRef
313.
Bahremand A, et al. Involvement of nitrergic system in the anticonvulsant effect of the cannabinoid CB(1) agonist ACEA in the pentylenetetrazole-induced seizure in mice. Epilepsy Res 2009;84:110-119.PubMedCrossRef
314.
Rudenko V, et al. Inverse relationship of cannabimimetic (R+)WIN 55, 212 on behavior and seizure threshold during the juvenile period. Pharmacol Biochem Behav 2012;100:474-484.PubMedCrossRef
315.
Di Maio R, Cannon JR, Timothy Greenamyre J. Post-status epilepticus treatment with the cannabinoid agonist WIN 55,212-2 prevents chronic epileptic hippocampal damage in rats. Neurobiol Dis 2014;73C:356-365.
316.
Rizzo V, et al. Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat. Neurosci Lett 2009;462:135-139.PubMedCrossRef
317.
318.
Kozan R, Ayyildiz M, Agar E. The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats. Epilepsia 2009;50:1760-1767.PubMedCrossRef
319.
Cakil D, et al. The effect of co-administration of the NMDA blocker with agonist and antagonist of CB1-receptor on penicillin-induced epileptiform activity in rats. Epilepsy Res 2011;93:128-137.PubMedCrossRef
320.
van Rijn CM, et al. Endocannabinoid system protects against cryptogenic seizures. Pharmacol Rep 2011;63:165-168.PubMed
321.
Vinogradova LV, Shatskova AB, van Rijn CM. Pro-epileptic effects of the cannabinoid receptor antagonist SR141716 in a model of audiogenic epilepsy. Epilepsy Res 2011;96:250-256.PubMedCrossRef
322.
Gholizadeh S, et al. Ultra-low dose cannabinoid antagonist AM251 enhances cannabinoid anticonvulsant effects in the pentylenetetrazole-induced seizure in mice. Neuropharmacology 2007;53:763-770.PubMedCrossRef
323.
Dudek FE, et al. The effect of the cannabinoid-receptor antagonist, SR141716, on the early stage of kainate-induced epileptogenesis in the adult rat. Epilepsia 2010;51(Suppl. 3):126-130.PubMedCentralPubMedCrossRef
324.
Echegoyen J, et al. Single application of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model. Epilepsy Res 2009;85:123-127.PubMedCentralPubMedCrossRef
325.
Sofia RD, Kubena RK, Barry, H, 3rd. Comparison among four vehicles and four routes for administering delta9-tetrahydrocannabinol. J Pharm Sci 1974;63:939-941.PubMedCrossRef
326.
Chesher GB, Jackson DM. Anticonvulsant effects of cannabinoids in mice: drug interactions within cannabinoids and cannabinoid interactions with phenytoin. Psychopharmacologia 1974;37:255-264.PubMedCrossRef
327.
Johnson DD, et al. Epileptiform seizures in domestic fowl. V. The anticonvulsant activity of delta9-tetrahydrocannabinol. Can J Physiol Pharmacol 1975;53:1007-1013.PubMedCrossRef
328.
Wada JA, Osawa T, Corcoran ME. Effects of tetrahydrocannabinols on kindled amygdaloid seizures and photogenic seizures in Senegalese baboons, Papio papio. Epilepsia 1975;16:439-448.PubMedCrossRef
329.
Boggan WO, Steele RA, Freedman DX. 9 -Tetrahydrocannabinol effect on audiogenic seizure susceptibility. Psychopharmacologia 1973;29:101-106.PubMedCrossRef
330.
Corcoran ME, McCaughran JA, Jr., Wada JA. Acute antiepileptic effects of 9-tetrahydrocannabinol in rats with kindled seizures. Exp Neurol 1973;40:471-483.PubMedCrossRef
331.
Wada JA, et al. Antiepileptic and prophylactic effects of tetrahydrocannabinols in amygdaloid kindled cats. Epilepsia 1975;16:503-510.PubMedCrossRef
332.
Turkanis SA, et al. An electrophysiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats. Epilepsia 1979;20:351-363.PubMedCrossRef
333.
Izquierdo I, Orsingher OA, Berardi AC. Effect of cannabidiol and of other cannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia 1973;28:95-102.PubMedCrossRef
334.
Karler R, Turkanis SA. Cannabis and epilepsy. Adv Biosci 1978;22-23:619-641.PubMed
335.
Consroe P, et al. Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice. Eur J Pharmacol 1982;83:293-298.PubMedCrossRef
336.
Shirazi-zand Z, et al. The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice. Epilepsy Behav 2013;28:1-7.PubMedCrossRef
337.
Hill TD, et al. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Br J Pharmacol 2013;170:679-692.PubMedCentralPubMedCrossRef
338.
Jones NA, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure 2012;21:344-352.PubMedCrossRef
Metadaten
Titel
Cannabinoids and Epilepsy
verfasst von
Evan C. Rosenberg
Richard W. Tsien
Benjamin J. Whalley
Orrin Devinsky
Publikationsdatum
01.10.2015
Verlag
Springer US
Erschienen in
Neurotherapeutics / Ausgabe 4/2015
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-015-0375-5

Weitere Artikel der Ausgabe 4/2015

Neurotherapeutics 4/2015 Zur Ausgabe

Review

Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis

Commentary

Parsing Physiological Functions of Erythropoietin One Domain at a Time

Review

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential

Review

The Endocannabinoid System and its Modulation by Phytocannabinoids

Editorial

Cannabinoids in the Treatment of Neurological Disorders

Review

Endocannabinoid Signaling in Autism

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Demenz Nachrichten

Der Einsatz von Antipsychotika gegen psychische und Verhaltenssymptome in Zusammenhang mit Demenzerkrankungen erfordert eine sorgfältige Nutzen-Risiken-Abwägung. Neuen Erkenntnissen zufolge sind auf der Risikoseite weitere schwerwiegende Ereignisse zu berücksichtigen.

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise