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Cannabis and Endocannabinoid Signaling in Epilepsy.
Handb Exp Pharmacol. 2015; 231:285-316.HE

Abstract

The antiepileptic potential of Cannabis sativa preparations has been historically recognized. Recent changes in legal restrictions and new well-documented cases reporting remarkably strong beneficial effects have triggered an upsurge in exploiting medical marijuana in patients with refractory epilepsy. Parallel research efforts in the last decade have uncovered the fundamental role of the endogenous cannabinoid system in controlling neuronal network excitability raising hopes for cannabinoid-based therapeutic approaches. However, emerging data show that patient responsiveness varies substantially, and that cannabis administration may sometimes even exacerbate seizures. Qualitative and quantitative chemical variability in cannabis products and personal differences in the etiology of seizures, or in the pathological reorganization of epileptic networks, can all contribute to divergent patient responses. Thus, the consensus view in the neurologist community is that drugs modifying the activity of the endocannabinoid system should first be tested in clinical trials to establish efficacy, safety, dosing, and proper indication in specific forms of epilepsies. To support translation from anecdote-based practice to evidence-based therapy, the present review first introduces current preclinical and clinical efforts for cannabinoid- or endocannabinoid-based epilepsy treatments. Next, recent advances in our knowledge of how endocannabinoid signaling limits abnormal network activity as a central component of the synaptic circuit-breaker system will be reviewed to provide a framework for the underlying neurobiological mechanisms of the beneficial and adverse effects. Finally, accumulating evidence demonstrating robust synapse-specific pathophysiological plasticity of endocannabinoid signaling in epileptic networks will be summarized to gain better understanding of how and when pharmacological interventions may have therapeutic relevance.

Authors+Show Affiliations

Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, Budapest, 1083, Hungary. katona@koki.hu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26408165

Citation

Katona, István. "Cannabis and Endocannabinoid Signaling in Epilepsy." Handbook of Experimental Pharmacology, vol. 231, 2015, pp. 285-316.
Katona I. Cannabis and Endocannabinoid Signaling in Epilepsy. Handb Exp Pharmacol. 2015;231:285-316.
Katona, I. (2015). Cannabis and Endocannabinoid Signaling in Epilepsy. Handbook of Experimental Pharmacology, 231, 285-316. https://doi.org/10.1007/978-3-319-20825-1_10
Katona I. Cannabis and Endocannabinoid Signaling in Epilepsy. Handb Exp Pharmacol. 2015;231:285-316. PubMed PMID: 26408165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabis and Endocannabinoid Signaling in Epilepsy. A1 - Katona,István, PY - 2015/9/27/entrez PY - 2015/9/27/pubmed PY - 2015/12/19/medline KW - 2-Arachidonoylglycerol KW - Anticonvulsant KW - CB1 cannabinoid receptor KW - Cannabidiol KW - Cannabis KW - Diaclyglycerol lipase-α KW - Epilepsy KW - GPR55 receptor KW - Glutamate KW - Hippocampus KW - Metabotropic glutamate receptor KW - Perisynaptic machinery KW - Seizure KW - Synapse KW - Synaptic circuit-breaker KW - Δ9-tetrahydrocannabinol SP - 285 EP - 316 JF - Handbook of experimental pharmacology JO - Handb Exp Pharmacol VL - 231 N2 - The antiepileptic potential of Cannabis sativa preparations has been historically recognized. Recent changes in legal restrictions and new well-documented cases reporting remarkably strong beneficial effects have triggered an upsurge in exploiting medical marijuana in patients with refractory epilepsy. Parallel research efforts in the last decade have uncovered the fundamental role of the endogenous cannabinoid system in controlling neuronal network excitability raising hopes for cannabinoid-based therapeutic approaches. However, emerging data show that patient responsiveness varies substantially, and that cannabis administration may sometimes even exacerbate seizures. Qualitative and quantitative chemical variability in cannabis products and personal differences in the etiology of seizures, or in the pathological reorganization of epileptic networks, can all contribute to divergent patient responses. Thus, the consensus view in the neurologist community is that drugs modifying the activity of the endocannabinoid system should first be tested in clinical trials to establish efficacy, safety, dosing, and proper indication in specific forms of epilepsies. To support translation from anecdote-based practice to evidence-based therapy, the present review first introduces current preclinical and clinical efforts for cannabinoid- or endocannabinoid-based epilepsy treatments. Next, recent advances in our knowledge of how endocannabinoid signaling limits abnormal network activity as a central component of the synaptic circuit-breaker system will be reviewed to provide a framework for the underlying neurobiological mechanisms of the beneficial and adverse effects. Finally, accumulating evidence demonstrating robust synapse-specific pathophysiological plasticity of endocannabinoid signaling in epileptic networks will be summarized to gain better understanding of how and when pharmacological interventions may have therapeutic relevance. SN - 0171-2004 UR - https://www.unboundmedicine.com/medline/citation/26408165/Cannabis_and_Endocannabinoid_Signaling_in_Epilepsy_ L2 - https://dx.doi.org/10.1007/978-3-319-20825-1_10 DB - PRIME DP - Unbound Medicine ER -