Cannabis and endocannabinoid signaling in epilepsy

Research output: Chapter in Book/Report/Conference proceedingChapter

26 Citations (Scopus)

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 evidencebased 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.

Original languageEnglish
Title of host publicationEndocannabinoids
PublisherSpringer International Publishing
Pages285-316
Number of pages32
ISBN (Print)9783319208251, 9783319208244
DOIs
Publication statusPublished - Sep 25 2015

Fingerprint

Endocannabinoids
Cannabis
Cannabinoids
Epilepsy
Seizures
Medical Marijuana
Anecdotes
Electric circuit breakers
Therapeutics
Refractory materials
Anticonvulsants
Synapses
Plasticity
Clinical Trials
Pharmacology
Safety
Research
Pharmaceutical Preparations

Keywords

  • 2-Arachidonoylglycerol
  • Anticonvulsant
  • Cannabidiol
  • Cannabis
  • CB cannabinoid receptor
  • Diaclyglycerol lipase-α
  • Epilepsy
  • Glutamate
  • GPR55 receptor
  • Hippocampus
  • Metabotropic glutamate receptor
  • Perisynaptic machinery
  • Seizure
  • Synapse
  • Synaptic circuit-breaker
  • Δ9-tetrahydrocannabinol

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Immunology and Microbiology(all)

Cite this

Katona, I. (2015). Cannabis and endocannabinoid signaling in epilepsy. In Endocannabinoids (pp. 285-316). Springer International Publishing. https://doi.org/10.1007/978-3-319-20825-1_10

Cannabis and endocannabinoid signaling in epilepsy. / Katona, I.

Endocannabinoids. Springer International Publishing, 2015. p. 285-316.

Research output: Chapter in Book/Report/Conference proceedingChapter

Katona, I 2015, Cannabis and endocannabinoid signaling in epilepsy. in Endocannabinoids. Springer International Publishing, pp. 285-316. https://doi.org/10.1007/978-3-319-20825-1_10
Katona I. Cannabis and endocannabinoid signaling in epilepsy. In Endocannabinoids. Springer International Publishing. 2015. p. 285-316 https://doi.org/10.1007/978-3-319-20825-1_10
Katona, I. / Cannabis and endocannabinoid signaling in epilepsy. Endocannabinoids. Springer International Publishing, 2015. pp. 285-316
@inbook{1fdac4f14c4c45e0a20b60048ab349cd,
title = "Cannabis and endocannabinoid signaling in epilepsy",
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 evidencebased 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.",
keywords = "2-Arachidonoylglycerol, Anticonvulsant, Cannabidiol, Cannabis, CB cannabinoid receptor, Diaclyglycerol lipase-α, Epilepsy, Glutamate, GPR55 receptor, Hippocampus, Metabotropic glutamate receptor, Perisynaptic machinery, Seizure, Synapse, Synaptic circuit-breaker, Δ9-tetrahydrocannabinol",
author = "I. Katona",
year = "2015",
month = "9",
day = "25",
doi = "10.1007/978-3-319-20825-1_10",
language = "English",
isbn = "9783319208251",
pages = "285--316",
booktitle = "Endocannabinoids",
publisher = "Springer International Publishing",

}

TY - CHAP

T1 - Cannabis and endocannabinoid signaling in epilepsy

AU - Katona, I.

PY - 2015/9/25

Y1 - 2015/9/25

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 evidencebased 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.

AB - 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 evidencebased 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.

KW - 2-Arachidonoylglycerol

KW - Anticonvulsant

KW - Cannabidiol

KW - Cannabis

KW - CB cannabinoid receptor

KW - Diaclyglycerol lipase-α

KW - Epilepsy

KW - Glutamate

KW - GPR55 receptor

KW - Hippocampus

KW - Metabotropic glutamate receptor

KW - Perisynaptic machinery

KW - Seizure

KW - Synapse

KW - Synaptic circuit-breaker

KW - Δ9-tetrahydrocannabinol

UR - http://www.scopus.com/inward/record.url?scp=84955753574&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955753574&partnerID=8YFLogxK

U2 - 10.1007/978-3-319-20825-1_10

DO - 10.1007/978-3-319-20825-1_10

M3 - Chapter

SN - 9783319208251

SN - 9783319208244

SP - 285

EP - 316

BT - Endocannabinoids

PB - Springer International Publishing

ER -