The Endocannabinoid System and Synthetic Cannabinoids in Preclinical Models of Seizure and Epilepsy
- 1 January 2020
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Clinical Neurophysiology
- Vol. 37 (1), 15-27
- https://doi.org/10.1097/wnp.0000000000000633
Abstract
Cannabinoids are compounds that are structurally and/or functionally related to the primary psychoactive constituent of Cannabis sativa, [INCREMENT]9-tetrahydrocannabinol (THC). Cannabinoids can be divided into three broad categories: endogenous cannabinoids, plant-derived cannabinoids, and synthetic cannabinoids (SCs). Recently, there has been an unprecedented surge of interest into the pharmacological and medicinal properties of cannabinoids for the treatment of epilepsies. This surge has been stimulated by an ongoing shift in societal opinions about cannabinoid-based medicines and evidence that cannabidiol, a nonintoxicating plant cannabinoid, has demonstrable anticonvulsant activity in children with treatment-refractory epilepsy. The major receptors of the endogenous cannabinoid system (ECS)—the type 1 and 2 cannabinoid receptors (CB1R, CB2R)—have critical roles in the modulation of neurotransmitter release and inflammation, respectively; so, it is not surprising therefore that the ECS is being considered as a target for the treatment of epilepsy. SCs were developed as potential new drug candidates and tool compounds for studying the ECS. Beyond the plant cannabinoids, an extensive research effort is underway to determine whether SCs that directly target CB1R, CB2R, or the enzymes that breakdown endogenous cannabinoids have anticonvulsant effects in preclinical rodent models of epilepsy and seizure. This research demonstrates that many SCs do reduce seizure severity in rodent models and may have both positive and negative pharmacodynamic and pharmacokinetic interactions with clinically used antiepilepsy drugs. Here, we provide a comprehensive review of the preclinical evidence for and against SC modulation of seizure and discuss the important questions that need to be addressed in future studies.Keywords
This publication has 77 references indexed in Scilit:
- CB1 and CB2 Cannabinoid Receptor Antagonists Prevent Minocycline-Induced Neuroprotection Following Traumatic Brain Injury in MiceCerebral Cortex, 2013
- The dynamic nature of type 1 cannabinoid receptor (CB1) gene transcriptionBritish Journal of Pharmacology, 2012
- Modulation of l-α-Lysophosphatidylinositol/GPR55 Mitogen-activated Protein Kinase (MAPK) Signaling by CannabinoidsOnline Journal of Public Health Informatics, 2012
- So what do we call GPR18 now?British Journal of Pharmacology, 2011
- Transcriptional Regulation of Cannabinoid Receptor-1 Expression in the Liver by Retinoic Acid Acting via Retinoic Acid Receptor-γOnline Journal of Public Health Informatics, 2010
- Cannabinoid-Mediated Inhibition of Recurrent Excitatory Circuitry in the Dentate Gyrus in a Mouse Model of Temporal Lobe EpilepsyPLOS ONE, 2010
- N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptorBMC Neuroscience, 2010
- Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyondAddiction Biology, 2008
- GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M currentProceedings of the National Academy of Sciences of the United States of America, 2008
- Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18Biochemical and Biophysical Research Communications, 2006