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Abstract
Epilepsy is characterized by repeated spontaneous bursts of neuronal hyperactivity and high synchronization in the central nervous system. It seriously affects the quality of life of epileptic patients, and nearly 30% of individuals are refractory to treatment of antiseizure drugs. Therefore, there is an urgent need to develop new drugs to manage and control refractory epilepsy. Cannabinoid ligands, including selective cannabinoid receptor subtype (CB1 or CB2 receptor) ligands and non-selective cannabinoid (synthetic and endogenous) ligands, may serve as novel candidates for this need. Cannabinoid appears to regulate seizure activity in the brain through the activation of CB1 and CB2 cannabinoid receptors (CB1R and CB2R). An abundant series of cannabinoid analogues have been tested in various animal models, including the rat pilocarpine model of acquired epilepsy, a pentylenetetrazol model of myoclonic seizures in mice, and a penicillin-induced model of epileptiform activity in the rats. The accumulating lines of evidence show that cannabinoid ligands exhibit significant benefits to control seizure activity in different epileptic models. In this review, we summarize the relationship between brain CB2 receptors and seizures and emphasize the potential mechanisms of their therapeutic effects involving the influences of neurons, astrocytes, and microglia cells. The unique features of CB2Rs, such as lower expression levels under physiological conditions and high inducibility under epileptic conditions, make it an important target for future research on drug-resistant epilepsy.
Highlights
Epilepsy is the third most common chronic neurological disorder that affects over 70 million people worldwide [1]
CB2 Rs were found in the peripheral region, while CB1 Rs were mainly expressed in the central nervous system (CNS), which led to a question of the existence of the CB2 Rs in the CNS
With the development of more sensitive detection technologies, CB2 Rs have been found in multiple brain regions in the CNS, though at a low level of expression compared to CB1 Rs
Summary
Epilepsy is the third most common chronic neurological disorder that affects over 70 million people worldwide [1]. Cannabidiol has been shown to reduce the frequency of seizures in animal models of epilepsy and greatly decrease the frequency of drop seizures among children and adults with Lennox–Gastaut syndrome [19]. Based on these concepts, numerous cannabinoid analogues have been examined in a variety of animal models [5,8,11,20,21,22,23]. We summarize the current state of knowledge on CB2 R expression and function, which could serve as an important tool for intervention and control of seizure activity by modulating neuronal excitability and neuroinflammation
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