Receptors and Channels Possibly Mediating the Effects of Phytocannabinoids on Seizures and Epilepsy

Senn, Lara; Cannazza, Giuseppe; Biagini, Giuseppe

doi:10.3390/ph13080174

Cited by 39 publications

(32 citation statements)

References 180 publications

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“…A definitive pharmacological target for CBD in epilepsy (and elsewhere) remains elusive, with various reports of pharmacologically relevant affinity at several molecular targets (Gray & Whalley, 2020; Senn, Cannazza, & Biagini, 2020). The best recognised targets include transient receptor potential vanilloid channels and GPCR 18 (GPR18) and GPR55 receptors (Alexander et al, 2019).…”

Section: Cbd Mechanism Of Actionmentioning

confidence: 99%

“…And, the FDA is committed to this kind of careful scientific research and drug development. "3 | CBD MECHANISM OF ACTIONA definitive pharmacological target for CBD in epilepsy (and elsewhere) remains elusive, with various reports of pharmacologically relevant affinity at several molecular targetsSenn, Cannazza, & Biagini, 2020). The best recognised targets include transient receptor potential vanilloid channels and GPCR 18 (GPR18)…”

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confidence: 99%

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Development of cannabidiol as a treatment for severe childhood epilepsies

Williams

Stephens

2020

British J Pharmacology

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In recent years, there has been a growing appreciation by regulatory authorities that cannabis-based medicines can play a useful role in disease therapy. Although often conflagrated by proponents of recreational use, the legislative rescheduling of cannabis-derived compounds, such as cannabidiol (CBD), has been associated with the steady increase in the pursuit of use of medicinal cannabis. One key driver in this interest has been the scientific demonstration of efficacy and safety of CBD in randomised, placebo-controlled clinical trials in children and young adults with difficult-to-treat epilepsies, which has encouraged increasing numbers of human trials of CBD for other indications and in other populations. The introduction of CBD as the medicine Epidiolex in the United States (in 2018) and as Epidyolex in the European Union (in 2019) as the first cannabis-derived therapeutic for the treatment of seizures was underpinned by preclinical research performed at the University of Reading. This work was awarded the British Pharmacological Society Sir James Black Award for Contributions to Drug Discovery 2019 and is discussed in the following review article.

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Section: Cbd Mechanism Of Actionmentioning

confidence: 99%

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confidence: 99%

Development of cannabidiol as a treatment for severe childhood epilepsies

Williams

Stephens

2020

British J Pharmacology

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“…The endocannabinoid system (ECS) is involved in regulation of excitatory and inhibitory synaptic transmission in the brain [65,66], and consists of two G protein-coupled receptors, CB 1 R and CB 2 R, with two known endogenous cannabinoid ligands, namely 2arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (NAN), respectively [10,11].…”

Section: Endocannabinoid Systemmentioning

confidence: 99%

The CB2 Receptor as a Novel Therapeutic Target for Epilepsy Treatment

Zeng

2021

IJMS

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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.

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“…In addition, glycerophosphodiesterase 3 can metabolize GPR55 ligand, arachidonoyl lysophosphatidylinositol (LPI), into 2-AG and also act as a signaling switch between GPR55 and CB2, thereby linking GRP55 to canonical cannabinoid receptors [187,188]. Moreover, neurological studies indicate that exogenous cannabinoids (i.e., CBD) also act on other noncanonical cannabinoid-sensitive receptors, such as transient receptor potential vanilloid 1 and opioid receptor µ and δ [189], that may be of interest in peripheral tissues. With respect to metabolic syndrome, emerging data suggest that GPR55 and LPIs are associated with obesity and adipogenesis [190].…”

Section: Other Receptors That Are Targeted By Cannabinoidsmentioning

confidence: 99%

Metabolic Consequences of Gestational Cannabinoid Exposure

Lee

Hardy

2021

IJMS

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Up to 20% of pregnant women ages 18–24 consume cannabis during pregnancy. Moreover, clinical studies indicate that cannabis consumption during pregnancy leads to fetal growth restriction (FGR), which is associated with an increased risk of obesity, type II diabetes (T2D), and cardiovascular disease in the offspring. This is of great concern considering that the concentration of Δ9- tetrahydrocannabinol (Δ9-THC), a major psychoactive component of cannabis, has doubled over the last decade and can readily cross the placenta and enter fetal circulation, with the potential to negatively impact fetal development via the endocannabinoid (eCB) system. Cannabis exposure in utero could also lead to FGR via placental insufficiency. In this review, we aim to examine current pre-clinical and clinical findings on the direct effects of exposure to cannabis and its constituents on fetal development as well as indirect effects, namely placental insufficiency, on postnatal metabolic diseases.

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Receptors and Channels Possibly Mediating the Effects of Phytocannabinoids on Seizures and Epilepsy

Cited by 39 publications

References 180 publications

Development of cannabidiol as a treatment for severe childhood epilepsies

Development of cannabidiol as a treatment for severe childhood epilepsies

The CB2 Receptor as a Novel Therapeutic Target for Epilepsy Treatment

Metabolic Consequences of Gestational Cannabinoid Exposure

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