Category Archives: Epilepsy

Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice.

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“Endocannabinoids, including 2-arachidonoylglycerol (2-AG), activate presynaptic cannabinoid type 1 receptors (CB1R) on inhibitory and excitatory neurons, resulting in a decreased release of neurotransmitters.

Event-specific activation of the endocannabinoid system by inhibition of the endocannabinoid degrading enzymes may offer a promising strategy to selectively activate CB1Rs at the site of excessive neuronal activation with the overall goal to prevent the development epilepsy.

The aim of this study was to investigate the impact of monoacylglycerol lipase (MAGL) inhibition on the development and progression of epileptic seizures in the kindling model of temporal lobe epilepsy.

In conclusion, the data demonstrate that indirect CB1R agonism delays the development of generalized epileptic seizures, but has no relevant acute anticonvulsive effects.

Furthermore, we confirmed that the effects of JZL184 on kindling progression are CB1R mediated.

Thus, the data indicate that the endocannabinoid 2-AG might be a promising target for an anti-epileptogenic approach.”

Attenuation of kainic acid-induced status epilepticus by inhibition of endocannabinoid transport and degradation in guinea pigs.

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“Status epilepticus (SE) is a medical emergency associated with a high rate of mortality if not treated promptly.

Exogenous and endogenous cannabinoids have been shown to possess anticonvulsant properties both in vivo and in vitro.

Here we study the influence of endocannabinoid metabolism on the development of kainic acid-induced SE in guinea pigs.

The present study provides electrophysiologic and behavioral evidences that inhibition of endocannabinoid metabolism plays a protective role against kainic acid-induced SE and may be employed for therapeutic purposes.”

http://www.ncbi.nlm.nih.gov/pubmed/25769371

http://www.thctotalhealthcare.com/category/epilepsy-2/

Marijuana: A Time-Honored but Untested Treatment for Epilepsy.

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“The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures.

However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done.

Proper dosage and means of administration remain unknown.

Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy.”

 http://www.ncbi.nlm.nih.gov/pubmed/25715711

http://www.thctotalhealthcare.com/category/epilepsy-2/

Fatty Acid Binding Proteins (FABPs) are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).

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“Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex.

Recent reports suggest that CBD and THC elevates the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance.

Fatty acid binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH).

By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and we demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs.

Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption.

Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD.

Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids.

These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy towards epilepsy and other neurological disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25666611

Phytocannabinoids and epilepsy.

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“Antiepileptic drugs often produce serious adverse effects, and many patients do not respond to them properly.

Phytocannabinoids produce anticonvulsant effects in preclinical and preliminary human studies, and appear to produce fewer adverse effects than available antiepileptic drugs.

The present review summarizes studies on the anticonvulsant properties of phytocannabinoids.

Preclinical studies suggest that phytocannabinoids, especially cannabidiol and cannabidivarin, have potent anticonvulsant effects which are mediated by the endocannabinoid system. Human studies are limited in number and quality, but suggest that cannabidiol has anticonvulsant effects in adult and infantile epilepsy and is well tolerated after prolonged administration…

 

Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25475762

http://www.thctotalhealthcare.com/category/epilepsy-2/

Cannabidiol: promise and pitfalls.

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“Over the past few years, increasing public and political pressure has supported legalization of medical marijuana.

One of the main thrusts in this effort has related to the treatment of refractory epilepsy-especially in children with Dravet syndrome-using cannabidiol (CBD).

Despite initiatives in numerous states to at least legalize possession of CBD oil for treating epilepsy, little published evidence is available to prove or disprove the efficacy and safety of CBD in patients with epilepsy. This review highlights some of the basic science theory behind the use of CBD, summarizes published data on clinical use of CBD for epilepsy, and highlights issues related to the use of currently available CBD products.

Cannabidiol is the major nonpsychoactive component of Cannabis sativa.

Over the centuries, a number of medicinal preparations derived from C. sativa have been employed for a variety of disorders, including gout, rheumatism, malaria, pain, and fever.

These preparations were widely employed as analgesics by Western medical practitioners in the 19(th) century.

More recently, there is clinical evidence suggesting efficacy in HIV-associated neuropathic pain, as well as spasms associated with multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25346628

http://www.thctotalhealthcare.com/category/epilepsy-2/

Seizing an opportunity for the endocannabinoid system.

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“Exogenous cannabinoids can limit seizures and neurodegeneration, and their actions are largely mimicked by endogenous cannabinoids (endocannabinoids).

Endocannabinoids are mobilized by epileptiform activity and in turn influence this activity by inhibiting synaptic transmission; both excitatory and some inhibitory synapses can be suppressed, leading to potentially complex outcomes.

Moreover, the endocannabinoid system is not a fixed entity, and its strength can be enhanced or reduced.

Endocannabinoids and their receptors are altered by epileptic seizures in ways that can reduce the efficacy of both exogenous and endogenous cannabinoids in sometimes unexpected ways.”

http://www.ncbi.nlm.nih.gov/pubmed/25346637

http://www.thctotalhealthcare.com/category/epilepsy-2/

Cannabis, cannabidiol, and epilepsy – From receptors to clinical response.

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“The use of cannabis for medicinal purposes is becoming more prevalent.

For this purpose, various preparations of cannabis of varying strengths and content are being used.

The recent changes in the legal environment have improved the availability of products with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) concentrations.

There is some anecdotal evidence of their potential efficacy, but the mechanisms of such action are not entirely clear.

Some suspect an existence of synergy or “entourage effect” between CBD and THC.

There is strong evidence that THC acts via the cannabinoid receptor CB1.

The mechanism of action of CBD is less clear but is likely polypharmacological.

The scientific data support the role of the endocannabinoid system in seizure generation, maintenance, and control in animal models of epilepsy.

There are clear data for the negative effects of cannabis on the developing and mature brain though these effects appear to be relatively mild in most cases.

Further data from well-designed studies are needed regarding short- and long-term efficacy and side effects of CBD or high-CBD/low-THC products for the treatment of seizures and epilepsy in children and adults.”

http://www.ncbi.nlm.nih.gov/pubmed/25282526

http://www.thctotalhealthcare.com/category/epilepsy-2/

The non-psychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability.

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“Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy.

Since the two non-psychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity.

These data suggest that CBDV anti-epileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/25029033

The case for assessing cannabidiol in epilepsy.

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“Intractable epilepsies have an extraordinary impact on cognitive and behavioral function and quality of life, and the treatment of seizures represents a challenge and a unique opportunity. Over the past few years, considerable attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of Cannabis sativa.

Basic research studies have provided strong evidence for safety and anticonvulsant properties of CBD. However, the lack of pure, pharmacologically active compounds and legal restrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports.

Pure CBD appears to be an ideal candidate among phytocannabinoids as a therapy for treatment-resistant epilepsy.

A first step in this direction is to systematically investigate the safety, pharmacokinetics, and interactions of CBD with other antiepileptic drugs and obtain an initial signal regarding efficacy at different dosages. These data can then be used to plan double-blinded placebo-controlled efficacy trials.”

http://www.ncbi.nlm.nih.gov/pubmed/24854434

http://www.thctotalhealthcare.com/category/epilepsy-2/