Tag Archives: anticonvulsant

Cannabidiol and epilepsy: rationale and therapeutic potential.

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“Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remains still poor. Unfortunately, besides several advantages, these new AEDs have not satisfactorily reduced the number of refractory patients. Therefore, the need for different other therapeutic options to manage epilepsy is still a current issue.

To this purpose, emphasis has been given to phytocannabinoids, which have been medicinally used since ancient time in the treatment of neurological disorders including epilepsy.

In particular, the nonpsychoactive compound cannabidiol (CBD) has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action.

However, it should be made clear that most phytocannabinoids do not act on the endocannabinoid system as in the case of CBD.

In in vivo preclinical studies, CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis.

Likewise, clinical evidence seem to indicate that CBD is able to manage epilepsy both in adults and children affected by refractory seizures, with a favourable side effect profile.

However, to date, clinical trials are both qualitatively and numerically limited, thus yet inconsistent. Therefore, further preclinical and clinical studies are undoubtedly needed to better evaluate the potential therapeutic profile of CBD in epilepsy, although the actually available data is promising.”

http://www.ncbi.nlm.nih.gov/pubmed/26976797

Plant-Derived and Endogenous Cannabinoids in Epilepsy.

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“Cannabis is one of the oldest psychotropic drugs and its anticonvulsant properties have been known since the last century.

The aim of this reveiw was to analyze the efficacy of cannabis in the treatment of epilepsy in adults and children. In addition, a description of the involvement of the endocannabinoid system in epilepsy is given in order to provide a biochemical background to the effects of endogenous cannabinoids in our body.

General tolerability and adverse events associated with cannabis treatment are also investigated. Several anecdotal reports and clinical trials suggest that in the human population cannabis has anticonvulsant properties and could be effective in treating partial epilepsies and generalized tonic-clonic seizures, still known as “grand mal.”

They are based, among other factors, on the observation that in individuals who smoke marijuana to treat epilepsy, cessation of cannabis use precipitates the re-emergence of convulsive seizures, whereas resuming consumption of this psychotropic drug controls epilepsy in a reproducible manner.

In conclusion, there is some anecdotal evidence for the potential efficacy of cannabis in treating epilepsy.

Though there has been an increased effort by patients with epilepsy, their caregivers, growers, and legislators to legalize various forms of cannabis, there is still concern about its efficacy, relative potency, availability of medication-grade preparations, dosing, and potential short- and long-term side effects, including those on prenatal and childhood development.”

http://www.ncbi.nlm.nih.gov/pubmed/26892745

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

Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures.

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“Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile.

β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity.

In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects.

Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice.

Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/26827298

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

The Pharmacological Basis of Cannabis Therapy for Epilepsy.

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“Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy patients including children who do not respond to current medications.

There is a large unmet medical need for new antiepileptics for refractory epilepsy and conditions associated with refractory seizures that would not interfere with normal function.

The two chief cannabinoids are delta-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major non-psychoactive component of marijuana.

There are claims of clinical efficacy of CBD-predominant cannabis or medical marijuana for epilepsy, mostly from limited studies, surveys or case reports.

However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy.

CBD is anticonvulsant, but it has a low affinity for the cannabinoid CB1 and CB2 receptors; therefore the exact mechanism by which it affects seizures remains poorly understood.

A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy for the treatment of epilepsy.

Identification of mechanisms underlying the anticonvulsant efficacy of CBD is additionally critical to identify other potential treatment options.”

http://www.ncbi.nlm.nih.gov/pubmed/26787773

http://jpet.aspetjournals.org/content/early/2016/01/19/jpet.115.230151.long

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

Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

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“Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals.

To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure.

Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment.

In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol.

Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy.

Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content.

Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase.

Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol.

In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model.”

http://www.ncbi.nlm.nih.gov/pubmed/26738731

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

Cannabidiol as potential treatment in refractory pediatric epilepsy.

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“In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children.

From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile.

In humans, CBD efficacy and safety is not supported by well designed trials and its use has been described by anecdotal reports.

It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other antiepileptic drugs alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.”

http://www.ncbi.nlm.nih.gov/pubmed/26567560

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

A pharmacological basis of herbal medicines for epilepsy.

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“Epilepsy is the most common chronic neurological disease, affecting about 1% of the world’s population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs).

Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures.

Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals.

Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs.

Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays.

To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids.

Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs.

Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites.

Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy.

Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development.

In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute seizures. At the same time, available data provide ample justification for clinical studies with selected standardized botanical extracts and plant-derived compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/26074183

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

Issues and promise in clinical studies of botanicals with anticonvulsant potential.

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“Botanicals are increasingly used by people with epilepsy worldwide. However, despite abundant preclinical data on the anticonvulsant properties of many herbal remedies, there are very few human studies assessing safety and efficacy of these products in epilepsy.Additionally, the methodology of most of these studies only marginally meets the requirements of evidence-based medicine.

Although the currently available evidence for the use of cannabinoids in epilepsy is similarly lacking, several carefully designed and well controlled industry-sponsored clinical trials of cannabis derivatives are planned to be completed in the next couple of years, providing the needed reliable data for the use of these products.

The choice of the best botanical candidates with anticonvulsant properties and their assessment in well-designed clinical trials may significantly improve our ability to effectively and safely treat patients with epilepsy. ”

http://www.ncbi.nlm.nih.gov/pubmed/26341963

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

Marijuana Use in Epilepsy: The Myth and the Reality.

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“Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia.

Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts.

This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD).

Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians’ and patients’ opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26299273

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

Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release.

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“Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders.

Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties.

Its effects against cocaine neurotoxicity, however, has remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms.

In conclusion, CBD protects against seizures in a model of cocaine intoxication.

CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.”

http://www.ncbi.nlm.nih.gov/pubmed/26283212