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.

“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/

Marijuana extract slashes pediatric seizures, landmark study confirms

Cannabis extract Epidiolex slashes seizures, a new study confirms.  (Photo by GW Pharmaceuticals)

“A batch of studies further confirms medical cannabis patients are right to try cannabidiol-rich marijuana products to treat intractable seizure disorders.

Three studies presented at the American Epilepsy Society’s 69th Annual Meeting in Philadelphia Dec. 7th found a marijuana-derived extract slashed pediatric seizures in half, and completely stopped seizures in nine percent of cases.”  http://blog.sfgate.com/smellthetruth/2015/12/15/marijuana-extract-slashes-pediatric-seizures-landmark-study-confirms/

“Study: marijuana medicine is safe, very effective on epilepsy” http://blog.sfgate.com/smellthetruth/2015/05/12/study-marijuana-medicine-is-safe-very-effective-on-epilepsy/

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

Cannabidiol Effective and Safe at 3 Months for Epilepsy

“New open-label data from the expanded-access treatment program involving the cannabidiol Epidiolex(GW Pharma) show the median reduction in frequency of convulsive seizures after 3 months of treatment was 45% in all patients but higher in those with Dravet syndrome, among the most severe types of epilepsy.

The data are “very positive and promising,” said lead author Orrin Devinsky, MD, professor, neurology, neurosurgery and psychiatry, and director, New York University Comprehensive Epilepsy Center.” http://www.medscape.com/viewarticle/855768

“More Positive Results With Cannabidiol in Epilepsy”  http://www.medscape.com/viewarticle/853781

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

Study: Marijuana-derived drug reduces epileptic seizures

“A new study involving 11 epilepsy centers across the United States shows that a drug made from a medical marijuana derivative can reduce seizures in children and young adults with epilepsy who don’t find relief from other treatments.

Almost a third of patients with epilepsy don’t respond to standard treatments, and marijuana-based medicines have drawn interest as having potential benefits, but scientific data on their effectiveness has been slim until now.

The new research involved 137 patients between the ages of one and 30 years old. It found that a medical marijuana derivative called cannabidiol (CBD) helped reduce seizure frequency in most children and young adults enrolled in the yearlong study.

Cannabidiol was also well-tolerated and safe, lead author Dr. Orrin Devinsky, professor of neurology, neurosurgery, and psychiatry and director of the Comprehensive Epilepsy Center at NYU Langone Medical Center, told CBS News.”

http://www.cbsnews.com/news/marijuana-derived-drug-reduces-seizures-in-hard-to-treat-epilepsy/

“Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.” http://www.ncbi.nlm.nih.gov/pubmed/26724101

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

Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.

“Cannabis-based treatments for epilepsy have generated much interest…

We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with treatment-resistant epilepsy…

Our findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26724101

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(15)00379-8/fulltext

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

Cannabidiol as potential treatment in refractory pediatric epilepsy.

“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/

Polypharmacology Shakes Hands with Complex Aetiopathology.

“Chronic diseases are due to deviations of fundamental physiological systems, with different pathologies being characterised by similar malfunctioning biological networks.

The ensuing compensatory mechanisms may weaken the body’s dynamic ability to respond to further insults and reduce the efficacy of conventional single target treatments.

The multitarget, systemic, and prohomeostatic actions emerging for plant cannabinoids exemplify what might be needed for future medicines.

Indeed, two combined cannabis extracts were approved as a single medicine (Sativex®), while pure cannabidiol, a multitarget cannabinoid, is emerging as a treatment for paediatric drug-resistant epilepsy.

Using emerging cannabinoid medicines as an example, we revisit the concept of polypharmacology and describe a new empirical model, the ‘therapeutic handshake’, to predict efficacy/safety of compound combinations of either natural or synthetic origin.”

http://www.ncbi.nlm.nih.gov/pubmed/26434643

Cannabis and Endocannabinoid Signaling in Epilepsy.

“The antiepileptic potential of Cannabis sativa preparations has been historically recognized.

Recent changes in legal restrictions and new well-documented cases reporting remarkably strong beneficial effects have triggered an upsurge in exploiting medical marijuana in patients with refractory epilepsy.

Parallel research efforts in the last decade have uncovered the fundamental role of the endogenous cannabinoid system in controlling neuronal network excitability raising hopes for cannabinoid-based therapeutic approaches.

However, emerging data show that patient responsiveness varies substantially, and that cannabis administration may sometimes even exacerbate seizures. Qualitative and quantitative chemical variability in cannabis products and personal differences in the etiology of seizures, or in the pathological reorganization of epileptic networks, can all contribute to divergent patient responses.

Thus, the consensus view in the neurologist community is that drugs modifying the activity of the endocannabinoid system should first be tested in clinical trials to establish efficacy, safety, dosing, and proper indication in specific forms of epilepsies.

To support translation from anecdote-based practice to evidence-based therapy, the present review first introduces current preclinical and clinical efforts for cannabinoid- or endocannabinoid-based epilepsy treatments.

Next, recent advances in our knowledge of how endocannabinoid signaling limits abnormal network activity as a central component of the synaptic circuit-breaker system will be reviewed to provide a framework for the underlying neurobiological mechanisms of the beneficial and adverse effects.

Finally, accumulating evidence demonstrating robust synapse-specific pathophysiological plasticity of endocannabinoid signaling in epileptic networks will be summarized to gain better understanding of how and when pharmacological interventions may have therapeutic relevance.”

http://www.ncbi.nlm.nih.gov/pubmed/26408165

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

A pharmacological basis of herbal medicines for epilepsy.

“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/