The Pharmacological Basis of Cannabis Therapy for Epilepsy.

“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.”

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Medicinal Cannabis: In Vitro Validation of Vaporizers for the Smoke-Free Inhalation of Cannabis.

“Inhalation by vaporization is a promising application mode for cannabis in medicine.

An in vitro validation of 5 commercial vaporizers was performed with THC-type and CBD-type cannabis.

Temperature-controlled, electrically-driven vaporizers efficiently decarboxylate inactive acidic cannabinoids and reliably release their corresponding neutral, active cannabinoids.

Thus, they offer a promising application mode for the safe and efficient administration of medicinal cannabis.”

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Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

“Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen.

Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis.

Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors.

Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease.

CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme.

Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD…

CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.”

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Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis.

“Pain is a common symptom of MS, affecting up to 70% of patients.

Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results.

 The aim of our study was to better investigate the role of Sativex® in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment.

 One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life.
Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways.”
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Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury.

“This work aimed to investigate the effects of the administration of cannabidiol in a kidney ischemia/reperfusion animal model…

The cannabidiol treatment had a protective effect against inflammation and oxidative damage in the kidney ischemia/reperfusion model.

These effects seemed to be independent of CB1/CB2 receptor activation.”

“In conclusion, the present study suggests that cannabidiol treatment has a protective effect against inflammation and oxidative damage in the utilized kidney ischemia/reperfusion model.”

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A cost-effectiveness model for the use of a cannabis-derived oromucosal spray for the treatment of spasticity in multiple sclerosis.

“Severity of spasticity in multiple sclerosis (MS) directly correlates with the level and cost of care required.

This study assessed whether a tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray for treatment of moderate-severe MS spasticity is a cost-effective use of healthcare resources in Wales.

The THC/CBD spray was found to be cost-effective for the treatment of spasticity in MS, and dominant, if home carer costs were included.

Use of THC/CBD has the potential to generate cost savings by significantly improving the symptoms of moderate to severe MS spasticity”

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Survey: medical pot treats migraines

“One hundred percent of migraine sufferers in a self-report survey said cannabis reduced migraine pain and discomfort.”

One hundred percent of migraine sufferers in a self-report survey said cannabis reduced migraine pain and discomfort. (Photo via Flickr TipsTimesAdmin with CC license)

“Cannabis treats a wide variety of conditions, but specific formulations are better for some symptoms than others, patients report in a new landmark survey by a medical cannabis industry company Care By Design.

A full 100 percent of respondents with headaches, migraines, fibromyalgia, irritable bowel syndrome (IBS), and spinal cord injury reported a decrease in pain or discomfort on medical marijuana rich in the molecule cannabidiol (CBD).”

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Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.

“Multiple Sclerosis (MS) is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system (CNS).

The pathology has an inflammatory/autoimmune origin; nevertheless, neuronal cell death mechanisms are not to be underestimated.

The present study was designed to test the effects of intraperitoneal administration of cannabidiol (CBD), the main non-psychotropiccannabinoid of Cannabis sativa (CS), in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis.

We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS.”

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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.”

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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.”

“Study: marijuana medicine is safe, very effective on epilepsy”

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