Category Archives: Epilepsy

Cannabidiol Reduces Seizures in Various Epilepsy Disorders

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“A purified oral formulation of cannabidiol (CBD; Epidiolex, GW Pharmaceuticals) significantly reduces seizures in treatment-resistant epilepsy, according to new research that included double-blind randomized controlled trials of patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), two of the most difficult-to-manage seizure conditions.

The new research, released here at the American Epilepsy Society (AES) 2016 Annual Meeting, also highlights the relative safety of this new drug, a prescription medicine derived from the cannabis plant.”

http://www.medscape.com/viewarticle/872763

Cannabidiol Mellows Out Resurgent Sodium Current

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“Cannabidiol has received abundant media attention as a potential therapy for intractable epilepsy, based mainly on anecdotal evidence.

These findings suggest that cannabidiol could be exerting its anticonvulsant effects, at least in part, through its actions on voltage-gated sodium channels, and resurgent current may be a promising therapeutic target for the treatment of epilepsy syndromes.”

http://www.epilepsycurrents.org/doi/full/10.5698/1535-7511-16.6.399

Endogenous cannabinoid system alterations and their role in epileptogenesis after brain injury in rat.

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“Post-traumatic epilepsy (PTE) is one of the most common complications resulting from brain injury, however, antiepileptic drugs usually fail to prevent it.

Several lines of evidence have demonstrated that the endogenous cannabinoid system (ECS) plays a pivotal role during epileptogenesis in several animal models.

A recent study has shown that a cannabinoid type 1 (CB1) receptor antagonist could suppress long-term neuron hyperexcitability after brain injury, but the underlying mechanisms remain largely unknown.

In this study, we first analyzed the dynamic expression of different components of the ECS at various time points after brain injury in rats. Then, we conducted a 12-month-long session of behavioral monitoring after the brain injury, and based on the results, the rats were divided into a PTE group and a non-PTE group. Finally, the changes in the ECS between the two groups were compared.

We found that the ECS exhibited a biphasic alteration after brain injury; the expression of the CB1 receptor and 2-arachidonoylglycerol (2-AG) in the PTE group was significantly higher than that of the non-PTE group 12 months after traumatic brain injury.

Our preliminary results indicated that the ECS might be involved in post-traumatic epileptogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27810514

The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats.

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“An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration.

The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults.

We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes.

Thus, a brief pharmacological stimulation of the endocannabinoid system soon after a brain insult exerts beneficial effects on its pathological outcome though does not prevent epileptogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27520083

Effects of Marijuana on ictal and interictal EEG activity in idiopathic generalized epilepsy.

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“Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series and clinical trials.

However, literature on their electroencephalography (EEG) effects is sparse.

Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy (IGE) treated with cannabis.

Using a novel approach to electroencephalographic data, we demonstrate a decrease in interictal and ictal electrographic events during marijuana use.

Larger samples of patients and EEG, with standardized cannabinoid formulation and dosing are needed to validate our findings.”

 https://www.ncbi.nlm.nih.gov/pubmed/27763968

Δ9-THC Intoxication by Cannabidiol-Enriched Cannabis Extract in Two Children with Refractory Epilepsy: Full Remission after Switching to Purified Cannabidiol.

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“Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy.

We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time.

The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract.

The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission.

These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy.

Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.”

https://www.ncbi.nlm.nih.gov/pubmed/27746737

Pharmacokinetic-pharmacodynamic influence of N-palmitoylethanolamine, arachidonyl-2′-chloroethylamide and WIN 55,212-2 on the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

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“We evaluated the effects of ACEA (selective cannabinoid (CB)1 receptor agonist), WIN 55,212-2 mesylate (WIN; non-selective CB1and CB2 receptor agonist) and N-palmitoylethanolamine (PEA; an endogenous fatty acid of ethanolamide) in DBA/2 mice, a genetic model of reflex audiogenic epilepsy.

PEA, ACEA or WIN intraperitoneal (i.p.) administration decreased the severity of tonic-clonic seizures.

PEA has anticonvulsant features in DBA/2 mice mainly through PPAR-α and likely indirectly on CB1 receptors, whereas ACEA and WIN act through CB1 receptors.

In conclusion, PEA, ACEA and WIN show anticonvulsant effects in DBA/2 mice and potentiate the effects several AEDs suggesting a possible therapeutic relevance of these drugs and their mechanisms of action.”

https://www.ncbi.nlm.nih.gov/pubmed/27663280

Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex.

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“Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder with highly variable expression.

The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment-resistant epilepsy.

Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol (CBD), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of TSC.

Although double-blind, placebo-controlled trials are still necessary, these findings suggest that cannabidiol may be an effective and well-tolerated treatment option for patients with refractory seizures in TSC.”

https://www.ncbi.nlm.nih.gov/pubmed/27696387

Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases.

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“Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients’ seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.”

http://www.ncbi.nlm.nih.gov/pubmed/27655472

Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes.

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“Since 24 states and the District of Columbia have legalized marijuana in some form, suppliers of legal marijuana have developed Cannabis sativa products for use in electronic cigarettes (e-cigarettes).

Personal battery powered vaporizers, or e-cigarettes, were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. The liquid formulations used in these devices are comprised of an active ingredient such as nicotine mixed with vegetable glycerin (VG) and/or propylene glycol (PG) and flavorings.

A significant active ingredient of C. sativa, cannabidiol (CBD), has been purported to have anti-convulsant, anti-nociceptive, and anti-psychotic properties. These properties have potential medical therapies such as intervention of addictive behaviors, treatments for epilepsy, management of pain for cancer patients, and treatments for schizophrenia.

However, CBD extracted from C. sativa remains a DEA Schedule I drug since it has not been approved by the FDA for medical purposes.

Two commercially available e-cigarette liquid formulations reported to contain 3.3 mg/mL of CBD as the active ingredient were evaluated. These products are not regulated by the FDA in manufacturing or in labeling of the products and were found to contain 6.5 and 7.6 mg/mL of CBD in VG and PG with a variety of flavoring agents. Presently, while labeled as to content, the quality control of manufacturers and the relative safety of these products is uncertain.”

http://www.ncbi.nlm.nih.gov/pubmed/27621706