Historical perspective on the medical use of cannabis for epilepsy: Ancient times to the 1980s.

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“There has been a dramatic surge in the interest of utilizing cannabis for epilepsy treatment in the US. Yet, access to cannabis for research and therapy is mired in conflicting regulatory policies and shifting public opinion. Understanding the current state of affairs in the medical cannabis debate requires an examination of the history of medical cannabis use. From ancient Chinese pharmacopeias to the current Phase III trials of pharmaceutical grade cannabidiol, this review covers the time span of cannabis use for epilepsy therapy so as to better assess the issues surrounding the modern medical opinion of cannabis use. This article is part of a Special Issue titled Cannabinoids and Epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/28089286

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

Pharmacology of cannabinoids in the treatment of epilepsy.

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“The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use.

This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA).

It has long been known that ∆9-THC has partial agonist activity at the endocannabinoid receptors CB1 and CB2, though it also binds to other targets which may modulate neuronal excitability and neuroinflammation.

The actions of Δ9-THCV and Δ9-THCA are less well understood. In contrast to ∆9-THC, CBD has low affinity for CB1 and CB2 receptors and other targets have been investigated to explain its anticonvulsant properties including TRPV1, voltage gated potassium and sodium channels, and GPR55, among others.

We describe the absorption, distribution, metabolism, and excretion of each of the above mentioned compounds. Cannabinoids as a whole are very lipophilic, resulting in decreased bioavailability, which presents challenges in optimal drug delivery. Finally, we discuss the limited drug-drug interaction data available on THC and CBD.

As cannabinoids and cannabis-based products are studied for efficacy as anticonvulsants, more investigation is needed regarding the specific targets of action, optimal drug delivery, and potential drug-drug interactions.”

https://www.ncbi.nlm.nih.gov/pubmed/28087250

Cannabis and epilepsy: An ancient treatment returns to the fore.

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“Cannabis has been associated with the treatment of epilepsy throughout history, and if ancient Assyrian sources referring to “hand of ghost” are considered credible, this relationship may span four millennia.

A tradition of usage continued in Arabic medicine and Ayurvedic practice in India, which led, in turn, to early experiments in Europe and North America with “Indian hemp.”

Lack of standardization, bioavailability issues, and ultimately prohibition were all factors in cannabis-based medicines failing to maintain mainstream usage in seizure treatment, but investigation was resumed in the 1970s with interesting signals noted in both laboratory and clinical settings.

Early case studies showed promise, but lacked sufficient rigor. Resumption of research coupled with mass experimentation by families of epilepsy patients has led to intense interest in cannabis-based medicines for its treatment once more, with greatest focus on cannabidiol, but additional investigation of tetrahydrocannabinol, tetrahydrocannabinolic acid, and other phytocannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/27989385

Marijuana Can Cure Epilepsy: Recent Studies Done By Scientists Of Birmingham Epilepsy Center Revealed

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“A series of trials on marijuana to treat epilepsy is conducted by the Birmingham Epilepsy Center revealed that Cannabidiol (CBD), purified from Cannabis plant or commonly known marijuana, has high beneficial effects in the treatment of epileptic patients. The study revealed that oral administration of CBD oil caused a significant reduction in the frequency of epileptic seizures in adult and pediatric patients.”

http://www.scienceworldreport.com/articles/53849/20161207/marijuana-cure-epilepsy-recent-studies-done-scientists-birmingham-center-revealed.htm

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

“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.”

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