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

Posted on October 18, 2016 by David

“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.

Posted on October 18, 2016 by David

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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.

Posted on October 5, 2016 by David

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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.

Posted on September 23, 2016 by David

“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.

Posted on September 14, 2016 by David

“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

Cannabidiol and Epilepsy: Sifting, Winnowing and Buzz

Posted on September 7, 2016 by David

“Over the past few years there has been a phenomenal resurgence in the interest in the use of Cannabis sativa and Cannabis indica for the treatment of epilepsy (among many other disorders as well). Clearly, the media and the proliferation of internet sites offering advice has fueled interest not only among patients and caregivers, but clinicians as well. Mainstream and social media interest in patient testimonials have, for better or worse, created a great deal of buzz. First, to the answer of does CBD provide benefit, the answer appears to be yes. With respect to safety perspective, CBD seemed to be well tolerated in most patients. At least we can finally say with some confidence to our patients, their families, and our colleagues, that there is more to this drug than media hype, and internet buzz.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988076/

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

From cannabis to cannabidiol to treat epilepsy, where are we?

Posted on September 3, 2016 by David

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“Several antiepileptic drugs (AEDs), about 25, are currently clinically available for the treatment of patients with epilepsy. Despite this armamentarium and the many recently introduced AEDs, no major advances have been achieved considering the number of drug resistant patients, while many benefits have been indeed obtained for other clinical outcomes (e.g. better tolerability, less interactions).

Cannabinoids have long been studied for their potential therapeutical use and more recently phytocannabinoids have been considered a valuable tool for the treatment of several neurological disorders including epilepsy.

Among this wide class, the most studied is cannabidiol (CBD) considering its lack of psychotropic effects and its anticonvulsant properties.

Several preclinical studies have tried to understand the mechanism of action of CBD, which still remains largely not understood.

CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures; beneficial effects were reported also in animal models of epileptogenesis and chronic models of epilepsy,

There is indeed sufficient supporting data for clinical development and important antiepileptic effects and the currently ongoing clinical studies will permit the real usefulness of CBD and possibly other cannabinoids.

Undoubtedly, several issues also need to be addressed in the next future (e.g. better pharmacokinetic profiling). Finally, shading light on the mechanism of action and the study of other cannabinoids might represent an advantage for future developments.”

http://www.ncbi.nlm.nih.gov/pubmed/27587196

Marijuana use in adults admitted to a Canadian epilepsy monitoring unit.

Posted on August 30, 2016 by David

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“Epidemiologic evidence supporting antiseizure properties of cannabis is limited and controversial.

We determined the prevalence of marijuana use and its perceived effects in patients with and without epilepsy.

Patients with uncontrolled epilepsy or nonepileptic events had a high rate of marijuana use with associated perceived improvements in seizure control, stress, sleep, and drug side effects.

Stress reduction may contribute to the perceived impact of marijuana on seizures and nonepileptic events in adults.”

http://www.ncbi.nlm.nih.gov/pubmed/27568641

Cannabinoid type 1 receptor antagonism ameliorates harmaline-induced essential tremor in rat.

Posted on August 23, 2016 by David

“Essential tremor (ET) is a neurological disorder with unknown etiology. Its symptoms include cerebellar motor disturbances, cognitive and personality changes, hearing and olfactory deficits. Excitotoxic cerebellar climbing fibre hyperactivity may underlie essential tremor and has been emulated in rodents by systemic harmaline administration.

Cannabinoid receptor agonists can cause motor disturbances although there are also anecdotal reports of therapeutic benefits of cannabis in motor disorders. We set out to establish the effects of cannabinoid type 1 receptor agonism and antagonism in an established rodent model of ET using a battery of accepted behaviour assays in order to determine risk and therapeutic potential of endocannabinoid system modulation in ET.

Overall, harmaline induced robust tremor that was typically worsened across the measured behavioural domains by CB type 1 (CB₁ ) receptor agonism but ameliorated by cannabinoid type 1 receptor antagonism.

CONCLUSIONS AND IMPLICATIONS:

These results provide the first evidence of effects of endocannabinoid system modulation on motor function in the harmaline model of essential tremor and suggest that CB₁ receptor manipulation warrants clinical investigation as a therapeutic approach to protection against behavioural disturbances associated with essential tremor.”

http://www.ncbi.nlm.nih.gov/pubmed/27545646

CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a.

Posted on August 16, 2016 by David

“The CB1 cannabinoid receptor is a G-protein coupled receptor that has important physiological roles in synaptic plasticity, analgesia, appetite, and neuroprotection.

We report the discovery of two structurally related CB1 cannabinoid receptor interacting proteins (CRIP1a and CRIP1b) that bind to the distal C-terminal tail of CB1. CRIP1a and CRIP1b are generated by alternative splicing of a gene located on chromosome 2 in humans, and orthologs of CRIP1a occur throughout the vertebrates, whereas CRIP1b seems to be unique to primates.

CRIP1a coimmunoprecipitates with CB1receptors derived from rat brain homogenates, indicating that CRIP1a and CB1 interact in vivo. Furthermore, in superior cervical ganglion neurons coinjected with CB1 and CRIP1a or CRIP1b cDNA, CRIP1a, but not CRIP1b, suppresses CB1-mediated tonic inhibition of voltage-gated Ca2+ channels.

Discovery of CRIP1a provides the basis for a new avenue of research on mechanisms of CB1 regulation in the nervous system and may lead to development of novel drugs to treat disorders where modulation of CB1 activity has therapeutic potential (e.g., chronic pain, obesity, and epilepsy).”

http://www.ncbi.nlm.nih.gov/pubmed/17895407