Antiepileptic potential of cannabidiol analogs.

“In audiogenic seizure (AGS) susceptible rats, the acute (intraperitoneal and intravenous) dose-response effects of (–)-cannabidiol (CBD) for preventing AGS and for causing rototod neurotoxicity (ROT) were determined.

Also, the anti-AGS and ROT effects of 10 CBD analogs, given in intravenous doses equivalent to the AGS-ED50 (15 mg/kg) and ROT-ID50 (31 mg/kg) of CBD, were ascertained.

Compared to CBD, (–)-CBD diacetate and (–)-4-(2′-olivetyl)-alpha-pinene were equally effective whereas (–)-CBD monomethyl ether, (–)-CBD dimethyl ether, (–)-3′-acetyl-CBD monoacetate, (+)-4-(2′-olivetyl)-alpha-pinene, (–)-and (+)-4-(6′-olivetyl)-alpha-pinene, (+/-)-AF-11, and olivetol were less effective anticonvulsants. Except for (–)- and (+)-4-(2′-olivetyl)-alpha-pinene and olivetol, all analogs showed less ROT than CBD.

Also, CBD and all analogs were not active in tetrahydrocannabinol seizure-susceptible rabbits, the latter a putative model of cannabinoid psychoactivity in humans.

These data suggest anticonvulsant requirements of 2 free phenolic hydroxyl groups, exact positioning of the terpinoid moiety in the resorcinol system and correct stereochemistry.

Moreover, findings of separation of anticonvulsant from neurotoxic and psychoactive activities, notably with CBD diacetate, suggest that additional structural modifications of CBD may yield novel antiepileptic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/7298873

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

Phytocannabinoids and epilepsy.

“Antiepileptic drugs often produce serious adverse effects, and many patients do not respond to them properly.

Phytocannabinoids produce anticonvulsant effects in preclinical and preliminary human studies, and appear to produce fewer adverse effects than available antiepileptic drugs.

The present review summarizes studies on the anticonvulsant properties of phytocannabinoids.

Preclinical studies suggest that phytocannabinoids, especially cannabidiol and cannabidivarin, have potent anticonvulsant effects which are mediated by the endocannabinoid system. Human studies are limited in number and quality, but suggest that cannabidiol has anticonvulsant effects in adult and infantile epilepsy and is well tolerated after prolonged administration…

 

Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25475762

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

The non-psychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability.

“Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy.

Since the two non-psychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity.

These data suggest that CBDV anti-epileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/25029033

The case for assessing cannabidiol in epilepsy.

“Intractable epilepsies have an extraordinary impact on cognitive and behavioral function and quality of life, and the treatment of seizures represents a challenge and a unique opportunity. Over the past few years, considerable attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of Cannabis sativa.

Basic research studies have provided strong evidence for safety and anticonvulsant properties of CBD. However, the lack of pure, pharmacologically active compounds and legal restrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports.

Pure CBD appears to be an ideal candidate among phytocannabinoids as a therapy for treatment-resistant epilepsy.

A first step in this direction is to systematically investigate the safety, pharmacokinetics, and interactions of CBD with other antiepileptic drugs and obtain an initial signal regarding efficacy at different dosages. These data can then be used to plan double-blinded placebo-controlled efficacy trials.”

http://www.ncbi.nlm.nih.gov/pubmed/24854434

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

Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB 2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model.

“The aim of this study was to characterize the influence of WIN 55,212-2 (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model…

These preclinical data would suggest that WIN in combination with clonazepam, phenobarbital and valproate is associated with beneficial anticonvulsant pharmacodynamic interactions in the mouse 6 Hz-induced psychomotor seizure test.”

http://www.ncbi.nlm.nih.gov/pubmed/24549572

Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression.

“To date, anticonvulsant effects of the plant cannabinoid, cannabidivarin (CBDV), have been reported in several animal models of seizure. However, these behaviourally observed anticonvulsant effects have not been confirmed at the molecular level…

These results provide the first molecular confirmation of behaviourally observed effects of the non-psychoactive, anticonvulsant cannabinoid, CBDV, upon chemically-induced seizures and serve to underscore its suitability for clinical development.”

http://www.ncbi.nlm.nih.gov/pubmed/24282673

Full-text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840466/

Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.

“Epilepsy is the most prevalent neurological disease and is characterised by recurrent seizures. Here we investigate: (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDS) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors.

CDBV BDSs exerted significant anticonvulsant effects… 

CONCLUSIONS AND IMPLICATIONS:

CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor, and were of comparable efficacy to purified CBDV.

These findings strongly support the further clinical development of CBDV BDSs for treatment of epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/23902406

“Cannabidivarin is anticonvulsant in mouse and rat… These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models.”  http://www.ncbi.nlm.nih.gov/pubmed/22970845

CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations.

“Drugs that modulate the endocannabinoid system and endocannabinoids typically play an anticonvulsant role although some proconvulsant effects have been reported both in humans and animal models.

 This study aims to characterize the role of cannabinoids in specific areas of the cortico-thalamic network involved in oscillations that underlie seizures in a genetic animal model of absence epilepsy, the WAG/Rij rat.

These results, together with previous reports, support therapeutic potential for endocannabinoid system modulators in absence epilepsy and highlight that attenuated endocannabinergic function may contribute to the generation and maintenance of seizures. Furthermore, the entire cortico-thalamic network responds to cannabinoid treatment, indicating that in all areas considered, CB receptor activation inhibits the pathological synchronization that subserves absence seizures.

 In conclusion, our result might be useful for the identification of future drug therapies in absence epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/23860329

Marijuana and its receptor protein in brain control epilepsy

“VCU study is first to test anticonvulsant potential of marijuana and brain recurrent seizures. 

Ingredients in marijuana and the cannabinoid receptor protein produced naturally in the body to regulate the central nervous system and other bodily functions play a critical role in controlling spontaneous seizures in epilepsy, according to a new study by researchers at Virginia Commonwealth University.

The study, the first to look at marijuana and the brain’s cannabinoid system in live animals with spontaneous, recurrent seizures, suggests new avenues that researchers can explore in their search for more-effective drugs to treat epileptic patients who don’t respond to today’s anticonvulsant medications or surgery.

The results appear in the Oct. 1 issue of the Journal of Pharmacology and Experimental Therapeutics.

“Although marijuana is illegal in the United States, individuals both here and abroad report that marijuana has been therapeutic for them in the treatment of a variety of ailments, including epilepsy,” says Dr. Robert J. DeLorenzo, professor of neurology in the VCU School of Medicine.

 “If we can understand how marijuana works to end seizures, we may be able to develop novel drugs that might do a better job of treating epileptic seizures.” 

Epilepsy is one of the most common neurological conditions, characterized by spontaneously recurrent seizures. Approximately 1 percent of Americans have epilepsy, and 30 percent of those patients are resistant to conventional anticonvulsant drug treatments.

Cannabinoids have been used as a natural remedy for seizures for thousands of years, and studies since at least 1974 have found that the primary psychoactive compound in marijuana displays anticonvulsant properties.” 

More:http://www.news.vcu.edu/news/Marijuana_and_its_receptor_protein_in_brain_control_epilepsy

Cannabis Treats Cancer and Epilepsy

Description: Medical Marijuana

Dr. Mark Sircus, Ac., OMD, DM (P)

Director International Medical Veritas Association

Doctor of Oriental and Pastoral Medicine

Dr. Sean McAllister and Pierre Desprez claim they’ve successfully used cannabidiol to fight animal genes involved in the spread of cancer. “We found this one compound had a specific effect on metastatic cancer cells, very aggressive tumor cells,” McAllister says. Cannabidiol, the research appears to show, helps shut down receptors that inhibit cancerous cells from metastasizing.  “We find when you treat with cannabidiol, you down regulate the expression of this protein, and that inhibits the disease process.” Unlike THC, the ingredient in marijuana that makes you feel stoned, cannabidiol is a non-toxic compound of the plant that has no psychoactive qualities.

I already published that marijuana is the best medicine for 3-year-old Cash Hyde of Missoula, Montana. The boy’s parent’s defied doctor’s orders—and Montana law—to get their hands on the medicinal treatment their son needed after he was diagnosed with recurring brain tumors at 22 months old. “I’ve had law enforcement threatening to kick my door down, but I would have done anything to keep Cashy alive,” said Mike Hyde, who has long been a proponent of the drug, told ABCNews.com.

My book on Medical Marijuana goes into the research from around the globe, including from Harvard University that sustains the conclusions of doctors McAllister and Desprez.

Dixie Botanicals is shipping Cannabidiol from Denver Colorado to all fifty states though of course one can grow marijuana oneself and or use regular marijuana strains if one lives in one of the now fifteen states that has made medical marijuana legal.

I take great exception to the Obama administration that has continued to resist the legalization on a federal level of medical marijuana. They still insist that there is no medical use for marijuana when all the science proves the government to be dead wrong. They hunt the world for terrorists but some of the worst live and work right in Washington DC. Terrorists are people who hurt others and I do not see the difference between those who use guns and those who use drugs or deny the population the natural substances they need to be well.

Of course marijuana is extremely effective for other diseases. The most recent I have read about: Medical pot treats boy’s epilepsy, without getting him high. The little boy has been swallowing droppers full of a solution made mostly of cannabidiol, or CBD, the second most prominent of marijuana’s 100 or so cannabinoids. Unlike the dominant THC, cannabidiol is not psychoactive, so the sweet-tasting infusion Jayden takes four times a day doesn’t make him high.

Down from 22 prescription pills per day to four, he now eats solid food, responds to his father’s incessant requests for kisses and dances in his Modesto living room to the “Yo Gabba Gabba!” theme song. The frequency and intensity of his seizures have been greatly reduced.

CBD was virtually bred out of U.S. plants decades ago by growers whose customers preferred the mind-altering properties of high-THC varietals. Yet it is experiencing a resurgence, having shown promise as an anti-inflammatory, anticonvulsant, neuroprotectant and cancer-fighting agent.

Studies have shown THC is “overwhelmingly anticonvulsant” in animals, said Dr. Ben Whalley, a researcher at Britain’s University of Reading, but CBD and some other non-psychoactive cannabinoids have shown similar effects without the mind-altering downside.”

http://drsircus.com/medicine/cancer/cannabis-treats-cancer-and-epilepsy#utm_source=Dr+Sircus+Newsletter&utm_campaign=820775ef59-Article_045&utm_medium=email