Δ⁹-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats.

“PURPOSE:

We assessed the anticonvulsant potential of the phytocannabinoid Δ⁹-tetrahydrocannabivarin (Δ⁹-THCV) by investigating its effects in an in vitro piriform cortex (PC) brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand-binding assays and in a generalized seizure model in rats.”

“DISCUSSION:

These data demonstrate that Δ⁹-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.”

http://www.ncbi.nlm.nih.gov/pubmed/20196794

Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.

“Delta(9)-tetrahydrocannabinol binds cannabinoid (CB(1) and CB(2)) receptors, which are activated by endogenous compounds (endocannabinoids) and are involved in a wide range of physiopathological processes (e.g. modulation of neurotransmitter release, regulation of pain perception, and of cardiovascular, gastrointestinal and liver functions).

The well-known psychotropic effects of Delta(9)-tetrahydrocannabinol, which are mediated by activation of brain CB(1) receptors, have greatly limited its clinical use. However, the plant Cannabis contains many cannabinoids with weak or no psychoactivity that, therapeutically, might be more promising than Delta(9)-tetrahydrocannabinol.

Here, we provide an overview of the recent pharmacological advances, novel mechanisms of action, and potential therapeutic applications of such non-psychotropic plant-derived cannabinoids. Special emphasis is given to cannabidiol,

the possible applications of which have recently emerged in inflammation, diabetes, cancer, affective and neurodegenerative diseases, and to Delta(9)-tetrahydrocannabivarin, a novel CB(1) antagonist which exerts potentially useful actions in the treatment of epilepsy and obesity.”

http://www.ncbi.nlm.nih.gov/pubmed/19729208

Phytocannabinoids as novel therapeutic agents in CNS disorders.

Abstract

“The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body’s endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB(1) receptors by the major pCB, Δ(9)-tetrahydrocannabinol (Δ(9)-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ(9)-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ(9)tetrahydrocannabivarin (Δ(9)-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ(9)-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ(9)-THC pCB-based medicines.”

http://www.ncbi.nlm.nih.gov/pubmed/21924288

Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects

“The roots of cannabis synergy.”

“Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL−1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.”

“Cannabis has been a medicinal plant of unparalleled versatility for millennia, but whose mechanisms of action were an unsolved mystery until the discovery of tetrahydrocannabinol (THC), the first cannabinoid receptor, CB1, and the endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG). While a host of phytocannabinoids were discovered in the 1960s: cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC) (Gaoni and Mechoulam, cannabidivarin (CBDV) and tetrahydrocannabivarin (THCV), the overwhelming preponderance of research focused on psychoactive THC. Only recently has renewed interest been manifest in THC analogues, while other key components of the activity of cannabis and its extracts, the cannabis terpenoids, remain understudied. The current review will reconsider essential oil (EO) agents, their peculiar pharmacology and possible therapeutic interactions with phytocannabinoids.”

“Should positive outcomes result from such studies, phytopharmaceutical development may follow. The development of zero-cannabinoid cannabis chemotypes has provided extracts that will facilitate discernment of the pharmacological effects and contributions of different fractions. Breeding work has already resulted in chemotypes that produce 97% of monoterpenoid content as myrcene, or 77% as limonene (E. de Meijer, pers. comm.). Selective cross-breeding of high-terpenoid- and high-phytocannabinoid-specific chemotypes has thus become a rational target that may lead to novel approaches to such disorders as treatment-resistant depression, anxiety, drug dependency, dementia and a panoply of dermatological disorders, as well as industrial applications as safer pesticides and antiseptics. A better future via cannabis phytochemistry may be an achievable goal through further research of the entourage effect in this versatile plant that may help it fulfil its promise as a pharmacological treasure trove.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/

Cannabis could be used to treat obesity

“Cannabis could be used in drugs to help people overcome obesity, according to new UK research.

Researchers at GW Pharmaceuticals have discovered two compounds in cannabis leaves that help our bodies burn more energy, the UK’s Daily Telegraph reported.

The company is developing a drug to treat “metabolic syndrome”, which occurs when people suffer obesity, diabetes and high blood pressure, which increases their risk of heart disease and stroke.

Tests in mice showed the cannabis compounds improved their metabolism, which resulted in lower cholesterol in the bloodstream, plus less fat in key organs, such as the liver.

Now a trial is underway with 200 people and researchers hope the drug can treat metabolic syndrome.

Dr Stephen Wright, director of research and development at GW Pharmaceuticals, said they expect results in late 2012.

“The results in animal models have been very encouraging. We are interested in how these drugs effect the fat distribution and utilisation in the body as a treatment for metabolic diseases,” Dr Wright said.

“Humans have been using these plants for thousands of years so we have quite a lot of experience of the chemicals in the plants.”

Cannabis is illegal in the UK but GW Pharmaceuticals has been granted permission to grow it in secret greenhouses in the country’s south.

They are growing a type of cannabis with different quantities of compounds called cannabinoids.

While cannabis is known for inciting the “munchies”, these compounds, called THCV and cannabidiol, appear to suppress the appetite, while helping control sugar levels in the blood and fat levels throughout the body.

It appears THCV also helps cells that produce insulin work more effectively.

Now researchers are hoping the drugs will help people suffering type 2 diabetes and other obesity-related diseases.”

http://health.msn.co.nz/healthnews/8496828/cannabis-could-be-used-to-treat-obesity

How marijuana could help cure obesity-related diseases

“According to a new British study, marijuana leaves (not the buds that Willie Nelson loves so dearly) contain two compounds that boost the metabolism of mice, leading to lower levels of fat and cholesterol in the body — the latest addition to a growing body of evidence that marijuana may be useful in countering ailments related to obesity. One study in March found that a brain chemical similar in structure to an active compound in cannibis could help people shed weight, while another study last September concluded that pot smokers were less likely to be obese than non-potheads, though for reasons that remain unclear.   

The two compounds, THCV and cannabidiol, boosted the rodents’ metabolisms — reducing fat levels in their livers and cholesterol levels in their bloodstreams — and also made the mice more sensitive to insulin and protected the cells that produce insulin, “allowing [the cells] to work better and for longer.” The combined effects improved the mice’s ability to burn off energy.

And the compounds didn’t make mice hungry the way smoking weed affects humans?
Actually, the compounds were found to have an appetite-suppressing effect, but the effect only lasted for a short time.”

 http://news.yahoo.com/marijuana-could-help-cure-obesity-related-diseases-175900182.html

Cannabis drug could help fight obesity

“Apparently scientists have discovered that a natural component of cannabis suppresses the appetite and that discovery may lead to a new class of drugs for treating obesity.

Scientist professor Roger Pertwee, a neuropharmacologist at Aberdeen University, says it was already well known that cannabis stimulated the appetite, but not widely known that the plant also contained substances that produced the opposite effect.

That substance is apparently called THCV and is chemically similar to another cannabis chemical, or cannabinoid, called THC that stimulates the appetite.

As drugs based on THC are already being used to increase the appetite of AIDS patients, the focus is now on developing THCV for use as an anti-obesity drug, said Professor Pertwee.

Pertwee says that cannabis is rich in substances that can mimic the natural or endogenous cannabinoids in the brain, that act as chemical messengers in the nervous pathways, involved in such activities as appetite control or pain relief.

These endogenous cannabinoids seem to act on the reward pathways to the brain, to increase the reward you get when you take food, but can have harmful effects.

By increasing appetite they can increase fat, which can give rise to obesity or overweight.

Drugs are apparently now being developed that can increase the levels of these chemicals in our brains by slowing down the rate at which they disappear once they have been released,says Pertwee.

Professor Pertwee has also found a method of potentially boosting the signals in the brain that are generated by these endogenous cannabinoids.”

http://www.news-medical.net/news/2005/09/10/13067.aspx

Cannabis can help treat obesity

“Two cannabis compounds can raise the quantum of energy the body burns and keep obesity at bay. Called THCV and cannabidiol, they were found to have an appetite suppressing effect too for a short while.

Animal tests have shown these compounds can help treat type two diabetes while also lowering levels of cholesterol in the blood stream and fat in key organs like the liver.

Scientists also found the compounds also had an impact on the level of fat and its response to insulin, a hormone that controls blood sugar levels, the Telegraph reports.

THCV was also found to increase the animals’ sensitivity to insulin while also protecting the cells that produce insulin, allowing them to work better and for longer.

Steph Wright, director of research and development at GW Pharmaceuticals developing the drugs, said: “The results in animal models have been very encouraging. We are interested in how these drugs effect the fat distribution and utilisation in the body as a treatment for metabolic diseases”.”

http://in.news.yahoo.com/cannabis-help-treat-obesity-121931025.html

Marijuana May Deflect Obesity

   

“Cannabis seems to have many different allures. It can produce a “high.” It can give the feeling of munchies. Now, it can possibly help combat obesity. Scientists recently revealed that they found two compounds from cannabis leaves that could up the total energy that the body burns.

Previous studies of two specific compounds demonstrated that they could be used to treat type-two diabetes. The compounds were also discovered to have the ability to reduce cholesterol levels in the blood stream and decrease fat in important organs such as the liver. With the aim of treating patients who have “metabolic syndrome,” the researchers are currently conducting clinical trials in 200 patients with the drug. With “metabolic syndrome,” diabetes, high blood pressure, and obesity combine to heighten the risk of heart disease and stroke in patients.

We are conducting four Phase 2a clinical trials and we expect some results later this year,” commented Dr. Steph Wright, director of research and development at GW Pharmaceuticals, in a Telegraph article. “The results in animal models have been very encouraging. We are interested in how these drugs effect the fat distribution and utilization in the body as a treatment for metabolic diseases… Humans have been using these plants for thousands of years so we have quite a lot of experience of the chemicals in the plants.”

GW Pharmaceuticals was given a license to grow cannabis in greenhouses that were specially constructed for project. The company produces cannabis plants that have a number of cannabinoids, which are varied compounds of cannabis. They are already working on creating drugs that can assist in treating epilepsy and multiple sclerosis. Interesting enough, when the scientists studied two specific compounds, THCV and cannabioidol, they found that they had the ability to suppress appetite but the effect lasted for a short amount of time. Upon further examination, the investigators discovered that the compounds could influence the fat level in the body as well as its effects to the hormone insulin.

Likewise, the studies of the compounds in mice showed that they increased the metabolism of the animals, causing decreased levels of fat in livers and minimized levels of cholesterol in the blood stream. In particular, THCV showed the ability of boosting the animals’ sensitivity to insulin but also shielding the insulin-producing cells. With these actions, the cells were able to work at a longer and more durable pace.

The researchers hope that the findings will help in the development of treatments for obesity-related illnesses and type-two diabetes.”

http://www.redorbit.com/news/health/1112653330/research-finds-marijuana-may-deflect-obesity/
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