Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.

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Cell Death Dis.

2013 Dec 5;4:e949.

doi: 10.1038/cddis.2013.471.

Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.

Rimmerman N, Ben-Hail D, Porat Z, Juknat A, Kozela E, Daniels MP, Connelly PS, Leishman E, Bradshaw HB, Shoshan-Barmatz V, Vogel Z. Source The Dr. Miriam and Sheldon G Adelson Center for the Biology of Addictive Diseases, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell proliferation and induces cell death of cancer cells and activated immune cells. It is not an agonist of the classical CB1/CB2 cannabinoid receptors and the mechanism by which it functions is unknown. Here, we studied the effects of CBD on various mitochondrial functions in BV-2 microglial cells. Our findings indicate that CBD treatment leads to a biphasic increase in intracellular calcium levels and to changes in mitochondrial function and morphology leading to cell death. Density gradient fractionation analysis by mass spectrometry and western blotting showed colocalization of CBD with protein markers of mitochondria. Single-channel recordings of the outer-mitochondrial membrane protein, the voltage-dependent anion channel 1 (VDAC1) functioning in cell energy, metabolic homeostasis and apoptosis revealed that CBD markedly decreases channel conductance. Finally, using microscale thermophoresis, we showed a direct interaction between purified fluorescently labeled VDAC1 and CBD. Thus, VDAC1 seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD. PMID:

24309936

[PubMed – in process]

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Wilson Family Leaving State After Fight For Marijuana For Toddler Comes Up Empty #MedicalMarijuana #Kids #Dravet #Seizures

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The Wilson family has made headlines for seeking medical marijuana for two-year-old Vivian who suffers from Dravet syndrome, a rare form of epilepsy that causes her violent and frequent seizures. Photo: Courtesy of Meghan Wilson

Wilson Family Leaving State After Fight For Marijuana For Toddler Comes Up Empty

 

After a long fight to loosen the state’s medical marijuana laws, the Wilson family of Scotch Plains say change is not happening quickly enough to treat their two-year-old daughter Vivian. The family has officially decided to move to Denver, Colorado, where they can more easily obtain the strains of marijuana that have proven effective in treating Dravet syndrome, a rare form of epilepsy that causes Vivian to suffer frequent and violent seizures.

The Wilsons have been at the center of a fight that came to a head in August, when Gov. Christie visited Scotch Plains on a campaign stop and Brian Wilson confronted him, urging “Please don’t let my daughter die.” 

The following week, Christie gave conditional approval to a law that eliminates a three-strain limit on dispensaries and allows edible marijuana products for children. 

Though the Wilsons were able to purchase medical marijuana from the Compassionate Care Foundation clinic in Egg Harbor Township recently, which they reduced to an oil so Vivian could ingest it, they were unable to get the oil tested to determine its strength and how to dose it to Vivian. Also, the strain was not high in CBD (cannabidols) – the non-psychoactive compound in the plant that has proven effective in treating Dravet syndrome, according to the Wilsons.

“They were calling it their CBD strain, but the label showed it had more THC than CBD and both levels were really low. Real CBD strains are hard to come by,” Meghan Wilson told Patch on Saturday. “Aside from one dose, we never used the product from CCF. We didn’t feel comfortable, and our gut was telling us not to give it to her.”

The Wilsons had then hoped a new bill introduced by Assemblywoman and former Fanwood Mayor Linda Stender might be the fix for a shortage of CBD strains here: It would allow for reciprocity of marijuana laws so that patients in New Jersey could order their treatments from out-of-state. 

Christie shot down the bill at a press conference earlier this month, saying, “I am done expanding the medical marijuana program under any circumstances. … And the program works fine for people who are truly ill.”

“I think a big turning point for us moving was the reciprocity bill,” Wilson told Patch. “And then the same day Gov. Christie said ‘I’m done moving this forward,’ a 15-month-old baby with Dravet died – Sabina Joana, whose parents had just gone through the whole process to get her card. We realized nothing is going to get better for as long as Christie is in office. This is Vivian’s life. We can’t wait anymore.”

The Joana family, from Hopatcong, has also taken up the fight,vowing to turn their grief into action and confront the Governor.

The Wilsons did get a bit of good news, though, since deciding to move. Magical Butter, a company that makes machines to turn marijuana into butters and oils, has donated $10,000 toward their moving expenses. Check out Magical Butter’s YouTube video of the family receiving the news on Christmas.

“We were shocked and thrilled,” said Wilson. “It is such a generous donation that will help tremendously. The cost of moving is huge.”

The Wilsons say though moving has become a necessity, it pains them to leave behind their families in New Jersey. 

“It’s heartbreaking,” said Meghan Wilson. “At this point, it’s a matter of let’s put our emotions aside and make this happen. We’re hoping we will only be out there for a couple years. In two years, the climate federally could be different, there could be special access laws for patients where they would be able to travel across state lines. And there are worse places to move. We’re glad Charlotte’s Web [a high-CBD strain named for a girl with Dravet] is in Denver.”

Still, the Wilsons worry about all the New Jersey patients who can’t move. 

“What would Christie do if this was his child?,” Meghan Wilson says. “He has no respect for this program, no respect for the fact that the plant has healing qualities. He’s doing everyone in the state a disservice and it’s a shame. Things are changing, views on marijuana are changing. One day he’ll get it, or one day he or someone he loves will be stricken with an illness marijuana can treat. Maybe then he will feel some remorse for the way he’s treated our family.”

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Can a tech startup change the way people think about medical marijuana?

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By November 27, 2013 2:34 PM

A California businessman says he has invented a new way of consuming marijuana that could change people’s attitudes and habits when it comes to the increasingly popular herb.

The pro-pot movement has made leaps and bounds in recent years. An October Gallup Poll for the first time found a majority of American voters favoring legalization of marijuana. Even former Microsoft executive Jamen Shively recently announced he wants to get into the medical marijuana business.

Still, not everyone is convinced.

The world of weed, including medical marijuana, remains largely shrouded in mystery. Even potential medical cannabis patients say they are denied potential health benefits, because their health conditions prevent them from ingesting or smoking it.

But what if there was a way to use medical marijuana without the negative physical side effects of smoking?

“I like to think of myself as a progressive person that’s always trying to become a better businessperson,” VapeXhale CEO Seibo Shen told Yahoo News in a recent interview.

Shen says a sign outside the University of San Francisco campus, which reads, “Become wildly successful without becoming a jerk no one likes,” has inspired him in his new business venture.

It’s become a mantra for the startup veteran and family man who decided to combine his experience in the tech world with the rapidly growing medical marijuana industry.

“I’ve always been into technology and health,” he said. “I wanted to create something that not only functioned the best but also has a health benefit.”

In December 2012, SF New Tech held its monthly showcase for emerging technological innovations. The offerings included a device to take pictures from space and even a brain-operated helicopter.

But perhaps the strangest entry was from Shen, an unassuming entrepreneur who entered his new invention, the VapeXhale Cloud, into the competition. And perhaps even more surprising, he won.

Technically, vaporizers have been around for years. They work by extracting the active ingredients from herbal materials, including cannabis. A number of scientific studies have found they offer a healthier alternative to combusting plant material, eliminating the vast majority of harmful material, such as tar and carcinogens, normally inhaled by a user.

“In our field of pain medicine, we are always looking for different, simpler and more easily tolerated routes of medication delivery,” Dr. Michael D. Halperin of Interventional Pain Management said. “Although standardization of dosing is a necessity, the simplicity of use, the portability and reliability of newer vaporizers is a step further toward the goal of rapid, targeted medication delivery through inhalation, which, in many ways, acts in much the same way as the administration of volatilized general anesthetics in common use.”

But Shen told Yahoo that his product is different, using new technology to create an even cleaner process for users. He also placed an emphasis on making the device user-friendly, discarding the rubber tubing and plastic bags traditionally used for inhalation in favor of high-quality glass.

In basic terms, Shen’s vaporizer combines the conductive (hot plate) and convective (hot air, converts solid to gas) methods of vaporizers into a single unit, maximizing the device’s ability to filter out tar and carcinogens.

Along with the SF New Tech event, the VapeXhale has swept every major medical marijuana competition in the U.S., winning the Seattle Medical Cannabis Cup in September 2012 and the High Times Medical Cupin February 2013.

After the SF New Tech competition, Shen launched a fundraising page for VapeXhale, hoping to raise $50,000 toward launching a commercial line of his vaporizers. He ended up raising more than $140,000.

He’s sold thousands of VapeXhale units already, but he says he’s more concerned with changing people’s habits when it comes to medical cannabis.

After all, Shen says, as a lifelong athlete, he has abstained from drinking and quit smoking once he realized how it was affecting his ability to perform in competitions.

Shen told one powerful anecdote about a VapeXhale user who recently had a physical for a life insurance policy. Although the individual uses medical cannabis on a daily basis, his insurance provider allowed him to designate himself as a “nonsmoker” because he uses his vaporizer only to consume the product.

“That gave me a lot of confidence,” Shen said. “Using data from someone who had been consuming for a decade. His lungs were not only healthy but above average.”

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Medical Marijuana Use up 30% in Israel

 

 

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Medical Marijuana Use up 30% in Israel

Pharmaceutical companies are being accused of trying to curb medicinal cannabis use in the country
By: Graham Sigurdson
Published: November 29th, 2013 in Health » Israel
Marijuana

According to figures released by the Israeli Health Ministry, an increase of 30 percent occurred in the number of patients that had been approved to use cannabis legally, rising to 13,000 in 2013, from 10,000 in 2012.

On Thursday morning, via Israel Radio, MK Haim Katz of the Labor party said that pharmaceutical companies that were “driven by economic interests” have been working to restrict the granting of medical marijuana permits due to it cutting into their profits.

A recent study, however, suggests legalizing medicinal marijuana will result in significant financial gains for Israel.

Katz is the current chair of the Knesset Labor, Welfare and Health committee.

Though widely considered one of the world’s most advanced countries when it comes to the use of medicinal cannabis, the Israeli government has continued to tread cautiously, despite even a rabbi’s claim that marijuana is kosher.

2009 saw a decision made to establish a separate government authority that would oversee the production and securing of cannabis. Despite this, a decision has yet to be implemented, which has left the issue in the Health Ministry’s hands. In May, Health Minister Yael German said during a Knesset hearing made the claim that “people who are helped by cannabis should be able to receive it.”

Work towards a formal proposal to regulate medical marijuana is underway by the Health, Agriculture and Public Security ministries.

As noted last Thursday by Israel Radio, the ministries are expected to present a plan within the next two weeks.

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Medical marijuana: More states legalizing, but scientific evidence lacking

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Medical marijuana: More states legalizing, but scientific evidence lacking

Medical marijuana has been gaining support among states and doctors, but one pot researcher points out much remains unknown scientifically about what medical conditions the drug can actually help.

Dr. Margaret Haney is the director of the Marijuana Research Laboratory at Columbia University in New York. Her lab is one of a handful that receives government funding for studies on marijuana, including research on potential therapeutic uses of the drug.

“I have no trouble finding volunteers,” she joked to CBS News’ Kera Rennert.

But these studies are crucial, Haney points out, because carefully controlled studies on marijuana’s effects are lacking. When a new drug gets approved by the Food and Drug Administration, researchers have to demonstrate in series of studies that the drug outperforms a placebo pill to cause a therapeutic effect. This is not the case for marijuana in its plant form.

“The testing is critical, because marijuana is the only medication that’s been voted in as a medication, where we have very established procedures for determining whether something is a medication,” she explained.

Marijuana contains about 60 chemical components called cannabinoids. The most well known and well-studied is delta-9-tetrahydrocannabinol, or THC, which is behind the drug’s “stoned” effect.

Scientists like Haney are starting to isolate those other compounds to see what effects they have. But the lack of research hasn’t stopped states from moving forward with legalization.

Medical marijuana is legalized in 20 states in addition to the District of Columbia: Alaska, Arizona, California, Colorado, Connecticut, Delaware, Hawaii, Illinois, Maine, Massachusetts, Michigan, Montana, Nevada, New Hampshire, New Jersey, New Mexico, Oregon, Rhode Island, Vermont and Washington. Other states are considering legislation.

The medical community also appears to be increasing acceptance. A survey in the New England Journal of Medicine last March found 76 percent of doctors were in favor of the use of medical marijuana when presented with a hypothetical case of a patient with breast cancer that’s spread and caused pain.

Dr. Sanjay Gupta publicly reversed course and came out in support of medical marijuana, and even apologized for being too dismissive of patients’ reports of symptoms improving.

While medical marijuana is approved in some states for conditions including epilepsy, inflammatory bowel disease multiple sclerosis and chronic pain, the scientific evidence has yet to catch up. Haney notes there is solid evidence marijuana can decrease nausea and increase food intake in people with HIV or cancer who are getting chemotherapy. This has also been shown with the pill form of THC, dronabinol.

One experiment suggests one cannabinoid called cannabidiol, when isolated in high levels, might treat neuropathic pain in mice, a type of chronic pain that can be caused by HIV and chemotherapy.

Research is also being done at other ways to isolate and deliver cannabinoids to patients, since smoking can be a respiratory irritant. Researchers have beentesting a marijuana mouth spray Sativex that contains delta 9-THC and cannabidiol. It’s currently approved in some European countries.

Such rigorous trials are necessary, Haney emphasized, to better understand how marijuana might treat medical conditions, if at all. Her tests include having people smoke real marijuana or a placebo so she can disseminate what the drug actually does for appetite, pain or withdrawal from what people think it will do.

But since this research is very much ongoing, she warns people should not believe marijuana is a cure-all as some rent-a-doctors in states with legalization may suggest.

“Just like you’re skeptical of a pharmaceutical industry and what they say a drug does, you have to be just as skeptical about what marijuana does, because people are making enormous profit from it,” said Haney. “That is again why we need carefully controlled studies to demonstrate what it works for and what it doesn’t work for.

  • Ryan Jaslow

    Ryan Jaslow is CBSNews.com’s health editor.

Click here for the original article.

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Medical marijuana provides ‘miraculous’ results for 6-year-old California boy with rare form of epilepsy

 

 

Medical marijuana provides ‘miraculous’ results for 6-year-old California boy with rare form of epilepsy that prevented him from walking, sleeping and eating

  • Jayden David suffers from a rare form of epilepsy called Dravet Syndrome
  • At one point, he was taking 22 different pills a day to treat the disease, none of which worked
  • Since he started using medical marijuana, Jayden started walking and living a much more normal life

By DAILY MAIL REPORTER

When he was just a baby, 6-year-old Jayden David was diagnosed with a rare form of epilepsy called Dravet Syndrome, which causes him to have violent seizures several times a day.

The seizures were so bad that they prevented the Modesto, California boy from walking, playing with friends and essentially living a normal life – he’s been rushed to the hospital by ambulance at least 40 times.

To combat the disease, Jayden was prescribed 12 different medications that he has to take every day. In all, the boy takes 22 pills a day.

Miracle: Before 6-year-old Jayden David started treating his epilepsy with marijuana, he couldn't even walk up stairs

Miracle: Before 6-year-old Jayden David started treating his epilepsy with marijuana, he couldn’t even walk up stairs

‘At one point Jayden had seizures 24 hours a day lasting an hour and a half,’ Jayden’s father, Jason David, told KCRA. ‘I went to my doctor and said, “I don’t think Jayden is going to last, he can’t sleep, can’t eat, he hasn’t used the restroom, he can’t do anything.”’

At one point, the debilitating disease got so bad for his son that Jason said he considered killing himself.

As a last resort, Jason David opted to try a liquid form of marijuana to treat Jayden’s seizures. And it worked.

‘(The) first day I gave him medical marijuana, thank God. (It was) the first day he went seizure free in his life,’ Jason David said.

Jayden's father, Jason, said he considered suicide because he was so distraught over his son's rare condition

Jayden’s father, Jason, said he considered suicide because he was so distraught over his son’s rare condition

The marijuana used to treat Jayden’s seizures contains a component called CBD (cannabidiol) that provides the same medical qualities as normal marijuana, but with less of a high.

Jayden has been getting a few drops of the CBD a day for the last two years, And his father says the results have been nothing short of remarkable – he plays, he can walk up and down stairs and he even gives his dad high-fives.

The pediatrician who prescribes the boy with the medical marijuana said he’s seeing a spike in children with autism and seizures benefitting from medical marijuana. In many cases, it works when other medications fail.

Prescription pot: Jayden's pediatrician says he's seeing a spike in parents opting to treat epileptic or autistic children with marijuana

Prescription pot: Jayden’s pediatrician says he’s seeing a spike in parents opting to treat epileptic or autistic children with marijuana

Jason says he wants to share his story to encourage other parents in similar situations to do what they think is best for their children – even if that means using medical marijuana.

Jayden’s paediatrician admits that there haven’t been many studies conducted to determine the medicinal benefits of marijuana, which is why doctors have differing opinions about whether it should be used to treat certain diseases.

Currently, however, researchers at the University of California-San Francisco currently are studying the affects CBD has on epileptic children.

Jayden and his father will be featured in a CNN special by Dr. Sanjay Gupta that examines the benefits of medical marijuana. Gupta wrote a column earlier this week saying that after doing research for the special, he now supports using medical marijuana to treat various illnesses. He previously opposed medical marijuana.

The special is set to air Sunday.

Flip-flop: Dr Sanjay Gupta now supports medical marijuana after opposing it for years

Flip-flop: Dr Sanjay Gupta now supports medical marijuana after opposing it for years

 

The Healing Power of Marijuana Has Barely Been Tapped

 

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The Healing Power of Marijuana Has Barely Been Tapped

Medical marijuana is now legal in 18 states, but it’s clear we’ve discovered a fraction of its potential for health. Continued from previous page Currently, science increasingly recognizes the role that cannabinoids play in almost every major life function in the human body.

It wasn’t until 1990 that endocannabinoids, produced by the human body, were discovered to act as a bio-regulatory mechanism for most human life processes and have receptors sites throughout the human body. CB2 receptors are found almost exclusively in the immune system, with the greatest density in the spleen. These CB2 receptors appear to be responsible for the anti-inflammatory and other newly recognized and very significant therapeutic effects of cannabis.

Cannabis medicine has distinct advantages. CBD, as well as THC, can be given in massive doses with no side effects. In fact, it has performed very effectively as an anti-psychotic when given in high doses.

CBD selectively targets and destroys tumor cells while leaving normal healthy cells unmolested.  On the other hand, chemotherapy and radiation are highly toxic and indiscriminately injure healthy cells in the brain and the body.

Industrial hemp is often high in healing CBD and very low in THC. Hemp CBD is a waste product — it’s thrown out by the ton every year when it could easily be harvested for tumor shrinking.

Medical cannabis farm Tikun Olam in Israel has been developing a strain of cannabis that is high in CBD (15.8%) but very low in THC (1%). This new strain is called Avidekel and seems to have the highest CBD to THC ratio of any other variant strain. Zack Klein of Tikun Olam told Reuters: “Sometimes the high is not always what is needed. Sometimes it is an unwanted side effect. For some of the people it’s not even pleasant.” The THC industry and its users worry that once CBD medicine grows in popularity, the medical badge might be torn from the sticky buds that makes being “stoned” possible.

Aside from THC’s significant medical benefits, surely its ability to make people feel happier and less stressed should not be considered without therapeutic value. More likely, all options will thrive, and 1,000 cannabis flowers will blossom: Indica, Sativa, CBD + THC, CBD Only, etc. Meanwhile, it’s useful to note that since 2003, the U.S. federal government has held a “medical patent” for the marketing of cannabinoids as antioxidants or neuroprotective agents. The patent states that cannabinoids are “useful in the treatment and prophylaxis of wide variety of oxidation associated diseases such as inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia.”

However, stoners may have it all wrong, medically speaking. It is unlikely a person can get a sufficient level of cannabidiol (pronounced kan-nəbə-dī’-ˌȯl) from smoking the raw plant to impact diseases like cancer in a curative manner, says Desprez. The marijuana plant offers many uses, but it may come as a surprise to most users that you have to choose early in a plant’s life if you want it to make you high or to heal you.

Research suggests that cannabis is most beneficial when the whole spectrum of cannabinoids are represented, including some THC. It is the ratio of cannabinoids in a specific strain of cannabis that most determines its therapeutic potential. Juicing the cannabis leaves raw, along with some carrots or other green veggies, has proven very beneficial as it involves the ingestion of the acid form of cannabinoids, which are non-psychoactive (even the THC). Cannabis oil also has enthusiastic fans who claim it has cured their cancers.

In India there are still large numbers of people who partake in an ancient practice of having a fresh raw cannabis drink called “Thandai” in which fresh cannabis leaves are made into a paste along with almonds, milk and sugar. This tasty drink is often consumed at religious festivals, and in some cities the government maintains distribution points for cannabis. A rolled sweet ball with similar ingredients is called “Bhang,” familiar for over a century to many Western seekers walking the ghats of sacred Banaras. Cannabis edibles in the West are emerging as one of the fastest growing new sectors of the food industry. Dispensaries in 18 states offer such goodies as ice cream, cough drops, peanut butter, honey, saliva tea, and myriad baked goods and savory snacks–all dosed with THC. Given the huge potential market for non-psychoactive cannabis, the introduction of CBD-rich medicine at the dispensary level has been surprisingly sluggish.

Owners have been reluctant to stock CBD-rich strains or edibles because their present customers are seeking —or are not adverse to— cannabis that provides euphoria or sedation. THC content is a known seller. Once the medical benefits of non-psychoactive cannabis become more widely known, one can only imagine the variety and volume of CBD-rich foods that will rush to market. Smoking, as opposed to vaporization, may be the least effective method of using cannabis as a medicine.

But many raw cannabis users are convinced that CBD is the source of medical miracles. Restrictions on research have impacted the accuracy with which we can prescribe cannabis and determine the most effective and least harmful ways to utilize its benefits. Perhaps in the very near future, instead of smoking cannabis to reduce nausea from chemotherapy, cancer patients will be consuming raw non-psychoactive cannabis, and be healed without having to suffer the additional damage of radiation and chemotherapy at all.

 

Allan Badiner is a writer, activist, and editor of three books: Dharma Gaia: A Harvest of Essays in Buddhism and Ecology, Zig Zag Zen: Buddhism and Psychedelics, and Mindfulness in the Marketplace: Compassionate Responses to Consumerism.

 

 

 

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