RESEARCH UPDATES from Americans for safe Access

Cancer Research Shows How Cannabinoids Fight Tumors

Brain Cancer. The effectiveness of cannabinoids in fighting glioblastoma multiforme (GBM), a form of brain cancer that is highly resistant to current treatments, has been demonstrated in numerous preclinical studies. New research shows that a combination of THC, CBD, and temozolomide (TMZ) "remarkably reduces the growth of glioma." The study revealed tumor growth is inhibited in part through "the stimulation of autophagy-mediated apoptosis," the biologic degradation of cells that leads to them dying off. The Spanish researchers conclude that "the combined administration of TMZ and cannabinoids could be therapeutically exploited for the management of GBM."

Torres S, et al. 2011. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther. 2011 Jan;10(1):90-103.

Oral Cancer. Medical researchers at the University of California report cannabinoids alleviate oral cancer pain and slow the spread of the disease both in vitro and in vivo. They also identified CB1 and CB2 cannabinoid receptors in human oral cancer cells. They suggest the endocannabinoid system may play "a direct role" in pain and proliferation. Noting proliferation of cancer cells was "significantly attenuated in a dose-dependent manner" by cannabinoids, they conclude "the systemic administration" of cannabinoids "may reduce morbidity and mortality of oral cancer."

Saghafi N, et al. 2011. Cannabinoids attenuate cancer pain and proliferation in a mouse model. Neurosci Lett. 488(3):247-51.

Gastric Cancer. Previous studies have shown cannabinoids significantly decrease the spread of gastric cancer tumors and kill off malignant cells. South Korean researchers have recently discovered some of the biologic mechanisms for those tumor-fighting properties. The new research on cellular mediators indicates cannabinoids play a role in halting cell cycles that cause the cancer to spread.

Park JM, et al. 2011. Antiproliferative mechanism of a cannabinoid agonist by cell cycle arrest in human gastric cancer cells. J Cell Biochem. Feb 10.

Cannabinoids Help MS Symptoms, Progression

Italian researchers used an animal model of multiple sclerosis to investigate the efficacy of cannabis extracts on motor symptoms. They found that treating with a THC-rich extract over time "resulted in a significant reduction of neurological deficits," that treatment with CBD affected only the relapse phase, and that combined THC-CBD treatment was ineffective. They suggest further investigation on each cannabinoid's action but conclude that cannabis extracts have potential for managing MS.

Another Italian research team reviewed studies on cannabinoid receptors in the lower urinary tract and their role in controlling urinary tract function, including the treatment of bladder dysfunction resulting from MS, finding that systemic cannabinoids may be clinically useful.
British scientists reviewing the clinical data on treating MS with cannabinoids note patient reports of symptomatic relief are confirmed by data showing cannabinoids improve muscle stiffness and spasms, neuropathic pain, and sleep and bladder disturbance. They note new evidence suggests that cannabinoids may affect "fundamental processes" in the progression of MS. They suggest "cannabinoids may have a longer term role in reducing disability and progression in MS."

Scientists who examined brain samples of deceased MS patients for CB1 and CB2 receptors, as well as an enzyme related to the synthesis of endocannabinoids, found differences in receptor concentration that correlated to MS damage. Their findings support animal studies that suggest the endocannabinoid system has a role in MS progression and cellular response to injuries from the disease.

Buccellato E, et al. 2011. Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis. J Ethnopharmacol. 133(3):1033-8.
Zajicek JP, Apostu VI. 2011. Role of cannabinoids in multiple sclerosis. CNS Drugs. 1;25(3):187-201.
Zhang H,et al. 2011. Cannabinoid Receptor and N-acyl Phosphatidylethanolamine Phospholipase D-Evidence for Altered Expression in Multiple Sclerosis. Brain Pathol.
Ruggieri MR Sr. 2011. Cannabinoids: potential targets for bladder dysfunction. Handb Exp Pharmacol. (202):425-51.

Studies Show Endocannabinoids Role in Anxiety Disorders

The anxiolytic, or anti-anxiety, properties of cannabis have been reported by sufferers of post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and others. Two new studies suggest that inhibiting the natural enzymes that break down endogenous cannabinoids may produce similar effects. Using a mouse model of obsessive compulsive behavior, they were able to show that increasing the natural cannabinoids by blocking the chemicals that degrade them decreased the behavior similar to THC but without the side effect of depressed motor activity. Similarly, Brazilian researchers published a review of the role of endocannabinoids in anxiety, noting that enhancement of endogenous cannabinoids avoids the dosage sensitivity to plant and synthetic cannabinoids such as THC, which frequently reduces anxiety in low doses but can trigger it in larger ones.

Kinsey SG, et al. 2011. Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay. Pharmacol Biochem Behav. 98(1):21-7.
Gomes FV, et al. 2010. Facilitation of CB1 receptor-mediated neurotransmission decreases marble burying behavior in mice. Prog Neuropsychopharmacol Biol Psychiatry.
Moreira FA, Wotjak CT. 2010. Cannabinoids and anxiety. Curr Top Behav Neurosci. 2:429-50.

Cannabinoids May Regulate Diabetes

Many people with diabetes turn to cannabis to treat their neuropathic pain. But recent research reveals that the endocannabinoid system is implicated in the regulation of insulin production and blood glucose. The majority of studies indicate that endocannabinoids in the pancreas decrease insulin secretion, but other studies have shown the opposite. As a Johns Hopkins researcher notes, "the exact nature of the effects of endocannabinoids on insulin secretion require rigorous study examining both acute and long-term effects at physiologically relevant doses employing both whole animal and clinically relevant models such as human islets in vitro and explanted in vivo, in rodent models of diabetes." What is clear is that the regulatory role of endocannabinoids in many of the body's most complex physiologic systems suggests a target for cannabinoid-based therapies.

Kim W, et al. 2011. Cannabinoids Inhibit Insulin Receptor Signaling in Pancreatic {beta}-Cells. Diabetes. Feb 23.
Doyle ME. 2011. The role of the endocannabinoid system in islet biology. Curr Opin Endocrinol Diabetes Obes. Feb 9.

Cannabinoids May Provide Treatment for Endometriosis

Scientists at Florida State University investigated the role of the endocannabinoid system in endometriosis, a disease common in women that is associated with severe pain and is difficult to treat. Using a rat model, they discovered CB1 cannabinoid receptors throughout the abnormal growths that characterize endometriosis. Blocking those CB1 receptors increased pain sensitivity, while stimulating them reduced it. They conclude that the endocannabinoid system plays a role in the development of the abnormal growths and pain associated with endometriosis, suggesting cannabinoids may provide "badly-needed new treatments."
Dmitrieva N,et al. 2010. Endocannabinoid involvement in endometriosis. Pain. Dec;151(3):703-10.

Cannabinoid Analgesic Action Studied

While the ability of cannabis and cannabinoids to control chronic pain is well known and amply demonstrated by a variety of historical, anecdotal, and clinical reports, the effect of different dosages, individual cannabinoids, and the mechanisms of action on different types of pain are still being investigated.
A review by German researchers notes that while "an increasing number of randomized, double-blind, placebo-controlled studies have shown the efficacy of cannabinoids" for treating chronic pain and painful spasticity, cannabinoids have not shown "convincing reduction of acute pain." Because patients who have problems adapting to stress and for whom other pain treatments have failed are the most likely to be helped by treatment with cannabinoids, they suggest exploring different modes of administration and new types of "endocannbinoid modulators."
Karst M, et al. 2010. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 70(18):2409-38.
The pain-control mechanisms for two non-psychoactive cannabinoids -- cannabidiol (CBD) and cannabichromene (CBC) -- have been demonstrated in an animal study conducted by Italian researchers. By monitoring the electrical activity of neurons in the brainstem, they found that both acted in a dose-dependent manner on the activity of proteins involved in a key pain pathway, though twice as much CBC as CBD was necessary to achieve maximum pain relief. Treating with CBC and CBD was also found to elevate endocannabinoid levels. The researchers conclude that "these compounds might represent useful therapeutic agents with multiple mechanisms of action."
Maione S, et al. 2011. Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. Br J Pharmacol. 162(3):584-96.

Cannabinoid Control of Nausea Explored

Researchers have recently revealed more about how cannabinoids control nausea. The anti-emetic properties of cannabis is one of its more well-established therapeutic uses, and is also one of the primary indications for prescribing marinol, the synthetic THC pill. A team of Canadian scientists using an animal study have now located an area of the brainstem that may be responsible for the effect. They also demonstrated that not just THC but CBD, the second most prevalent cannabinoid in the plant, has powerful anti-nausea effects within a limited dose range.

BMW Betting on Electric Lounge Car With Hemp Floor to Hold Off VW’s Audi

By Chris Reiter - Jul 29, 2011 8:38 AM ET

• Bayerische Motoren Werke AG (BMW) will give a new electric-powered city car a lounge feel with bench seats, naturally tanned “mocha brown” leather and hemp fibers in the floor covering to hold off Volkswagen AG (VOW)’s Audi.

BMW for the first time showed concept versions of the i3 electric city car and the i8 hybrid supercar, which Chief Executive Officer Norbert Reithofer said will cost more than 100,000 euros ($143,000), in Frankfurt today. The models, developed from scratch, will anchor BMW’s new “i” sub-brand.
“The majority of current electric vehicles are so-called conversions of traditional vehicles but conversions are always compromises,” development chief Klaus Draeger said. “We wanted to bring e-mobility to the streets without compromise.”
BMW is betting that the 530 million euros investment to set up production of the vehicles will pay off in the race with Audi, which overtook Daimler AG (DAI)’s Mercedes-Benz this year and has vowed to topple the Munich-based carmaker as the luxury-car leader by 2015. Initial volumes for the models could be in the “tens of thousands,” with the potential to grow rapidly depending on market and regulatory developments, sales chief Ian Robertson told Bloomberg TV.
“If the project is successful, it will give BMW an edge in innovation, which is a key attribute for premium car manufacturers,” said Ferdinand Dudenhoeffer, director of the Center for Automotive Research at the University of Duisberg- Essen. “It would be a difficult situation for Audi.”

Carbon Fiber

Both of BMW’s electric cars are built around a carbon-fiber frame and an aluminum underbody to lower weight and consequently reduce battery costs. Investments for the project include a new carbon-fiber factory in the U.S. and a 400 million-euro expansion of its factory in Leipzig, Germany. The i3 will go on sale in 2013, followed by the i8 in 2014.
The four-person city car, which has a range of about 150 kilometers (93 miles), features narrower tires to reduce road friction and a faster charging system that can reload the battery to 80 percent capacity in an hour. That compares with more than seven hours for standard electric-vehicle chargers. The front and rear doors also open away from each other.
The i8 plug-in hybrid combines an electric motor with a three-cylinder gasoline engine to accelerate to 100 kilometers per hour in 4.6 seconds, while getting more than 78 miles per gallon. It has a top speed of 250 kilometers per hour and can drive for up to 35 kilometers just on the energy stored in its lithium-ion power packs. Both cars have oversized windows on the doors.

Audi Offerings

Audi’s first electric-powered vehicle, the R8 e-tron sports car, will come to market at the end of next year as a limited production model, spokesman Armin Goetz said. Audi will test about 20 electric-drive A1 compacts in Munich later this year and is preparing for a similar project with the A3 in Shanghai.
Audi aims to roll out its first serial production plug-in hybrid at the end of 2013 or in early 2014, Goetz said.
BMW plans to offer versions with an on-board generator to extend the range and is considering other variants, sales chief Robertson said. The company will look to sell the vehicles using a mobile sales force and the Internet in addition to conventional dealers. The cars will be “relatively expensive” because of the large amount of technology in them, he said.

Sub-Brand Risks

BMW created the separate sub-brand, which will bear a BMW emblem with a blue ring around it, to market electric vehicles. The approach is in contrast to Audi and Mercedes-Benz, which plans to integrate electric vehicles into their overall lineups. The risk for BMW is the main brand’s image of fuel-burning models could suffer by pushing the sub-brand too much, said Christoph Stuermer, a Frankfurt-based IHS Automotive analyst.
“With a sub-brand, BMW risks creating a floating island around the mainstream products, but they’re not going to make money on that technology unless they bring it into the mainstream products,” Stuermer said. “The challenge will be to spread that technology, while maintaining the integrity of the core brand.”
BMW will use some of the technology in the electric cars in other models and the electric offerings will “support” BMW’s target to generate a return on sales of 8 percent to 10 percent, Chief Financial Officer Friedrich Eichiner said today.
To contact the reporter on this story: Chris Reiter in Berlin at creiter2@bloomberg.net
To contact the editor responsible for this story: Chad Thomas at cthomas16@bloomberg.net

Natural Foods Retailer Nutiva Challenges DEA, Embraces Hemp

By Greg T. Spielberg - Mar 3, 2011 4:01 PM ET

Nutiva founder John Roulac poses in a hemp field in Southern Alberta, Canada. Source: Nutiva via Bloomberg

In August 1999, the U.S. Customs Service -- acting on a Drug Enforcement Administration order -- seized a Canadian hemp-food exporter’s truck with 20 tons of hemp seeds entering Detroit from Ontario. The nongerminating seeds, en route to U.S. natural food businesses, have always been legal to import, though illegal to grow without a DEA permit since the Controlled Substances Act of 1970. In addition to the truck seizure, the agency, which declines to comment on its then unprecedented move, ordered the exporter’s American customers to fork over previous orders of seed and other hemp-food products.
The demand put Sebastopol (Calif.) hemp-food retailer Nutiva in a tough spot. Founder John Roulac had launched the business earlier that month, investing $30,000 in two tons of seed and other hemp-food products with the goal of turning the legal, nonpyschoactive plant often confused with its illegal twin brother, marijuana, into a mainstream food product.
Confident the seizure was bogus, Roulac, a buoyant serial entrepreneur and bestselling author of such manuals as “Backyard Composting,” refused to capitulate. Instead of handing his hemp to the DEA, he helped launch a public relations campaign with all 200 members of the trade group Hemp Industries Assn. to turn popular opinion against the DEA’s move.

BAN IT, PERMIT IT, REPEAT

Over the next month, they tapped friends and customers to call the customs officers’ desk line and persuaded Pulitzer-winning newspaper columnist Jack Anderson to pen a syndicated piece lambasting the DEA. The move didn’t cost Roulac a dime. By the fall of 1999, newspapers in the U.S. and Canada quoted an unnamed DEA officer saying the agency would permit hemp exports into the States. In March 2000, the U.S. Justice Dept. issued a statement essentially saying the DEA couldn’t stop hemp-food imports.
Despite the statement, frustration reigned among hemp sellers and buyers for the next two years as the DEA’s stance on importing hemp switched six times, from banning it to permitting it and back again. Then, a few weeks after 9/11, the DEA published a rule that banned hemp-food imports and sales. Nutiva and 10 HIA members sued the DEA and won two consecutive cases -- the final one in early 2004. “I think the court recognized the law was clear, and there was no risk to public health or safety involved here,” says Joe Sandler, the trade group’s lawyer.
Roulac’s company gained traction shortly thereafter, reaching $2.7 million in revenue in 2005. At the time, it was one of roughly six companies in the U.S. selling hemp seed, protein powders, shakes, and energy bars to food stores and individuals. (Roulac, seeking to diversify, was also exploring other natural products, such as coconut oil and chia, a protein-rich Latin American seed.) Nutiva got another boost in 2008 when RSF Social Finance, a foundation in San Francisco that supports social entrepreneurs, began to extend credit lines worth $1.2 million, which Roulac used to increase inventory and, last year, move into a new warehouse six times larger than its previous space. Ted Levinson, a senior lending manager at RSF, says Roulac’s track record in increasing mainstream consumer awareness about natural food products impressed him. “John has a habit of being on the very early end of these things … and ultimately capturing the attention of millions of people,” Levinson says.

FOUNDING FATHERS GREW IT

The American hemp-food market is growing quickly, according to natural food market analyst SPINS, which pegged it at around $40 million in 2010 (not including sales at Whole Foods), up 10 percent from 2009, and reports that Nutiva leads its 26 U.S. competitors in hemp oil and seed sales. Errol Schweizer, Whole Foods’ global senior grocery coordinator, says hemp is “one of the fastest-growing [natural food] trends.” Nutiva had $12 million in revenue in 2010, Roulac says, and he projects $24 million this year for the 25-employee company. “You don’t have to be mainstream to do well,” says Harry Balzer, chief food analyst at market research firm NPD Group, adding that shoppers will have to view hemp as more than a novelty for the ingredient to gain significance in the $1 trillion U.S. food and drink market.
American presidents George Washington and Thomas Jefferson grew hemp, and Virginia required all landowners to do the same. During World War II, the federal government spent more than $1 million to subsidize hemp farming in Illinois, Indiana, Iowa, Kentucky, Minnesota, and Wisconsin to produce fibers for rope and uniforms. In 1943, some 146,000 acres were harvested, according to hemp historian John Dvorak. No farmers in the U.S. grow hemp commercially today -- the last was in Wisconsin in 1957. “I don’t know if the stigma will ever go away with hemp; if people will ever understand it’s not a THC product,” says Anna Soref, editor-in-chief of trade publication Natural Foods Merchandiser.
That’s one reason Roulac is glad he diversified into coconut and chia. Coconut oil now drives 60 percent of Nutiva’s sales, and Roulac recently bought more than 200 tons of chia seed. Still, hemp is Roulac’s first love, and despite lower profit margins and a tough supply chain, he has no plans to forsake it.
Neither, it seems, do policymakers. In mid-February, California’s Mark Leno, a Democratic state senator, introduced a bill that would once again allow commercial hemp farming -- a bill he plans to have on the governor’s desk by the end of August. “I have not yet spoken to the governor, but I am hopeful that he would understand the benefits California would experience allowing our farmers to grow industrial hemp,” Leno says. “It’s a safe, viable crop.” Roulac looks forward to when he can source hemp domestically and take advantage of lower production and transportation costs. Of course, that likely means more competition for Nutiva. “Bring it on,” he says with characteristic enthusiasm.
To contact the reporter on this story: Greg T. Spielberg at gregtspielberg@gmail.com
To contact the editor responsible for this story: Nick Leiber at nleiber@bloomberg.net