Cannabis Revolution: an Exploration of Hemp and CBD by Josh Long Cannabis Revolution: an Exploration of Hemp and CBD by Josh Long

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December 2014 US$39.00

SPECIAL REPORT Cannabis Revolution: An Exploration of Hemp and CBD by Josh Long Cannabis Revolution: An Exploration of Hemp and CBD by Josh Long

n October 10, during SupplySide West 2014 in Las Vegas, Informa OExhibitions LLC hosted the Agricultural Hemp Summit: CBD and the Hemp Revolution. The summit drew nearly 160 attendees and was underwritten by CannaVest Corp., a distributor of hemp- and cannabidiol-based products. CannaVest executives joined medical and science experts to share key developments affecting an American crop that dates back to English settlers. The experts also reviewed the burgeoning market for CBD, a cannabis compound whose purported health benefits are promising, but still undergoing clinical research. Hemp: An American Legend Hemp derives from Cannabis sativa L., a plant that is indigenous to Central Asia, Pakistan, China and the Kashmir region of India, according to Chris Boucher, CannaVest’s vice president of product development. Boucher, who has been championing the hemp industry for 25 years, explained that hemp is one of Earth’s oldest vegetable and fiber plants, dating back to the Neolithic period more than 12,000 years ago. Cultivated for its fiber, oil and seed, hemp is used in more than 25,000 products, according to the North American Industrial Hemp Council. Unlike its brother marijuana, hemp produces very little of the psychoactive substance known as THC, or tetrahydrocannabidinol. The crop played a part in the exploration of the New World well before English settlers began growing hemp in the 1600s. “Christopher Columbus’ ships were fully rigged in hemp,” the website, truthabouthemp.org, declares. For four centuries, Boucher noted, hemp sails, ropes and oakum powered ships that crossed the ocean. American hemp farming was born in Jamestown, Virginia, and the Massachusetts Pilgrims were required by law to grow the crop. Two centuries later, Thomas Jefferson—the draftsman of the Declaration of Independence— received a patent for breaking hemp stalks into fibers. “Hemp is of first necessity to the wealth and protection of the country,” Jefferson famously said. In the early 20th Century, the Marijuana Tax Act of 1937 placed a tax on cannabis affecting hemp. But just a few years later, during World War II, USDA called on farmers to grow hundreds of thousands of acres, according to the organization Vote Hemp. U.S. military forces had relied on hemp from the Philippines for such

NATURAL PRODUCTS INSIDER • CANNABIS REVOLUTION 2 naturalproductsinsider.com products as canvas, uniforms and rope—until their supply was cut off after the Philippines fell to Japan. The event triggered a “Hemp for Victory” campaign in the United States, hemp advisor David West explained in a report for the North American Industrial Hemp Council. A 1942 short film (“Hemp for Victory”) released by USDA (and available on YouTube) touts the history of hemp, declaring “Hemp for Victory” at the end while depicting U.S. warships at sea. The last commercial hemp fields were planted in Wisconsin in 1957, according to West. Federal drug laws and policies such as the Controlled Substances Act in 1970 led to a halt in the planting of American hemp for decades—until now. Farm Bill Congress this year gave American farmers the right to plant hemp for limited purposes: research and development. Section 7606 of the 2014 Farm Bill authorizes institutions of higher education or state agriculture departments to study the growth, cultivation or marketing of industrial hemp in states that permit such activity. CannaVest chief executive Michael Mona, Jr., and others in the hemp industry are hopeful that the legislation will pave the way for federal legalization of hemp cultivation for commercial purposes in the United States. CannaVest presently sources its hemp from Europe. “It was the first time since World War II that there was federal legislation legalizing industrial hemp,” Boucher told the hemp summit audience. The Farm Bill defines industrial hemp as “the plant Cannabis sativa L. and any part of such plant, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis.” Joshua Hartsel, CannaVest’s director of research and development, explained that Canada and most of Europe set 0.3 percent THC as the limit for legal hemp.

Several universities in Kentucky have begun to experiment with the growth of hemp under the Farm Bill. A number of other states also have legalized hemp, including:

California Colorado Hawaii Indiana Maine Montana Nebraska

North Dakota Oregon Utah Vermont Washington West Virginia

Source: Vote Hemp

NATURAL PRODUCTS INSIDER • CANNABIS REVOLUTION 3 naturalproductsinsider.com American farmers are exploring what varieties grow well in the United States. It hasn’t been all smooth sailing since the Farm Bill took effect. The Drug Enforcement Administration (DEA) seized Italian hemp seeds that had been delivered to Kentucky, then later agreed to release them after the state agriculture department filed a lawsuit. Boucher said most state agriculture departments will obtain the licenses to grow hemp and issue them to farmers. He noted authorities conduct background checks and request GPS coordinates of the hemp fields. Boucher is hopeful that USDA will eventually exert oversight over licensing agricultural hemp. “It’s sweeping the country,” Boucher said of the hemp movement. “You cannot stop something like this. This goes back to rural America. This goes back to our roots. It goes back to our economy.” Cannabis Sativa: Relationship to Human Body Cannabis sativa L. contains an astonishing 525 natural compounds, including 86 so-called cannabinoids, according to Alexandros Makriyannis, the director of the Center for Drug Discovery at Northeastern University. Two well-known cannabinoids are THC—the It was Sanjay Gupta, the substance in marijuana that causes psychotropic effects—and CBD, American neurosurgeon which is found abundantly in hemp and affects a signaling system in and chief medical humans that had not been discovered until the late 20th century. correspondent for CNN, Endocannabinoids are local hormones produced by the human who brought CBD to body, while phytocannabinoids such as CBD and THC are plant molecules that act like endocannabinoids, said Joseph Maroon, a the nation’s attention neurosurgeon, professor and vice chairman of the Department of last year. He reported on Neurological Surgery and Heindl Scholar in Neuroscience at the Charlotte Figi, a little girl University of Pittsburgh Medical Center. in Colorado who suffered Cannabinoid receptors are found throughout the body, with a never-ending seizures large concentration of CB1 receptors in the brain. CBD, a non- psychoactive ingredient, works through these receptors. and was diagnosed with “Keep in mind, for example, the cannabinoid receptors that are Dravet Syndrome, a rare in the brain are the most numerous receptors in the human body,” form of epilepsy that can said Makriyannis, a Northeastern University professor and Behrakis cause developmental Trustee Chair in Pharmaceutical Biotechnology. disabilities. He said CB2 receptors are present in the brain in small amounts, but they proliferate when a person suffers inflammation or a degenerative condition, such as cancer, or Alzheimer’s or Huntington’s diseases.

Promising Health Effects of CBD Research has shown CBD may be effective in producing a number of health benefits, from relieving seizures to reducing inflammation.

NATURAL PRODUCTS INSIDER • CANNABIS REVOLUTION 4 naturalproductsinsider.com If you look at the pathways through which CBD acts, they are the same pathways as Celebrex, ibuprofen, [and] all of the billion-dollar-a-year agents that are used for inflammation,” said Maroon, the Pittsburgh Steelers’ neurosurgeon and a triathlete who scaled Mount Kilimanjaro earlier this year with a group of amputees. It was Sanjay Gupta, the American neurosurgeon and chief medical correspondent for CNN, who brought CBD to the nation’s attention last year. He reported on Charlotte Figi, a little girl in Colorado who suffered never-ending seizures and was diagnosed with Dravet Syndrome, a rare form of epilepsy that can cause developmental disabilities. Her parents, Matt and Paige, tried in vain to rescue their daughter from the ceaseless attacks with drugs and diets, but Charlotte’s condition eventually deteriorated to 300 seizures a week, according to the CNN documentary. Matt and Paige Figi turned to cannabis, which was legal in Colorado, for medical use. Charlotte was administered cannabis that was low in THC and high in CBD content. As of last year, at age 6, Charlotte was only having two or three seizures a month, and in the words of a CNN writer, she was “thriving.” “It’s the CBD,” Gupta explained in the documentary, that “scientists think modulates electrical and chemical activity to help quiet the excessive activity in the brain that causes seizures.” In 2012, the journal Pharmaceuticals identified 34 CBD studies, including 16 studies of healthy subjects and 18 studies conducted in clinical populations, including multiple sclerosis (six), schizophrenia and bipolar mania (four), social anxiety disorder (two), neuropathic and cancer pain (two), cancer anorexia (one), Huntington’s disease (one), insomnia (one) and epilepsy (one).1 The results have been promising. “Experimental studies suggest that high-dose CBD may decrease anxiety and increase mental sedation in healthy individuals,” the authors wrote in the May 21, 2012, review, “Cannabidiol in Humans-The Quest for Therapeutic Effects.” “Clinical trials suggest the high-dose CBD may be useful for the treatment of social anxiety disorder, and possibly, insomnia and epilepsy.” Maroon cited published CBD studies showing varied effects such as reducing acne in teenagers,2 relieving pain associated with cancer and multiple sclerosis,3 and suppressing nausea and vomiting.4 He also referenced a study in which seven of eight patients suffered fewer seizures.5 “Again, not enough to really make hard claims,” Maroon said. “But now, due to Sanjay Gupta and others, there are controlled studies going on with epilepsy to really evaluate this.” “And the dosing is certainly a problematic area in terms of what is a correct dosage for CBD,” the neurosurgeon added. “It ranges from 10 to 800 mg a day for a variety of human diseases.” It’s still early to draw any final conclusions about the health benefits of CBD. Maroon acknowledged there has been a limited number of human trials.

NATURAL PRODUCTS INSIDER • CANNABIS REVOLUTION 5 naturalproductsinsider.com Drug Trials Pharmaceutical companies are charging ahead with studies in the hopes of administering CBD-infused drugs to treat epilepsy and other conditions. Earlier this year, Insys Therapeutics Inc. announced that FDA had granted orphan drug designation (ODD) to its pharmaceutical cannabidiol for the treatment of glioblastoma multiforme (GBM), the most common malignant brain tumor. The company was previously granted ODD to its same pharmaceutical for the treatment of two rare forms of epilepsy: Lennox-Gastaut Syndrome and the form suffered by Charlotte Figi, Dravet Syndrome. Maroon said he has operated on hundreds of patients who suffered from GBM. “Although they survive the operation, very few if any ever survive more than 12 to 18 months,” he said. “And to use this [CBD] for this particular tumor is certainly very … intriguing.” United Kingdom-based GW Pharmaceuticals plc is also studying CBD and working with FDA for approval of the compound as a drug. In June, GW Pharmaceuticals announced the results of a CBD study on 27 adults and children who suffered from epilepsy. Of the patients who responded to the drug known as Epidiolex, GW Pharmaceuticals reported a significant reduction in seizures. And at the end of the 12-week treatment, 15 percent of the patients stopped having seizures. GW Pharmaceuticals recently announced it had commenced a Phase 2/3 clinical trial of Epidiolex for the treatment of Dravet Syndrome. The company anticipates starting additional trials next year for both Dravet Syndrome and Lennox-Gastaut Syndrome. Stuart Tomc, CannaVest’s vice president of human nutrition, said the natural products industry is interested in CBD. During SupplySide West 2014, he was invited to a meeting of the top CEOs in the industry. “CBD came up 50, 60, 75 times from 1 in the afternoon until 8 p.m. when we were done,” he said, adding that many companies have done their own research. “Wellness in the nutraceutical space is what we are doing. We’re not so much pursuing and developing a market as we are filling a need,” Joe Dowling, CannaVest chief financial officer, told the hemp summit. “To get there, though, we do have to change perception. We work at that every single day. We think the best way to do that is to prove the science, as you heard this morning. As we change public perception, public policy will follow.” q

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NATURAL PRODUCTS INSIDER • CANNABIS REVOLUTION 6 naturalproductsinsider.com Stuart Tomc, CannaVest’s vice president of human nutrition, weighed in on the current opportunities in the hemp-based market. INSIDER: Why is now the right time to explore developing products with hemp-based ingredients? Tomc: According to The Washington Post, the [cannabis] market could be bigger than the NFL by 2020 and is valued at USD $35 billion. INSIDER: What are some of the top opportunities for product developers? Tomc: Product developers have a rare opportunity to stay relevant in the public nutrition discourse. The top opportunity for product developers is simply to meet existing need; hemp-based products sell themselves. Avoid the claim game and, in the words of perhaps the greatest retailer in American history, Marshall Field, “Give the lady what she wants.” We will never find another plant that was under prohibition for over 75 years that was once part of the pharmacopeia that delivers such broad spectrum health benefits. Better yet, a plant that grows like a weed. The world is mesmerized by cannabinoids’ unique “easement” properties that modulate multiple systems within the body. INSIDER: How can companies ensure they are meeting consumer needs with their new products? Tomc: The three thing companies can insist from suppliers of hemp products to ensure they are meeting consumer needs are: 1 Proven supply chain custody from seed to shelf; 2 Third-party testing for efficacy and safety; and 3 Transparency.

References:

1. Zhornitsky S, Potvin S. “Cannabidiol in Humans—The Quest for Therapeutic Targets.” Pharmaceuticals 2012, 5, 529-552. 2. Olah A et al. “Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes.” J Clin Invest. 2014;124(9):3713–3724. doi:10.1172/JCI64628. 3. Russo EB. “Cannabinoids in the management of difficult to treat pain.” Therapeutics and Clinical Risk Management 2008; 4(1): 245-259 4. Parker, LA et al. “Effects of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew)”. Psychopharmacology (Berl). 2004 Jan;171(2):156-61. 5. Cunha JM et al. “Chronic administration of cannabidiol to health volunteers and epileptic patients.” Pharmacology. 1980;21(3):175-85.

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