Mary's Primer Issue #5: It's a Hemp Thing by Alice O'Leary Randall

PRIMER issue #5

ITâ&#x20AC;&#x2122;S A HEMP THING

PRIMER issue #5

Editor-in-Chief: Alice O’Leary Randall Design: Jesica Clark Contributors: David Bonvillain, Realm of Caring Special Thanks: Project CBD and Cannabis.info Published by: Mary’s Medicinals and Mary’s Nutritionals This publication was produced by Mary’s Medicinals and Mary’s Nutritionals in consultation with medical professionals and scientists. However, our understanding of cannabis medicine is constantly evolving and so we can only share what we have learned from patients and the research that is currently available. Every patient will have individual reactions to different treatments. Use of this information is not intended to be a substitute for professional medical judgment and you should promptly contact your own health care provider regarding any medical conditions or medical questions that you have or before beginning any treatment. Mary’s Medicinals  Denver, CO  MarysPubs.com

EDITOR’S NOTE

emp has exploded onto the scene in recent years. Once scorned by marijuana users as “ditch-weed,” the lowly hemp plant has undergone a renaissance due in large part to the expanding knowledge of the cannabinoid known as CBD (cannabidiol). The distinguishing feature between hemp and marijuana is hemp’s minimal delta-9 tetrahydrocannabinol (THC) content. THC is, of course, the cannabinoid that makes people “high,” but in hemp the THC content is 0.3% or less. This lack of psychoactivity means hemp is legal in all 50 states (although some state regulations prohibit its growth) and its products can be shipped nationwide. As a result CBD derived from hemp is available in nearly every state and can often be bought in your local health food store or online. But is hemp medicine? Technically no…but maybe yes. CBD derived from hemp does have properties that can be helpful for many conditions but some argue that it may be more realistic to view hemp-derived-CBD as a nutritional supplement. CBD derived from cannabis, as opposed to hemp, has many cannabinoids (most notably THC) and terpenes. These molecules work together in a synergistic process known as “the entourage effect” and, while we still have a lot to learn about the whole plant cannabis and its components, the general consensus among medical professionals is that THC is a critical component of therapeutic cannabis. The Project CBD interview with Dr. Ethan Russo explains more of this concept. (page 13) The cannabis issue is already quite complex and “the hemp thing” just adds to the complexity. But understanding what hemp is, its legal stature and its limitations helps you become a better consumer. The best patient is an educated patient. This issue of the Primer features articles by two of the finest cannabis education resources in the U.S. --- Project CBD and Realm of Caring. David Bonvillain grows hundreds of acres of hemp in Colorado and is the founder of Elite Botanicals. He puts the importance of hemp into perspective (see page 9) Finally, the Resources Guide on page 22 will lead you to more information. Keep learning! Alice O’Leary Randall Editor-in-Chief

Table of Contents The Hemp Renaissance . . . . . . . . . . .

What is this Hemp Thing? . . . . . . . . .

RoC Facts. . . . . . . . . . . . . . . . .

Hemp & Cannabis â&#x20AC;&#x201C; The Debate, Misconceptions and Misinformation. . . . . . . . . . . . . 9 About Elite Botanicals. . . . . . . . . . .

Dr. Ethan Russo: CBD & Clinical Endocannabinoid Deficiency. . . . . . . . .

Hemp & the Human Body. . . . . . . . . . .

Healthy! Nutritional Value of Hemp Seeds. .

Resources. . . . . . . . . . . . . . . . .

THE HEMP RENAISSANCE by Alice O’Leary Randall

arijuana, Mary Jane, pot, ganja, dank, weed … cannabis has more names than you can count. Indeed, according to Wikipedia, cannabis has “more than 1,200 slang terms.” And many of those terms have entered the modern network of medical cannabis dispensaries thus presenting a bewildering array of product to the thousands of medical cannabis users who are flocking to this ancient and venerable plant. But there is one term for cannabis that is not just slang, it describes a variant of the plant that has reemerged on the cannabis stage and given us a new and exciting array of products: that term is “Hemp.” Predominantly used in industry, hemp has also found its way into the medical cannabis debate and this has caused confusion in recent years. In the U.S., hemp is defined as cannabis having less than 0.3% delta-9 THC, the cannabinoid that causes people to “get high.” This low THC content was codified into law in the 2014 U.S. Farm Bill and this has allowed the hemp movement to make great strides with respect to re-introducing legal hemp into the U.S. market. Concurrently, scientific research with cannabidiol (CBD), revealed numerous therapeutic applications. Hemp farmers began

experimenting with their plants, boosting the CBD content and developing CBD products in many forms. Today, CBD specific products made from hemp can be found in trendy grocery stores and, most significantly, online at specific websites and even Amazon.com. These developments, while exciting, have also created massive confusion among consumers since all hemp is cannabis but not all cannabis is hemp. Therein lies the difference. Hemp is legal and currently grown in 34 states, according to the National Conference of State Legislatures. (The NCSL website has an excellent explanation of the history of hemp laws in the U.S.) In this issue of Mary’s Primer the focus is on hemp grown specifically for its CBD content and converted into tinctures, salves, patches, compounds, pills and other formulations which allow individuals to use the CBD as a supplement or remedy for health and medical conditions. When it comes to CBD the most frequent question becomes: is CBD from hemp different from CBD derived from the more traditional cannabis plant? The simple answer is: no. A molecule is a molecule regardless of which plant the molecule is taken from.

But traditional hemp grown for fiber is not a good candidate for CBD extraction. Project CBD, a California-based nonprofit dedicated to promoting and publicizing research into medical uses of CBD, provides a helpful explanation why: “Compared to whole plant CBDrich cannabis, industrial hemp grown for fiber or seed is typically low in cannabinoid content. A huge amount of fiber hemp is required to extract a small amount of CBD.…” Hemp

farmers

and

scientists,

high-percentage and high-quality CBD. (See Elite Botanicals on page 12). Forbes Magazine in August 2017 reported that “Hemp-derived cannabidiol (CBD) is projected to be a billion-dollar market in just three years.” (The Forbes article, “Hemp Cannabis Product Sales Projected to Hit $1 Billion in 3 Years” is informative about the history of this industry growth, as well as current markets and uses.) The magazine report also noted that nearly 65%

Hemp harvesting on Rhine bank however, began to breed a new form of hemp with much higher CBD content. Just as cannabis plants have been developed with extremely high content of delta-9 THC, so too the hemp farmers have genetically manipulated their hemp plants for high CBD content. The result is

of hemp-derived-CBD is distributed via online sales! With so much money to be made it is not surprising that problems arise. The hemp plant has a remarkable facility for absorbing heavy metals and other contaminants from the soil. (Indeed, hemp is recommended 2

for environmental cleaning of industrial sites.) Obviously hemp that is exposed to these environments, or treated with fertilizers, is not the best product for human consumption. Additionally, some manufacturers import their hemp from China and other markets where environmental regulations are not particularly stringent.

still many problems with respect to supply. The resource list in this issue of Mary’s Primer provides websites with additional information on CBD producers. Project CBD has a good starting point in their “What to Look for in Your Cannabis Medicine.” This issue of Mary’s Primer will hopefully educate you in finding and using the best product.

So the maxim “Buyer beware” is pertinent in today’s hempderived-CBD market. Hemp and cannabis are regaining their place in our society after more than eight decades of prohibition but there are

Note: Visit www.maryspubs.com for the digitized version of Mary’s Primers and find all website links in an easy click-on format.

Hemp workers

WHAT IS THIS HEMP THING? Prepared by the staff at Realm of Caring in Colorado Springs, Colorado. Visit realmofcaring.org for more information.

WHAT IS THIS HEMP THING ALL ABOUT ANYWAY? First, let’s start with the legal definition of hemp from National Conference of State Legislatures: A wide range of products, including fibers, textiles, paper, construction and insulation materials, cosmetic products, animal feed, food, and beverages all may use hemp. The plant is estimated to be used in more than 25,000 products spanning nine markets: agriculture, textiles, recycling, automotive, furniture, food/nutrition/beverages, paper, construction materials and personal care. While hemp and marijuana products both come from the cannabis plant, hemp is typically distinguished by its use, physical appearance and lower concentration (less than 0.3%) of delta-9 tetrahydrocannabinol (THC). Hemp producers often grow the plant for one or more parts — seeds, flowers and stalk. The plant is cultivated to grow taller, denser and with a single stalk.

NOW YOU MIGHT BE WONDERING,

‘WHAT IS CBD?’ The cannabis plant can produce over 100 unique natural compounds called cannabinoids, one of which is cannabidiol, or CBD. Unlike THC, CBD causes no intoxicating or euphoric effects. Research is also showing CBD to be the cannabinoid with the longest list of potential therapeutic benefits.

IS IT TRUE THAT CBD CAN ONLY BE PRODUCED FROM HEMP PLANTS? Some think that THC only comes from marijuana and CBD only comes from hemp. This isn’t quite right. The only legal difference between marijuana and hemp is that hemp contains no more than 0.3% THC in the US, and up to 1% internationally. A plant that produces large quantities of THC is also capable of producing lots of CBD (strains like AC/DC, Cannatonic, Harlequin). And a plant variety bred for industrial hemp will still contain trace levels of THC, and could contain virtually no CBD. In general though, CBD is being derived from proprietary hemp strains naturally high in this cannabinoid.

CAN I BUY HEMP PRODUCTS (LIKE CBD) IN MY LOCAL STORES OR ONLINE? CBD and hemp products can be 4

CBD derived from cannabis

CBD derived from hemp

What’s the difference between these CBD molecules? See answer page 20 ordered online and shipped to all 50 states. Some health food stores carry these products and you do not need a prescription or recommendation from a doctor to purchase. If you are accessing hemp-derived highCBD products from companies that are growing under a research and development license with their state agricultural department, or an institution of higher learning, you are protected by the Agricultural Act of 2014. You should be aware that not all products are equal, and some companies are not “legally” producing hemp products.

HOW DOES THIS TREATMENT WORK?

CANNABINOID

Researchers have called CBD the “boy scout molecule,” meaning it does the right thing, in the right place, at the right time. 5

Naturopaths would use the term regulator, modulator or adaptogen to describe the actions of CBD. In the same light, some researchers call CBD a “promiscuous” molecule, which means it interacts with many different receptors and systems. CBD builds up in the fatty tissue, is re-circulated in the blood plasma and is excreted slowly out of the body. This is why you can stop CBD cold turkey and it will not shock the body into withdrawal. Furthermore, CBD does not generally bind to receptors in the body like a traditional drug. Opioids, for example, like oxycodone, bind to opioid receptors in the brain, killing pain, but the body adapts to the binding, creating a tolerance and a need to increase the dose to receive the same benefits. It has a low affinity for binding to

receptors, instead it works in most situations in a “hands-off manner” communicating with other systems to promote balance. CBD does not produce addiction, habituation or tolerance. Cannabis use is associated with a feeling of being “high,” but that effect can be solely attributed to THC. CBD does not cause any type of euphoria or mind-altering effects.

TECHNICALLY… Unlike a targeted therapy, medicine, or chemical that acts on one system or even one receptor like antidepressants in the SSRI family (selective serotonin reuptake inhibitors, which target the serotonin receptor 5HT1A), CBD works with many receptors and electrochemical signaling systems to exert its effects. To date, research has discovered over 50+ mechanisms of actions of CBD. It is a veritable “jack of all trades” for the brain and body. To describe it in a nutshell, CBD mainly works via the endocannabinoid system CB2 receptors to promote and maintain homeostasis or balance in the body. Although it does act on other receptors, including 5HT1A.

WHAT ARE THE BENEFITS OF CBD FROM HEMP PRODUCTS? HAVE THEY BEEN PROVEN? CBD can help restore balance and proper function to virtually any cell, tissue, or organ in the body. Due to this, the list of symptoms and conditions

that CBD can help alleviate is extensive. Preclinical research and anecdotal evidence suggest that CBD can be anti-inflammatory, neuroprotective, neuro-regenerative, antioxidant, anti-convulsant, anti-spasmodic, antiemetic, antitumoral, anti-pathogenic, antianxiety, antidepressant, and antipsychotic, to name a few.

MY DOCTOR SAYS THERE ARE NO “REAL” STUDIES ABOUT CANNABIS OR HEMP. IS THIS TRUE? The U.S. has made it EXTREMELY difficult to conduct human studies using cannabis or the compounds produced by the plant. So while there are tens of thousands of research articles pertaining to cannabis, there is a lack of the “gold standard” type of study, which is called a doubleblind placebo controlled study. Internationally, especially in Israel where they have been researching cannabis since the 1960’s, there have been some double-blind placebo controlled studies. For example, in the 1980’s, Dr. Raphael Mechoulam and a group of Brazilian researchers conducted a small double-blind placebo controlled study testing CBD administration in a small group of people (10 patients) with epilepsy and the results did show promising outcomes for the epileptic subjects who were administered CBD. However, one study of ten people is not enough evidence to constitute scientific canon. The study itself (and many more diverse studies) must be repeated with larger and more diverse groups, with the same 6

results. Although clinical research isn’t practically possible on humans in the U.S. at this point in time, the next best type of research that can be conducted is observational in nature. This is where the Realm of Caring Foundation is filling a research void. In partnership with researchers at Johns Hopkins University and University of Pennsylvania, we are operating an online Observational Research Registry (ORR), which is the largest of its kind in the country. There are cannabis and non-cannabis users with a plethora of diagnoses who are participating, allowing us to gather a wide and deep longitudinal data set with which we can make internal and external comparisons. (See RoC Facts, page 8)

LET’S TALK ABOUT SIDE EFFECTS Reported side effects of CBD are extremely mild when compared with those of most pharmaceutical drugs. The most frequently reported side effects are better mood, increased alertness, better sleep, drowsiness, decreased self-stimulation, fatigue, and decreased appetite. CBD is non-toxic and high doses of up to 1.5 grams per day are reportedly well tolerated in humans.

WHO SHOULD AND SHOULDN’T TRY CBD AND HEMP PRODUCTS? No matter where you fall on the spectrum from healthy to sick, and no matter your age, CBD may be beneficial for you. Those who have seizures or take pharmaceutical 7

medications, especially blood pressure medications and antiepileptic drugs, should be cautious when adding CBD to their regimen as these drugs can interact with CBD. As long as you consult the use of CBD with your doctor and research how to acquire and use it responsibly, then almost anyone can try it. Assessing the quality of available products is critical to making a selection when you purchase CBD products. It is suggested that pregnant and nursing mothers refrain from using CBD due to a lack of research on potential outcomes. Also anyone who is subject to drug testing needs to be aware that CBD products contain trace amounts of THC that can build up in the system after prolonged use and thus trigger a “positive” on a drug test.

HOW LONG DOES SOMEONE HAVE TO USE CBD TO REAP THE BENEFITS? Everyone is different, and according to the tone and sensitivity of your own endocannabinoid system, some users will see results quicker than others. Some have seen results after one dose; however, this is not the majority. Especially when following a “slow and steady” responsible administration regimen, it can take anywhere from a few weeks to months to see the full benefits.

ROC FACTS

w w w. t h e r o c . u s

...because quality of life matters

• The Realm of Caring Foundation is a nonprofit organization based in Colorado Springs, Colorado. RoC has 15 full and part time staff members supporting over 45,000 clients worldwide. • RoC is designated by the IRS as a 501(c)(3) non-profit entity. Contributions are tax-deductible. • RoC Research Library - a free, online repository of published cannabinoid research studies compiled by disease category. A must read for anyone seeking factual information on the use of cannabinoid therapies. • RoC’s Observational Research Registry is one way you can be part of an ongoing, observational research project. The RoC has partnered with Johns Hopkins University School of Medicine to compile a database of patients. Whether you are currently using cannabinoid therapies or not, your input will be invaluable to other families, doctors, and researchers. • Webinar Orientation Series - a biweekly event where participants can ask questions in real time. • Physician Education - provided quarterly to catch you up on the most recent research articles. One-on-one consultations are also available from RoC Care Specialists. Call 719-347-5400 or email info@theroc.us

HEMP & CANNABIS –

THE DEBATE, MISCONCEPTIONS AND MISINFORMATION

By David Bonvillain Owner and Chief Science Officer Elite Botanicals

egardless of whether you research online, attend a conference, or just talk to ‘those in the know,’ there is a wealth of misinformation regarding CBD and Hemp. We want to clear up some misinformation and provide some basics in the hopes of allowing the reader to properly differentiate between the sources of products that are available on the market. Let’s address the “CBD from hemp vs. cannabis” debate first. Historically speaking—as in 4+ years ago—this would have been a fairly straightforward discussion. The differentiation was the source of the CBD. On one hand you had industrial hemp crops (oilseed and fiber varieties) farmed in other countries that contain almost no cannabinoids at all and were processed by the hundreds of thousands of pounds to produce isolated CBD. The counterpoint to that was cannabinoid rich (type3 drug, see “Cannabis Botanical Classifications” page 10) varieties that are very high in CBD in addition to having a full spectrum of other naturally occurring cannabinoids, terpenoids and flavonoids that all play a synergistic effect with

each other. This is thought to be significantly more therapeutic as a whole than any one component alone. Hence the sentiment – CBD from hemp = bad, CBD from cannabis = good. I prefaced that paragraph with ‘historically speaking’ because such a clean distinction no longer exists outside of botanical and science circles. The United States originally had no real definition of ‘hemp’ outside of the exclusionary sentence in the U.S drug code removing seeds and stalks from the definition ‘Marijuana’ in the Controlled Substances Act. That definition changed with the introduction of a clause in the 2014 Farm Bill (also known as the 2014 Agricultural Act) that defined 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.” Well…now we have a U.S. definition for hemp that has nothing to do with its industrial purpose, botanical lineage of the plant, or the scientific category it may be placed in. This “new” definition of hemp is purely based on the cannabis plant’s cannabinoid percentage and, even then, of one specific cannabinoid.

That changed things. As it turns out there were many of us that were active in the CBD rich cannabis space for years prior to the evolution of the hemp definitions and regulatory structures. This was a challenging space to be in as it was fraught with desperate families, minimal supply, and incredibly limited research. Licensed cannabis businesses traditionally avoided

3 cannabis drug varieties that only maximize their delta-9 THC concentration at under 1% AND you understand the fact that the THC increases over 0.3% only in the final stages of maturity when the CBD is already over 9%, suddenly there seems to be a clear path to solving a shortage of a life-saving plant by simply calling it ‘hemp’, harvesting it early, and cultivating it by the

Cannabis Botanical Classifications: »Cultivars » »Oil » Seed Cultivars »Drug » Cultivars (chemotype classifications below) * Type 1 – THC dominant * Type 2 – Balanced THC/CBD concentrations * Type 3 – CBD dominant * Type 4 – Propyl cannabinoid content (CBDV, THCV, etc.)

products that weren’t intoxicating in some way (possibly because of the exorbitant investments necessary for them to operate), genetics/ cultivars were in very short supply, and caregivers were (and still are) limited by plant count restrictions that were ongoing impediments to any foreseeable ‘surplus’. BUT, when you are dealing with type-

acre instead of the thousand watt lamp. As of the 2014 season, farmers in Colorado (and subsequently Kentucky, Vermont, and Oregon) have all been producing licensed crops using cannabinoid rich type-3 drug varieties under industrial hemp regulations. While there are still U.S. 10

farmers that are working with fiber and oilseed varieties, it is important to recognize that there is now more high-CBD cannabis being grown as ‘industrial hemp’ in the United States than by all of the licensed cannabis/marijuana licensees across the country combined. Hence – the discussion is no longer “I want my CBD from cannabis, not hemp!” – and now, more accurately “I want my CBD from cannabinoid rich type-3 drug varieties regardless of whether you call them hemp or cannabis plants, not from field oilseed or fiber varieties!” All Hemp Is Not Created Equal!

the

David Bonvillain, CEO

difference

At Mary’s, we believe that the best path to a full and active life starts with an open mind. While our bodies have a natural tendency to repair and restore, there are opportunities to be more proactive in building wellness into your daily routine. For busy people looking to incorporate relief and relaxation into their lives, alternatives exist – and we are leading the way. The Mary’s Difference: »Novel » use of plant nutrients »Clean » delivery methods »100% » organic U.S. grown industrial hemp »In-house » testing and third-party validation

Available online and in retailers nationwide. marysnutritionals.com | #MarysNutritionals

ABOUT ELITE BOTANICALS Elite Botanicals focuses on non-psychotropic cannabinoid cultivation, research and product development. Elite offers the best quality oils and cannabinoid products in the market today; leveraging decades of experience cultivating, breeding and analyzing the cannabis plant in collaboration with leading chemists, medical doctors, breeders, and product manufacturers. Elite Botanicals has spent years analyzing various cannabis chemotypes and phenotypes to cultivate a broad portfolio of cannabinoid rich hemp varietals. While very low in THC (THC is <0.3% by dry mass), these cultivars are all very rich in cannabidiol (CBD), at least 15% and some as high as 23%. Elite Botanicals is developing a pipeline of new cultivars focusing on cannabinoids such as tetrahydrocannabivarin (THCV), cannabichromene (CBC), and cannabigerol (CBG) to continue leadership in breeding for selective cannabinoid ratios and laying the groundwork for future breakthrough products. Elite Botanicals rigorously adheres to the industrial hemp regulatory structure, striving to carry on the mantra taught by the late Jack Herer “Hemp can save the planet!...” The cannabis plant can be used for food, fuel, fiber and medicine! In Jack’s eyes it was all ‘hemp,’ just different cultivars for different applications. Elite Botanicals applies these principles using living organic cultivation methodologies developed at both of our farms and in our greenhouses located in Loveland, Colorado. Elite Botanicals has been licensed under the Colorado Department of Agriculture starting in 2014 and has a current annual production output of approximately 20,000 pounds of botanical material. While Elite isn’t the largest operation in the state, the focus on quality, delivery and customer service make Elite Botanicals a great choice for customers seeking a true partnership.

DR. ETHAN RUSSO:

CBD & CLINICAL ENDOCANNABINOID DEFICIENCY

Editor’s Note: This is a partial transcript from the Project CBD video series “Cannabis Conversations.” The interview was conducted by Martin A. Lee, director of Project CBD and author of the best selling Smoke Signals: A Social History of Marijuana — Medical, Recreational and Scientific. To see the complete video and/or transcript visit www.projectcbd.org and click on “Videos.” Mary’s extends its thanks to Project CBD for allowing reproduction of this transcript and encourages readers to support this pre-eminent source of information on CBD. Transcript Project CBD: Today we’re talking with Dr. Ethan Russo. Dr. Russo, a board certified neurologist, is the medical research director at Phytecs*, a biotechnology company that specializes in developing different ways of targeting the endocannabinoid system for therapeutic benefit. Dr. Russo was formerly the senior medical advisor to GW Pharmaceuticals and a widely published author in many scientific journals, as well as a contributor and editor of several books. He has also been a faculty member at the University of Washington, a guest teacher at Harvard Medical School, and other academic institutions. Welcome to Cannabis Conversations. 13

Russo: Thank you for having me. Project CBD: Ethan, you’ve been way ahead of the curve with respect to cannabidiol (CBD), years before most people in the medical marijuana community had ever heard of it, you were emphasizing its significance. Tell us briefly, what is the significance of CBD? Russo: Well I think we need a little background first to indicate that cannabidiol has always been part of the capabilities of cannabis. Its just that it’s been pushed into the background through selective breeding, basically another byproduct of prohibition where the emphasis has been on maximum psychoactivity to the exclusion, for the most part, of medicinal benefits that might go beyond that. But, clearly, this is a substance that has a lot to offer on many levels. Firstly, it synergizes with THC, so it complements the ability of THC to treat pain while in its own right it’s an excellent antiinflammatory without the liabilities that we say get from non-steroidal anti-inflammatory drugs with their tendencies to produce serious side effects like ulcers, heart attacks, and strokes, these just aren’t a liability with cannabidiol. So cannabidiol, on the one hand, can counteract some of the less desirable effects of THC such as this tendency to produce anxiety and

rapid heart rate. But at the same time, cannabidiol on its own has many properties that THC doesn’t – as an anti-anxiety agent, as an anti-psychotic, and doing all this without producing intoxication, if you will, that can happen with too much THC. So this is just a few of the things. Project CBD: You mentioned CBD in the context of it being combined with THC; you also mention it as an isolate. And GW Pharmaceuticals, when you were involved with the company, has done extensive clinical trials focusing on CBD in combination with THC for Sativex. It’s been approved in a couple of dozen countries as a sublingual spray. But also GW has been focusing more recently on Epidiolex, which is more like a single molecule formula. I realize there are some other things in there, but it’s mainly CBD. Russo: That’s true. Project CBD: So what are the advantages and disadvantages of both ways of looking at it, both as an isolate or as a whole plant mixture? Russo: So in Sativex, basically it’s a 1:1 mixture of THC and CBD, plus some other terpenoid components. That turned out to be the best approach for treating a large variety of symptoms such as spasticity in MS, some pain conditions, particularly neuropathic pain, and worked out quite well. In the early days, the company looked at different ratios and different modes of administration and the

oral mucosa spray with Sativex with this 1:1 mixture turned out to be a good balance of efficacy and safety, meaning fewer side effects. On the other hand, cannabidiol alone, again, would be very good in treating a variety of other conditions. One is epilepsy. CBD as an anticonvulsant has a broad spectrum of activity. In other words, it works on many different kinds of seizures and has the possibility, again, of doing this without any of the liability that THC might produce, both in terms of side effects but also legal constraints. So that’s a big advantage. Additionally, as an anti-psychotic, say to treat schizophrenia, there’s already been a Phase 2 clinical trial with Epidiolex, in essence, with good success apparently. That hasn’t been published yet. But the preliminary results were announced online. Project CBD: So I’ve heard it described that CBD is like THC without the psychoactivity. Is that accurate? Or is that sort of a blunt description that really doesn’t get at what’s going on here? Are there other conditions that really CBD seems more suitable than THC? Russo: More the latter. It is really distinct. Something I haven’t mentioned is that in its own right cannabidiol is an endocannabinoid modulator, in other words, when given chronically it actually increases the gain of system, which is, at its core, a homeostatic regulator. To explain that: homeostasis is a state of balance. Many diseases 14

interfere with a balance in a given system and if we can bring that balance back to where it should be there’ll be improvement in the overall condition. This is one reason that cannabidiol is such a versatile medicine because so many disorders operate on that kind of level. So, if there’s too much activity in a system homeostasis requires that it be brought back down. If there’s too little, it’s got to come up. And that’s what cannabidiol can do as a promoter of endocannabinoid tone, we call it. Project CBD: Well usually when we think of a drug, it goes in one direction or the other. But you’re suggesting that CBD really has a bi-directional effect. It can balance either excess or deficiency. Can you explain how that works? Or would that require a kind of in-depth scientific … Russo: It would but, looking at the endocannabinoid system, it is sort of a buffer. So CBD can be thought of as a buffer as well – a buffer is something that will work both ways as need be. So, for example, in the endocannabinoid system one of its main roles in the brain is to regulate neurotransmitter function and again, if there’s too much of one kind of neurotransmitter it will bring it down, if there’s too little it will bring it up. Without diagrams, that’s probably as well as we’re going to do this evening. Project CBD: Now does THC do something similar, but in a different way? 17

Russo: Yes. Okay, we can think of THC as acting directly on the cannabinoid receptors. In contrast, CBD is quite distinct. It doesn’t tend to bind directly, what’s called the orthosteric site where THC binds. Rather, it binds on what’s called an allosteric site, another site on the receptor, and so it alters the binding of both THC and the endogenous cannabinoids, the endocannabinoids. So, cannabidiol is what’s called the negative allosteric modulator, which is a fancy way of saying that when THC is present it interferes with its activity – which is a good thing in terms of wanting too much psychoactivity and again limiting side effects like anxiety or rapid heart rate that can be a problem if someone has too much THC. Project CBD: So the idea that CBD is a negative allosteric modulator of the cannabinoid receptor, that would suggest – if it’s impeding or reducing the signaling of a particular receptor – that it might be helpful for diseases that are an expression of an excess, because you want then a limit, and the opposite would be if you had some kind of allosteric modulator, unlike CBD, that would have a enhancing effect on a receptor that would then perhaps be helpful for disease of deficiency of the endocannabinoid system. Now you’ve written a very important paper, I think it was published back in 2001, on clinical endocannabinoid deficiency, maybe you can explain the thesis of that? Russo: It was a concept I introduced then, I had a larger review paper

in 2004, and just this year 2016, I submitted further review that’s currently under consideration for publication. Basically it occurred to me that many diseases affect neurotransmitter levels. A couple of examples: We know one of the primary problems in Alzheimer’s disease or other dementias is a lack of Acetylcholine, the memory molecule in the brain; similarly in Parkinson’s disease there’s not enough dopamine and you try to replace that with a medicine with a medicine call L-Dopa. So what would a deficiency of endocannabinoid function look like? Well, we already knew that. If you don’t have enough endocannabinoids you have pain where there shouldn’t be pain. You would be sick, meaning nauseated. You would have a lowered seizure threshold. And just a whole litany of other problems. It occurred to me that a number of very common diseases seem to fit a pattern that would be consistent with an endocannabinoid deficiency, specifically these are migraine, irritable bowel syndrome, and fibromyalgia. They have some things in common. They’re all hyperalgesic syndromes, meaning that there’s seems to be pain out of proportion to what should be going on, in other words you can look at the tissues they look okay, but there’s biochemically something that’s driving the pain.

syndrome. Previously there wasn’t a lot of genetic linkage, but we’re still looking for evidence of that and there seems to be a possibility that there’s some linkages there. But again, the theory as it started out was that they would have in common an endocannabinoid deficiency. Subsequently to the review paper in 2004, there’s been a great deal of work done both clinically and experimentally that supports the concept.

Additionally, they occur in the same individuals. If someone has a chronic problem with migraine there’s a high likelihood they’re going to have fibromyalgia at some point in their life; similarly, with the irritable bowel

*As of the date of this publication Dr. Russo, is Director of Research and Development for International Cannabis and Cannabinoids Institute.

The complete transcript and video is available at the Project CBD website. Note: Visit www.maryspubs.com for the digitized version of Mary’s Cannabis Primers and find all website links in an easy clickon format.

HEALTHY! NUTRITIONAL VALUE OF HEMP SEEDS By Cannabis.info Used With Permission aBring up the topic of hemp seeds at your next social gathering and you’re likely to turn a few heads. The sheer mention of anything related to cannabis is a lot for some people to handle, immediately conjuring up a mental image of getting high. In actuality, consuming hemp seeds does not result in any psychotropic effects. However, they do provide a myriad of nutritional benefits like no other seed on earth. The verdict? Hemp is healthy! Nutritional value of hemp seeds cannot be overstated, as they feature a complex profile of proteins, fats, vitamins and minerals, that reduce and prevent life threatening diseases, such as cancer and heart disease.

RICH SOURCE OF PROTEIN Hemp seeds are an excellent source of protein. Containing all 9 essential amino acids (EAA’s), that the human body does not produce, hemp seeds are second only to soybeans in protein content. In total, hemp seeds contain all 20 amino acids known to man, helping to stimulate muscle growth and strengthen the body’s natural defense system. For vegetarians and vegans, hemp 19

seeds are a perfectly valid meat substitute at around 10g of protein per three tablespoons. Seeds are relatively high in calories as well, making them a perfect dietary addition for athletes and other highly active individuals.

EXCELLENT SOURCE OF FATS Some of the most important nutritional implications of hemp seeds originate in its rich concentration of fats. Indeed, over 30% of hemp seeds are made up of fats, with an uneven split of 7580% polyunsaturated fats and 9-11% saturated fats. As such, hemp seeds are “perfectly balanced” with a 3:1 ratio of omega-6 to omega-3 fatty acids. Humans need both types of these fats to be healthy. Contrary to popular belief, some types of fats are good for you! Hemp contains a naturally occurring compound known as gamma linolenic acid or GLA. GLA is categorized as an omega-6 fatty acid, that shows particular promise in the realm of cancer treatments and promotes many other health benefits as well.

HEART AND HORMONE HEALTH GLA is also essential in maintaining proper cardiovascular and hormonal health. The omega-3 fatty acids help to reduce inflammation and ease

pain. Hemp seeds contain arginine, an amino acid, that produces nitric acid, which ultimately helps to reduce your risk of heart disease. Hemp seeds are quickly being recognized as beneficial for premenstrual syndrome (PMS). GLA produces prostaglandin E1 to reduce the adverse effects of the hormone prolactin, which is responsible for causing symptoms of pain. GLA can help to ease the physical and emotional symptoms

HIGH DOSES OF VITAMINS AND MINERALS A wealth of phytonutrients are contained in hemp seeds, making these the ideal avenue for receiving your necessary vitamins and minerals. Among some of

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digestive health. By cultivating a healthy digestive system, these fibers help manage symptoms of high cholesterol and strengthen probiotics for total immune health.

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Hemp seeds contain all nine essential amino acids that many women experience.

GOOD FOR DIGESTIVE HEALTH Hemp seeds contain both soluble and insoluble fibers, that encourage healthy bowel movements and overall

the most occurring minerals are calcium, iron, phosphorus and zinc. Vitamins run the gamut with at least seven appearing in different concentrations, including vitamin A and vitamin B12. This strong phytocomplex allows for consumers

From page 5 The answer is: None. There is no difference between the CBD in hemp or the CBD in cannabis. Hemp is cannabis.

to ingest a well-rounded course of nutrients, without having to purchase many different supplements contained in capsules and tinctures.

SKIN RELIEF Hemp seeds contain antioxidants, that penetrate deep into the skin to relieve inflammation, dryness and redness. Hemp seed oil can be found in many popular skincare and haircare products, that spur healthy cell growth. Hemp oils frequently appear as ingredients in eczema treatments, moisturizers and can be applied to help prevent acne. Hemp seeds encourage a quicker recovery from superficial wounds as the superfood does its best to supplement natural skin and cell regeneration.

NON-PSYCHOACTIVE Before moving any further, it’s necessary to squash the rumor, that ingesting hemp seeds will make you feel high. You can rest assured this is not the case. While it’s true, that hemp is a genetic of the cannabis sativa plant, it contains negligible levels of THC. You will never have to worry about getting hit with a major stone half an hour after sprinkling some hemp seeds on your lunch. Years of stringent regulations have made consumers feel, that anything associated with cannabis is bad and unhealthy when in reality, the opposite is true!

COOKING WITH HEMP SEEDS Surprisingly, hemp seeds aren’t actually seeds at all – they’re nuts. 21

Once you taste them, it will all make sense. The beauty of this product is, that it can be infused into so many different types of food and beverage. If you’re short on time, you can easily sprinkle hemp seeds over hot dishes and salads. At the same time, you can blend them into smoothies and shakes to add an all-natural protein supplement to your regular routine. Anywhere you’d put chia seeds, you can easily sub in hemp. Since hemp seeds are hunger suppressants, they naturally facilitate weight loss. Eating them as a snack in the form of a energy bar is a great way to get good fats and protein on the go, without having to craft an entire meal. This is especially useful for those with busy jobs who eat their lunch with one hand and type with the other.

HOW AMAZING IS HEMP?! It isn’t outrageous to deem hemp a miracle plant. In addition to containing game-changing cannabinoids like THC and CBD, as well as aromatic terpenes, hemp also provides a well rounded course of nutritional benefits, that inspires real impacts on human emotional and physical health. Hemp is healthy! Nutritional value of hemp seeds cannot be overstated, as they feature a complex profile of proteins, fats, vitamins and minerals, that reduce and prevent life threatening diseases.

RESOURCES

ant to know more? There are plenty of articles on the web. Here are just a few. You can find live links to these articles at the Mary’s Publications website. Just go to www.maryspubs.com and click on Issue #5.

PROJECT CBD This site has so many useful articles for the hemp/CBD consumer from beginner to expert. Here are just a few. And be certain to read the Project CBD interview with Dr. Ethan Russo in this issue. CBD User’s Manual A “beginner’s’ guide addressing key questions of CBD users. The Re-Emergence of CBD: A Brief History A quick discussion of CBD’s emergence as a therapeutic cannabinoid. 8 Things You Didn’t Know About Hemp - PBS News Hour What do Woody Harrelson and Mitch McConnell have in common? This site will tell you. Industry Snapshot: Hemp-Based CBD Companies Marijuana Business Magazine looks at the “players” in hemp-based CBD. Realm of Caring has numerous articles about CBD on its website. Here is just one. New Report Highlights The Importance of Selecting A High Quality Hemp-Based CBD Product Summary of article from Journal of the American Medical Association prepared by Realm of Caring. Hemp vs. Marijuana An easy to read article about the never ending question: are marijuana and hemp the same? 22

FORBES MAGAZINE Forbes Magazine is a good source for information on the business side of the hemp/CBD market. Hemp Cannabis Product Sales Projected to Hit $1 Billion in 3 Years The Cannabis Market That Could Grow 700% by 2020 Not All CBD-Oil Companies are Created Equal An independent review of CBD producers and distributors CBD is Cannabis That Wonâ&#x20AC;&#x2122;t Get You High. So Why Are So Many People Using It? A recent article from The Washington Post.

Notes:

Envisioning a world without pain

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