The Tip of the Iceberg Some Information on Cannabidiol (CBD) for Medical Professionals Collated by Sian Phillips for CBD users UK Facebook Group. Contents Introduction Introduction .................................................................... 2 This document has been collated from several website sources. It contains the information, data History of CBD ................................................................. 3 and links for further research. What is CBD? ................................................................... 3 Understanding that medical professionals cannot CBD rich Cannabis ........................................................... 4 prescribe or advocate food supplements, this is just Some misconceptions about CBD ................................... 5 an insight into what knowledge is currently What are cannabinoids ................................................... 7 available. CBD and THC Synergy ........................................... 7 How CBD works ............................................................... 8 Sian Phillips has Fibromyalgia with related CBD and FAAH ........................................................... 8 conditions such as IBS, CFS, CRPS etc. She is group The Vanilloid Receptor ............................................. 8 owner of CBD users UK – a facebook group The Serotonin Receptor............................................ 8 supporting new users in the UK and beyond. The Adenosine Receptor .......................................... 9 GPR55 ......................................................................... 9 PPARs ......................................................................... 9 Synthetic v Whole Plant ................................................ 10 CBD-Drug Interactions: Role of Cytochrome P450........ 12 CBD and the law. ........................................................... 16 Licensing & The Forthcoming Regulation & What It Means To the producer and seller. ............................... 16 What does current UK law have to say regarding CBD oil, hemp and cannabis? What is legal, what is illegal and what lies in the grey area between? ............................. 16 CBD OIL: LEGAL IN THE UK ........................................ 17 The Facts About CBD In The UK. December 2016. ........ 17 BACKGROUND ................................................... 17 IS CBD LEGAL IN THE UK? .............................. 18 IS THE MHRA GOING TO BAN CBD? ............. 18 WHAT WILL HAPPEN IN THE FUTURE? ........ 18 Further reading ............................................................. 19 Cannabidiol and information for medical professionals. UK History of CBD1 Some California doctors kept abreast of the In the spring of 1998, the British government research and O’Shaughnessy’s 5reported on it, but licensed a company called GW Pharmaceuticals2 to we were merely observers, not participants, until grow cannabis and develop a precise and the fall of 2009, when Oakland’s Steep Hill consistent extract for use in clinical trials. GW’s co- Laboratory tested cannabis samples provided founder Geoffrey Guy, MD, was convinced—and by Harborside Health Center and found a few had convinced the Home Office—that by using strains with more CBD than THC. CBD-rich plants, GW could produce a cannabis- Before long, several dozen labs in medical based medicine with little or no psychoactive marijuana states were calibrating cannabinoid effect. ratios and identifying the occasional CBD-rich That summer Guy described his approach at a strain. For data collection purposes, we initially meeting of the International Cannabinoid Research defined “CBD-rich” as 4% or more by dry weight. In Society (ICRS)3. In addition to countering the addition to balanced strains with roughly equal psychoactivity of THC, Guy said, CBD conferred amounts of CBD and THC, a handful of CBD- benefits of its own. GW got its CBD-rich strains by dominant strains—with 20-to-1 CBD:THC ratios or acquiring the genetic library of HortaPharm, a higher were discovered, fostering a cottage Dutch seed company run by American expatriate industry of CBD-rich concentrates, oil extracts, and horticulturists, David Watson and Robert Clarke. other CBD-rich products. CBD-rich cannabis has a long history of being used to treat health problems. Queen Victoria used CBD- rich cannabis for menstrual cramps in the 19th century. Animal studies had long suggested that What is CBD?6 CBD lessens anxiety and reduces the severity and Cannabidiol—CBD—is a cannabis compound that frequency of seizures. But, up until a few years ago, has significant medical benefits, but does not make CBD-rich strains were generally not available to people feel “stoned” and can actually counteract cannabis users in California and other areas. the psychoactivity of THC. The fact that CBD-rich Generations of breeding marijuana for maximum cannabis is non-psychoactive or less psychoactive THC and a strong “high” had reduced the CBD to than THC-dominant strains makes it an appealing trace amounts in most cannabis strains in Northern option for patients looking for relief from: California, America’s cannabis breadbasket. inflammation, pain, anxiety, psychosis, seizures, Dr. Tod Mikuriya, founder of the Society of spasms, and other conditions without Cannabis Clinicians4, expressed hope that “our disconcerting feelings of lethargy or dysphoria. Burbanks in the hills” of Northern California would Scientific and clinical research—much of it develop CBD-rich strains if and when analytic labs sponsored by the US government—underscores began serving the medical cannabis industry. CBD’s potential as a treatment for a wide range of As the years went by, more and more promising conditions, including: scientific studies involving CBD were described at arthritis, diabetes, alcoholism, MS, chronic meetings of the ICRS, the International Association pain, schizophrenia, PTSD, depression, antibiotic- for Cannabinoid Medicine, and Patients Out of resistant infections, epilepsy, and other Time. neurological disorders. CBD has demonstrable 1 https://www.projectcbd.org/re-emergence-cbd-brief- 4 http://cannabisclinicians.org/ history 5 http://www.beyondthc.com/ 2 https://www.gwpharm.com/ 6 https://www.projectcbd.org/what-cbd 3 http://icrs.co/ Page 3 of 21 Cannabidiol and information for medical professionals. UK neuroprotective and neurogenic effects, and Tested several times by various analytical labs, the its anti-cancer properties are currently being initial CBD-rich strains (such as Harlequin, Sour investigated at several academic research centers Tsunami, Jamaican Lion, and Omrita Rx) ranged in the United States and elsewhere. from 8 to 10% CBD and 5.5 to 7% THC—about a 3:2 Project CBD responds to inquiries from all over the CBD:THC ratio. Yet anecdotal evidence suggested world. Almost everyone wants to know where to differing effects conferred by these strains. It get CBD-rich products and how to use them for seems likely that these differences lay in their maximum benefit. After decades in which only respective terpenoid profiles. high-THC cannabis was available in North America Another strain found in the early going, Women’s and beyond, CBD-rich strains and products are now Collective Stinky Purple, registered ten times the available to medical users. amount of CBD than THC. A few more strains with a similar CBD-dominant phenotype would soon be “CBD-rich” versus “CBD dominant:” identified and cloned for distribution. These CBD- By “CBD-rich,” we mean a cannabis strain or dominant strains (with names like Cannatonic, product that has equal amounts of CBD and THC, or ACDC, Charlotte’s Web, and Valentine X) are being more CBD than THC (usually at least 4 percent CBD grown largely to harvest cannabidiol for making oil by dry weight.). By “CBD-dominant,” we mean extracts. strains or products that are CBD-rich but have very It appears that some of these CBD-dominant little THC content. strains have different names but are actually the same plant. The LA-based Werc Shop analyzed the terpene content of two CBD-dominant strains, CBD rich Cannabis7 “Oracle” and “ACDC,” and found that they were CBD is the predominant cannabinoid in hemp— identical. cannabis grown for fiber or growing in the wild. “A terpene analysis is like a fingerprint,” explains Traditionally, plants grown for hashish in the Kush Werc Shop’s president Jeff Raber. “It can tell you if contained THC and CBD in equal measure. But in it’s the same strain with different names. We can recent times in the United States and elsewhere, see strains going by different names that have the cannabis genetics changed to accommodate a same terpene profile. We now know the strains are grassroots demand for high THC content. identical.” Consequently, CBD almost disappeared from the grassroots gene pool in Northern California, America’s cannabis breadbasket. Two broad categories of CBD-rich cannabis strains have emerged since the serendipitous rediscovery of whole plant CBD by Northern California growers in late 2009. There are a handful of CBD-dominant strains with little THC (just the opposite of what’s readily available on the recreational market and the medical marijuana gray market). And there are also more balanced cannabis strains with roughly equal—or significant—amounts of both CBD and THC. 7 https://www.projectcbd.org/cbd-rich-strains Page 4 of 21 Cannabidiol and information for medical professionals. UK Some misconceptions about CBD8 make you high like THC does. Project CBD categorically rejects this moralistic, reefer It doesn’t get you high, but it’s causing quite a buzz madness dichotomy in favor of whole plant among medical scientists and patients. The past cannabis therapeutics. (Read the foundational year has seen a surge of interest in cannabidiol science paper: A Tale of Two Cannabinoids.) (CBD), a non-intoxicating cannabis compound with 3. “CBD is most effective without THC.” THC and significant therapeutic properties. Numerous CBD are the power couple of cannabis commercial start-ups and internet retailers have compounds—they work best together. Scientific jumped on the CBD bandwagon, touting CBD studies have established that CBD and THC derived from industrial hemp as the next big thing, interact synergistically to enhance each other’s a miracle oil that can shrink tumors, quell seizures, therapeutic effects. British researchers have and ease chronic pain—without making people feel shown that CBD potentiates THC’s anti- “stoned.” But along with a growing awareness of inflammatory properties in an animal model of cannabidiol as a potential health aid there has colitis. Scientists at the California Pacific Medical been a proliferation of misconceptions about CBD. Center in San Francisco determined that a 1. “CBD is medical. THC is recreational.” Project combination of CBD and THC has a more potent CBD receives many inquiries from around the anti-tumoral effect than either compound alone world and oftentimes people say they are when tested on brain cancer and breast seeking “CBD, the medical part” of the plant, cancer cell lines. And extensive clinical research “not THC, the recreational part” that gets you has demonstrated that CBD combined with THC high. Actually, THC, “The High Causer,” has is more beneficial for neuropathic pain than awesome therapeutic properties. Scientists at either compound as a single molecule. the Scripps Research Center in San Diego 4. “Single-molecule pharmaceuticals are superior reported that THC inhibits an enzyme implicated to ‘crude’ whole plant medicinals.” According to in the formation of beta-amyloid plaque, the the federal government, specific components of hallmark of Alzheimer’s-related dementia. The the marijuana plant (THC, CBD) have medical federal government recognizes single-molecule value, but the plant itself does not have medical THC (Marinol) as an anti-nausea compound and value. Uncle Sam’s single-molecule blinders appetite booster, deeming it a Schedule III drug, reflect a cultural and political bias that privileges a category reserved for medicinal substances Big Pharma products. Single-molecule medicine with little abuse potential. But whole plant is the predominant corporate way, the FDA- marijuana, the only natural source of THC, approved way, but it’s not the only way, and it’s continues to be classified as a dangerous not necessarily the optimal way to benefit from Schedule I drug with no medical value. cannabis therapeutics. Cannabis contains several 2. “THC is the bad cannabinoid. CBD is the good hundred compounds, including various cannabinoid.” The drug warrior’s strategic flavonoids, aromatic terpenes, and many minor retreat: Give ground on CBD while continuing to cannabinoids in addition to THC and CBD. Each demonize THC. Diehard marijuana of these compounds has specific healing prohibitionists are exploiting the good news attributes, but when combined they create what about CBD to further stigmatize high-THC scientists refer to as a holistic “entourage cannabis, casting tetrahydrocannabinol as the effect,” so that the therapeutic impact of the bad cannabinoid, whereas CBD is framed as the whole plant is greater than the sum of its single- good cannabinoid. Why? Because CBD doesn’t 8 https://www.projectcbd.org/article/cbd- misconceptions Page 5 of 21 Cannabidiol and information for medical professionals. UK molecule parts. The Food and Drug foreign-grown hemp was already legal Administration, however, isn’t in the business of throughout the United States. approving plants as medicine. (See the scientific 7. “'CBD-only’ laws adequately serve the patient evidence.) population.” Fifteen U.S. state legislatures have 5. “Psychoactivity is inherently an adverse side passed “CBD only” (or, more accurately, “low effect.” According to politically correct drug war THC”) laws, and other states are poised to follow catechism, the marijuana high is an unwanted suit. Some states restrict the sources of CBD-rich side effect. Big Pharma is keen on synthesizing products and specify the diseases for which CBD medically active marijuana-like molecules that can be accessed; others do not. Ostensibly these don’t make people high—although it’s not laws allow the use of CBD-infused oil derived obvious why mild euphoric feelings are from hemp or cannabis that measures less than intrinsically negative for a sick person or a 0.3 percent THC. But a CBD-rich remedy with healthy person, for that matter. In ancient little THC doesn’t work for everyone. Parents of Greece, the word euphoria meant “having epileptic children have found that adding some health,” a state of well-being. The euphoric THC (or THCA, the raw unheated version of THC) qualities of cannabis, far from being an helps with seizure control in many instances. For unwholesome side effect, are deeply implicated some epileptics, THC-dominant strains are more in the therapeutic value of the plant. “We should effective than CBD-rich products. The vast be thinking of cannabis as a medicine first,” said majority of patients are not well served by CBD- Dr. Tod Mikuriya, “that happens to have some only laws. They need access to a broad spectrum psychoactive properties, as many medicines do, of whole plant cannabis remedies, not just the rather than as an intoxicant that happens to low THC medicine. One size doesn’t fit all with have a few therapeutic properties on the side.” respect to cannabis therapeutics, and neither 6. “CBD is legal in all 50 states.” Purveyors of does one compound or one product or one imported, CBD-infused hemp oil claim it’s legal strain. (Read more: Prohibition’s Last Gasp: “CBD to market their wares anywhere in the United Only.”) States as long as the oil contains less than 0.3 8. “CBD is CBD—It doesn’t matter where it comes percent THC. Actually, it’s not so simple. Federal from.” Yes it does matter. The flower-tops and law prohibits U.S. farmers from growing hemp leaves of some industrial hemp strains may be a as a commercial crop, but the sale of imported, viable source of CBD (legal issues low-THC, industrial hemp products is permitted notwithstanding), but hemp is by no means an in the United States as long as these products optimal source of cannabidiol. Industrial hemp are derived from the seed or stalk of the plant, typically contains far less cannabidiol than CBD- not from the leaves and flowers. Here’s the rich cannabis. Huge amounts of industrial hemp catch: Cannabidiol can’t be pressed or extracted are required to extract a small amount of CBD, from hempseed. CBD can be extracted from the thereby raising the risk of toxic contaminants flower, leaves, and, only to a very minor extent, because hemp is a “bio-accumulator” that draws from the stalk of the hemp plant. Hemp oil start- heavy metals from the soil. Single-molecule CBD ups lack credibility when they say their CBD synthesized in a lab or extracted and refined comes from hempseed and stalk. Congress may from industrial hemp lacks critical medicinal soon vote to exempt industrial hemp and CBD terpenes and secondary cannabinoids found in from the definition of marijuana under the cannabis strains. These compounds interact with Controlled Substances Act. Such legislation CBD and THC to enhance their therapeutic would not be necessary if CBD derived from benefits. (See also: Sourcing CBD: Marijuana, Industrial Hemp & the Vagaries of Federal Law.) Page 6 of 21 Cannabidiol and information for medical professionals. UK What are cannabinoids9 impact. For example, a preclinical study by Dr. Sean McAllister and his colleagues at the California Cannabis has been at the center of one of the most Pacific Medical Center in San Francisco report on exciting—and underreported—developments in how CBD destroys breast cancer cells by down- modern science. Research on marijuana’s effects regulating a gene called ID-1, which is implicated in led directly to the discovery of a hitherto unknown several types of aggressive cancer. Silencing the ID- biochemical communication system in the human 1 gene is, thus, is a potential strategy for cancer body, the Endocannabinoid System, which plays a treatment. crucial role in regulating our physiology, mood, and “Cannabidiol offers hope of a non-toxic everyday experience. therapy that could treat aggressive forms of cancer The discovery of receptors in the brain that without any of the painful side effects of respond pharmacologically to cannabis—and the chemotherapy,” says McAllister. subsequent identification of endogenous cannabinoid compounds in our own bodies that CBD and THC Synergy bind to these receptors—has significantly advanced According to McAllister’s lab, the best results were our understanding of human biology, health, and obtained when CBD was administered along with disease. THC. Several studies underscore the therapeutic It is an established scientific fact that cannabinoids advantages for combining CBD and THC— and other components of cannabis can modulate particularly for treating peripheral neuropathy, a many physiological systems in the human brain and painful condition associated with cancer, multiple body. Cannabinoids are chemical compounds that sclerosis (MS), diabetes, arthritis, and other trigger cannabinoid (and other) receptors. More neurodegenerative ailments. Clinical research than 100 cannabinoids have been identified in conducted by with GW Pharmaceuticals, a British the marijuana plant. Of these marijuana molecules, company, has also shown that CBD is most tetrahydrocannabinol (THC) and cannabidiol (CBD) effective as an analgesic when administered in have been studied most extensively. In addition to combination with whole plant THC. cannabinoids produced by the plant, there are endogenous cannabinoids (such as anandamide and 2AG) that occur naturally in the mammalian brain and body, as well as synthetic cannabinoids created by pharmaceutical researchers. Extensive preclinical research—much of it sponsored by the U.S. government—indicates that CBD has potent anti-tumoral, antioxidant, anti- spasmodic, anti-psychotic, anti-convulsive, and neuroprotective properties. CBD directly activates serotonin receptors, causing an anti-depressant effect, as well. In recent years, scientists associated with the International Cannabinoid Research Society (ICRS) have elucidated a number of molecular pathways through which CBD exerts a therapeutic 9 https://www.projectcbd.org/endocannabinoid- system Page 7 of 21 Cannabidiol and information for medical professionals. UK How CBD works10 the CB1 receptor, thereby muting the psychoactive effects of THC. Cannabidiol (CBD), a non-psychoactive component CBD also stimulates the release of 2-AG, another of the marijuana plant, has generated significant endocannabinoid that activates both CB1 and CB2 interest among scientists and physicians in recent receptor. CB2 receptors are predominant in the years—but how CBD exerts its therapeutic impact peripheral nervous system and the immune on a molecular level is still being sorted out. system. Cannabidiol is a pleiotropic drug in that it produces many effects through multiple molecular pathways. The Vanilloid Receptor CBD acts through various receptor-independent While CBD has little binding affinity for either of channels and by binding with a number of non- the two cannabinoid receptors, it has been shown cannabinoid receptors and ion channels. to directly interact with other “G-protein-coupled” Here are some of the ways that CBD confers its receptors and ion channels to confer a therapeutic therapeutic effects. effect. CBD, for example, binds to the TRPV-1 receptor, which is known to mediate pain CBD and FAAH perception, inflammation and body temperature. Unlike psychoactive THC, CBD has little binding TRPV is the technical abbreviation for “transient affinity to either the CB1 or CB2 cannabinoid receptor potential cation channel subfamily V.” receptors. Instead, CBD indirectly stimulates There are several dozen TRP receptor variants or endogenous cannabinoid signaling by suppressing subfamilies that mediate the effects of a wide the enzyme fatty acid amide hydroxylase (FAAH)— range of medicinal herbs. the enzyme that breaks down anandamide, the Scientists also refer to TRPV-1 as the “vanilloid first endocannabinoid discovered in the receptor,” named after the flavorful vanilla bean. mammalian brain in 1992. Vanilla contains eugenol, an essential oil that has Whereas the cannabinoid molecules found in antiseptic and analgesic properties; it also helps to cannabis are considered “exogenous ligands” to unclog blood vessels. Historically, the vanilla bean the cannabinoid (CB) receptor family, anandamide has been used as a folk cure for headaches. is an “endogenous” cannabinoid ligand—meaning CBD is a TRPV-1 “agonist” or stimulant. This is likely it binds to one or more cannabinoid receptors and one of the reasons why CBD-rich cannabis is an is found naturally inside the mammalian brain and effective treatment for neuropathic pain. body. Anandamide favors the CB1 receptor, which Capsaicin—the pungent compound in hot chili is concentrated in the brain and central nervous peppers—activates the TRVP-1 receptor. system. Because FAAH is involved in the metabolic Anandamide, the endogenous cannabinoid, is also breakdown of anandamide, less FAAH means more a TRPV-1 agonist. anandamide remains present in the body for a longer duration. More anandamide means greater The Serotonin Receptor CB1 activation. Jose Alexandre Crippa and his colleagues at the CBD enhances endocannabinoid tone by supressing University of San Paulo in Brazil and at the King’s FAAH. College in London have conducted pioneering By inhibiting the enzyme that metabolizes and research into CBD and the neural correlates of degrades anandamide, CBD enhances the body’s anxiety. innate protective endocannabinoid response. At At high concentrations, CBD directly activates the the same time, CBD opposes the action of THC at 5-HT1A (hydroxytryptamine) serotonin receptor, 10 https://www.projectcbd.org/how-cbd-works Page 8 of 21 Cannabidiol and information for medical professionals. UK thereby conferring an anti-depressant effect. This blood pressure and bone density, among other receptor is implicated in a range of biological and physiological processes. neurological processes, including (but not limited GPR55 promotes osteoclast cell function, which to) anxiety, addiction, appetite, sleep, pain facilitates bone reabsorption. Overactive GPR55 perception, nausea and vomiting. receptor signaling is associated with osteoporosis. 5-HT1A is a member of the family of 5-HT GPR55, when activated, also promotes cancer cell receptors, which are activated by the proliferation, according to 2010 study by neurotransmitter serotonin. Found in both the researchers at the Chinese Academy of Sciences in central and peripheral nervous systems, 5-HT Shanghai. This receptor is expressed in various receptors trigger various intracellular cascades of types of cancer. chemical messages to produce either an excitatory CBD is a GPR55 antagonist, as University of or inhibitory response, depending on the chemical Aberdeen scientist Ruth Ross disclosed at the 2010 context of the message. conference of the International Cannabinoid CBD triggers an inhibitory response that slows Research Society in Lund, Sweden. down 5-HT1A signaling. In comparison, LSD, By blocking GPR55 signaling, CBD may act to mescaline, magic mushrooms, and several other decrease both bone reabsorption and cancer cell hallucinogenic drugs activate a different type of 5- proliferation. HT receptor that produces an excitatory response. The Adenosine Receptor PPARs CBD’s anxiolytic (anti-anxiety) properties may in CBD also exerts an anti-cancer effect by activating part be attributable to its activation of the PPARs [peroxisome proliferator activated adenosine receptor. Adenosine receptors play receptors] that are situated on the surface of the significant roles in cardiovascular function, cell's nucleus. Activation of the receptor known as regulating myocardial oxygen consumption and PPAR-gamma has an anti-proliferative effect as coronary blood flow. The adenosine (A2A) receptor well as an ability to induce tumor regression in has broad anti-inflammatory effects throughout human lung cancer cell lines. the body. PPAR-gamma activation degrades amyloid-beta Adenosine receptors also play a significant role in plaque, a key molecule linked to the development the brain. They down-regulate the release of other of Alzheimer’s disease. This is one of the reasons neurotransmitters such as dopamine and why cannabidiol, a PPAR-gamma agonist, may be a glutamate. useful remedy for Alzheimer’s patients. PPAR receptors also regulate genes that are GPR55 involved in energy homeostasis, lipid uptake, Whereas cannabidiol activates the TRPV-1 vanilloid insulin sensitivity, and other metabolic functions. receptor, the A2A adenosine receptor, and the 5- Diabetics, accordingly, may benefit from a CBD-rich HT1A serotonin receptor, some studies indicate treatment regimen. that CBD functions as an antagonist that blocks, or CBD’s enzyme-mediated activation of the PPAR- deactivates, another G protein-coupled receptor alpha receptor may have antipsychotic effects. known as GPR55. Polymorphisms or mutations in the gene encoding GPR55 has been dubbed an “orphan receptor” PPAR-alpha can result in deficient PPAR-alpha because scientists are still not sure if it belongs to a signaling, which has been linked to schizophrenia. larger family of receptors. PPAR-alpha activation is both anti-inflammatory GPR55 is widely expressed in the brain, especially and can decrease dopamine release, thereby in the cerebellum. It is involved in modulating minimizing schizophrenic symptoms. Page 9 of 21 Cannabidiol and information for medical professionals. UK Synthetic v Whole Plant11 The Israeli team sought to determine whether the administration of a whole plant CBD-rich extract A ground breaking study from Israel has would also generate a bell-shaped dose-response documented the superior therapeutic properties of curve when administered to mice. Or would whole plant CBD-rich cannabis extract as compared cannabidiol extracted from CBD-rich Cannabis to synthetic, single-molecule cannabidiol (CBD). avoid this liability? “The aim of the present study,” Published in the journal Pharmacology & the authors explained, “was to find a CBD source Pharmacy (Feb. 2015), the article directly that could eliminate the bell-shaped dose-response challenges one of the sacred cows of Big Pharma of purified CBD.” and the medical-industrial complex -- the notion The scientists obtained a CBD-rich strain called that “crude” botanical preparations are inherently “Avidekel” from Tikkun Olam, an Israeli medical low grade and less effective than pure, single- marijuana producer. Referred to as “clone 202” in molecule compounds. this study, Avidekel has hardly any THC and Entitled “Overcoming the Bell-Shaped Dose- therefore is not intoxicating. The origins of Response of Cannabidiol by Using Cannabis Extract Avidekel can be traced to Spain, where breeders Enriched in Cannabidiol,” the article is all the more developed several phenotypes of “Cannatonic” (as noteworthy given the contribution of co-author in “cannabis tonic”), including a strain that Lumir Hanus, who was instrumental in the measures close to 20 percent CBD by dry weight discovery of anandamide, the endogenous with almost no intoxicating ingredients. (The same cannabinoid compound first identified in the high-yielding CBD-dominant strain is known as mammalian brain in 1992. “ACDC” in California.) Hanus and two Israeli colleagues from Hebrew The Israeli researchers extracted CBD-rich oil from University of Jerusalem surveyed the scientific clone 202. The extract—consisting of 17.9 percent literature and noted that during the past fifteen CBD, 1.1 percent THC, 1.1 percent years numerous preclinical studies had focused on cannabichromene (CBC), 0.2 percent cannabigerol the anti-inflammatory effects of pure, single- (CBG), and “traces” of cannabinol (CBN) and molecule CBD in animal models of various cannabivarol (CBDV)—was given to mice to pathologies, including rheumatoid arthritis, evaluate its anti-inflammatory and painkilling inflammatory bowel disease, multiple sclerosis, and effect. diabetes. (See preclinical data regarding CBD.) For comparative purposes, the scientists These studies showed that administration of pure, administered pure, synthetic CBD to another group single-molecule CBD resulted in a bell-shaped dose- of mice and assessed its anti-inflammatory and response curve, meaning that when the amount of analgesic properties. They also compared the CBD exceeded a certain point its therapeutic extent to which single-molecule CBD and whole impact declined dramatically. “Healing was only plant CBD inhibited the production of tumor observed when CBD was given within a very limited necrosis factor alpha (TNFa), a systemic dose range, whereas no beneficial effect was inflammatory signaling molecule. Dysregulation of achieved at either lower or higher doses,” the TNF-alpha production has been implicated in authors observed. This characteristic of single- several diseases including cancer, Alzheimer’s, molecule CBD — manifested as a bell-shaped dose clinical depression, and irritable bowel syndrome. response — imposes serious obstacles that limit its The pure CBD tests confirmed the findings of usefulness in a clinical context. earlier preclinical research. Once again, single- 11 https://www.projectcbd.org/article/synthetic-vs- whole-plant-cbd Page 10 of 21