Doctors of Chiropractic have long cared for their patients through the trifecta of Mind, Body and Spirit. Understanding the Endocannabinoid System (ECS) and how it affects all vertebrates is essential to all health care providers today, particularly those that are interested in chronic pain management. The American College of Physicians stated in its updated 2017 Guidelines that Chiropractic care is a preferred form of care for this condition. The ACP (http://www.aafp.org/afp/2008/0601/p1607.html) also recommended the immediate reduction of opiates from the treatment of Lower Back Pain – because more people (approximately 50,000) die from prescription opiate use every year than motor vehicle accidents.

The following Module is designed to offer all health care providers, particularly Chiropractors a model to include legal and available cannabinoids to the armamentarium of available treatment modalities currently offered to their patients.

A GENERAL OVERVIEW OF INDUSTRIAL HEMP AND MEDICAL CANNABIS

The hemp plant has provided food, clothing and shelter for the human race for over 10,000 years. Its roots go back to ancient China and India proven by the discoveries of hemp fabrics and paper in many archeological discoveries in Europe and Asia. Through time and civilizations, the many uses and benefits of hemp have been documented demonstrating the versatility in both nutritional and functional applications. The U.S. market is importing over $500 million in food and fiber from industrial hemp; mostly from Canada and China

Hemp is a complete source of nutrition containing 33% protein – the most digestible protein of any plant. Hemp contains all 20 known essential amino acids (“EAAs”) including the ten of which our bodies cannot produce and must be supplied in the food eaten daily. Amino acids are the building blocks of proteins and are necessary for building and repairing muscle tissue and are vital to the maintenance of a healthy immune system. Hemp also contains over 80% essential fatty acids (“EFAs”), the most compared to all other oilseeds. EFAs are considered “the good fats” because they cannot be produced by the body and must be consumed through diet for proper growth and body functioning. EFAs help burn excess fat, restore health to the cardiovascular system, relieve arthritis pain and inflammation, and strengthen the immune system. Hemp is also rich in Omega 3, 6 and 9 EFAs, which are essential to the proper development and functioning of the brain, reproductive systems, metabolism, as well as helping maintain the health of skin and hair and energy production. Hemp has long been recognized by the health and nutrition industry as a superfood, cited in many publications as a balanced source of all the ingredients required to achieve health and wellness.

Marijuana (Medical Cannabis) and Industrial Hemp are different varieties of the same species of plant, Cannabis sativa L. In comparison to hemp, marijuana has a higher THC content and a lower CBD content. A comparison of THC and CBD is provided below.

• THC, which provides the psychoactive effects, has been shown in some tests to have mild to very strong painkilling (analgesic) effects, and can be used for the treatment of pain. THC alters transmitter release in the spinal cord, resulting in chronic, nociceptive pain relief. The compound is also known to stimulate appetite, induces a relaxed state, and has effects on the person's sense of smell, hearing and eyesight. It can also cause fatigue. In some people, THC may reduce symptoms of aggression. Some limited studies have shown that THC shows promise for the treatment of nausea and/or
• CBD, which provides the non- psychoactive effects, has been shown in some studies to have a sedative effect and increase CBD has also been shown to relieve the symptoms of nausea, anxiety, inflammation and convulsions and have been suggested by oncologists to inhibit the growth of cancer cells. Scientists in more recent studies say CBD may be useful in treating atypical psychosis in schizophrenia patients, as well as relieving dystonia symptoms. Dystonia is a general term which describes involuntary movements and extended muscle contractions – the patient has tremor, unusual or awkward postures, and twisting body movements.

Industrial hemp is a cultivated, low-THC variety of Cannabis sativa L. It is grown for its seeds, oil and fiber. Industrial hemp contains up to 0.3% Delta-9 THC while marijuana contains approximately 5% to 30+% of THC. The U.S., Canada and the European Union maintain the distinction between hemp and marijuana by strictly regulating the THC levels of industrial hemp, requiring it to be less than 0.3%, compared to THC levels of between 3% and 30% percent in marijuana. In the U.S. and Canada, cultivars having less than 0.3% THC can be cultivated under legal federal, state and local license, while cultivars having more than that amount remain federally illegal.

The History of Medical Cannabis Use

Cannabis’ long and storied history begins in 2900 BCE, when the Chinese emperor Fu Hsi espoused its popularity as a medicine for a variety of ailments¹. In the next 3000 years, cannabis has appeared in an astonishing number of religious and medicinal texts from across the world: in 1500 BCE, it was lauded in the Chinese Rh-Ya pharmacopeia for treating hundreds of ailments²; cannabis residue was found on the body of King Ramses II of Ancient Egypt, where it was prescribed for pain and glaucoma³; the plant and its extracts were extolled as the most important of 10,000 medicines in the Venidad and the Vedas, the two most important texts for Zoroastrianism and Hinduism⁴; and Roman and Greek medical texts from circa 0 CE cite cannabis as treatment for various forms of inflammation like gout and joint pain^5,6.

This knowledge of cannabis’ medicinal power did not disappear after antiquity. The Oxford scholar and clergyman Robert Burton suggested cannabis as a treatment for depression in The Anatomy of Melacholy in 1621⁷ while Napoleonic France widely prescribed it as treatment for pain and insomnia⁸. By the middle of the 19^th century, every medical establishment in the world, be it professional or folk, had accepted the profound and varied uses of cannabis. In 1850, it was admitted into the United States Pharmacopeia, an official standards-setting authority for all prescription and over-the-counter medications. There, it listed cannabis as a treatment for neural pain, opiate and alcohol addiction, among many other conditions⁹, and American pharmaceutical companies like Eli Lilly produced standardized extracts for patients across the nation. However, this vast cultural and medical intimacy with cannabis was soon to be repressed and forgotten.

By 1936, every US state had outlawed or heavily regulated cannabis consumption¹⁰. New, more profitable and addictive drugs like morphine were developed, replacing cannabis as the West’s preferred pain medication. Hysteria and misinformation¹¹ about cannabis were spread by pharmaceutical, alcohol, and wood fiber companies (Specific citation needed), pushing cannabis further and further from the medical canon. Prohibition deepened until, in 1970, marijuana was classified by the Controlled Substances Act as a Schedule I drug—one so dangerous as to not have any conceivable medical merit¹². This downward trend in federal acceptance continues to the present day^13,14,15.

However, we have the power to reverse this current. Building the body of knowledge about cannabis is the first step to shaping a new cultural, political, and medicinal place for this plant in our society. This knowledge begins with study of the primary active constituents of cannabis: the cannabinoids. Eighty-five unique cannabinoids have been identified in the cannabis plant¹⁶, while only a handful has been chemically and pharmacologically characterized. The chemical mainly responsible for cannabis’ psychoactivity—including the euphoric and analgesic effects that have caused its demonization for the last 70 years—is Δ⁹-tetrahydrocannabinol, or Δ⁹- THC¹⁷.

Because of its outright and visible effects, Δ⁹-THC has been the most studied and characterized cannabinoid by far. Thousands of studies have been produced on human and animal pathways, effects, and pharmacokinetics of this one molecule (as evidenced by a search of its name on Google Scholar). Δ⁹-THC has been shown to have mild to moderate analgesic ability, proving successful in treatment of cancer pain¹⁸, as well as reducing the amount of morphine needed in acute, escape medication treatments¹⁹. THC’s anti-inflammatory ability is contested¹⁹, but success has been demonstrated in significant inhibition of atherosclerosis progression in mice. Atherosclerosis is the primary cause of heart disease and stroke in the West, and these effects were noted at much lower doses than typical doses producing psychotropic effects²⁰. We do know that THC is a potent neuroprotective anti-oxidant²¹, making it a powerful candidate for treatment of Alzheimer’s and other neurodegenerative disorders²². We also see significant anti- depressant like effects of THC in animal trials²³ However, by most clinical measures of therapeutic value, the much more visible THC is dwarfed by its lesser-known sister cannabinoid, Cannabidiol.

Cannabidiol, or CBD, is the other main active constituent in cannabis, and is an isomer of THC. This molecule is non-psychoactive²⁴, producing none of the intoxication that is associated with THC, but is no less physiologically powerful. Cannabidiol’s therapeutic actions on the brain are incredibly wide: it has not only anti-anxiety^27,28 and anti-psychotic^29,30 effects, but even stronger neuroprotective power than THC. This is by virtue of its potent antioxidant action³¹, which is significantly stronger than a- and b-tocopherol (vitamin E) and ascorbate (vitamin C). By virtue of this, there have been numerous successes and indications of success in treatment using CBD of degenerative neurological disorders, like Parkinson’s³⁰, Alzheimer’s³², and epilepsy³³. This last use has already been publicized by Sanjay Gupta’s documentary on the incredible story of Charlotte Figi, a little girl with Dravet’s syndrome—an intractable and severe form of childhood epilepsy—who was successfully treated with CBD; she went from hundreds of seizures a day to two or three a month, without any other prescription medication³⁴.

In the medical literature, there is a very interesting synergy between CBD and THC. CBD antagonizes or blocks the CB1 receptor and serves as the “antidote” to the high caused by THC. CBD appears to modulate the body’s metabolism of THC²⁵; thereby, antagonizing many of the psychotropic effects of THC. This results in a decrease in the often-reported negative effects of the psychoactive cannabinoid, like anxiety and loss of cognitive function²⁶. Other synergies have already been shown preliminarily³⁷, and we will only learn more of the subtle and complex interaction between the two main cannabinoids in the future.

Sources Cited

1. Dietch, Hemp: American History Revisited: The Plant with a Divided History, 2003
2. National Institute of Drug Abuse, Marijuana Research Findings https://archives.drugabuse.gov/pdf/monographs/14.pdf
3. Manniche, An Ancient Egyptian Herbal, 1989.
4. Booth, Cannabis: A History. 2005.
5. Booth, Cannabis: A History. 2005.
6. Lumír Ondrej Hanuš, Doctor of Sciences, CSc, RNDr "Discovery and Isolation of Anandamide and Other Endocannabinoids," Chemistry and Biodiversity, 2007
7. Grinspoon, “History of Cannabis as a Medicine," Statement for hearing by DEA Law Judge, Aug.16, 2005
8. US National Commission on Marihuana and Drug Abuse. "Marihuana, A Signal of Misunderstanding," org, 1972
9. Richard Glen Boire, Kevin Medical Marijuana Law. 2007.
10. Mark Eddy CRS Report for Congress: "Medical Marijuana: Review and Analysis of Federal and State Policies"  (515 KB) 2, 2010
11. Kevin Murphy Dan Studney  "Reefer Madness History," www.reefer-madness- com (accessed May 30, 2011
12. The Controlled Substances
13. Frontline "Busted: America's War on Marijuana," pbs.org (accessed July 21, 2010)
14. Kambiz Akhavan "Marinol Marijuana: Politics, Science, and Popular Culture," drugtext.org, 1997
15. Francis Young "Ruling in the matter of Marijuana Rescheduling Petition"  (2.6 MB), Sep. 6, 1988
16. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/
17. Cannabinoid pharmacology: the first 66 Pertwee RG. Br J Pharmacol. 2006 Jan; 147 Suppl 1():S163-71.
18. Noyes et al., 1975a J Noyes, S.F Brunk, D.A Baram. A Canter Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol, 15 (1975), pp. 139–143
19. A Holdcroft, M Smith, A Jacklin, H Hodgson, B Smith, M Newton, F Evans. Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia, 52 (1997), pp. 483– 486
20. Sabine Steffens, et Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 434, pp 782-786. 7 April 2005.
21. J. Hampson, M. Grimaldi, J. Axelrod, D. Wink. Cannabidiol and (−)Δ⁹- tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences and the USA. Vol 95, No. 14. July 7, 1998.
22. Mario van der Stelt, Vincenzo Di Marzo. Cannabinoid receptors and their role in Neuromolecular Medicine, Volume 7 Issue 1, pp 37-50. January 2005.
23. El-Alfy, T., Ivey, K., Robinson, K., Ahmed, S., Radwan, M., Slade, D., … Ross, S. (2010). Antidepressant-like effect of Δ⁹-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology, Biochemistry, and Behavior, 95(4), 434–442. http://doi.org/10.1016/j.pbb.2010.03.004
24. Barbara Costa, et Oral anti-inflammatory activity of Cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. 12 February 2004. Springer.
25. L.M. Bornheim, M.P. Grillo. Characterization of cytochrome P450 3A inactivation by Cannabidiol: possible involvement of Cannabidiol-hydroxyquinone as a P450 inactivator.
26. S.R. Calhoun, Gh.P. Galloway, D.E. Smith. Abuse potential of dronabinol (Marinol). J Psychoactive Drugs, 30 (2) (1998), pp. 187–196
27. A.W. Zuardi, I. Shirakawa, E. Finkelfarb, I.G. Karniol. Action of Cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology, 76 (3) (1982), pp. 245–250
28. S. Guimarães, T. M. Chiaretti, F. G. Graeff, A. W. Zuardi. Antianxiety effect of Cannabidiol in the elevated plus-maze
29. W. Zuardi, et al. Effects of Cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology 1991.
30. W. Zuardi, et al. Cannabidiol for the treatment of psychosis in Parkinson’s Disease. Journal of Psychopharmacology. Sept 18, 2008.
31. AJ Hampson, M Grimald, J Axelrod, D Cannabidiol and (−)Δ⁹- tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA, 95 (1998), pp. 8268–8273
32. Ana Maria Martin-Moreno. Cannabidiol and Other Cannabinoids Reduce Microglial Activation In Vitro and In Vivo: Relevance to Alzheimer's
33. Report of a parent survey of Cannabidiol-enriched cannabis use in pediatric treatment- resistant Brenda E. Porter, Catherine Jacobson
34. http://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/
35. se Alexandre de Souza Crippa, et al. Effects of Cannabidiol on Regional Cerebral Blood Neuropsychopharmacology 2004.
36. CARLINI, A. and CUNHA, J. M. (1981), Hypnotic and Antiepileptic Effects of Cannabidiol. Journal of Clinical Pharma, 21: 417S–427S. doi: 10.1002/j.1552- 4604.1981.tb02622.x
37. Russo, Ethan and Guy, Geoffrey W. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and Medical Hypotheses, 2006.

U.S. Industrial Hemp Legalization: Legal CBD Research Development & Commercialization: A Major Opportunity for ALL Health Care Providers

For centuries, industrial hemp has been a source of fiber and oilseed used worldwide to produce a variety of industrial and consumer products. Currently, more than 30 nations grow industrial hemp as an agricultural commodity, which is sold worldwide. Until 2014, U.S. domestic Industrial Hemp production was banned and controlled by the Drug Enforcement Agency (DEA).

However, the Agricultural Act of 2014 (Section 7606 of the U.S. Farm Bill) provided that certain research institutions and state departments of agriculture may grow industrial hemp, as part of an agricultural pilot program, if allowed under state laws where the institution or state department of agriculture is located. 2014’s Research, Development and Commercialization of Industrial Hemp encourages the research, development and commercialization of all things derived from Industrial

Hemp, including CBD. Summarily, the 2014 Farm Bill removes Industrial Hemp and all its byproducts from the U.S. Controlled Substances Act (CSA) to specify that the term “marijuana” does not include industrial hemp, thus excluding USDA “compliant”, domestically grown Industrial Hemp and its byproducts from the CSA as a controlled substance subject to DEA regulation.

The Farm Bill also established a statutory definition of “industrial hemp” as the plant Cannabis sativa L. and any part of such plant with a THC concentration of not more than 0.3% on a dry weight basis. The enacted fiscal year 2015 Appropriations Bill (Federal Omnibus) further blocked federal law enforcement authorities from interfering with state agencies, commercial hemp growers, hemp sellers and agricultural research by removing any federal funds from all federal enforcement agencies; such as, the DEA, FBI, and Department of Justice; thereby, ensuring legal INTERSTATE commerce of Industrial Hemp and all of its byproducts.

Very importantly, per FDA Guidelines, USDA “compliant”, Industrial Hemp derived, whole plant extracted CBD is not a “drug” but is considered a “food”; thereby, increasing the potential for clinical research of Industrial Hemp derived, whole plant extracted CBD by doctors and clinicians throughout the U.S. Summarily, this status affords CBD as a “non-prescription” item.

Our Group, Apothio, has worked with several Universities and State/Federal Attorneys to provide a complete legal Memorandum to the doctors and clinicians that are interested in the Research, Development and Commercialization of USDA “compliant”, Industrial Hemp derived, whole plant extracted CBD. Apothio has several University research/data sharing programs available for doctor-patient participation via crowdsourced data and individual case study. The patients purchase the CBD oil from the doctors and clinicians. The doctors and clinicians determine each patient’s dosages and clinical protocols. The patient then logs their HIPPA compliant data into a Mobile App. As the Data is collected, patient outcomes are tabulated by condition from across the U.S., tabulated and eventually submitted as white papers regarding the patient safety, outcomes and efficacy by condition and whole plant extracted CBD dosage.

Whole Plant Cannabis Extractions are a “Game Changer”

This is an important opportunity for the doctors and clinicians working with the Holistic Cannabis Academy. Medical Cannabis, whether Industrial Hemp or Medical Marijuana derived may be a game changer to the Allopathic Community. Based upon the medical literature, my professional clinical experience with cannabinoids and most importantly, the “Entourage Effect” theories of Dr. Raphael Mechoulam and HCA Instructor, Dr. Ethan Russo, strongly supports the notion that whole plant extracted cannabinoid oils are far safer, cheaper and more effective to the patient than fractionated/isolated cannabinoid preparations.

Simply put, the synergistic combination of ALL natural constituents in the cannabis plant are critical to the toxicology, safety, outcome and efficacy of cannabis use. Research must now focus, not only on the cannabinoid ratios, but also on the combinations of terpenes, flavonoids, chlorophyll, fats, waxes, enzymes, and all other active ingredients found in this whole, natural plant medicine. Based upon our emerging data, the whole plant combination, or “Entourage Effect” profoundly reduces dosage demand levels of CBD by patient and by disease; thereby, reducing the risk of drug to drug interaction risks. For example, this is quite evident in the

dosage levels of young children with catastrophic seizures using fractionated, isolated cannabinoid molecules found in GW Pharmaceutical’s epilepsy drug, Epidiolex. Per current anecdotal patient outcomes in the State of Missouri, these children are on CBD doses from 5 to 50 mg/kg of total body weight. To date, we have seen whole plant extracted CBD doses on these same patients that do not exceed 2 mg/kg of body weight. CBD doses this low do not appear to create issues with the p450 pathway in the liver; thereby, reducing or eliminating the risk of drug to drug interactions like those seen between fractionated or isolated CBD and the benzodiazepine category.

The current work of Perry Fine, MD (reference attached) solidly supports this clinical finding as well. Dr. Fine’s focus on chronic pain, CBD and Beta-Caryophyllene are well done and offer excellent explanations of the metabolic activities found in these two “cannabinoids”.

“The Entourage Effect” of Whole Natural Plant Extracted Cannabis

The “entourage effect” was first described in 1998 by Dr. Raphael Mechoulam (discoverer of cannabinoids and the endocannabinoid system). It was observed that a dose of pure synthetic cannabinoid had weaker physiologic effects than the same dose of cannabinoid derived from a whole-plant extract (containing the other molecules in the plant, such as the sterols, terpenes, and other cannabinoids).

“The results of these studies have implicated the endocannabinoid system (ECS) in a variety of physiopathological processes, both in the peripheral and central nervous systems and in various peripheral organs. They further suggested that modulating ECS activity may have therapeutic potential in almost all diseases affecting humans, including obesity/metabolic syndrome, diabetes and diabetic complications, neurodegenerative, inflammatory, cardiovascular, liver, gastrointestinal, skin diseases, pain, psychiatric disorders, cachexia, cancer, chemotherapy-induced nausea and vomiting, among many others.”

-2014 paper by Dr. Pal Pacher, MD/PhD & Dr. George Kunos, MD/PhD, Senior Investigators, Laboratory of Physiologic Studies, U.S. National Institutes of Health

“…pre-clinical research (including both cell culture and animal models) has shown CBD to have a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties.…alterations in thinking and perception caused by THC are not observed with CBD. A review of 25 studies on the safety and efficacy of CBD did not identify significant side effects across a wide range of dosages, including acute and chronic dose regimens, using various modes of administration. CBD is present in nabiximols which, as noted earlier, is approved throughout most of Europe and in other countries. Because of this there is extensive information available with regard to its metabolism, toxicology, and safety” -Dr. Nora Volkow, MD, Director, U.S. National Institute on Drug Abuse, testifying in front of congress in 2015.

Doctors of Chiropractic CAN Legally Prescribe USDA Compliant, Industrial Hemp Derived, Whole Plant Extracted Cannabidiol (CBD)

Cannabidiol, or CBD, is the leading active cannabinoid in Industrial Hemp. This molecule is non-psychoactive¹, producing none of the intoxication that is associated with THC, but is no less physiologically powerful. Cannabidiol’s therapeutic actions on the brain are incredibly wide: it has not only anti-anxiety^3,4 and anti-psychotic^5,6 effects, but even stronger neuroprotective power than THC. Chris Evans, PhD is the Director of UCLA’s Brain Institute. Through personal communication with Dr. Evans, he states that CBD is the most potent anti-inflammatory to the brain that he has seen to date. In theory, CBD may be restoring control of the microglia (macrophages of the brain) cells; thereby, reducing or eliminating unbridled inflammation in the brain. By virtue of this, there have been numerous successes and indications for treatment using CBD for degenerative neurological disorders, like Parkinson’s⁷, Alzheimer’s⁹, and epilepsy¹⁰.

This last use has already been publicized by CNN’s Sanjay Gupta documentary on the incredible story of Charlotte Figi, a little girl with Dravet’s syndrome—an intractable, catastrophic form of childhood epilepsy—who was successfully treated with CBD; she went from hundreds of seizures a day to two or three a month, without any other prescription medication¹¹. The unfortunate part of the Charlotte’s Web strain is that it is marijuana and federally illegal because its THC content exceeds 0.3%.

Our research team at Apothio, developed multiple federally legal Industrial Hemp strains from high CBD low THC marijuana strains. The leading strain was named “Noah” after whom the first child this cannabis variety was administered to over 3 years ago. Apothio developed these cannabis varieties naturally, organically in Apothio’s patented aquaponic systems. The Noah strain is different from the Charlotte’s Web strain because Noah is Industrial Hemp, while Charlotte is marijuana. Charlotte’s Web contains about 1% THC content; thereby, classifying Charlotte’s Web as Marijuana under U.S. Federal Law. The Noah strain is less than 0.3% THC; thereby, ensuring that Noah is an Industrial Hemp strain and federally legal under the USDA Farm Bill, Section 7606. Adding to the “Entourage Effect”, the Noah strain also concentrates up to 50 mg/g of terpenes, including a variety of concentrations of beta-caryophyllene, humulene, caryophyllene oxide, linalool, limonene, myrcene, bisabolol, terpinolene, phytol and more.

CBD’s benefits are not limited to extreme cases; CBD has been shown preliminarily to increase circulation in areas of the brain¹², as well as global anti-inflammatory action^1,2,16. This could prove useful for a wide variety of pain, from arthritis to non-disease related, acute pain in healthy individuals. And because no toxicity or negative effects have been recorded^11,16, CBD presents a safe treatment for almost any kind of patient.

Because of the many natural benefits of CBD in all vertebrates, CBD will have a tremendous international economic effect. Thus, the production of Industrial Hemp derived, federally legal CBD will strongly the economic development of agriculture. It is apparent that CBD will satisfy a complete consumer spectrum as a widely used food additive, nutraceutical and in some cases, a

pharmaceutical^15,16. USDA and FDA Policy is shifting towards strong support of domestically derived, industrial hemp derived CBD sources as opposed to the existing foreign sources of CBD^15,16. Also, the FDA considers CBD derived from whole plant extractions of Industrial Hemp to be a “food” and not a “drug”; thereby, making CBD a candidate for inclusion into the entire U.S. food chain.^15,16. Without reservation, the U.S. States that lead and support deploying CBD as an Industrial Hemp derived “food” via Section 7606 of the USDA Farm Bill will enjoy immediate and long term significant economic benefits from the production of Industrial Hemp.

As a Chiropractor, this point is very important to understand. Our Chiropractic training teaches that our “food is medicine”. Understanding the metabolic pathways from our dietary intake plays a significant role in everyday wellness and clinical intervention. The following key points should be taught to each and EVERY one of our patients going forward:

• Endocannabinoids are normal to the human
• Mother’s milk contains These endocannabinoids help stabilize the child’s natural homeostasis system, while stimulating the baby to nurse and eat.
• Omega-3 Essential Fatty Acids are the metabolic pre-cursor to the natural production of
• Over 75% of the Westernized Diet consumers are deficient in Omega-3 EFA’s due to the very high presence of Omega-6 EFAs found in corn and
• Excessive Omega-6 dietary intakes drive the cytokine chains in humans; thereby, leading to a chronically proinflammatory body, CNS and immune This is a leading cause of dietary induced heart disease, type 2 diabetes, metabolic syndrome, chronic pain syndromes, autoimmune syndromes, some cancers and the list goes on.
• Chronic deficiencies of Omega-3 EFA’s lead to chronic deficiencies of natural endocannabinoids; thereby, leading to whole body, brain and immune system chronic
• This chronic inflammation can lead to and perpetuate a myriad of human
• The phytocannabinoid found in Industrial Hemp, Medical Cannabis and in other whole natural plants, can replace the endocannabinoid and effectively “turn off” the chronic inflammatory patterns in the body, brain and immune
• Chronic pain patients “burn up” excessive amounts of tryptophan because of the positive feedback loops found in the cytokine chains. This is why we often provide chronic pain patients with 5-HTP, so we can restore the tryptophan base, while suppressing the activity of the cytokine
• CBD appears to have the following actions on chronic pain patients’ metabolic pathways:
  • Reduces acute and chronic pain patterns through 45 known, metabolic pathways in humans (Jeff Chen references). Ibuprofen is known to reduce pain patterns through only two pathways (COX pathways)
  • CBD appears to not only increase tryptophan and serotonin production levels, but also acts as a tryptophan and serotonin recycler (SSRI) by reducing the enzymes that breakdown tryptophan and
  • Increased levels of tryptophan to serotonin increases melatonin production and availability; thereby, improving the patient’s ability to rest, sleep and
  • CBD is known to reduce nociceptive pain generation at the spinal cord. (Perry Fine reference)

1. Barbara Costa, et Oral anti-inflammatory activity of Cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. 12 February 2004. Springer.
2. M. Bornheim, M.P. Grillo. Characterization of cytochrome P450 3A inactivation by Cannabidiol: possible involvement of Cannabidiol-hydroxyquinone as a P450 inactivator
3. S. Guimarães, T. M. Chiaretti, F. G. Graeff, A. W. Zuardi. Antianxiety effect of

Cannabidiol in the elevated plus-maze

6. W. Zuardi, et al. Effects of Cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology 1991.
7. W. Zuardi, et al. Cannabidiol for the treatment of psychosis in Parkinson’s Disease. Journal of Psychopharmacology. Sept 18, 2008.
8. AJ Hampson, M Grimald, J Axelrod, D Cannabidiol and (−)Δ⁹- tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA, 95 (1998), pp. 8268–8273
9. Ana Maria Martin-Moreno. Cannabidiol and Other Cannabinoids Reduce Microglial Activation In Vitro and In Vivo: Relevance to Alzheimer's
10. Report of a parent survey of Cannabidiol-enriched cannabis use in pediatric treatment- resistant Brenda E. Porter, Catherine Jacobson
11. http://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/
12. se Alexandre de Souza Crippa, et al. Effects of Cannabidiol on Regional Cerebral Blood Neuropsychopharmacology 2004.
13. CARLINI, A. and CUNHA, J. M. (1981), Hypnotic and Antiepileptic Effects of Cannabidiol. Journal of Clinical Pharma, 21: 417S–427S. doi: 10.1002/j.1552- 4604.1981.tb02622.x
14. Russo, Ethan and Guy, Geoffrey W. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and Medical Hypotheses, 2006.
15. Grahn, Michael and Martin, Memo Re: Foreign vs. Domestic CBD Oil, 10-4- 15.
16. Jones, Trent and Shontz, Production of CBD from the Hemp Stalk ONLY Revised, 11-18-15.

Noah’s Activities of Daily Living Post-CBD Treatment per OT/PT 1-25-16:

Young Noah was born with Dravet’s syndrome. Before Noah began Industrial Hemp derived, whole plant extracted CBD treatment as a 7 year old boy, he had up to 200 seizures per day. He

could barely walk or get out of bed, he could not run, could not talk, could not go to school or leave his home. He and his entire family suffered terribly from these horrible seizures.

3 years later, based upon my research and clinical experience within this sector, the children within the catastrophic seizure and possibly Autism Spectrums, appear to have a genetic, metabolic fracture in their ability to convert Omega-3 EFAs into endocannabinoids. As a result, the brains of these children are “on fire” and administration of the phytocannabinoids CBD and THC (appropriate ratios) immediately and dramatically reduce the whole CNS inflammation.

These children enjoy immediate reductions in seizures, their sleep patterns immediately improve and their cognitive development accelerates at unprecedented rates. In these cases, when phytocannabinoids work, it is truly magic! As any form of health care provider, I would encourage as much research and activity as possible with these patients. Autism is an epidemic and Catastrophic Seizures are heartbreaking without supportive treatment. Help these patients wherever you can.

To date, Noah has 1 or 2 light seizures per month. He is thriving, growing and able to enjoy life with his family. The positive changes to Noah and his entire family are profound.

Vast areas of improvement AND STABILITY in ADLs (Activities of Daily Learning) including but not limited to:

• Eating
• Sleeping
• Play/social interaction
• Education
• Significant areas to note:
• Better sleep patterns
• Going to age appropriate public places - Toys R Us, Lowe's, Meijer, Disney, playgrounds (safer), hotels, etc.
• School: increased frequency, more social interactions with friends, ability to deal with changes, knowledge of the school routine, fantastic joint

Other HUGE improvements:

• Fine motor skills
• Gross motor skills
• Safety in movements throughout his environments
• Completing puzzles, stacking blocks and objects
• Developmental skills that he missed and is now going back and performing (crawling, interest in dramatic play manipulatives)
• Movement and gait improvement - running smoothly
• Direct handing and showing others objects
• Playing reciprocal games such as rolling/throwing a ball
• Initiating games of his choice
• More direct and consistent yes/no responses, making true choices
• Fast and direct responses to others' comments and questions
• Generalization of skills throughout multiple environments with a variety of

Joe’s Before and After “Noah’s CBD” Treatment Video https://www.youtube.com/watch?v=AXCFDGXOQC0&feature=youtu.be

One can quickly see why this patient should be co-managed by a Doctor of Chiropractic for mechanical issues alone. The CBD is managing the drop seizures; however, serious biomechanical issues are yet to be resolved. Joe is also autistic. As his seizures dropped from 300 per day down to 2 – 3 “head nods”, his cognitive skills improved dramatically as well.

Clearly, untreated autism is unbridled inflammation between the gut and CNS. CBD appears to help relieve both.

Noah’s CBD Oil Dosage Recommendations:   www.beleafco.com

The Missouri BeLeaf Group is exclusively focused on catastrophic seizures. However, the dosage rates are comparable. The following dosages are in milligrams of CBD per total pounds of body weight per day (24 hour period).  Normally, these dosages are reported in milligrams per kilogram, but patients tend to understand mg per pound of their own body weight better, not requring metric conversions.

In general, begin a patient at 1 mg of CBD per 1/4 pound of total body weight per day (24 hour period) for the first 2 weeks. Use this dosage as the base and after 2 weeks, create a forced dose escalation of the total CBD milligrams per day, notching up to 1 mg of CBD per 1/3 of total body weight for 2 weeks. Please assess your patient’s overall improvements and determine if that patient should decrease, remain at the same level or increase the CBD dosage to the next increment (1/2 pound) and so on up to 1 mg per 1.0 pound of total body weight per day (24 hour period).

ALWAYS Shake the bottle of CBD Tincture Bottle Vigorously BEFORE Consumption

The following is revised from the www.beleafco.com website regarding CBD administration:

Noah’s CBD is bottled at a 15 mg/ml concentration, which means for every milliliter of oil (20 drops from an eyedropper) in the bottle, there are 15 mg of CBD oil derived from the whole plant extraction of the Noah Industrial Hemp strain that is grown in the U.S.A.

Appropriate dosage is suggested to be up to 1 mg of CBD oil per pound of body weight per 24 hour period. It is also recommended that this dosage be divided upon into two increments AND WITH FOOD (as it appears that taken with food increases absorption rates by 5 – 6 fold):

1. 1/3 of the total dosage delivered in the morning, and

1. 2/3 of the total dosage delivered in the

The included pipette makes it simple to pull the appropriate milliliters of oil from the bottle for a “swish and swallow” sublingual delivery of the CBD oil. For example, if the consumer weighs 100 pounds, and assuming for that person the recommended dosage for that person is 1 mg per

pound of body weight per day, then that patient would consume 100 mg of CBD per 24-hour period (WITH FOOD), calculated as such:

2. The morning dosage is approximately 33 mg of CBD, and at 15 mg/ml CBD concentration, this person will consume 33 divided by 15 (mg/ml concentration) = 2.2 ml of the
3. The evening dosage is 67 mg of CBD, and at 15 mg/ml concentration, this person will consume 67 divided by 15 = 4.5 ml of the

This 100 pound person is consuming approximately 6.7 ml of the CBD tincture per 24 hour period and within this 6.7 ml of oil, there are 100 mg of CBD.

Additional Nutritional Considerations for Our Patients

It is clear that chronic, severe inflammation to the central nervous system, regardless of original cause, is the key player for the Chiropractor to control. Cannabinoids are known to reduce inflammation to both the body and brain through many chemical and neurological pathways.

CBD is specifically used to treat the neurological inflammation, while all other modalities available to the Doctor of Chiropractic can help manage the mechanical aspects of chronic and acute pain. In addition to the CBD, we have learned through extensive patient care that the following recommendations will also support the patient’s ability to positively affect chronic inflammation and pain.

Please do whatever you can to absolutely always AVOID these foods, beverages and ingredients as they can aggravate and increase pain perception and chronic inflammation. (PLEASE READ YOUR FOOD AND BEVERAGE LABELS!):

• Glutamates (MSG, hydrolyzed vegetable protein, and many more names. Please review the list of the various MSG food label names as there as many as 100 different names for glutamates),
• Aspartame (the blue packet of artificial sweeteners…many diet beverages and foods contain Aspartame),
• Processed foods have so many unwritten ingredients in them, and can become terrible sources of inflammation to the central and peripheral nervous If you can avoid processed foods, then please do.
• Margarine and Vegetable oils: Please use butter (grass fed is always best) and cooking oils that add Omega-3’s to your daily Hemp Seed, Olive Oil, Walnut Oil, Almond Oil, etc. They are much better for our bodies and brains than processed oils.

• Trans-Fats fit into this They are terribly pro-inflammatory to the cardiovascular and neurological systems.

• When using the microwave, use glass only and do not use plastics in the microwave. Plastics, styrenes, solvents, leach into the foods and beverages while microwaving and that’s bad for the whole family. Microwaves are okay, just use glass.
• High Fructose Corn Syrup: That sugar is so concentrated that it goes straight to fat and is hard on the liver when metabolizing the sugar substitute. High Fructose Corn Syrup is more proinflammatory to the liver than alcohol consumption, so buyer beware!
  • Use honey, brown sugar, stevia and other natural
• One of the best ways to remember what to eat or what not to eat….try this: If man (processed) made it is likely best to avoid it, but if God (all natural) made it, then eat up!

Please ADD the following to your patients’ diets and daily routines to further decrease proinflammatory conditions (this will work for most conditions, but also particularly helpful for catastrophic seizures):

• Organic Foods and beverages: It is unbelievable the number of chemicals in our environment today and eating organic is a simple way to reduce exposure to these pro- inflammatory
  • If you have the ability to grow your own garden, then please do! Not only can you produce some of the finest foods your family could ever consume, gardening will add vitamin D3 (sunshine vitamin) to your body, while also offering a beautiful space to relax and commune with family, friends and
  • Free Range Chicken eggs: Eggs are a wonderful source of nutrition and the Free Range egg is known to offer triple the nutrient density over a “factory chicken egg”, including the flavone glutathione. Glutathione is very helpful to the removal of heavy metals and contaminants from our body and brain.
  • Cilantro is another great food and herb that will help with the removal of heavy metals and contaminants from the brain and body. Please add that to your garden and
• Probiotics: EVERY day there is more and more supportive clinical data regarding the importance of the natural bacteria in our gastrointestinal systems play a vital role to homeostasis, mood control and vitamin K

• Please add and increase live culture yogurts, sauerkraut, Kim-Chi, kombucha and other fermented foods and beverages can strongly support the gut and normal brain
• Also, please do NOT over sanitize/clean your house with bleach and “anti- bacterial soaps” as the data suggests that this over-sterilized environment is pro- inflammatory to our body and brains.

• Vitamin D3: A natural anti-inflammatory to the central nervous system. Please consult with your doctor to determine normal blood Vitamin D3 A daily supplement up to 10,000 International Units may be necessary to normalize D3 blood levels, especially throughout the winter months.
  • Since many chronic pain patients are not in the sun, these patients will be chronically deficient in Vitamin D3, so supplementation may be the best route to further decrease inflammation and pain
• Omega-3 Essential Fatty Acids: A normal Omega-6 to Omega-3 ratio in our body ranges from 1:1 to 1:3 Omega-6 to Omega-3. Today’s diet is terribly overrun with Omega-6 (corn and soybeans) and terribly deficient in Omega-3’s. Please determine if the dosage levels of your patients should meet or exceed 2,000 mg of Omega-3
  • Dietary Sources of Omega-3’s are wild caught fish, especially sardines, mackerel, salmon, bluegill, crappie, largemouth bass and striped bass, AND grass fed beef, free range chicken eggs and some forms of edible grasses/algaes.
• Multivitamin/Multimineral: Our food is not what it used to be, so it is recommended by many leading alternative health care providers, that we take 1 – 2 of these supplements per day. Always take vitamins with food to ensure the highest absorption rates of the
  • Please make sure that these supplements are great sources of the entire B- Complex of vitamins, as the B vitamins strongly support the nervous system.
• Adequate hydration is vital to a healthy body. Water is always the best source of hydration, along with organic teas, some coffees and cold pressed juices. These additional forms of hydration can also provide excellent sources of supportive nutrients, anti-oxidants and anti-inflammatories. Of course, watch the caffeine, especially on an empty
• Sensory Afferentation: Our brain is driven by sensory input. We know that our friends with catastrophic seizures can sometimes become overwhelmed with sensory input and fall into a However, during the calmer times of this person’s life, sensory input to the spinal cord and brain through massage, chiropractic adjustments, acupressure,

vibratory sensation, crawling, walking, and more will help the entire brain further develop, re-map (neuroplasticity) and reduce pain perception over time.

• Stress Management: The world can be a very stressful place and helping to manage the activity of catastrophic seizures can sometimes seem insurmountable, so please do not forget to take a breath every now and again by:
  • If the capacity and activities are available, please don’t forget to go for walks, try yoga, listen to music, sing, laugh, play, listen to the rain, birds singing and enjoy your families…one simple moment at a
  • If you are a spiritual person, the last recommendations will make even more sense to commune with nature and say a prayer while enjoying those
• Sleeping and Dreaming: One of the first things noticed with CBD therapy, the consumer’s sleep patterns will improve quickly. Lots of sleep and that is a very good thing for our brains, especially for the catastrophic seizure patient. It is also likely to notice that this person has begun to dream within a few weeks of CBD onset. Dreaming is an excellent activity for the brain and strongly supports neuroplasticity (re-wiring or re- mapping) of the brain. For the children with catastrophic seizures, the onset of dreaming may be a new activity for that child, so be prepared to explain “dreaming” to the

List of Glutamates as Labeled: (Interestingly, the U.S. Government (US 6,630,507) owns a patent on CBD and its antioxidative and neuroprotectant effects from glutamates)

Various Ways Free Glutamate (MSG) is Labeled on Foods

CBD Side Effects

As a practicing Chiropractor, I treated more than 20,000 patients over a 25+ year career. I retired at the end of 2013 to begin the research on Industrial Hemp derived CBD. I have “consumed” this subject by living off-grid in the Mojave Desert for 2 and ½ years developing these Industrial Hemp CBD varieties, while treating hundreds and hundreds of patients of varying conditions with CBD. I wanted to understand, firsthand, what worked

clinically and what did not work clinically by disease, while also deeply understanding the safety, toxicology, dosage by delivery system and ultimate patient outcomes. The following are a few key notes to remember:

• Cannabinoids are incredibly effective in a myriad of diseases in all
• Cannabinoids are not a panacea and are not without side
• Cannabinoids CANNOT cause direct death to the No one has EVER died from cannabinoid use because the brain stem is devoid or nearly devoid of any cannabinoid receptors. Unlike cannabinoid receptors, the brain stem does have a high concentration of opiate and alcohol receptor sites, which is how opiates and alcohol literally “turn off” our innate reflex to breathe.
• CBD is best used for chronic conditions; such as, autism, anxiety, some autoimmune syndromes, epilepsy, chronic pain syndromes, insomnia, metabolic syndromes, neurodegenerative syndromes, some cancers, and much
• CBD is anti-microbial and shown to kill
• As an anti-inflammatory, THC is up to 3 – 4 times more potent than corticosteroids, and without the horrible side effects of THC works very well for acute pain.
• THC is likely to become a game changer in the treatment of Alzheimer’s because it is being shown to reduce or eliminate amyloid plaquing in the degenerating
• In the appropriate ratios, CBD can completely control the psychoactive side effect of THC, making CBD and THC a “dynamic duo” targeted at a myriad of
• Chronic THC use does adversely affect short term memory at the hippocampus/hypothalamus/amygdala.
• The half-life of CBD is 4 hours for the first half of the molecule; however, the second half of the CBD molecule administered is consumed at a much slower The second half takes between 24 and 36 hours to consume. Thus, if your patient is taking CBD every day, then that patient has an ability to build up a reserve of CBD. During this time, this is the art of the clinician, ensuring that each patient is consuming the appropriate amounts of CBD.
• We have seen very few side effects from CBD, but they are:
  • Drowsiness: This is actually a good sign. Chronic pain patients typically do not sleep CBD patients usually begin to sleep better the very first night of dosage.   This appears to be due to the increase in the tryptophan, serotonin and melatonin levels.
  • “Flat Feeling”: CBD is an antagonist to the CB1 receptor in the    This is how it blocks the high from THC. This also can affect the “drive” center to the brain if the patient is taking too much CBD. So if a patient feels flat or less motivated, perhaps you want to lower the dosage for a period of 3 – 4 weeks to determine clinical effects.
  • Isolated or Fractionated CBD (and THC) become proinflammatory due to the lack of the “Entourage Effect”. This is seen most dramatically in the treatment of epilepsy The fractionated CBD requires exponentially higher dosages to reduce seizure rates, while delivering significantly more side effects, including status epilepticus in seizure patients.

CBD As Opiate Replacement Therapy

On a final note about CBD, there is an enormous opportunity for the all health care providers that do NOT prescribe Opiates. Chiropractors are especially aligned (pun intended) to excel as non-opiate pain managers because of joint manipulation, nutritional and wellness backgrounds. CBD literally blocks the reward centers (CB1 receptors) for alcohol, nicotine and opiates in the brain. We have performed many, many case studies on the safety and efficacy of CBD as opiate replacement therapy. The dosages remain the same as above. CBD is administered while the patient is steadily weaned away from their prescription opiate use. Please collaborate with these patients’ Medical Doctors to ensure patient safety.

A Call for Case Studies and Crowdsourced Data from Our Mutual Patients

The following study drafts are for your review and comments.   Apothio would love to support research, development and limited commercialization of USDA compliant Industrial Hemp derived, whole plant extracted CBD. Please contact leadership at HCN/HCA if you have a desire to participate in these and other research models.

Respectfully submitted
Trent Jones, DC
drtjones@comcast.net
765-327-1016 (cell)

Trent can add a few research protocols if desired.

Potential, Future Research Projects for the Chiropractic Community via the Holistic Cannabis Network and University Affiliations of NICER and Apothio

Severe Drug Resistant Forms of Epilepsy include Dravet’s, Doose and Lennox-Gestault syndromes as well as many other forms of infantile onset catastrophic seizures: This document very briefly outlines current thoughts, suggested Integrative Clinical Management, suggested areas of study and suggested testing protocols.

Prepared and Submitted by: Trent Jones, DC March 3, 2016

The Pediatric Neurologist is the lead physician in these cases, while supportive, integrative care is found with Chiropractors, Clinical Nutritionists, Speech and Occupational Therapists, Teachers, and most importantly Mom and Dad.

The following physiological categories should be reviewed as treatment protocols of patients suffering from catastrophic seizures:

Neuroplasticity: Per existing anecdotal data, personal clinical management, existing case studies, ongoing clinical trials published in current scientific journals, there are immediate and profound neurological changes in the CNS of these children when they are properly dosed with varying doses and deliveries of Cannabidiol (CBD). To varying degrees, the supportive natural whole cannabis plant companion molecules; such as the beta-caryophyllene, linalool, myrcene and more, also play a role in the changes in the CNS. Design studies to better understand the metabolic and neurological mechanisms in play during these positive changes. Because of the seizures, these children must endure catastrophic effects regarding their neurological and intellectual development. Based upon the last 23 months of clinical outcomes with whole plant CBD treatment, positive clinical affects begin quickly. Because of the significant effects, it is appears that the brain is not unilaterally, permanently impaired by these syndromes. Why? This provides an opportunity to develop a SERIES of integrative health care studies to identify the sources of causation, best treatment practices and clinical outcomes for these children and adults.

The link below shows an autistic child who also suffers from catastrophic drop seizures, before and after treatment with whole plant CBD oil. He has been a patient participant for 23 months and has found significant relief in both seizure rates and overall neurological/cognitive development.

https://www.youtube.com/watch?v=DWEJsNDwY0g

Chronic Inflammation: The CNS (and possibly the entire body) of these children is under constant, severe inflammation. What are the mechanisms chemically and neurologically? Are these children genetically or metabolically deficient in endocannabinoids? If so, are there any chemical markers or other inflammatory-related agents that will help predict clinical management methods and outcomes/for these children? Regarding inflammation, another goal of this research is to also review the current known laboratory and imaging inflammatory indicators, as well as the nutritional players found in chronic inflammatory conditions. For example, Omega-3 deficiencies have been identified in the persistence of whole body/and brain inflammation in a multitude of diseases. The goal of these studies is to identify the inflammatory markers (metabolic and nutritional) as potential indicators to predict case severity and case outcomes.

Genetic inability to produce/metabolize endocannabinoids: Omega-3 EFAs are a metabolic precursor to endocannabinoids. Is there a break in the chemical chain converting Omega-3 EFAs into endocannabinoids? Do these patients have a genetic deficiency of endocannabinoids; thereby, predisposing these children to massive brain and/or body inflammatory patterns that cannot be broken without intervention? Is this why CBD is helpful to most of these patients, when Omega-3s are not very effective in these children? Perhaps this can be an integrative focus of the research in Missouri.

Summary of known articles: There is NOT a lot of published data. Thus, the Integrative Clinical Research Model: The current published data does suggest that Cannabidiol (CBD) has a significant effect reducing the seizure rates ranging from “no effect” up to complete elimination of seizures.

Is there any data that establishes NORMAL serum endocannabinoid levels in healthy individuals versus chronically inflamed or diseased humans? This integrative health effort may consider developing those levels in normal populations versus those suffering from catastrophic seizures.

Dietary Habits and Seizure Rates: Lifestyle changes are typically beneficial in many disease states. A simple lifestyle change for these patients surrounds dietary sources of excitatory amino acids. Simply put, REMOVE dietary excitatory amino acids; namely, glutamate and aspartame, from the diet of these children as these chemicals appear to increase seizure rates. A direct correlation is consistently observed by both parents and physicians caring for these children.

There are many more dietary modifications that will significantly help these patients, further supporting the need for Integrative clinical management of these patients.

Testing modalities:

• fMRI and PET
• EEG
• Blood serum/chemistry to further understand the mechanisms behind these seizures:
  • Hair analyses for any potential heavy metals and toxicity,
  • CBD/WBC/UA,
  • C-reactive protein (high sensitivity),

• SED rate,
• Homocysteine,
• Cytokines,
• Prostaglandins,
• Omega-3 and Omega-6 ratios,
• Alpha and gamma linolenic acid,
• Vitamin D3,
• Tryptophan (including 5-HTP, Tryptophan Hydroxylase 1 (TPH1 – gut) and 2 (TPH2 – brain),
• Serotonin (brain (anti-inflammatory) and gut (can be proinflammatory levels),
• Melatonin,
• Endocannabinoids (anandamide, ),
• Glutathione,
• Glucose levels, and
• A1c levels,
• Standard Pediatric neurological protocols

Toxicology summary of CBD: PubMed offers a series of journal articles supporting the low risk of whole plant Cannabidiol. In fact, the data clearly supports that the whole plant derived CBD is far safer than the fractionated CBD molecule.

Dosage and delivery systems: (Trent’s clinical, other anecdotal, as well as existing literature):

• Tinctures,
• Beverages,
• Transdermal patches,
• Dissolvable tongue strips,
• Gums,
• Tablets and Gel Capsules, and
• “Vaping” or smoking, which is NOT an acceptable delivery system in this

Plant genetics approved for use in Missouri:

• Noah: This domestically grown, USDA compliant, Industrial Hemp derived high CBD, high terpene cultivar has approximately two years of clinical data and patient outcomes, specifically for catastrophic seizures, autism, chronic pain, anxiety, insomnia, and smaller applications in some autoimmune disorders and

Number of Study Participants:

• 1 to 25 children per study type (case study or clinical trial) and desired outcomes
• Individual case studies for extraordinary cases
• 12 month+ study of patient outcomes

Research Protocols:

• Daily notes (ADLs) by parents
• Weekly to monthly progress notes by teachers and supportive caregivers
• Weekly to monthly review by leading Pediatric Neurologist, supporting clinicians and additional health care providers (speech therapist, occupational therapist, )
• Discharge Narratives from all current and past physicians
• Protocols per study with the Noah

Integrative Medicine and supportive forms of sensory afferents to drive Neuroplasticity: As part of their treatment protocols, these patients benefit profoundly from sensory afferents via many mechanisms. The patients’ rates of CNS changes are likely to increase with these supportive modalities as well. Below are some of those modalities for consideration:

• Active and passive exercise,
• Massage,
• Chiropractic Spinal and joint manipulation,
• Acupressure or Acupuncture,
• Vibratory modalities, and

Other modalities that drive CNS and PNS sensory afferentation.

Specific Proposal:

Step 1: Get acquainted and Develop a TEAM. This Integrative Team works synergistically to understand the most appropriate clinical management for these patients that includes pharmaceuticals, whole plant, Industrial Hemp derived CBD, clinical nutrition and CNS/PNS sensory afferentation modalities that will help these patients not only control their seizures, but also help their brains and bodies develop appropriately.

Step 2: Evaluate the mutual desire towards case studies, and eventually clinical trials with per the protocols developed in Step 1. The RAND Corporation is an Apothio research partner with Noah and its affiliates. RAND will help design the study protocols and assist in drafting case studies and clinical trials.