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Hemp: Positioning Yourself as the Truth Expert

Hyman Phelps & McNamara, P.C.Karla L. Palmer, Esq.

Director

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LEGAL NOTE

• Nothing set forth in this slide deck or anything communicated by me constitutes the rendering of legal advice

• There are no relevant financial relationships with ACCME-defined commercial interests for anyone who was in control of the content of the activity.

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Pharmacist & Pharmacy Technician Learning Objectives• Discuss federal and state laws related to hemp-based

products and associated risks and opportunities. • Identify potential uses, formulation considerations, and

potential side effects of hemp. • Describe strategies for educating prescribers, patients, and

the community on hemp.

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Cannabis as a Controlled Substance Under Federal Law

• Regulation Depends on THC Content and Plant Material• The CSA defines “marijuana” as:• All parts of the Cannabis sativa L. plant whether growing

or not; • Its seeds; • Resin extracted from any part of the plant; and • Every compound, manufacture, salt, derivative, mixture

or preparation of the plant, its seeds or resin. • Marijuana is a Schedule I controlled substance.

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Cannabis as a Controlled Substance Under Federal Law (cont’d)The Controlled Substances Act (CSA) definition of “marijuana” expressly excludes:1. Hemp (cannabis and derivatives with a THC content < 0.3% by dry weight)2. The following plant parts and products derived therefrom:

• Mature stalks of the plant; • Fiber produced from such stalks; • Oil or cake made from the seeds; • Any other compound, manufacture, salt, derivative, mixture

or preparation of the mature stalks (except extracted resin) fiber, oil or cake; and • sterilized seeds incapable of germination.

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Hemp-Related Legislation

• Agricultural Act of 2014• Authorized institutions of higher education and state departments of agriculture to

grow or cultivate industrial hemp for research under an agricultural pilot program or for other agricultural or academic research.

• “Industrial hemp” was defined as the Cannabis plant and any part of the plant with a THC concentration of not more than 0.3 % on a dry weight basis.

• Did not authorize general commercial activity.• Hemp Farming Act of 2018

• Proposed to remove “hemp” from the CSA definition of “marijuana” and exclude THC in “hemp” from control.

• Proposed to define “hemp” as the Cannabis plant and any part with a THC concentration of not more than 0.3 % on a dry weight basis.

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*** Agriculture Improvement Act of 2018 (a/k/a “The Farm Bill”)***

• Adopted the definition of “hemp” proposed in Hemp Farming Act• Authorized interstate commerce in hemp-derived products• Established a framework for regulation of hemp production by

USDA pursuant to USDA-administered plans or state plans approved by USDA• Left it up to states to decide whether to allow hemp production

and marketing within their borders• Disclaimed any intent to affect or modify the Federal Food, Drug

and Cosmetic Act (FD&C Act)

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Then FDA Commissioner Gottlieb’s Statement:

• December 2018• Recognizes “hemp” as defined is no longer controlled under federal law• FDA still has authority to regulate cannabis and cannabis-derived

compounds under the FD&C Act.• Aware of growing interest in CBD• Continue to be concerned about drug claims of therapeutic benefit made

about unapproved products

https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-signing-agriculture-improvement-act-and-agencys

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Then FDA Commissioner Gottlieb’s Statement:

• “Selling unapproved products with unsubstantiated therapeutic claims is not only a violation of the law, but also can put patients at risk, as these products have not been proven to be safe or effective. This deceptive marketing of unproven treatments raises significant public health concerns, as it may keep some patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.”• “… it’s unlawful under the FD&C Act to introduce food containing added CBD or THC

into interstate commerce, or to market CBD or THC products as, or in, dietary supplements, regardless of whether the substances are hemp-derived. This is because both CBD and THC are active ingredients in FDA-approved drugs and were the subject of substantial clinical investigations before they were marketed as foods or dietary supplements.”

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Then FDA Commissioner Gottlieb’s Statement:

• Most importantly:

“We’ll take enforcement action needed to protect public health against companies illegally selling cannabis and cannabis-derived products that can put consumers at risk and are being marketed in violation of the FDA’s authorities .…”

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FD&C Act: Prohibited Acts

• The FDCA is a strict liability statute that specifies a number of prohibited acts• Examples of prohibited acts:• introduction into interstate commerce of an adulterated food• introduction into interstate commerce of an unapproved,

adulterated, misbranded drug• Prohibited acts are potentially punishable by civil and criminal

penalties

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FDA Enforcement Actions

• CBD companies in question allegedly marketed their products for, among other things, Alzheimer’s disease, fibromyalgia, inflammation, skin conditions, autoimmune disorders, anxiety, cancer pain, PTSD and depression, to name a few symptoms. • Companies are making food, dietary supplements, and

cosmetic products, as well as products for pets (CBD for dogs).

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FDA Enforcement Actions

• CBD isolate product not permissible. • Products are misbranded, unapproved new human or animal

drugs.• FDA says the products are marketed as dietary supplements, but

do not meet the definition of a dietary supplement.• Can’t say CBD fights cancer and has an anti-tumor effect.• Use of a nutrition facts panel on a CBD oil is inappropriate

because the oil is a food to which a drug (CBD) has been added (FDCA prohibits the introduction into interstate commerce of any food to which a drug has been added).

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Federal Trade Commission

• Also issued warning letters in 2019:• Claims must have “competent and reliable scientific

evidence to support such claims.”• Claims that have drawn scrutiny: • CBD “works like magic” against “even the most agonizing pain.” • “Clinically proven” to treat diseases like cancer and multiple

sclerosis, • Reference to “thousands of hours of research” the firm has

participated in, in conjuncture with Harvard University.

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Federal Trade Commission (cont’d)

• “Miracle pain remedy” for a variety of chronic and acute pain, autism, anorexia, bipolar disorder, post-traumatic stress disorder, schizophrenia, anxiety, depression, Alzheimer’s disease, Lou Gehrig’s Disease (ALS), stroke, Parkinson’s disease, epilepsy, traumatic brain injuries, diabetes, Crohn’s disease, psoriasis, MS, asthma, fibromyalgia, cancer, and AIDS.

• Highly effective at treating “the root cause of most major degenerative diseases, including arthritis, heart disease, fibromyalgia, cancer, asthma, and a wide spectrum of autoimmune disorders.”

• CBD oil, gummies, tinctures• FTC cautions: Unproven health claims could result in a federal injunction and

forced reimbursements to customers who purchased the products.

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FD&C Act: Intended Use

• “Intended use” determines regulatory status• An article is potentially a drug or medical device if it is intended to• Affect a structure or function of the body (unless it’s food)• Treat, cure, prevent, mitigate, or diagnose a disease

• Structure/function claims are permitted for dietary supplements and food, but not cosmetics

• “Disease claims are not permitted for dietary supplements, food, or cosmetics”

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BUT…. CBD is an “FDA-Approved Drug”

• FDA approved Epidiolex, an oral CBD solution derived from cannabis, for treatment of seizures associated with Lennox-Gastaut and Dravet syndromes on June 25, 2018.• On September 28, 2018, DEA rescheduled FDA-approved drugs that contain CBD derived

from cannabis with no more than 0.1 % THC in Schedule V.• NOT SO FAST…• DEA closed its Epidiolex Federal Register scheduling notice stating:• “[A]ny material, compound, mixture, or preparation other than Epidiolex that falls

within the CSA definition of marijuana set forth in 21 U.S.C. 802(16), including any non-FDA-approved CBD extract that falls within such definition, remains a schedule I controlled substance under the CSA.”

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Next: CBD as a Dietary Supplement: “The Exclusionary Clause”

• The definition of “dietary supplement” excludes an article:• Approved as a drug, or• Authorized for investigation as a new drug for which substantial

clinical investigation shave been instituted and made public, unless…

• The article was previously marketed as a dietary supplement or food (prior marketing exception)• FDA can issue a regulation voiding the exclusion

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FDA: CBD is “Excluded”

• Based on available evidence, CBD products are excluded from the statutory definition of “dietary supplement”• The existence of substantial clinical investigations regarding CBD have

been made public, e.g., studies of GW Pharmaceuticals’ Sativex and Epidiolex• The prior marketing exception does not apply, based on available

evidence• FDA has encouraged submission of relevant evidence• FDA has indicated willingness to consider rulemaking

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State Regulation of CBD

• Some states’ definition of “marijuana” is broader than the federal CSA definition, so more products are regulated as controlled substances.• It follows that CBD may or may not be a controlled

substance, regardless of whether it is derived from hemp

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State Regulation of CBD

• Alabama• California• Colorado• Maine• Ohio

• CBD is a controlled substance• Cannabis excludes industrial hemp• Medical use of CBD is allowed• CBD cannot be added to dietary

supplements or food• CBD can be added to cannabis

edibles• All parts of hemp are allowed for

use in food

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Key Takeaways

• Regulation of cannabis/CBD/Hemp is evolving rapidly• 2018 Farm Bill opened door to commercial production of

hemp• 2018 Farm Bill did not affect FDA’s regulation of the use of

hemp derivatives in any product regulated by FDA• Manufacturers and distributors assume liability for

compliance with all applicable provisions of the FD&C Act

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Key Takeaways

• Manufacture and distribution of hemp derivatives might or might not be prohibited or restricted under state laws• Its important to know what your state, and your state Board

is doing about CBD/Hemp• There are various limits or prohibitions defined by may

states for pharmacies seeking to use CBD. • Be knowledgeable and careful in this evolving, yet booming

marketplace.

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Hemp: Positioning Yourself as the Truth Expert

Jesica Thomason Mills, PharmD, MBA, RPh, CNHPPharmacist, Naturopath, Hemp Expert

Owner, Owensboro Family Pharmacy and Wellness

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Potential Uses

• Inflammation/ Pain

• Sleep

• Memory

• Mood (Anxiety, Depression)• Skin Issues

• Decreases Nausea and Vomiting, regulates appetite, digestion

• Acts as an antioxidant against free-radicals

• THC-induced memory-impairment and paranoia

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Effects of Cannabinoids

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What is CBD?

• Hemp-based CBD has over 6000 years of medicinal usage• Cannabidiol is the official term• It’s a main component of cannabis• It interacts with our Endocannabinoid system• CB1 and CB2 receptors• It interacts indirectly- unlike marijuana• This system uses neuromodulatory lipids to wake and strengthen

the immune system, nervous system, and digestive system

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Endocannabinoid System

• The Endocannabinoid System (ECS)- 5064 studies on PubMed• 1st endocannabinoid discovered in 1992

• CB1 in the brain, reproductive organs, and connective tissue• CB2 in the gut, spleen, liver, heart, kidneys, bones, blood vessels, lymph

cells, reproductive organs, and skin• Endogenous cannabinoids: AEA (anandamide) and 2-AG. This is not CBD. This

is what your body makes. • Endocannabinoid system is responsible for homeostasis

• Regulates nerve function, stress recovery, inflammation levels, immune function, energy intake, cell life cycles, circulatory system, appetite, and pain signals

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CBD vs THC

• THC (tetrahydrocannabidiol) is the main psychoactive cannabinoid in cannabis

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How it works…

• Mechanism of Action of CBD• Suppreses cytokines (dysregulation can cause inflammation,

depression, cytokine storm, Alzheimers, cancer)• Suppression of chemokines (pro-inflammatory)• Regulatory T cells (multitalented master of immune regulation,

prevents over-reactivity of immune system to allergens)• Enhance anandamide signaling- inhibits FAAH (fatty-acid amide

hydrolase enzyme) that breaks down anandamide in the body• Entourage effect• Each cannabinoid helps other cannabinoids be more effective

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All the other receptors

• Serotonin receptor- CBD directly activates 5-HT1A receptor (anti-anxiety effects, addiction, appetite, sleep, pain perception, nausea). • Vanilloid receptors- TRPV1 mediates pain perception, inflammation,

body temperature. CBD binds to TRPV1• Orphan receptor- activates GRP55- in the brain, modulates bone

density, cancer, and blood pressure. Possibly the CB3 receptor.• Nuclear receptor- PPAR-gamma activation- neuroprotection, reward,

memory, analgesia, anti-tumor effects via apoptosis, vasorelaxation, satiety and nausea

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Formulations

• Oil- full spectrum with THC vs THC-free isolate• Quickest acting• Place and hold under the tongue for 20-60 seconds

• Capsule• Balm/Salve• Vape/Flower• Edibles- for pets too (4th of July)• Bioavailability• Quality

• Ethanol vs CO2 Extraction Methods

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Best Formulation Per Patient

• Oils-systemic issues, multiple joint pain, autoimmune conditions, deep joint pain (spine, hips, etc). Use THC if you can, but don’t risk a failed test.• THC free- for anyone who needs help with multiple issues but is drug tested

• Capsules- For those who don’t like measuring drops, want an exact dosage every time, are used to taking pills, aversion to the taste

• Balms/Salves- for those who don’t want to ingest any form of cannabis, knee, elbow, muscle pain. Skin conditions.

• Edibles- For those without chronic/complex issues, wellness benefit as the doses are smaller. Also for pets

• Flower/Vape- for those that really want to smoke something

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Questions I Get on CBD/CBC/CDC/CNN/WeedOil• Does CBD interact with the CNS?

• What is the legal limit of THC?

• Will patients fail drug tests?

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Potential Side Effects

• Drowsiness- usually from too high of a dose

• GI upset- take with food or use capsules to avoid

• Drug Interactions- CYP enzymes -CYP2C9, CYP2C19, and CYP3A4 catalyze most of their hydroxylations. CBD is a potent inhibitor of enzymes.

• Liver issues- depends on the study and dosage• Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of

hepatic encephalopathy in mice- 5mg/kg dosing • “CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in

accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain.”

• Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model – 2460mg/kg dosing• “In conclusion, CBD exhibited clear signs of hepatotoxicity, possibly of a cholestatic nature. The involvement of numerous

pathways associated with lipid and xenobiotic metabolism raises serious concerns about potential drug interactions as well as the safety of CBD”

• Common sense recommendations- Narrow Therapeutic Index Drugs- continue monitoring

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Anti-Epilepsy Drug Interactions

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Group Discussion

• What Hemp-Derived CBD products can be recommended for a patient who is on blood thinners and has joint pain in their knee?• A patient comes in with their teen who has test-based

anxiety. They just received their drivers license, and they’re excited to be able to get a job now that they can drive. They want to purchase a CBD product, what is your main concern to address with them?

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Educating Patients

• Host an event inside your pharmacy• Have samples available• Use social media to promote it

• Create an event on facebook- it could result in free news coverage• Place products near check-out or consult areas

• Also place infographics they can have from companies • Don’t overdo it

• Don’t be salesy. You are doing a disservice to not share your knowledge

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Patient Education vs Sales

• Every action a person takes is motivated by improvement• Tie in the benefit they will FEEL. Identify their needs.

• Why buy from you? Why take your recommendation?• You’re their pharmacist. You already have their “know/like/trust”

• Presenting your message• Don’t focus on price. People buy because they desire gain and

FOMO (1 vs 2.5)

• Answering Honestly• Don’t fake it til you make it. You have more to lose than gain

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Educating Providers

• Position yourself as the expert• Get professional help• Marketing materials available from companies

• Know your market- especially your warm market• Host an event for providers

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Educating the Community

• Write-ups and interviews for your local news• HARO- Elements Magazine• Facebook lives• Mini-courses• Offer courses/events for law enforcement, school systems, addiction

treatment facilities, and elected officials• Find a tribe- online and locally• Make passive income by being an expert for them• Local Events

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What I’ve Learned

• The price point really doesn’t matter: we aren’t in the realm of $7 vitamins• You have a huge market of people who know about it and want to try

it• There’s a ton of people selling this product (and they all have the best

product)- but pharmacist’s have the KNOWLEDGE, and that’s what people want• This will bring in “crunchy” patients. You can be a wellness destination.• The impact the right formula has on the right patient is staggering• Don’t be ruled by fear. Step into your power

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Key Takeaways

• CBD MOA- it decreases inflammation via cytokines and chemokines, stimulates the immune system, and works with a system to balance the body and reach homeostasis.• Who is a good candidate for each formulation-

Full-Spectrum Oils Systemic issues, autoimmune, chronic inflammation

THC-Free Isolates Same as above- can’t fail a drug test

Capsules Want consistent dosage, dislike taste, upset stomach by oils

Balm Individual joint inflammation, skin conditions

Edibles Maintenance of health from low dosage, pets

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Key Takeaways

• Positioning yourself as the expert takes no money, just time and dedication• Resources for further education and support are vital

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Resources

•Alger BE. Getting High on the Endocannabinoid System. Cerebrum Dana Forum Brain Sci. 2013;2013

•Avraham, Y. (2010, November 25). Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. BritshJournal of Pharmacology, 162, 1650-1658. https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1476-5381.2010.01179.x

•De Laurentiis A, Araujo HA, Rettori V. Role of the endocannabinoid system in the neuroendocrine responses to inflammation. Curr Pharm Des. 2014;20(29):4697-4706.

•Friedman, et al. The effect of Epidiolex(cannabidiol) on serum levels of concominantanti-epileptic drugs in children and young adults with treatment-resistant epilepsy in an expanded access program. American Epilepsy Society. Seattle, WA2014. https://theroc.us/images/AED%20interaction.pdf

•Mackie K. Cannabinoid receptors: where they are and what they do. J Neuroendocrinol. 2008;20 Suppl 1:10-14. doi:10.1111/j.1365-2826.2008.01671.x.

•McPartland JM, Matias I, Di Marzo V, Glass M. Evolutionary origins of the endocannabinoid system. Gene. 2006;370:64-74.doi:https://doi.org/10.1016/j.gene.2005.11.004.

•O'Sullivan SE. An update on PPAR activation by cannabinoids. Br J Pharmacol. 2016;173(12):1899–1910. doi:10.1111/bph.13497

•Project CBD. (2019). How CBD Works. In Science. Retrieved from https://www.projectcbd.org/science/how-cbd-works

•Siefert, W. (2017, April). Get to Know CBD Oil. In American College of Apothecaries. Retrieved from https://acainfo.org/wp-content/uploads/2017/04/Get-to-Know-CBD-Oil-Seifert.pdf

•UCLA Health. (2019). UCLA Cannabis Research Initiative. In Human Endocannabinoid System . Retrieved from https://www.uclahealth.org/cannabis/human-endocannabinoid-system

•Zendulka, O. et al. (2016). Cannabinoids and Cytochrome P450 Interactions. Current Drug Metabolism, 17(3), 206-226. https://www.ncbi.nlm.nih.gov/pubmed/26651971

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Thank You!Karla L. Palmer, Esq.

Director, Hyman Phelps & McNamara, PCkpalmer@hpm.com

202-737-7542www.hpm.comVisit our BLOG!

www.FDAlawblog.new

Jesica Thomason Mills, PharmDPharmacy Owner, Naturopath, CBD Expert

Jesica.1120@gmail.comwww.ofpwellness.comFacebook- DrJesicaMills

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