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Mid-America Institute on Aging and WellnessAugust, 2019

Diane E. Vance, Ph.D.

CBD 101

Purposes of this presentation

• Provide basic information about cannabidiol (CBD) to help you better understand what you may read or hear about it

•Discuss the claims made for CBD and what research has found

• Explain how to interpret consumer information commonly found on product labels

• List some things to think about if you decide to buy

Disclaimers

• I am not affiliated with any grower / processor / retailer

• I am not an advocate for or against Cannabis product use

• Director of the EKU Forensic Science Program (retired)• Taught marijuana chemistry and analysis to students and law

enforcement• Instruction gradually expanded to include more on Cannabis toxicology,

medical marijuana, and issues related to DUIC• During volunteer work with Alzheimer’s and Parkinson’s support groups

got increasing questions about medical marijuana

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Topics

1. What is CBD? Basic cannabis chemistry

2. The endocannabinoid system (ECS)

3. The claims for CBD and the research

4. CBD product types, routes of administration,

dosing, reading labels

1. What is CBD? Cannabis Chemistry

• It is one of the many chemicals (“cannabinoids”) produced by the plant Cannabis sativao Commonly called “marijuana” or “hemp” -

distinction later

• There are over 100 cannabinoids

• Humans have known about the medicinal uses and psychoactive effects of Cannabis for thousands of years

CBD and THC

The only cannabinoid known to be psychoactive (i.e., “make you high”) is D-9-tetrahydrocannabinol, or THC

CBD is not psychoactive

Cannabinoids and other chemicals are mainly located in small resin glands (“trichomes”) on the female flowers

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Legal distinction between “hemp” and “marijuana”

• Same genus and species: Cannabis sativa

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• The difference is in the chemistry:

• Marijuana: contains more than 0.3% THC

• Hemp: contains less than 0.3% THC

CBD as it occurs in the plant

• CBD in the plant is mostly in a chemical form that makes it a weak acid (A)

CBDA

CBD

• This must be heated to convert it to the non-acid form

• These are sometimes referred to as “acidic” and “decarboxylated” forms

Properties and effects are somewhat different

• Similarly, THCA is the most abundant plant form

THCA is not psychoactive but THC is

• You may see this distinction on certificates of analysis

Other chemicals in cannabis: terpenes

• Terpenes are chemicals found in many plant oils; responsible for the strong smell and/or flavor of some plants

• Cannabis has 25-30 different terpenes

• Terpenes may enhance the action of cannabinoids and have some physiological action themselves

myrcene

limonene

pinene

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Brief note about CBD regulation

• The Food and Drug Administration (FDA) regulates CBD as an approved drug (Epidiolex ®)

• FDA regulates foods and dietary supplements that contain hemp-derived chemicals

• It is currently illegal to sell a food or supplement to which CBD has been added• Drugs are regulated differently than supplements

• FDA has not been enforcing this stringently

• National public hearing and comment period May 31 – July 16, 2019• maybe this will lead to federal standards

https://www.fda.gov/news-events/fda-voices-perspectives-fda-leadership-and-experts/fda-committed-sound-science-based-policy-cbd

Difficulty of doing cannabis/CBD research

• Legal controls on cannabis have hampered research but the number of clinical trials is growing

• Few published studies of CBD effects in humans

•As of July 2019 there were 77 cannabidiol-related studies in the US; 191 world-wide (clinicaltrials.gov)

2. The Endocannabinoid System (ECS)

•Cannabis obviously affects the brain – so there must be something in our bodies that responds to cannabinoid-type compounds

• In the 1990s a system was discovered that responds to cannabinoid-type compounds that we make naturally –it’s called the endocannabinoid system (ECS)

• This system consists of ligands, receptors, and enzymes

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Components of the ECS

Receptors: structures on our cells that respond to chemical signals

• CB1 receptors are abundant in the central nervous system (brain & spinal cord)

• CB2 receptors are mostly in the peripheral nervous system, often associated with immune system

Ligands are chemicals that can attach to the receptors and bring about a response

• The 2 main endocannabinoids (made within our bodies) are

• AEA (anandamide or N-arachidonoylethanolamide )

• 2AG (two-arachidonolylglycerol)

• Exogenous cannabinoids are those that we put into our bodies that affect the receptors

Enzymes are chemicals in our bodies that help chemical reactions take place

• The two main enzymes for the ECS are FAAH and MAGL

Functions of the ECS

• Existed in biological systems for hundreds of millions of years

• Found in all animals except insects

• Effects are complex and not fully understood

• Communicates with all other body systems - neuromodulatory• it uses one or more chemicals to regulate functions of other systems, including

perception, pain, mood, memory and reward

• Important in maintaining homeostasis• the ability of an organism to maintain steady conditions

• Because of the extensive interaction with other body systems, modulating activity of the ECS has wide therapeutic potential

THC and CBD act differently on receptors

• THC triggers the CB1 and CB2 receptors – this is responsible for the

“high”

• CBD doesn’t do that – it can actually reduce the CB1 and CB2

response

• Thus - people don’t feel as “high” when using CBD-rich cannabis

compared to when they consume THC-rich cannabis

• This is called “modulating” the effects of THC

• CBD also interacts other receptors – its effects are widespread

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Entourage effect

• The many cannabinoids and terpenes in cannabis interact within the human body to produce a stronger influence than any one of those components alone

• This is referred to as the “entourage effect”

3. The claims for CBD and the research

A few claims found online for Cannabis generally

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A few claims found online for CBD

“Prevents early onset of wrinkles; good for getting rid of acne” “CBD fights iron buildup in the

brain that can cause Alzheimer’s and Parkinson’s”

“All You Need to Know About Alzheimer’s Disease And How CBD Oil Can Help To Reverse it”

“Researchers have suggested that the CBD in cannabis could potentially suppress, reverse, and cure diabetes”

“CBD is a natural cure for cancer”

“CBD is good for your pet!”

•There is no evidence that cannabis or any of the individual cannabinoids can cure or prevent any disease or condition

•Labels cannot make medical claims; FDA warning letters have been sent to some companies

Brief note about scientific evidence

• Anecdotes

• Expert opinion

• Observational studies

• Randomized controlled trials (RCT; the “gold standard” for medical research)

• Systematic reviews

Weak evidence

Strong evidence

Marketing claims

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Cell / animal results don’t always translate into the same effects for humans

• In vitro means that studies have been done in a lab setting with cells

• Pre-clinical in vivo means that studies have been done with living organisms (typically mice or rats)

• What works in vitro may or may not work in a live organism

• What works in animals may or may not work in humans

• Exaggerated claims for cures are often based on unwarranted extrapolation of in vitro or in vivo results

CBD Effects

• In vitro, pre-clinical in vivo, and a few observational human studies have shown the following effects of CBD:

• Anticonvulsant / anti-seizure

• Antioxidant

• Anti-inflammatory

• Analgesic (pain relief)

• Anxiolytic

• Anti-nausea and anti-emetic

• Neuroprotective

• Antimicrobial

How do these effects translate into treatment?

Anti-convulsant / anti-seizure

• This property has the most well-documented evidence

• There is an FDA-approved drug (99% plant-derived CBD) for severe childhood epilepsies

• More research is being done; of the 77 clinical trials in the US currently related to CBD almost a third are related to anti-seizure conditions

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Antioxidant

• The body produces molecules that are very active (“reactive oxygen species,” or ROS)

• If ROS accumulate, they can harm the body -oxidative stress

• ROS can play a role in numerous diseases

• An “antioxidant” can destroy the excess ROS• CBD has been shown to have antioxidant properties• Many recommended foods have anti-oxidant properties

• Blueberries, dark chocolate, artichokes, etc

ROS contributions to various disease

families

Katharine Brieger, et al., Reactive oxygen species: from health to disease, Swiss Med Wkly. 2012;142:w13659, 17.08.2012DOI: https://doi.org/10.4414/smw.2012.13659

Anti-inflammatory

• Inflammation is a complex array of physiological responses to foreign organisms

• Chronic inflammation – ongoing inflammatory response in absence of stimulant

• Has been linked to a number of diseases

• Anti-inflammatory substances slow down the immune response

• CBD has been shown to have anti-inflammatory properties

• Many recommended foods have anti-inflammatory properties• Green leafy vegetables, several highly colored fruits, certain fish

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Role of Antioxidants and Natural Products in

Inflammation. Palanisamy Arulselvan, et al.,

Oxidative Medicine and Cellular Longevity, Volume 2016, Article ID 5276130, http://dx.doi.org/10.1155/2016/5276130

Involvement of chronic

inflammation in various disease

families

Could it potentially help symptoms? Yes

Will it have the same effect on everyone? No

But – simply consuming CBD or other anti-oxidant or anti-inflammatory substances will not be a definite prevention, treatment or cure for those diseases

Analgesic (pain relief)

• There are many types of pain and many causes

• Acute pain – CBD not helpful

• Chronic pain – complex condition with many possible causes• Arthritis, back pain, fibromyalgia, nerve damage, many others

• Animal studies have shown CBD provides pain relief • Mechanism not yet clear but involves non-ECS pathways

• A few observational human studies have shown therapeutic potential

• 11 of 77 current CBD clinical studies in US related to pain

• The presence of THC can enhance analgesic effects• Remember entourage effect

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Anxiety/depression

• Complex group of conditions with many potential causes• generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-

compulsive disorder, post-traumatic stress disorder, major depressive disorder, persistent depressive disorder, etc

• Anxiety reduction has been one of the most consistent effects observed in both animal and human case studies• Mechanism of action is not yet clear

• Doses of several hundred mg of CBD were used in most studies• These decrease anxiety but may also increase mental sedation

• CBD appears to be well tolerated even at the higher doses

Other

• Limited research indicates that CBD may be helpful with “quality of life” for Parkinson’s disease patients, but not movement issues

• Dementia (Alzheimer’s, Lewy body, vascular, frontotemporal) – no evidence of direct benefit to improve cognitive issues; may help with anxiety or some behavioral issues

• Cancer – CBD has been shown to have anti-tumor properties in vitro, but there are no studies that show CBD as a treatment or cure for cancer

• Addiction, schizophrenia, cardiovascular disease – limited data that CBD has therapeutic potential

4. CBD product types, routes of administration, dosing, reading labels

• Dozens of products (oils, creams, lotions, shampoo, suppositories, drinks, capsules, gels, candies, etc.)

• No federal standards or guidelines for labeling, testing, etc

• Cannabinoid content variable – 3 common types include

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Comments about CBD dosing

• There are no FDA guidelines - as with other OTC supplements or dietary aids, it’s trial and error

• Suggested doses given by manufacturers/retailers

• Typical starting dose suggestion would be a few mg per day

• Increase slowly

• Typical maximum doses might be 30-100 mg/day

• “Start low and go slow”

• Favorable safety and tolerability profile in humans

• No evidence that it results in dependence or abuse

• You should let your physician know if you take CBD; physicians may/may not give suggestions

Ingestion / Sublingual

• Various edibles and consumable oils

• Oils often packaged either in a dropper bottle or in a capsule

• No labeling standards so different information provided

Labels are not always accurate

Marcel O. Bonn-Miller, et al., Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 2017 Nov 7; 318(17): 1708–1709. Published online 2017 Nov 7. doi: 10.1001/jama.2017.11909

•A study of 84 products purchased online showed that only about a third were correctly labeled for CBD content•Underlabeled: 43%•Overlabeled: 26%•Accurately labeled: 31%

•Other studies have shown similar problems

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Labels can be confusing

Use of terminology not always consistent

Some may only say “hemp oil extract” and not give CBD amounts

Some may give CBD amounts in a range of percentages

Servings (dosages) can be confusing

• Many CBD oils come in 1 fluid ounce bottles (30 mL)

• One milliliter is defined as anything from 15-40 drops

• Many labels give only total mg on the front

• Look for serving size and number of mg CBD

Capsule and edible doses are usually easier to figure out –but you have less control over dose size

Full Cannabinoid Spectrum, All-Natural CBD (Cannabidiol)

•~600 mg of CBD, ~10mg of CBD/capsule, 60 capsules

•Produced from C. Sativa Blooms

•Not derived from aerial parts (stalk/stem), seeds, or isolates

•Lab-Certified Pure

•Non-intoxicating

•Contains less than .3% Tetrahydrocannbinol (THC) in

accordance with the Federal Farm Bill of 2014

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Topical• Applied to skin but active ingredient is not absorbed to bloodstream

• Creams, lotions, salves, suppositories

• Limited local action

• Actual dosage approximate

Inhalation

• Traditional smoking of plant material• There are CBD-rich strains in states with legal marijuana

• Actual dose dependent on strain, how it’s smoked and inhaled, age of the plant, temperature, etc.

• Vaporize cannabis extract (several devices can do this)• Vape pens and vaporizers where you inhale the vapor

• Dose dependent on extract used, temperature, how inhaled

• Inhalers available for CBD• Similar to asthma inhalers

• Dose can be better metered

Transdermal

• Applied to skin and gets into the blood

• Mostly in the form of patches

• Not commonly found in retail stores

• May contain THC

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Certificate of Analysis (COA)

• Ensuring accurate label information about content is a major concern now in the industry and for consumers

• Products should be tested by an independent laboratory, and test results should be readily available to consumers

• No federal guidelines now for testing; some states have them

Amount of CBD/CBDA and THC/THCA Other cannabinoids Terpenes Pesticides

Microbials (mold, yeast, bacteria) Heavy metals Residual solvents

Products may be tested for

CBD interactions with other medications

• CBD inhibits the cytochrome P450 liver enzymes

• These enzymes metabolize many pharmaceutical products – so, if CBD is present there may be too much of a prescribed drug

• Initial indicator: does the drug say not to eat grapefruit? If so, use caution taking CBD

• Consult your physician

Tips for CBD buying

• Choose CBD products made with American-grown hemp (CO, OR, KY, etc)

• Local suppliers may be more reliable; use caution with online orders

• Decide if you want isolate / full spectrum / broad spectrum

• Ask about availability of analytical results

• Look for product labels that indicate the amount of CBD per serving

• Beware of products that make explicit health claims about CBD products (this is not allowed by the FDA)

• Avoid vape cartridge products with potentially toxic thinning agents (such as propylene glycol and ethylene glycol)

• Think twice about products that claim their CBD is derived from the seed and stalk of the hemp plant

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Questions?

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Selected references

http://nationalacademies.org/hmd/reports/2017/health-effects-of-cannabis-and-cannabinoids.aspx The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, 2017, The National Academies of Science, Engineering, and Medicine

https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf World Health Organization CBD report, preliminary, 2018

https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis FDA information for consumers about CBD

https://www.sciencenews.org/article/cbd-product-boom-science-research-hemp-marijuana The Allure of CBD, Science News, March 2019

https://www.aan.com/Guidelines/home/GuidelineDetail/649 Patient summaries and clinician guidelines about medical marijuana from the American Academy of Neurology

https://www.mdpi.com/1422-0067/19/3/833 Zou, S., et al., Int. J. Mol. Sci. 2018, 19(3). Detailed technical article about the endocannabinoid system; open access