Closer Media Webinar 2020

Conflict of Interest Statement /

Disclosure

• Founder and Chief Medical Officer of Peak

Therapeutics, a pet CBD company
Cannabis Medicine for
Animals: Is it Real?

James S. Gaynor, DVM, MS, DACVAA, DAIPM. CCBDC

jgaynor@PeakVets.com
PeakVets.com

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Goals for this lecture

• Pertinent Terminology
• History in the World and Colorado
• The Endocannibinoid System
• Medical Use
• Veterinary Use
• Legal Issues

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Pertinent Terminology Pertinent Terminology

• Cannabis • Cannabis
• Industrial hemp • Industrial hemp
• Cannabinoid • Cannabinoid
• Endocannabinoid • Endocannabinoid
• Phytocannabinoid • Phytocannabinoid
• Synthetic cannabinoid • Synthetic cannabinoid
• Terpenes • Terpenes
• Flavanoids • Flavanoids

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Cannabis Pertinent Terminology

• The plant from which both • Cannabis

“marijuana” and hemp • Industrial hemp
derive
• Cannabinoid
• Difference is purpose of
breeding • Endocannabinoid
• Psychoactive (THC) • Phytocannabinoid
marijuana
• CBD – Marijuana , hemp • Synthetic cannabinoid
• Fiber, oil - hemp • Terpenes
• Flavanoids

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Industrial Hemp Pertinent Terminology

• Cannabis
• Defined by the Federal
government as a Cannabis • Industrial hemp
sativa plant with <0.3% of • Cannabinoid
the psychoactive
component or • Endocannabinoid
cannabinoid - THC • Phytocannabinoid
• Medical cannabis vs • Synthetic cannabinoid
medical marijuana • Terpenes
• Flavanoids

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Cannabinoid Pertinent Terminology

• Cannabis
• Any chemical compound • Industrial hemp
that interacts with
receptors found • Cannabinoid
throughout the body and • Endocannabinoid
can be divided into three • Phytocannabinoid
main categories
• Endocannabinoid • Synthetic cannabinoid
• Phytocannabinoid • Terpenes
• Synthetic cannabinoid
• Flavanoids

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Endocannabinoid Pertinent Terminology

• Cannabis
• Produced in cellular • Industrial hemp
membranes • Cannabinoid
throughout the
body on an as- • Endocannabinoid
needed basis • Phytocannabinoid
• Synthetic cannabinoid
• Terpenes
• Flavanoids

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Phytocannabinoid Pertinent Terminology

• Found in plants like
Cannabis sativa, Echinacea
purpura, and others that
interact with receptors in
the endocannabinoid
system
• Cannabis
• Industrial hemp
• Cannabinoid
• Endocannabinoid
• Phytocannabinoid
• Synthetic cannabinoid
• Terpenes
• Flavanoids

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Synthetic Cannabinoid Pertinent Terminology

• Created outside of • Cannabis

the body and • Industrial hemp
designed to interact • Cannabinoid
with cannabinoid
receptors • Endocannabinoid
• Pharmaceutical • Phytocannabinoid
companies • Synthetic cannabinoid
• Illicit labs • Terpenes
• Flavanoids

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Terpenes Pertinent Terminology

• Compounds that provide plants with their aroma

• Cannabis
• May have therapeutic use and contribute to
entourage effect • Industrial hemp
• Cannabinoid
• Endocannabinoid
• Phytocannabinoid
• Synthetic cannabinoid
• Terpenes
• Flavanoids

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Flavanoids

• Compounds that
provide plants with
their flavor
• May have History of Cannabis Use
therapeutic use and
contribute to
entourage effect

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History of Marijuana in the US

• 1906
• President Roosevelt signed the Food and Drugs Act (aka
the Wiley Act), which established regulations for product
labeling and specifically stated that packaging must have
a statement of the quantity of alcohol, morphine, opium,
cocaine, heroin, chloroform, cannabis, or any derivative
thereof.

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1911-1929 1930s

• 15 US states pass • Parke Davis & Eli Lilly:

anti-marijuana laws standardized extracts
• US pharmaceutical • Analgesia
companies grow • Sedation
60,000+ pounds • Anti-convulsants

• US is self sufficient • Henry Anslinger:

in hemp Commissioner Federal
Bureau of Narcotics

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The Endocannibinoid
System : Homeostasis

Science and Data

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ECS Receptors The Endocannibinoid System (ECS)

• CB1
• Largest receptor system in mammals
• Brain, organs, widespread
• G protein coupled • All animals – not insects- Homeostasis
• CB2 • Brain, CNS, periphery, immune cells
• Organs • Neuromodulatory, immunomodulatory,
• Liver: metabolism homeostasis
• GI: motility, secretion,
inflammation (IBD?), feeding • Neuroprotection, pain modulation, motor
behavior activity regulation, CV controls, anti-
proliferative
• ECS->”Runners high” not
endorphins

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The Endocannibinoid System (ECS) The Endocannibinoid System (ECS)

• CNS / PNS • Inflammation

• Reduces influx of Ca++ at presynaptic neuron-> • Localized increased receptors
• Decreases excitatory neurotransmitters • Increased endocannabinoid levels
• Decreases • Down regulation of inflammatory proteins
• Pain response • Decreased chemotaxis of inflammatory cytokines
• Muscle tremors
• Spasticity

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Hashish. I. The Structure of

Endocannabinoids
Cannabidiol
Mechoulam R, Shvo Y.
Best Understood Tetrahedron. 1963
Less Understood
Dec;19(12):2073-8
• Anandamide (N- • Noladin ether,
arachidonoyl • Virodhamine
ethanolamide, AEA, the
“bliss molecule”) • NADA
• 2-arachidono glycerol
(2-AG).

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Hashish. IV. The isolation and structure

of cannabinolic, cannabidiolic, and
Pharmacokinetics of cannabidiol
cannabigerolic acids in dogs.
• The oral bioavailability ranged from 13 to 19%.
Mechoulam R, Gaoni Y.
Tetrahedron. 1965 The results of this study show that CBD is barely
May;21(5):1223-9 absorbed after oral administration to dogs. This
low bioavailability may be due to a first pass
effect.
• Samara E1, Bialer M, Mechoulam R. Drug Metab
Dispos. 1988 May-Jun;16(3):469-72.
Dog data has been around for a long time

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Phytocannabinoids

• Bind CB1 and CB2 receptors

• Similar effects as endocannabinoids
• >80 identified- 20 extensively studied

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Phytocannabinoid Use In
People Phytocannibinoid: CBN

• Sedative /Sleep aid

• THC • CBD
• Psychoactive • Seizures • Anticonvulsant
• Glaucoma • Pain • Anti-inflammatory
• Insomnia • Anti-inflammatory
• Topical for MRSA
• PTSD • Anxiolytic
• Anxiety • Anitpsychotic • Sativex® Mouth Spray
• Anti-carcinogenic • 1:1 CBN: THC
• Modulates THC • Neuropathic and cancer pain
• Spasticity
• Overactive bladder
• Multiple sclerosis

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Phytocannabinoid: CBG Phytocannabinoid: CBC

• Anticonvulsant • Analgesia
• Anticancer • Anti-inflammatory
• Antimicrobial • Antimicrobial
• Antidepressant • Neuroprotective
• Neuroprotection

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Phytocannabinoid: CBDA Epidiolex

• Precursor to CBD • First FDA approved

• Found in raw oil or pharmaceutical CBD
now a stabilized • Plant-derived
form
• A first-in-class antiepileptic drug
• Appetite (AED) for the treatment of
• Sleep seizures associated with
Lennox-Gastaut syndrome (LGS)
• Immunity or Dravet syndrome in patients 2
years of age and older.
• > $32,000 / year - $15,000 / year
• 10-20 mg/kg/ day
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Pharmacokinetics of CBD and THC

Terpenes in Dogs at Clinically Relevant Doses
• Gaba augmentation, dopamine activity enhancers • CBD: 2.2 mg/kg PO BID
• Caryophyllene - gastroprotective, auto-immune • 21 days CBD Peak CBD half life THC Peak THC
modulator (ng/ml) (hr) (ng/ml) Trough
(ng/ml)
• Myrcene - sleep aid, analgesia, alleviates depression
• Limonene - mood elevator, anti-fungal, anti-bacterial, 129.7* 4.4** 4.65*** 1.35
anti-neoplastic *CBD Therapeutic target 100ng/ml
• Beta-caryophyllene-anti-inflammatory(in rosemary, basil,
**Half life of CBD consistent with other published data
cloves, and black pepper and is an FDA-approved additive
for food products)
***THC <10ng/ml supports product is hemp origin

Gaynor Js, Jurgens D. To be Published

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Randomized blinded controlled clinical trial to assess
the effect of oral cannabidiol administration in addition
to conventional antiepileptic treatment on seizure
frequency in dogs with intractable idiopathic epilepsy
• CBD-infused oil (2.5 mg/kg [1.1 mg/lb], PO) twice daily
for 12 weeks in addition to existing antiepileptic
treatments
• 2 dogs in the CBD group developed ataxia
• Dogs in the CBD group had a significant (median change,
33%) reduction in seizure frequency, compared with the
placebo group.
• Dogs in the CBD group had a significant increase in
serum alkaline phosphatase activity. No adverse
behavioral effects were reported by owners.
• McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL.
J Am Vet Med Assoc. 2019 Jun 1;254(11):1301-1308.
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Pharmacokinetics of cannabidiol
administered by 3 delivery methods at
2 different dosages to healthy dogs.
• Oral CBD-infused oil provides the most favorable
pharmacokinetic profile.
• Prior data: CBD uptake is 4-5x higher with a high fat
meal
• Bartner LR, McGrath S, Rao S, Hyatt LK, Wittenburg
LA.
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Pharmacokinetics, Safety, and Clinical Efficacy of
Cannabidiol Treatment in Osteoarthritic Dogs
• Single-dose pharmacokinetics was performed using two different doses
of CBD enriched (2 and 8 mg/kg) oil
• CBD oil (2 mg/kg) or placebo oil every 12 h.
• Elimination half-life of 4.2 h at both doses and no observable side
effects.
• Significant decrease in pain and increase in activity (p < 0.01)
with CBD oil. Veterinary assessment showed decreased pain
during CBD treatment (p < 0.02). No side effects were reported by
owners, however, serum chemistry showed an increase in alkaline
phosphatase during CBD treatment (p < 0.01). Clinical significance: This
pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice
daily can help increase comfort and activity in dogs with OA.
• Gamble LJ, Boesch JM, Frye CW, Schwark WS, Mann S, Wolfe L, Brown
H, Berthelsen ES, Wakshlag JJ.Front Vet Sci. 2018 Jul 23;5:165.
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US Veterinarians’ Knowledge, Experience,
and Perception Regarding the Use of
Cannabidiol for Canine Medical Conditions
• CBD was most frequently discussed as a potential
treatment for pain management, anxiety and
seizures
• The most commonly used CBD formulations were
oil/extract and edibles. These were most helpful
in providing analgesia for chronic and acute pain,
relieving anxiety and decreasing seizure
frequency/severity
• he most commonly reported side-effect was
sedation.
• Kogan L, Schoenfeld-Tacher R, Hellyer P, Rishniw
M.
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Veterinary Use

• Early research with high doses

• Oil tinctures had highest and most reliable
bioavailability
Veterinary Use of • Elevated liver enzymes with no disease
• GI upset
Cannabinoids • Dosing and product selection done on an ad hoc
basis

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Canadian dog owners' use and Owner observations of full

perceptions of cannabis products. spectrum CBD in dogs
• Pain, inflammation, and anxiety in dogs, and
perceived these preparations to be equally or more Client Data- June 2019
effective than conventional medications. Most Owners who responded moderate to great deal
owners reported only minimal side effects in 100%
their dogs. 95%
90%
• An adjuvant to other therapies, and the perception 85%

of it being a natural substance. 80%

75%

• Kogan LR1, Hellyer PW1, Silcox S1, Schoenfeld- 70%

PainR elief Ner vous Sys tem Reduced Aid wit h Sleep Relieve Anxiety Reduced
Tacher R1. Can Vet J. 2019 Jul;60(7):749-755. Support Inflammation Seiz ures

Dogs Column1 Column2

Gaynor JS, Jurgen D. To be published

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CONSUMERS’ PERCEPTIONS OF
HEMP PRODUCTS FOR ANIMALS Dog Owners Reported Efficacy
• Pain relief (95%) • Nausea (82%)
• 93% of all
respondents favored • Age-related changes in • Muscle spasm(79%)
the use of medical behavior including
sleep/wake cycle • Anti-cancer activity (73%)
cannabis over some disturbances, excessive • GI issues (unspecified) 71%
medications vocalization and neediness,
• Noise phobias
and some repetitive
behaviors (93%) (thunderstorms, fireworks)
(65%)
• Seizures (92%)
• Skin conditions (unspecified)
Kogan :2016 Journal of the • Inflammation (92%) (62%)
American Holistic Veterinary
Medical Association Volume 42, • Sleep quality(89%)
Spring Issue, 2016
• Anxiety (83%)

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Cat Owners Reported Efficacy Owner Reported Information

• Pain relief(100%) • Side effects: sedation / increased appetite

• Sleep quality(96%) • 43% did not talk to their veterinarian
• Inflammation (90%)
• Nausea reduction
(86%)
• Anti-cancer activity
(82%)
• Skin conditions
(unspecified) 75%

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Our Current World

• Hemp is becoming popular

• Hemp industry: unregulated, non transparent
• Look for :
• Domestic sourcing
Legal Issues
• Continual analysis
• Reputable
• Dosing

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Cannabis Legal Issues Colorado VMA December 2016

• Veterinarians have an obligation to provide
• C1 drug companion animal owners with complete
• federal issues education in regard to the potential risks and
• Study issues benefits of marijuana products in animals
• Legalized for medical / recreational use in • Any discussion regarding a specific marijuana
some states product as part of a companion animal’s
• Industrial hemp therapeutic regimen should be consistent with a
• Legal (<0.3% THC) valid Veterinarian-Client-Patient Relationship.
• High CBD content • It is illegal in the State of Colorado for a
veterinarian to prescribe marijuana for animal
use.
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AVMA

• The term marijuana does NOT include hemp

• Marijuana is illegal
• Illegal for veterinarians to prescribe marijuana

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Proposed Uses: High CBD, Low-Zero

Federal Budget THC: Hemp
• President Trump’s budget bill:
• Pain: inflammatory, neuropathic, cancer
“SEC. 729. None of the funds made available by this Act or any
other Act may be used— • Vomiting, other GI
(1) in contravention of section 7606 of the Agricultural Act of
2014 (7 U.S.C. 5940); or • Seizures / Anxiety
(2) to prohibit the transportation, processing, sale, or use of
industrial hemp, or seeds of such plant, that is grown or cultivated • Appetite stimulation
in accordance with subsection section 7606 of the Agricultural
Act of 6 2014, within or outside the State in which the industrial • Cancer
hemp is grown or cultivated.
• MCT oil
SEC. 537. None of the funds made available by this Act may be • Flavored oils
used in contravention of section 7606 (‘‘Legitimacy of Industrial
Hemp Research’’) of the Agricultural Act of 2014 (Public Law 113–
79) by the Department of Justice or the Drug Enforcement
Administration.”
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What to look for in a product…. Final Words

• Sourced in US • Cannabis has along positive history

• Organic? No current certification • Relatively short negative history
• Analysis • Interesting data for decades
• Content especially in final product
• THC <0.3% - does a little matter? • Vets have an obligation to guide clients
• Contaminants, pesticides, heavy metals • Efficacy
• Sources?
• Growing data

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970-884-3422
info@PeakTherapeutics.net
www.PeakTherapeutics.net

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