Curious about Cannabis? Navigating the cannabis

landscape in Pennsylvania

LINDSEY MESTON, PHARMD

ASHLEY FIRM, PHARMD

Speaker Disclosures

We have/had no financial relationships

with any commercial interests related to

the content of this presentation.

Objectives

Provide a general overview on cannabinoids and

the endocannabinoid system

Describe current state/federal regulations on

products derived from the Cannabis plant

Review general uses, product selection

considerations, possible drug interactions and

counseling points regarding cannabis products

Assessment Questions

1. Which of the following is NOT an approved

condition for treatment with medical marijuana

through Pennsylvania's Medical Marijuana Program?

A. Parkinson's Disease

B. Anxiety

C. Opioid Use Disorder

D. Inflammatory Bowel Disease

Assessment Questions

2. Which of the following medications/supplements has

the potential to interact with a cannabinoid product?

A. Warfarin

B. Bupropion

C. Diltiazem

D. All of the above

Assessment Questions

3. In the United States, the allowable THC-content for a

product to be considered 'hemp' is:

A. Nondetectable

B. < 0.3% THC

C. < 0.8% THC

D. < 1% THC

Brief history of Cannabis

The origins of cannabis use trace back over

5,000 years

Evidence of medicinal use as early as 400 AD

Widely utilized in patient medicine in 19th and

early 20th century

First appeared in US Pharmacopoeia in 1850

P T. 2017 Mar; 42(3): 180–188.

Brief history of Cannabis

Federal restriction of cannabis use/sale in 1937

Marihuana Tax Act of 1937 – taxation of cannabis products

Boggs Act of 1952- sentences for drug convictions

Narcotic Control Act of 1956- increased penalties

Prohibition of cannabis in the Controlled Substances Act of 1970

Any cannabis-derived product is considered Schedule I

"No accepted medicinal use, high abuse potential, concerns

for dependence, lack of accepted safety for use under medical supervision"

Current National Landscape

Berke, Jeremy. Business Insider, Business Insider, 7 Nov. 2018,

www.businessinsider.com/legal-marijuana-states-2018-1.

What is Cannabis?

Cannabis refers to a group of plants including Cannabis sativa,

Cannabis indica, and Cannabis ruderalis

Cannabis is made up of more than 120 chemical compounds

known as cannabinoids

Cannabinoids have been extracted from the plant for their medicinal

or pleasurable effects

P T. 2017 Mar; 42(3): 180–188.

The Endocannabinoid (eCB) System

The human body's eCB system is made up of two primary receptors, CB1 and CB2, and the naturally occurring eCBs that interact with them

The primary function of the eCB system is to maintain homeostasis for various processes throughout the body through retrograde signaling

Deficiencies in eCB signaling have been shown to contribute to several medical conditions including

Fibromyalgia

Depression

Irritable bowel syndrome

Parkinson's Disease

Mayo Clin Proc. Dec 2018;93(12):1842-1847

The Endocannabinoid (eCB) System

Physiologic regulation occurs when cannabinoid receptors are stimulated

CB1 CB2

Immune system Immune system

Central Nervous System Central Nervous System

Pain Receptors Pain Receptors

Endocrine/Exocrine Glands Liver, Spleen Tonsils

The most common exogenous cannabinoids are trans-Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD)

THC-partial agonist of CB1 and CB2

CBD- negative allosteric modulation

Mayo Clin Proc. Dec 2018;93(12):1842-1847

Hemp vs Marijuana

Hemp and marijuana are both members of the Cannabis sativa family

Hemp, historically used for industrial purposes, has very low THC content

THC is a psychoactive cannabinoid

Legally to be considered hemp <0.3% THC

Marijuana THC content 15-40%

Proposed Benefits of Cannabinoids

JAMA. 2015 Jun 23-30;313(24):2456-73

Condition # Studies Conclusion

Nausea/Vomiting 3 RCTs THC & THC/CBD > Placebo

Weight gain HIV/AIDS 1 RCT THC > Placebo

Spasticity in MS/Paraplegia 14 RCTs THC/CBD > Placebo

Depression 3 RCTs Placebo > THC/CBD

Anxiety 1 RCT CBD > Placebo

Sleep 12 RCTs THC & THC/CBD > Placebo

Tourette Syndrome 1 RCT THC > Placebo

Proposed Benefits of Cannabinoids

THC CBD

Decrease gastric acid secretion Anti-inflammatory

Decrease motility/contractility Controls hunger

Pain management Pain management

Nausea Nausea

Constipation relief

Gastrointestinal Tract

Proposed Benefits of Cannabinoids

Pain management

Evidence of cannabis benefit in neuropathic and cancer-related pain

Decreased pain intensity and psychological distress, improved sleep

Arthritis

CBD with evidence of inflammation-reducing properties

Migraines

Low dose THC for prophylaxis

Cannabis use may reduce migraine frequency

Fibromyalgia

Patient survey results indicate increased benefit compared to standard

Proposed Benefits of Cannabinoids

Parkinson's Disease

Some evidence of neuroprotective benefits of CBD

May help regulate dopamine and minimize progression

Dose dependent benefit for:

Anxiety

Insomnia

Tremors/rigidity

Autism/behavior

Research using animal mdels have suggested possible dysregulation of the eCS

Controlled human studies are lacking

Cannabinoids in Healthcare

Drug US Approval Current DEA Schedule Indication

Dronabinol

(Marinol)

1985 Solid= III Liquid= II Chemo induced nausea/vomiting

or loss of appetite in patients with

AIDS

Nabilone

(Cesamet)

2006 II Chemo induced nausea/vomiting

Cannabidiol

(Epidolex)

2018 V Seizures in patients >2 years with

Lennox-Gastaut syndrome or Dravet

syndrome

Nabiximols

(Sativex)

Not approved NDA listed as I Approved in other countries for

severe spasticity due to MS

THC CBD • Dronabinol

• Nabilone

• Cannabidiol

•N

ab

ixim

ols

Cannabinoids in Healthcare

Cannabinoids in Healthcare

New drug code- 7350- for marijuana extract

Does NOT include materials or products that are excluded from the definition of

marijuana set forth in the Controlled Substances Act

CSA states: "The term 'marihuana' means all parts of the plant Cannabis sativa L., whether

growing or not;…"

Code only includes the extracts within the CSA definition

Primary intent of the code was to give the DEA more precise accounting to assist

the agency in carrying our obligations to provide certain reports required by U.S.

treaty obligations

Extract containing solely CBD and no other cannabinoids would fall within code

7350

https://www.deadiversion.usdoj.gov/schedules/marijuana/m_extract_7350.html

Cannabis in America

https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf Access January 6, 2019

Cannabinoids in Pennsylvania

On April 17, 2016, Gov. Tom Wolf signed into law SB 3,

Pennsylvania’s compassionate medical cannabis legislation

Legalizing patient's in Pennsylvania to register for a medical marijuana ID

card through the Department of Health to obtain product from a licensed dispensary

One of 3 states requiring a healthcare professional on site for dispensing

No legislation in the Commonwealth specifically mentions the use

or possession of cannabidiol, CBD, or CBD oil.

Also means no regulation on what is required to be labeled as such

Approved Indications for Medical

Marijuana

Cancer, including remission therapy

HIV or AIDS

Amyotrophic lateral sclerosis

Parkinson's disease

Multiple sclerosis

Damage to nervous tissue of the CNS (with qualifications)

Epilepsy

Inflammatory bowel disease

Neuropathies

Dyskinetic and spastic movement disorders

Huntington's disease

Crohn's disease

Post-traumatic stress disorder (PTSD)

Intractable seizures

Glaucoma

Sickle cell anemia

Severe pain (with qualifications)

Autism

Neurodegenerative disease

Terminal illness

Opioid use disorder (with qualifications)

Medical Marijuana

Physicians can NOT prescribe medical marijuana

Can "certify" patient would benefit from medical marijuana

Illegal federally even with ID card

Cannabidiol (CBD)

Considered a supplement in Pennsylvania

No regulating body to assure quality

No qualifications required to sell product

No recommended consistency in dosing

No psychoactive properties

<0.3% THC content

Illegal according to federal regulations

Administration and

Pharmacokinetics

Inhalation

Bioavailability 10-60%

Dependent on depth of inhalation, temperature,

smoking vs vaporization

Onset 0-10 minutes

Duration 2-4 hours

Administration and

Pharmacokinetics

Oral

Bioavailability increased with high fat meal

Onset 30-120 minutes

Absorption variable

Duration 4-12 hours

Administration and

Pharmacokinetics

Topicals

Minimal systemic absorption

Primarily CBD-based products

Used commonly for targeted

pain/inflammation relief or wound healing

Concentrations and Dosing

CBD-Dominant Ex. CBD only, 1: >20

Balanced

Ex. 1:1, 4:1

THC-Dominant

Ex. 50:1, 19:1, 16:1

Goal is lowest effective dose

Once a day dosing, may increase to 2x day

Start THC at night, may require as low as 1-2 drops

CBD as low as 5-10mg to start

Wait appropriate time (~5-7 days) between titrations

Tolerance based on age, sensitivity, experience

Ensure known potency

Drug Interactions

Metabolizing Enzyme Enzyme Inhibition Enzyme Induction

THC 2C9, 3A4 3A4 -

CBD 2C19, 3A4 2C9, 3A4, 2D6 -

Smoked Cannabis 2C9, 2C19, 3A4 3A4, 2C9, 2D6 1A2

Adverse Effects

CBD

Dizziness

Dry mouth

Diarrhea

Headache

THC

Impaired short term memroy

Altered judgement

Paranoia

Altered brain development

Dizziness

Cardiol Ther. 2018 Jun; 7(1): 45–59.

Often dose dependent

Affected by tolerance of THC, age, sensitivity

Special Populations Pregnancy

Lipophilic, so can enter placenta, breast milk

Fetal plasma levels 10-30% of maternal plasma level

CB receptors are involved in fetal brain development

American Academy of Obstetrics strongly recommends against cannabis use

Transplant recipients

Evidence of immune modulation with cannabis products

Drug interaction potential with immunosuppressants

Recent ASCVD

Population analysis of inhaled illegal product showed increased risk of MI/death

Cardiol Ther. 2018 Jun; 7(1): 45–59.

Assessment Questions

1. Which of the following is NOT an approved

condition for treatment with medical marijuana

through Pennsylvania's Medical Marijuana Program?

A. Parkinson's Disease

B. Anxiety

C. Opioid Use Disorder

D. Inflammatory Bowel Disease

Assessment Questions

1. Which of the following is NOT an approved

condition for treatment with medical marijuana

through Pennsylvania's Medical Marijuana Program?

A. Parkinson's Disease

B. Anxiety

C. Opioid Use Disorder

D. Inflammatory Bowel Disease

Assessment Questions

2. Which of the following medications/supplements has

the potential to interact with a cannabinoid product?

A. Warfarin

B. Bupropion

C. Diltiazem

D. All of the above

Assessment Questions

2. Which of the following medications/supplements has

the potential to interact with a cannabinoid product?

A. Warfarin

B. Bupropion

C. Diltiazem

D. All of the above

Assessment Questions

3. In the United States, the allowed THC-content for a

product to be considered 'hemp' is:

A. Nondetectable

B. < 0.3% THC

C. < 0.8% THC

D. < 1% THC

Assessment Questions

3. In the United States, the allowed THC-content for a

product to be considered 'hemp' is:

A. Nondetectable

B. < 0.3% THC

C. < 0.8% THC

D. < 1% THC

Curious about Cannabis? Navigating the cannabis

landscape in Pennsylvania

LINDSEY MESTON, PHARMD

ASHLEY FIRM, PHARMD