Curious about Cannabis? Navigating the cannabis landscape in Pennsylvania LINDSEY MESTON, PHARMD ASHLEY FIRM, PHARMD

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 Immune system Central Nervous System Pain Receptors Endocrine/Exocrine Glands CB2 Immune system Central Nervous System Pain Receptors Liver, Spleen Tonsils The most common exogenous cannabinoids are trans-δ⁹tetrahydrocannabinol (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 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 JAMA. 2015 Jun 23-30;313(24):2456-73

Proposed Benefits of Cannabinoids Gastrointestinal Tract THC Decrease gastric acid secretion Decrease motility/contractility Pain management Nausea CBD Anti-inflammatory Controls hunger Pain management Nausea Constipation relief

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) Nabilone (Cesamet) Cannabidiol (Epidolex) Nabiximols (Sativex) 1985 Solid= III Liquid= II Chemo induced nausea/vomiting or loss of appetite in patients with AIDS 2006 II Chemo induced nausea/vomiting 2018 V Seizures in patients >2 years with Lennox-Gastaut syndrome or Dravet syndrome Not approved NDA listed as I Approved in other countries for severe spasticity due to MS

Nabiximols Cannabinoids in Healthcare THC Dronabinol Nabilone CBD Cannabidiol

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/sc hedules/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 Huntington's disease Crohn's disease Amyotrophic lateral sclerosis Post-traumatic stress disorder (PTSD) Parkinson's disease Intractable seizures Multiple sclerosis Damage to nervous tissue of the CNS (with qualifications) Epilepsy Inflammatory bowel disease Neuropathies Dyskinetic and spastic movement disorders 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 THC-Dominant Ex. 50:1, 19:1, 16:1 CBD-Dominant Ex. CBD only, 1: >20 Balanced Ex. 1:1, 4:1 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 Often dose dependent Affected by tolerance of THC, age, sensitivity Cardiol Ther. 2018 Jun; 7(1): 45 59.

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