4/9/2021
Kevin T. Schleich, PharmD, BCACP Clinical Pharmacy Specialist, Department of Family Medicine University of Iowa Hospitals and Clinics
Objectives • Review historical context of medical cannabis and literature that addresses efficacy of cannabis for multiple medical conditions
• Discuss safety concerns from both an acute and chronic use standpoint
• Compare and contrast available formulations of medical cannabis in Iowa
• Highlight the process by which patients in Iowa can receive medical cannabis
United States' "Dealers”
https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx
1 4/9/2021
Weed 101
• Marijuana contains numerous extractable substances – Steroidal components – Volatile compounds
• 60 cannabinoids can be isolated – Delta-9-tetrahydrocannabinal (THC): main psychoactive cannabinoid – Cannabidiol (CBD): main non-psychoactive cannabinoid
Brand Name Active Ingredient FDA-Indication DEA Schedule
Epidiolex® Cannabidiol (plant derived extract) Seizures V
Marinol®, Syndros® Dronabinol (Synthetic THC) III AIDS: loss of appetite Cancer: chemotherapy-induced n/v Cesamet® Nabilone (Synthetic THC-analog) II
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations.
Weed 101
• Two main cannabinoid receptors throughout the human body
– CB1: brain, spinal cord, some periphery – CB2: intestinal tract, peripheral organs, immune system
• Neither CBD or THC directly agonize
either the CB1 or CB2 receptor – THC a partial agonist of CB1 – CBD influences endogenous cannabinoids
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations.. http://sensipharma.com/ecs
Weed 101
• CBD antagonizes the effects of THC at the
CB1 receptor THC THC + CBD
• CBD + THC CBD – Pain relief – Anti-spasmodic
• CBD only – Epilepsy
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. www.analyticalcannabis.com
2 4/9/2021
Iowa Qualifying Conditions
• Cancer, AIDS/HIV, or any • Crohn’s disease/ulcerative colitis terminal illness if: – Severe/chronic pain • Chronic pain* – Nausea/severe vomiting – Cachexia or severe wasting • Severe autism, intractable with self-injurious/aggressive • Neuromuscular disorders: behavior (pediatric and adult)* – Multiple sclerosis (with severe/persistent muscle spasms) • Post-Traumatic Stress Disorder – Amyotrophic lateral sclerosis (PTSD)* (ALS; Lou Gehrig’s Disease) – Parkinson’s disease • Corticobasal degeneration*
• Seizures (including those characteristic of epilepsy) * Update since original legislation
https://idph.iowa.gov/omc/For-Patients-and-Caregivers
Does the Stuff Work?
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Efficacy Data • The National Academies of Sciences, Engineering, and Medicine (NASEM) – “The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research”
– Comprehensive report highlighting the health effects of recreational/therapeutic cannabis use
– Published in 2017
– Cannabis still DEA Schedule I substance • Limited research capability (federal funding) • 194 current trials on ClinicalTrials.gov
http://www.nationalacademies.org/hmd/Reports/2017/health-effects-of-cannabis-and-cannabinoids.aspx
3 4/9/2021
Efficacy Data • Chronic Pain – “…there is substantial evidence that cannabis is an effective treatment for chronic pain in adults”
– NASEM cites 5 systematic reviews (n=2454) • Low-quality evidence • 2 studies focused on fibromyalgia • Pain scores decreased by ~30% on average
– Generally, higher THC content = greater pain relief
– 49 active trials on ClinicalTrials.gov
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health-effects-of-cannabis-and-cannabinoids.aspx www.clinicaltrials.gov
Efficacy Data
Demonstrated ~# of Current Clinical Condition Efficacy Trials Chronic Pain 115
Cancer/HIV-Related Symptoms 176*
Seizures 14
MS Spasticity Symptoms 29
Parkinson’s 6
Crohn’s/UC/IBD 8
Autism 1
PTSD 17
*Majority are associated with pain control
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health-effects-of-cannabis-and-cannabinoids.aspx
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Short-Term Adverse Effects • Marijuana inhalation/ingestion Impaired motor coordination Short-term memory Paranoia/psychosis impairment Dry mouth
Tachycardia Hypertension
Nausea/ vomiting
www.google.com/images N Engl J Med. 2014;371(9):879
Long-Term Adverse Effects
Addiction* Altered brain • 9%: overall development* • 17%: begin as adolescent • 25-50%: daily user Worsening educational Cognitive outcomes* impairment*
Diminished life Increased risk of satisfaction* chronic psychosis disordersΩ
* = effect strongly Ω = in those with a associated with initial use predisposition to such in adolescence disorders
“Pharmacy stuff… pharmacy stuff… pharmacy stuff… pharmacy stuff… pharmacy stuff”
www.google.com/images
5 4/9/2021
Pharmacokinetics
Sublingual Trans- Inhaled Oral /Buccal cutaneous Onset Seconds 5-15 min ? 60 min Time to Peak 30 min 4 hours ? 4-6 hours Duration 2-4 hours ? ? > 8 hours
Absorption < inhaled 10-35% CBD> THC ~5% Bioavailability > oral • Distributes readily into well-vascularized organs (lung, heart, brain, liver) Distribution • Chronic use accumulates in adipose tissue • THC highly lipophilic crosses placenta; excreted into breast milk Metabolism THC CYP2C9, CYP3A4 Active CBD CYP2C19, CYP3A4 (by CYP enzymes) metabolite (2x as potent) Inactive metabolite Routeof Elimination Half-Life THC: 22 hours Excretion Feces: 70% (5% unchanged) CBD, occasional use: 24-31 hours Urine: 30% CBD, frequent use: 2-5 days
Ku, Jennifer. (2018). Cannabis Can Do What? Pharmacological Considerations with Cannabinoids.
Drug-Drug Interactions
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What Effects Cannabis
Increase Cannabinoid Decrease Cannabinoid Levels Levels
• Grapefruit • Rifampin • Azole antifungals • Carbamazepine • Clarithromycin • St. John’s Wort • Amiodarone • Barbiturates • HIV Antivirals
• Common offenders for drug-drug interactions when utilizing the CYP enzyme system
• Current manufacturers recommend monitoring efficacy and safety if administering concurrently with above drugs • No preemptive dose adjustments necessary
Ku, Jennifer. (2018). Cannabis Can Do What? Pharmacological Considerations with Cannabinoids.
6 4/9/2021
What Cannabis Effects Cannabis Induces Cannabis Inhibits CYP2C8, CYP2C9, CYP2C19, UGT1A9, Enzymes CYP1A2, CYP2B6 UGT2B7 Decreases efficacy of the following Increases efficacy of the following Effect drugs drugs Neuro/psych: • Citalopram Neuro/psych: • Diazepam • Duloxetine • Lamotrigine • Haloperidol • Lorazepam • Olanzapine Platelet inhibitors: Musculoskeletal/analgesia: • Clopidogrel • Cyclobenzaprine Drugs Musculoskeletal/analgesia: • Naproxen • NSAIDS • Tizanidine Lipid-lowering: Opioids: • Fibrates • Methadone Anti-hyperglycemic: Hormones: • Sulfonylureas • Estradiol Opioids: • Morphine
Ku, Jennifer. (2018). Cannabis Can Do What? Pharmacological Considerations with Cannabinoids.
www.google.com/images
Products in Iowa
20:1 2:1 1:1 1:20 (CBD:THC) (CBD:THC) (CBD:THC) (CBD:THC)
5 mg:5 mg 0.25 mg:5 mg Capsule 600 mg:30 mg/cap 0.5 mg:10 mg 10 mg:10 mg 1 mg:20 mg 5 mg:0.25 mg/0.25 mL Tincture ~5 mg:5 mg/0.25 mL 0.25 mg:5 mg/0.25 mL 25 mg:2 mg/0.25 mL 17.5 mg:8.75 mg/0.5 tsp* 17.5 mg:8.75 mg/0.5 tspΩ Cream 3.75 mg:1.875 mg/pump* 3.75 mg:1.875 mg/pumpΩ Vaporizer 215 mg: 10 mg/inhalation pediatric formulation; * = no scent; Ω = rosemary extract scent • Rectal and vaginal suppositories allowable (not currently supplied)
www.medpharmiowa.com/products www.google.com/images
7 4/9/2021
What’s In Recreational?
Product Weight/Size THC (mg) Pretzels 0.18 oz (5 g) 3 Honey 1 tsp: 0.2 oz (7 g) 8 Cookie 0.56 oz (16g) 10 Gummy Bear 0.09 oz (2.5 g) 25 Green Tea 0.07 oz (1.9 g) 40 ChocolateBar 1.5 oz(43 g) 200 Brownie 3.5 oz (100 g) 250
www.latimes.com/projects/la-me-weed-101-1hc-calculator/ www.google.com/images
Can Anyone Afford This? • Insurance does not cover – Cash and debit cards only form of payment accepted – Credit card not permitted due to “federal regulations”
• Price of all products published on MedPharm website
• Cost obviously varies widely based on dose utilized/product
www.medpharmiowa.com/products www.google.com/images
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8 4/9/2021
Prescribing Review
Amoxicillin 500 mg Take 2 caps 3 times daily x 10 days
#60 0 refills
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“Attesting” Review
You have a condition
Dr. XYZ
My high school degree and 2- week training course leads me to believe your child needs this dose of cannabis.
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Application/Registration
• Patients submit a three-page application to the Iowa Department of Public Health (IDPH) to receive a medical cannabidiol registration card – Available online at IDPH website – $100 non-refundable application fee – $25 non-refundable reduced application fee for low-income – Electronic application now accepted (https://idph.iowa.gov/cbd)
• Patient must be > 18 years of age – Caregiver can obtain card for those < 18 years of age
9 4/9/2021
Application/Registration
• Provider Attestation Requirements (page 3) – Established patient-provider relationship with the patient
– A primary care provider of the patient involved in the diagnosis and treatment of the debilitating medical condition
– Confirmation that the patient suffers from a qualifying condition
– Have counseled patient (including guided patient to IDPH website) about benefits/risks of medical cannabidiol
– Agree to annually evaluate continuing need
Dispensary Sites
Sioux City Waterloo
Windsor Heights **Davenport and Council Bluffs sites closed in 2020**
www.idph.iowa.gov/cbd/Program-Data-and-Statistics
Iowa Cannabis Statistics (2/1/21)
Role in Registry (11/16/18) (11/30/18) (1/11/19) (2/1/19) (3/25/19) 4/14/20 07/1/20 2/1/21
Issued Cards: # patients with active, DOT-issued 499 663 1197 1361 2170 4770 4408 5120 cards Healthcare Practitioners: unique # 325 353 463 505 619 982 1079 1310 of physicians who have certified patients
www.idph.iowa.gov/cbd/Program-Data-and-Statistics
10 4/9/2021
Iowa Cannabis Statistics
www.idph.iowa.gov/cbd/Program-Data-and-Statistics
Updates to Legislation House File 2589
Chronic pain Autism & wording PTSD
DMV no longer ARNP and PA involved attestation
THC quantity Dispensary limits employment https://www.legis.iowa.gov/legislation/BillBook?ga=88&ba=H-8130
Updates to Legislation
• “Untreatable pain” “chronic pain”
• Two new conditions added – Autism (both pediatric and adult) – PTSD
• Advanced Registered Nurse Practitioners (ARNP) and Physician Assistants (PA) may now sign attestation – Podiatrists also added
• Dispensaries now must employ either to provide dosing recommendations – Licensed pharmacist – Licensed pharmacy technician
https://www.legis.iowa.gov/legislation/BillBook?ga=88&ba=H-8130
11 4/9/2021
Updates to Legislation
• Medical cannabis cards no longer go through the department of motor vehicles (DMV) – Cards now issued directly from the Office of Medical Cannabis (OMC)
• 4.5 g of THC per 90 days with exceptions – Terminal illness – Patient previously enrolled, and has escalated dose > 4.5 g /90 days • With both situations, attestor must provide new THC cap/90 days
https://www.legis.iowa.gov/legislation/BillBook?ga=88&ba=H-8130
Is My Patient Getting High?
20 mg THC/capsule 600 mg THC/bottle
www.medpharmiowa.com/products www.google.com/images
Is My Patient Getting High?
350 mg THC/cartridge (200-400 inhalations/device)
$65/cartridge
12 4/9/2021
Review • Marijuana contains hundreds of substances, including CBD and THC which have been produced for medical use
• Medical cannabis was able to be distributed to patients in Iowa as of December 1, 2018
• While efficacy data is present for some indications of medical cannabis, it is lacking for others
• Like any substance, medical cannabis does have adverse effects that must be considered
Questions? Questions?
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