cannabis conundrums: navigating drug-thc and …...cannabis strains • generally divided into...

CANNABIS CONUNDRUMS: NAVIGATING DRUG-THC AND CBD INTERACTIONS

Jenna Carmichael, PharmD

Columbia Care

Wilkes-Barre, PA

OBJECTIVES

• Describe Pennsylvania Medical Marijuana Program

• Evaluate the available data on drug-cannabis interactions

• Apply knowledge learned in program to a patient case

PA MEDICAL MARIJUANA PROGRAM

https://www.webmd.com/a-to-z-guides/medical-marijuana-

faq

THE PROGRAM

• The program was signed by Gov. Tom Wolf on April 17, 2016

• As of November 2019

• 147,000 certified patients

• 72 dispensaries

• 1,200+ physicians licensed to certify patients

• 65,000 patient visits per week

• $120 average purchase per person

• $524 million in total sales

• $6.45 million in tax revenue

https://www.ydr.com/story/news/2019/02/19/first-year-pas-medical-marijuana-sales-thousands-patients-millions-dollars-pennsylvania-first-

year/2913574002/

PENNSYLVANIA CERTIFYING CONDITIONS

• ALS

• Anxiety disorders (as of 7/20/19)

• Autism

• Cancer

• Crohn’s Disease

• Damage to the nervous tissue of the central nervous system with objective neurological

indication of intractable spasticity, and other associated neuropathies

• Dyskinetic and spastic movement disorders

• Epilepsy

• Glaucoma

• HIV/AIDS

• Huntington’s disease

PENNSYLVANIA CERTIFYING CONDITIONS

• Inflammatory bowel disease

• Intractable seizures

• Multiple sclerosis

• Neurogenerative disorders

• Neuropathies

• Opioid use disorder for which conventional therapeutic interventions are contraindicated or ineffective, or

for which adjunctive therapy is indicated in combination with primary therapeutic interventions

• Parkinson’s disease

• PTSD

• Severe chronic or intractable pain of neuropathic origin or severe chronic or intractable pain

• Sickle cell anemia

• Terminal illness

• Tourette syndrome (as of 7/20/19)

WHAT IS THE BREAKDOWN BY CONDITION?

• Over half of all permits issued are for severe

or chronic pain

• PTSD is at a far second at 13.5%

https://www.pennlive.com/news/2019/06/chronic-pain-ptsd-amount-to-half-of-need-for-medical-marijuana-use-in-

pa.html

SUGGESTED USES FOR CANNABINOIDS

• THC

• Opiate like pain relief

• Appetite stimulant

• Nausea/GI issues

• Sleep

• Muscle relaxant

• CBD

• Neuropathic pain

• Anti-inflammatory

• Anxiety

• Spasticity

THE ENTOURAGE EFFECT

• Cannabinoids are not the only part of the plant to focus on

• Terpenes also play a role

• Called the ‘entourage effect’

• The sum is greater than the individual parts

• Perhaps why CBD isolate oils may not be as effective

CANNABIS STRAINS

• Generally divided into Sativa, Hybrid and Indica

• Sativa - Sunshine - activating, daytime

• Indica - Into The Couch - relaxing, evening, help sleep

• Hybrid - can have characteristics of both Sativa and Indica

• CBD - medical cannabis with CBD will have higher THC than hemp

• Hemp legally has to have < 0.3% THC

https://www.cannainsider.com/reviews/cannabis-

terpenes/

HOW TO OBTAIN A MEDICAL CARD

https://www.solevowellness.com/get-medical-marijuana-id-

card/

STEPS TO OBTAINING A MEDICAL CARD

• Have a medical condition that is covered by the act

• See a physician that is registered with the state to certify patients

• Be warned that this visit is usually not covered by insurance

• Register online with Department of Health, pay and MD will certify online

• Wait for card to come in the mail

• Physician determines how long the card is good for - max is 1 year

AT THE DISPENSARY

PHARMACIST ROLE

• Consultant for new patients

• Explain the program

• Potential benefits of cannabis

• Discuss the various forms

• Determine which way to medicate will be best for the patient based on other health

factors and needs

MODES OF ADMINISTRATION

• Inhalation/Vaporization

• Effect immediately to 15 minutes; lasts about 2 hours

• Sublingually/Tincture

• Effect 30 minutes to 1 hour; lasts 4-6 hours

• Orally/Capsule

• Effect 1 hour to 1.5 hours; lasts 6-8 hours

• Topically

SIDE EFFECTS

• The 3 D’s: dizziness, drowsiness, dry mouth

• THC is responsible for psychoactive effect, adding CBD brings this down without taking

away benefits

• THC alone can cause confusion, anxiety and feelings of panic (dose related)

• Other cannabinoids are not psychoactive

VAPING LUNG ILLNESS

• Now called e-cigarette or vaping associated lung injury (EVALI)

• As of December 27, 2019, 2,561 hospitalizations or deaths have been reported to the CDC

• 55 deaths have been confirmed in 27 states

• Vitamin E acetate has been associated with many of the cases

• Cartridges sold in PA dispensaries only have cannabis oil and no accelerants or additives

• CDC recommends purchasing THC containing vapes only from reputable sources

https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html

DOSING

• Dosing can be difficult to quantify while inhaling medication

• Generally find that 5-10mg orally works for most patients for pain

• Can you overdose?

• Yes, but it is not fatal - may be very unpleasant (hallucinations, paranoia, panic, rapid

heart beat, nausea) until the medicine wears off

• More likely to happen with oral administration or edibles

TIME TO EFFECT

• Will see effects of THC within first use, as long as dose is high enough

• CBD takes longer to build up in system

• Recommend a month of consistent use before patient can say ‘yes’ or ‘no’

FREQUENTLY ASKED QUESTIONS FROM PATIENTS

• Can I still take my other medications?

• Yes, as long as there are no interactions

• When can I stop taking my [insert drug name here]?

• Most patients want to get off their current regimen, we advise patients to continue all

current medications until they are seeing benefit from cannabis then to work with

provider about weaning off meds

FAQ FROM PATIENTS

• Will I develop a tolerance to the medication?

• You may find that over time, you will need increased levels of THC to help with pain

• CBD once it has built up in system does not seem to need increased doses

• Taking a break for a short period depending on length of use may help reset receptors

but many medical users don’t wish to be in pain for a few days

FAQ FROM PATIENTS

• Can I smoke whole flower cannabis?

• No, the state has approved medical cannabis for vaporization only

• How much can I purchase at a time?

• The state says you can purchase a 30 day supply at a time

FAQ FROM PATIENTS

• Can I buy [gummies, brownies, other edibles] here?

• No, edibles are not allowed currently under the state law

• We can give guidance on how to make own edibles at home

FAQ FROM PATIENTS

• Can my [wife/husband/daughter/son] come with me to my appointment with the

pharmacist?

• Only patients with valid medical cards can enter a dispensary

• Family members can apply for a caregiver card

FAQ FROM PATIENTS

• Can I buy CBD oil at your dispensary?

We do not sell CBD only products at the dispensary, all products have some THC in

them

We do have products with high CBD and lower THC

TIPS ON PURCHASING CBD

• The 2018 Farm Bill legalized hemp and CBD is everywhere

• Hemp is classified as having < 0.3% THC

• As there is already an FDA approved CBD product (Epidiolex), the cannabinoid can’t be

considered a neutraceutical or dietary supplement

• Look for ‘full spectrum’ or ‘whole plant extract’ over ‘isolate’

• Ask the company about third party testing

DRUG INTERACTIONS

https://www.wikileaf.com/thestash/thc-

pills/

DRUG-THC INTERACTIONS

• THC is metabolized by CYP2C9 and CYP3A4

• CYP2C9 inhibitors such as amiodarone, cimetidine, cotrimoxazole, metronidazole, fluoxetine,

fluvoxamine, fluconazole and voriconazole may inhibit THC elimination

• Ketoconazole has been reported to increase peak concentration of THC by 1.2;

clarithromycin, erythromycin, cyclosporine, verapamil, itraconazole, voriconazole, and

boceprevir would be expected to produce similar results

• Rifampin has been reported to reduce THC levels by 20-40%

• Potential for interaction with warfarin (increase INR)

https://www.pharmacytimes.com/publications/issue/2014/december2014/drug-interactions-with-

marijuana

DRUG-CBD INTERACTIONS

• Epidiolex is an FDA approved CBD extract for seizures

• Consider dose reduction of Epidiolex when coadministered with moderate or strong

inhibitor of CYP3A4 or CYP2C19

• Consider dose increase when coadministered with strong CYP3A4 or CYP2C19 inducer

• Consider reduction in dose of substrates of UGT1A9, UGT2B7, CYP2C8 and CYP2C9 if

side effects are seen (potential inhibition of enzyme activity)

• Consider change in dose of CYP1A2 substrates or CYP2B6 substrates (potential for

induction and inhibition of enzymes)

• Omeprazole, a modest inhibitor of 2C19, did not alter plasma concentration of CBD in a

study


marijuana

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

https://www.pharmacytimes.com/publications/issue/2014/december2014/drug-interactions-with-marijuana

DRUG-CBD INTERACTIONS IN EPILEPSY

● Non-significant increase of clobazam plasma level

● Significant change of plasma level of N-desmethylclobazam but no significant change in level

of valproate, stiripentol and levetiracetam

● Increasing CBD doses showed changes in clobazam, N-desmethylclobazam, eslicarbazepine,

rufinamide and topiramte

● Suggest checking LFTs in patients taking valproate or clobazam (baseline, 1, 3 and 6 months

after starting treatment with CBD)

Alsherbiny MA, Li CG. Medicinal Cannabis-Potential Drug Interactions. Medicines (Basel). 2018;6(1):3. Published 2018 Dec 23. doi:10.3390/medicines6010003

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

DRUG-CANNABIS INTERACTION IN PAIN

• A study found vaporized cannabis increased analgesic effects of opioids without altering

plasma opioid levels

• An open label trial found that medicinal cannabis reduced the consumption of opioids

• Fentanyl + CBD did not affect the level of CBD or fentanyl

• Co-administration did not produce cardiovascular complications or respiratory

depression


OTHER DRUG-CANNABIS INTERACTIONS

• Found to not affect clinical pharmacokinetics of irinotecan and docetaxel in cancer patients

• Patients with chronic use of cannabis may need higher doses of anesthesia


Alexander JC, Joshi GP. A review of the anesthetic implications of marijuana use. Proc (Bayl Univ Med Cent). 2019;32(3):364–371. Published 2019 May 21. doi:10.1080/08998280.2019.1603034

DRUG-SMOKING INTERACTION

• PA regulations are against smoking

• A case report found an increased response to warfarin in a patient smoking 4-5 joints per

week

• Smoked cannabis, but not oral administration, has been shown to increase metabolism of

theophylline and chlorpromazine with about 50% reduction in plasma concentrations

• CYP1A2 induced by smoking more than 2 joints per week


marijuana

PHARMACODYNAMIC INTERACTIONS

• Potential for interactions with drugs that have:

• Sympathomimetic activity (tachycardia, hypertension)

• CNS depressants (drowsiness, ataxia)

• Drugs with anticholinergic effects (tachycardia, drowsiness)

• Case reports of stroke and heart attack in vulnerable patients


marijuana

CANNABIS-FOOD INTERACTIONS

• Cannabinoids are fat soluble

• May have increased absorption in tinctures, capsules and edibles if taken with fat

PATIENT CASE

https://unsplash.com/s/photos/cannabis

MEET MARY JANE

• Mary Jane is a 65 yo female with back pain from DDD. She was advised by her pain doctor

that Medical Marijuana may be something that could help her pain. She has her card and

presents to the dispensary for a pharmacist consult. Upon looking at her paperwork and

medical history, you see that she had a heart attack about 2 months ago but is now

medically stable.

• She reports that her pain is constant. She has had injections that didn’t work and is

currently taking oxycodone/APAP around the clock for her pain. She does have numbness

in extremities but not all the time. She has never used cannabis before.

IS MJ A GOOD CANDIDATE FOR CANNABIS?

A. No, her recent heart attack makes cannabis too risky for her

B. Yes, cannabis could help with pain as an adjunct to other therapies

C. No, her age makes cannabis unlikely to work

D. Yes, she should stop all her pain medications and change to cannabis

CASE CONTINUED

• MJ meets with the pharmacist and elects to try a tincture with a 1:1 THC:CBD ratio. After

being on the therapy for 3 weeks, she calls the dispensary for advice. She was diagnosed

with a UTI and started on cotrimoxazole for 3 days and wanted to know if this would

impact her tincture. She reports that the tincture is helping with her pain and she has

decreased her need of the oxycodone/APAP.

WHAT DO YOU RECOMMEND TO MJ?

A. Stop the tincture as the interaction with the cotrimoxazole will increase the THC to toxic

levels

B. Increase the tincture as the interaction with the cotrimoxazole will decrease the THC

C. No need to stop the tincture as the course of antibiotic therapy is short

D. No need to stop the tincture as there is no interaction with cotrimoxazole

What would you recommend to MJ if the antibiotic therapy was longer?

CASE CONTINUED

• MJ returns to the dispensary with her daughter, Juanita, who is a caregiver for her 6 year

old son with seizures. MJ is so impressed at how you were able to help with her pain that

she recommended you to her daughter to help. Her son is currently taking valproic acid for

his seizures. Juanita reports that his seizures are mostly under control with this medication

but she notices many behavioral issues and other side effects that she doesn’t like since

starting him on this therapy. She is looking for a more natural alternative for his seizures.

WHAT SHOULD BE DISCUSSED WITH JUANITA?

A. A. If the medication her son is currently on is working, then they should just stay the same

B. B. She should stop the valproate before starting on cannabis

C. C. She should have a discussion with her son’s neurologist about adding the cannabis and

the need for extra lab monitoring while on the combination therapy

D. D. There is no need for extra monitoring with the addition of cannabis, so no extra

discussion is needed

WHAT SHOULD BE DISCUSSED WITH JUANITA?

A. A. If the medication her son is currently on is working, then they should just stay the same

B. B. She should stop the valproate before starting on cannabis

C. C. She should have a discussion with her son’s neurologist about adding the

cannabis and the need for extra lab monitoring while on the combination

therapy

D. D. There is no need for extra monitoring with the addition of cannabis, so no extra

discussion is needed

CONCLUSIONS

• There is potential for drug-cannabis interactions with typical offenders such as strong

CYP3A4 inducers/inhibitors

• Dose adjustments should be based on whole clinical picture

• More research is needed

QUESTIONS?

[email protected]

THANK YOU!!

cannabis conundrums: navigating drug-thc and …...cannabis strains • generally divided into...

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