As a pharmacist one of the most common questions I get is, “Can I take CBD with my prescription medications?”
This is why patients arrange to have paid consultations with me: to answer this question. They want to know what to look out for.
Yes, drug interactions are possible…
As you can see by the image below, the World Health Organization believes that “CBD is generally well tolerated with a good safety profile. Reported adverse effects may be a result of drug-drug interactions between CBD and patient’s existing medications.”
CBD’s drug interactions with other pharmaceuticals can be difficult to pinpoint due to different resources stating different information about how CBD is metabolized, and CBD’s effects on the liver enzymes.
(Check out my References at the end of this article and you’ll see what I mean about varied information.)
(For more information about drug interactions and drug metabolism I suggest you check out Episode 6 of the Medical Cannabis podcast. [Available on iTunes]. We provide some simplified information to make drug metabolism understandable.)
(CBD) Drug Interactions – Explaining my approach
I take a conservative approach and document the various potential interactions that might occur based on data I have accumulated from various sources.
Most data indicate that CBD could impair, or inhibit one or a combination of the following liver enzymes: CYP2C19, CYP2C9, CYP2C8, CYP2D6, and CYP3A4.
This means that other pharmaceuticals metabolized by these same enzymes could become elevated (or too much) in the bloodstream, leading to increased risk of adverse events from the pharmaceuticals.
References vary on how extensively (or potently) CBD inhibits these enzymes so I take the cautious approach and take all interactions into consideration and then list what adverse events we would monitor for.
Some drug interactions with CBD are documented (such as CBD causing increased Clobazam drug levels in the blood due to CBD inhibiting the CYP2C19 enzyme), and others are theoretical: meaning there is a potential risk of an interaction occurring because the pharmaceutical is metabolized by an enzyme that CBD may inhibit.
And dose appears to make a difference. In the Nabiximols drug monograph (brand name is Sativex®) they state they didn’t see clinically relevant drug interactions when their mouth spray was administered up to around 30mg’s per day.
Yet in the Epidiolex drug monograph (a prescription CBD medication in the USA) they used hundreds of milligrams of CBD per day, and did see drug interactions.
Other Drugs affecting CBD Levels
Other medications that either induce, or inhibit CYP3A4 and CYP2C19 have the potential to decrease or increase CBD blood levels respectively.
This means that a patient may either need to take more, or less CBD than they otherwise would if they weren’t on the other pharmaceutical.
I am not too concerned with this when a patient is first starting CBD though because I believe in the “Start low and go slow” approach to dosing CBD.
This means a patient can find the best dose for them by starting at a low dose and waiting a few days between each small, incremental dose increase.
But when we need to be concerned with this is when the other pharmaceuticals are either decreased, increased, stopped or a new drug is started.
Then this could possibly throw off the balance the patient has achieved on their previous CBD dose and they would need to monitor for either decrease in CBD’s benefits, or increase in CBD adverse events.
A Patient’s Monitoring Chart…what to look out for
When a patient calls me to arrange a paid consultation I get their list of prescription medications. They either give me the information over the phone or email it to me.
Then I analyze each drug on the list.
I don’t have total faith in drug interaction software when it comes to Cannabis and CBD (yet). I prefer to look up each drug and examine how that drug is metabolized by the liver.
If it is metabolized by an enzyme that CBD may inhibit or does inhibit (such as CYP2C19), then I write down what could occur as a result of the interaction.
An example would be if a drug is metabolized by the CYP2C19 enzyme. If it’s taken along with CBD, then there is a risk that “too much” of that other drug could end up circulating in the blood stream. This is because if CBD inhibits that enzyme system it can’t metabolize (or change) the other drug as efficiently as it used to. That means the other drug could increase in the bloodstream and put the patient at increased risk of adverse events.
What adverse events would they experience? Well that is what I list in a section called “What to monitor for, and what to do about it .” And the adverse events they may experience are dependent upon that “other” drug.
If that other drug is a sleeping pill like Zopiclone, and if it increased in the bloodstream – “too much” – then the patient is at increased risk of excessive drowsiness, increased risk of falls, morning sedation and grogginess (among others).
Then if a patient does experience one of the side effects of “too much” of the other drug they need to speak to their doctor.
Then together the doctor and the patient can make a decision. Do they want to lower the dose of the “other” drug? Or if CBD isn’t helping like they wanted, they could lower the CBD dose.
I remind people that come to see me that most of the interactions I list don’t mean they are going to occur…because many of them are theoretical interactions…but I prefer the person be aware and know what to look out for just in case.
I hope this has helped explain my approach to CBD and drug interactions.
Below you’ll find some of the references I have used to come up with my approach.
Nabiximols (Sativex®) Drug monograph – accessed online
- “There may be a potential risk of drug-drug interactions due to CYP450 inhibition by SATIVEX®. Caution should be exercised in patients taking drugs known to be substrates for CYP450 3A4 or CYP450 2C19…”
Epidiolex Drug monograph – accessed online
- It states that CBD may inhibit CYP2C8, CYP2C9, and CYP2C19, and theoretically may either induce or inhibit CYP1A2 and CYP2B6.
Gaston, T. E., Bebin, E. M., Cutter, G. R., Liu, Y. , Szaflarski, J. P. and , (2017), Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia, 58: 1586-1592. doi:10.1111/epi.13852
- Claims that CBD is a potent inhibitor of CYP2D6, CYP2C9 and CYP2C19, and may be an inhibitor of the CYP3A family of enzymes
Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791–802. doi:10.1111/epi.12631
- Accessed online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707667/
- Claims that, “CBD is a potent inhibitor of P450 isozymes, primarily CYP2C and CYP3A classes of isozymes, in vitro and in animal models. This is particularly important because many medications are substrates for CYP3A4. However, inhibition has typically not been observed at concentrations used in human studies.”
Sekar K, Pack A. Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. F1000Res. 2019;8:F1000 Faculty Rev-234. Published 2019 Feb 28. doi:10.12688/f1000research.16515.1
- Accessed online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396837/
- Claims that “CBD is metabolized primarily by cytochrome P450 (CYP) 2C19 and CYP3A4 and can inhibit the CYP2C and CYP3A4 families of isoenzymes.”
Devinsky O, Patel AD, Thiele EA, et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90(14):e1204–e1211. doi:10.1212/WNL.0000000000005254
- Accessed online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890607/
- Claims that “CBD can also inhibit the CYP2C family of isozymes (inhibition constant [Ki] = 1–10 μM) and CYP3A4 (Ki = 1 μM).”