CBD Oil Drug Interactions: Can mixing CBD with medication be dangerous?

WRITTEN by Caleb

 | Last revised

When you speak with a trained cannabis clinician, one of the most important questions they’ll ask is whether you’re taking other medications or even recreational drugs.

Why? Despite the World Health Organization stating that CBD is safe, there is still the risk it may interact with certain medications.

What you should be aware of before adding CBD into your wellness routine?

We’ll answer all these questions, plus share some information about how CBD may interact with other substances such as cocaine, MDMA, or psilocybin mushrooms.

Let’s start with legal drugs.

Does CBD Interact with Other Medications?

Research shows CBD inhibits cytochrome P450 enzymes. This family of proteins oxidize steroids and fatty acids and are essential for the metabolism of drugs.[1]

The fact that CBD deactivates this enzyme is kind of important. It means these medications stay in your system longer. That Xanax you take may be stronger than you think.

So let’s look at some of the common medications CBD interacts with.

CBD & Aspirin

When you’ve got a pounding headache, aspirin can be a lifesaver. But what if you’re on a daily regimen of CBD oil?

A 2012 study found CBD influenced platelet formation. Platelets react to bleeding from blood vessel injury by clumping, creating a blood clot.[2]

CBD’s influence on platelet formation means it might be able to delay or prevent cardiovascular disorders. However, the researchers say further studies are required to strengthen their hypothesis.

Since aspirin and CBD involve CYP450, and there haven’t been any longitudinal scientific studies on the subject, researchers don’t recommend mixing the two.

CBD and Blood Thinner Medication

The body metabolizes blood thinners through the cytochrome P450 (CYP450) system. And as we know, CBD inhibits these enzymes.

A 2017 report by the U.S. National Library of Medicine National Institutes of Health warned that CBD competes with the same metabolic pathway as warfarin, a popular blood thinner medication.[3]

CBD and blood thinner medication don’t work well together. CBD ensures the blood thinner stays in your system longer by preventing it from breaking down.

Staying in your system longer can cause side effects like bleeding or an overdose. Patients on blood thinners should speak with a medical professional before trying CBD.

A gloved hand holding a CBD tincture and a stethoscope like its offering a choice between the two

Can You Take CBD Oil with Antidepressants?

Can you take CBD oil with antidepressants like Lexapro or Zoloft?

CBD is known for its anti-anxiety, anti-epileptic, and anti-psychotic properties.[4] So taking them together would be like a super antidepressant, right?

Not quite. At least one study suggests CBD inhibits liver enzymes essential for metabolizing antidepressants.[5]

Taking CBD oil with antidepressants like an SSRI may reduce the efficacy of both drugs. Your antidepressant will be less effective, and so will your CBD.

If you’re on antidepressants and want to try CBD, we suggest you discuss it with your doctor.

CBD and Benadryl

Benadryl is the brand name of an antihistamine. Most people use Benadryl to alleviate allergy symptoms.

Antihistamines work by blocking histamine activity. But Benadryl is also an anticholinergic, which inhibits actions in the central nervous system.

This makes Benadryl useful but not recommended for combating insomnia.[6]

There is no known interaction between CBD and Benadryl. But, as with many other drugs, Benadryl is metabolized through the cytochrome P450 enzyme system.

Because of this, the concentration of the drug in your system could remain higher for longer when taken with CBD.

The problem is Benadryl has different effects on different people. As an antihistamine, Benadryl can cause drowsiness in some people. Yet, for others, it keeps them awake.

Until we have specific studies looking at CBD and Benadryl (or antihistamines in general), your best to speak with a health care professional if mixing these two is a concern.

CBD & Xanax

Alprazolam (Xanax) is an anti-anxiety medication metabolized by the CYP3A4 enzyme. It is considered a benzodiazepine.

A Japanese study indicated that CBD most likely inhibits the CYP3A system of enzymes. This can lead to higher levels of Xanax in your system, which can cause unwanted side effects and even an overdose.[7]

The authors of this study do not recommend taking CBD with Xanax or any other benzodiazepine drug.

Illegal Drug Interactions with CBD Oil

So now we have a little more understanding about CBD and other medications. But what about illegal drugs and CBD?

For example, psilocybin mushrooms are known to cause some anxiety in people, especially with the onset of the effects. But CBD is known to reduce anxiety.

So what happens when you take both?

CBD & Psilocybin

Unfortunately, we’re not sure. There have been no studies that look into CBD and psilocybin specifically. But we can make some educated guesses.

Both substances help stimulate new brain cells through a process called hippocampal neurogenesis.[8][9][10]

But, like the other drugs mentioned, psilocybin is metabolized in the liver.[11]

Does this make psilocybin or CBD less effective? Or does this mean psilocybin will remain in your system longer?

Unfortunately, until we get some studies on CBD and psilocybin, we can’t say one way or the other.

CBD & Cocaine

CBD has been shown as a promising treatment for substance use disorders. So there must be some good news regarding CBD and cocaine, right?

A 2019 study showed that CBD reversed the toxicity and seizures caused by excessive use of cocaine. The paper also suggested it changed people’s desire to use cocaine.[12]

Observational studies confirm CBD’s role in reducing addiction, withdrawal symptoms, craving, and impulsive behaviour. [13]

When cocaine reaches the liver, it’s metabolized into benzoylecgonine and exerted through urine. Does CBD affect this metabolism the way it does with other liver enzymes?

Unfortunately, we don’t know. Most research on CBD and cocaine look at CBD as a treatment option for substance use disorders.

But given that researchers are looking at CBD as a treatment option for cocaine addicts, if there were significant adverse reactions to mixing the two, we probably would have heard about it by now.


Researchers think CBD might compete with MDMA in the brain. CBD effect on 5-HTP1A receptors may block the serotonin released by MDMA.[14]

This means CBD may mediate the effects of MDMA, similar to how CBD mediates the effects of THC. But our research on CBD and MDMA is lacking.

We know CBD is a partial agonist of our dopamine receptors, so researchers think it interferes with MDMA’s dopamine binding dynamic.[15]

Does CBD Interact with Medications?

Does CBD Interact with Medications? Yes, it most definitely does.

Suppose the medication is metabolized in the liver, as most drugs are. In that case, you’ll want to do your research and possibly consult with a health care professional.

A lot of CBD drug interactions appear harmless. Still, if you’re not careful, CBD can cause a build-up of certain drugs in your system, which can cause unwanted side effects or even an overdose.

As far as illegal drugs go, if you’re adamant about trying them, do it without CBD. Just in case.

But if you find yourself addicted to drugs like cocaine, CBD might help break the habit.

Overall, drug interactions with CBD oil range from minor to severe side effects. So if you’re getting CBD through the TGA, talk to your doctor about what drugs should not be taken with CBD.

If you’re like millions of other Australians and prefer to buy from the “green” market, be sure you’re getting a high-quality product by researching the brand.

CBD is safe and effective. But you want to be mindful of CBD oil drug interactions.

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1. Shamema Nasrin, Christy J W Watson, Yadira X Perez-Paramo, Philip Lazarus, "Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions".
2. Christopher P Stanley, William H Hind, Saoirse E O'Sullivan, "Is the cardiovascular system a therapeutic target for cannabidiol?".
3. Leslie Grayson, Brannon Vines, Kate Nichol, Jerzy P. Szaflarski,, "An interaction between warfarin and cannabidiol, a case report".
4. José A. Crippa, Francisco S. Guimarães, Alline C. Campos, Antonio W. Zuardi, "Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age".
5. Satoshi Yamaori, Juri Ebisawa, Yoshimi Okushima, "Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety".
6. N/A, "Is It Safe to Take an Antihistamine for Sleep Every Night?".
7. Satoshi Yamaori, Juri Ebisawa, Yoshimi Okushima, "Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety".
8. Satoshi Yamaori, Juri Ebisawa, Yoshimi Okushima, "Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement".
9. Briony J Catlow, Shijie Song, Daniel A Paredes, "Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning".
10. N/A, "Can you grow new brain cells?".
11. F Hasler, D Bourquin, R Brenneisen, "Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man ".
12. Claudia Calpe-López, M. Pilar García-Pardo,Maria A. Aguilar, "Cannabidiol Treatment Might Promote Resilience to Cocaine and Methamphetamine Use Disorders: A Review of Possible Mechanisms".
13. Gustavo Gonzalez-Cuevas, Remi Martin-Fardon, Tony M. Kerr, at el., "Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle".
14. P Seeman, "Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose".
15. N/A, "What are MDMA’s effects on the brain?".


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Disclaimer. While we strive to relay the most factual education available, this shouldn’t replace official medical or legal consultation and recommendation. This is for educational and entertainment purposes only. Happy days.

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