Marijuana and prescription drugs: a dangerous combination Each time you pick up a prescription, your pharmacist might ask if you have any questions about how to take your medication or advise you Drug interactions with cannabinoids Department of Family and Community Medicine (Antoniou), St. Michael’s Hospital and University of Toronto; Li Ka Shing Knowledge Institute (Antoniou), St. Studies have shown CBD to be a safe substance, but you should be mindful of possible CBD drug interactions if you are taking other medications.
Marijuana and prescription drugs: a dangerous combination
Each time you pick up a prescription, your pharmacist might ask if you have any questions about how to take your medication or advise you about which other prescriptions might cause a dangerous interaction. Now, several local pharmacists, including Dr. Seung Oh, the pharmacy supervisor at Sharp Rees-Stealy Santee Medical Center, want you to also be cautioned that your medications could lead to potentially harmful reactions when combined with using marijuana, also known as cannabis.
In San Diego, the county records 29 marijuana-related ER visits every day. Marijuana-related medical conditions include cannabis-induced psychosis, severe vomiting, cardiac and pulmonary complications, contamination, allergies, addiction, and withdrawal. Additionally, marijuana and prescription drug interactions are increasing.
In response, 17 local pharmacies have come together to spread the word about the San Diego Marijuana Prevention Initiative, a program created to provide much-needed consumer information about marijuana and possible interactions with prescription medications.
Which drugs interact with marijuana?
According to Dr. Oh, he and the other pharmacists are neither advocating nor discouraging the use of marijuana. However, they want the public to know that just as pairing grapefruit with statins can cause a dangerous interaction, THC and CBD — chemicals found in marijuana and cannabis products, such as gummies and other edibles — can interact with prescription medications and lead to serious side effects.
These side effects can include bleeding complications, increased drowsiness, reduced heart rate and breathing rate, extreme confusion and memory loss, poor judgement, and aggression. THC, the psychoactive ingredient in cannabis, interacts with nearly 400 prescription medications, and CBD (cannabidiol) interacts with more than 540.
Common types of drugs that can have dangerous interactions with marijuana include:
- Sedatives — such as Ambien, Lunesta and Benadryl
- Anti-anxiety medications — such as Xanax, Valium and Librium
- Antidepressants — such as Zoloft, Prozac and Lexapro
- Pain medications — such as codeine, Percocet and Vicodin
- Anticonvulsants (seizure medications) — such as Tegretol, Topamax and Depakene
- Anticoagulants (blood thinners) — such as Coumadin, Plavix and heparin
“Currently very few — if any — pharmacies in San Diego provide information on drug interactions with marijuana products, but it is standard practice to include prescription label warnings about possible interactions with a number of other products,” Dr. Oh says. “While marijuana is legal for adults over age 21 in California, and medically recommended in some cases, it is rare to find consumer protections regarding combining prescriptions with marijuana.”
How the San Diego Marijuana Prevention Initiative will help
To ensure that San Diegans know of the dangers of marijuana use while taking prescription medications, thousands of people will receive information — in English and Spanish — about possible drug interactions. Patients will be referred to drugs.com to use as a resource to check for dangerous drug interactions between THC, CBD and their own prescription medications. They will also be directed to fill out a quick survey about marijuana and drug interactions to be entered for a chance to win a $100 gift card.
“The use of marijuana can, at times, be confusing for the general public because it is legal for adults in California,” says Dr. Oh. “It is important to remember that THC can cause impairment, no matter how it is used, and marijuana can be dangerous when combined with prescribed medications. We want everyone to be aware about possible drug interactions so that they can protect themselves and their loved ones from harm.”
Talk to your pharmacist about possible drug interactions between your prescription medications and other products, food or drink items, and other medications or drugs, such as marijuana. Learn more about possible interactions at drugs.com.
Drug interactions with cannabinoids
Department of Family and Community Medicine (Antoniou), St. Michael’s Hospital and University of Toronto; Li Ka Shing Knowledge Institute (Antoniou), St. Michael’s Hospital, Toronto, Ont.; Department of Medicine (Bodkin, Ho), McMaster University, Waterloo, Ont.; Grand River Hospital (Bodkin), Kitchener, Ont.; Schlegel Research Institute for Aging (Ho), Waterloo, Ont.
Cannabinoid levels can be increased by other medications
Delta-9-tetrahydrocannabinol (THC) and cannabidiol are pharmacologically active cannabinoids in marijuana that are metabolized by cytochrome P450 (CYP)3A4; THC is also metabolized by CYP2C9, a liver enzyme. 1 A pharmacokinetic study found that the CYP3A4 inhibitor ketoconazole nearly doubled THC and cannabidiol concentrations, 2 and similar interactions could occur with other CYP3A4 inhibitors, including macrolides and verapamil, augmenting the psychoactive effects of THC and dose-related adverse effects of cannabidiol (e.g., somnolence, transaminase elevation). 1 , 2 CYP2C9 inhibitors such as cotrimoxazole, fluoxetine and amiodarone would also be expected to increase THC exposure and psychoactive effects. 1
Cannabinoids can affect levels of other drugs
Cannabidiol inhibits CYP2C19, increasing levels of the active metabolite of clobazam threefold. 1 , 3 Interactions with other drugs metabolized by CYP2C19 (Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.191097/-/DC1) should be anticipated. Very high international normalized ratio levels and bleeding have been reported with combined used of warfarin and marijuana. 1 A case reporting a threefold increase in tacrolimus levels following the addition of cannabidiol shows that CYP3A4/5 inhibition can also occur. 4
Smoking marijuana can increase clearance of some drugs
Smoked marijuana increases the clearance of theophylline 40%. 1 Similar findings would be expected for other drugs metabolized by CYP1A2, such as olanzapine. Increased drug clearance occurs with regular marijuana use (> 2 marijuana cigarettes per week); no effect of occasional use has been reported.
Additive effects can occur with other drugs
Additive effects can occur when marijuana is combined with sympathomimetics (e.g., tachycardia, hypertension), central nervous system depressants such as alcohol and opioids (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia, confusion). 5
There are potential “red flag” interactions
Though further research is needed, marijuana may have serious interactions with drugs including warfarin (increased international normalized ratio and risk of bleeding); clobazam (increased risk of benzodiazepine toxicity); central nervous sytem depressants and sympathomimetics (additive effects); and theophylline, clozapine and olanzapine (reduced efficacy). Patients should be advised about possible increased cannabinoid effects with concomitant CYP3A4 and 2C9 inhibitors (Appendix 1). 1 , 5 Alternatives that do not interact with marijuana should be selected when clinically feasible.
Competing interests: None declared.
This article has been peer reviewed.
1. Cox EJ, Maharao N, Patilea-Vrana G, et al. A marijuana-drug interaction primer: precipitants, pharmacology, and pharmacokinetics . Pharmacol Ther 2019; 201 :25–38. [PMC free article] [PubMed] [Google Scholar]
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Articles from CMAJ : Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association
A Patient’s Guide to CBD and Drug Interactions
Does CBD interact with medications? Studies have shown CBD to be a safe substance, but as with any new drug, you must make sure it doesn’t negatively interact with your medications.
CBD drug interactions vary on the type of medication you are taking, so discussing CBD use with your doctor is crucial before starting a CBD regimen.
© MysteryShot | Getty Images
Cannabidiol (CBD) is a well-known component of hemp with diverse health benefits such as reducing pain and inflammation after physical activity, relief from occasional sleeplessness, as well as improvements in focus, mood and resilience to stress.
Numerous studies have shown that CBD is a safe, non-impairing, and non-habit-forming substance. The safety profile of CBD has been acknowledged by major health agencies, such as the World Health Organization (WHO), showing that it’s well-tolerated by animals and humans and rarely produces any dangerous side effects.
Jump to: Blood Thinners | Seizure Medications | Statins | Antibiotics | Antidepressants | Immunosuppressants
However, while CBD is safe to take with many medications, it has the potential to produce problematic interactions with others. Most often, CBD interacts with other drugs via liver metabolism.
In this article I’ll explain how and why these interactions occur and describe the classes of medications that are processed by the same liver enzymes the body uses to process CBD.
The key takeaways for you to remember are:
- CBD is unlikely to cause drug interactions at low and moderate doses used by most consumers of artisanal products. Drug interactions reported in the scientific literature most often occur at very high doses used in clinical trials of epilepsy and other conditions.
- The most important drug interactions can be predicted by comparing the CYP450 metabolic pathways used by CBD and other drugs.
- You can help educate your medical providers on drug interactions and other aspects of CBD and medical cannabis by using the information you’ve learned from this article and our cannabis education site to ask informed questions.
How Do CBD Drug Interactions Occur?
There are two main types of drug interactions: those that change the absorption, metabolism, and excretion of one or both drugs (pharmacokinetic interactions), and those based on the mechanism of action of the drugs (pharmacodynamic interactions). Since cannabinoids, including CBD, share metabolic pathways with other drugs, and have similar mechanisms of action with other drugs, the potential for interaction exists. Most of the clinically relevant interactions of CBD with other drugs are related to competition in the liver’s detoxification pathways. Sometimes the combination can make each substance stronger, by slowing metabolism and increasing the levels of the drugs in the body, or one can weaken the effects of the other by speeding up its metabolism. Either can lead to unintended side effects.
Of the 50+ liver enzymes that make up the CYP450 family of drug-metabolising enzymes, two are primarily responsible for metabolizing CBD: CYP3A4 and CYP2C19. Knowing these can allow you or your healthcare provider to look up the metabolism of a pharmaceutical drug and determine if a CBD-drug interaction is possible.
Most of the documented CBD-drug interactions in humans, as well as in rodent studies, have resulted from high doses of CBD that are not typical of most users, but may be used under medical supervision in the treatment of seizures or other serious conditions.
In general, most of the potential drug interactions are theoretical and unlikely to occur in most CBD users. Based on my clinical experience, it is rare for people to experience CBD-drug interactions at doses below 100mg daily. 
Most Common CBD Drug Interactions
CBD and Warfarin and other blood thinners
I’m most often asked about interactions that can occur with the blood thinner warfarin (also known as by the brand names Coumadin® and Jantoven®). The more accurate concern with warfarin is its interaction with THC because both warfarin and THC are metabolized by the liver enzyme CYP2C9. When warfarin and THC compete for processing by this enzyme, warfarin levels can increase and thereby increase the risk of bleeding. Patients using warfarin need to have their blood INR level tested after adding THC-containing cannabis to their regimen.
While it is possible that taking large amounts of CBD with warfarin or other blood thinners can cause a harmful interaction, the risk is less concerning because the enzyme that metabolizes CBD (CYP2C19) is different. One case report, however, was published demonstrating the need to adjust warfarin dosage after starting and titrating CBD to a very high dose. 
Based on this one report, individuals using high doses of CBD concurrently with warfarin should also notify their medical provider and have their blood INR tested. In my clinic, I have never seen any changes in INR when my patients add CBD.
There is also a theoretical interaction between CBD and the direct-acting oral anticoagulants like apixaban and rivaroxaban, based on the CYP3A enzyme (and P-gp efflux transporter), potentially increasing the risk of bleeding. While no cases of interactions between CBD and these drugs have been reported in the scientific literature, people using these drugs and high doses of CBD should monitor for signs of easy bruising and bleeding. 
Finally, the antiplatelet drug clopidogrel is metabolized into its active metabolite by CYP2C19, and to a lesser extent, CYP3A4. Therefore, taking CBD with clopidogrel could result in decreased therapeutic effects of the clopidogrel, and clinicians may choose to monitor for appropriate platelet response and aggregation. Again, this interaction is theoretical, with no case reports in the scientific literature. 
CBD and Seizure Disorder Medications
Drug interactions with CBD are most common in patients with seizures, especially those using high doses of CBD. When administered with CBD, the blood levels of the following drugs may increase: 
- n-des-methylclobazam (an active metabolite of the drug clobazam)
Patients combining CBD with the seizure drug valproic acid should monitor liver function for potential abnormalities.
CBD and Statin Cholesterol Medications
Statins are a common family of drugs to consider for interaction with CBD because most are processed by the CYP3A4 enzyme. Taking CBD with statins can theoretically raise the levels of statins in the body, increasing the risk of side effects. Additionally, statins are less compatible with CBD because statins tend to cause side effects that are common and similar to the symptoms we tend to treat with CBD. For example, most statin drugs can cause memory issues, muscle pain, fatigue and muscle weakness.
Because I treat a large number of patients with chronic pain, who are already are taking the maximum allowed daily dose of their statin, I frequently discuss alternatives with their prescriber, including switching to pravastatin, a statin that is metabolized by other routes, reducing the amount of the current statin, or adding coenzyme Q10 to mitigate potential statin-related adverse effects.
CBD and Erythromycin and Azole Antifungals
The antibiotic erythromycin and the azole family of antifungals are common medications that inhibit CYP enzymes that metabolize CBD. Taking them together could theoretically increase the risk of adverse effects.
CBD and Antidepressant Drugs
Several antidepressant and antipsychotic drugs are metabolized by the same enzymes as CBD, and taking them in combination could theoretically increase the likelihood of adverse effects. In six patients on citalopram or escitalopram, the addition of CBD (200 – 800 mg daily) significantly increased citalopram blood concentrations. Adverse events reported for these participants were mild and included fatigue, diarrhea, and nausea. 
Furthermore, like many antidepressants, CBD stimulates serotonin receptors, and taking more than one drug with this mechanism of action could theoretically increase the risk of a rare condition called serotonin syndrome. No case reports of this interaction have been described in the scientific literature.
CBD and Immunosuppressant Medications
CBD has the potential to affect the metabolism of the immunosuppressant drugs cyclosporine and tacrolimus via liver metabolism, which may result in increased blood levels of these drugs and an increase in the potential toxic side effects. 
CBD and Glaucoma
Glaucoma is still the first condition many people think of when they consider cannabis as a medicine. The evidence is clear that THC can reduce elevated intraocular (eye) pressure (IOP), a hallmark of the condition.
Does CBD also help? While the answer is not entirely straightforward, the evidence suggests that it does not, and may actually cause harm.
- A recent animal study found that, unlike THC, CBD actually raised intraocular pressure. The researchers determined the pressure elevation was caused by the effects of CBD on the CB1 receptor (negative allosteric modulation). The same study found that adding CBD to THC completely blocked the IOP-lowering effects of the THC. 
- One human study on patients with elevated IOP found that 20 mg of CBD had no effect, but 40mg caused a slight increase in IOP. 
Unlike CBD, CBDA is not likely to have any impact on IOP since it does not share CBD’s activity on the CB1 receptor.
If you have glaucoma and start using CBD products, I recommend having your eye pressures checked to determine if the CBD is causing elevated pressure.
People with glaucoma wishing to use cannabis to lower their IOP will likely do best with THC-dominant, low-CBD preparations. People with glaucoma who wish to use hemp products to address other symptoms will likely do best with CBDA formulas.
People with glaucoma who have well-controlled IOPs wishing to use cannabis to protect the retina are most likely to benefit from a combination of CBD and THC.
Talk with Your Doctor Before CBD Use
If you take several different medicines, see more than one doctor, or have certain health conditions, you and your doctors need to be aware of all the medicines you take to avoid potential drug interactions.
A consultation with a doctor experienced in CBD and cannabis use can help you establish the right routine for your medications and supplements to avoid potentially negative interactions. Some compounds work synergistically with CBD, so asking your doctor can help you maximize the effect of your treatment.
Use online drug interaction checkers to see which cytochrome p450 enzymes are used. If they overlap with CBD (You may have to enter “Epidiolex” if it does not recognize cannabidiol), then monitor more closely and be sure to tell your medical provider. The need for caution increases with higher doses. Using small amounts poses a very low risk of drug interactions.
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Dustin Sulak, DO
Dustin Sulak, DO, one of the first physicians in Maine to incorporate the legal use of cannabis as a medicine in 2009, is the founder of Integr8 Health, a medical … Read More