Medical cannabis and drug interactions

Karen Berger, PharmD, Medical Writer


Anna is a NJMMP medical cannabis patient. She has been using cannabis for several years. Recently, she saw her doctor for anxiety and he put her on Klonopin (clonazepam). She was happy with the decision, because she had tried Klonopin several years ago and had great results and few side effects. However, this time, she noticed that she was feeling extremely tired and disoriented. What happened?


When you take any medication (whether it is prescription or over-the-counter) or have certain medical conditions, you always have to be aware of potential drug interactions. For example, if you have high blood pressure, it is not safe to take medications that contain decongestants, because decongestants can raise your blood pressure.  


So, what about medical cannabis? While we all think of medical cannabis as a plant, we still have to think about potential drug interactions. 


The good news in general with medical cannabis is that serious adverse effects are rare, and deaths from overdose do not occur.  


A quick pharmacology lesson: drug interactions are often caused by certain enzymes which process medications in your body. 

Certain enzymes are known as:

  • Inhibitors: An enzyme inhibitor slows down the metabolism of another drug – for example, if drug A is an enzyme inhibitor, it may inhibit the metabolism of drug B. What does this mean? Your body is not processing drug B as efficiently as it normally would, and this can result in higher drug levels and effects (potentially toxic) of drug B, as well as increased intensity of side effects. 
  • Inducers: This is basically the opposite scenario. An enzyme inducer speeds up the metabolism of another drug. So, if drug A is an enzyme inducer, it can potentially induce the metabolism of drug B. This means drug B may be removed from your body faster, and may not be as effective. With certain drugs, it can even cause withdrawal symptoms.


Some of the most common enzymes involved with drug interactions are known as cytochrome P450 3A4 (CYP450 3A4), cytochrome P450 1A2 (CYP450 1A2), and cytochrome P450 2C9 (CYP450 2C9). 


Because both THC and CBD are metabolized by CYP3A4 and CYP2C9, cannabis is involved in many drug interactions. 


Also, THC induces CYP1A2. That means THC can potentially interact with any of these drugs, lowering the levels of the drug in your body, and making it less effective: 

  • Clozaril (clozapine) 
  • Cymbalta (duloxetine) 
  • Naprosyn, Anaprox (naproxen) 
  • Flexeril (cyclobenzaprine)
  • Zyprexa (olanzapine)
  • Haldol (haloperidol)
  • Thorazine (chlorpromazine)


CBD is a strong inhibitor of both CYP3A4 and CYP2D6. Because CYP3A4 is involved with metabolism of about 25% of all drugs, CBD may increase levels of:

  • Macrolide antibiotics 
    • Zithromax (azithromycin)
    • Biaxin (clarithromycin)
    • Erythromycin
  • Calcium channel blockers
    • Calan (verapamil)
    • Cardizem (diltiazem)
  • Benzodiazepines
    • Valium (diazepam)
    • Xanax (alprazolam)
    • Klonopin (clonazepam)*
    • Ativan (lorazepam)
  • Cyclosporine
  • Certain erectile dysfunction medications
    • Viagra (sildenafil)
    • Cialis (tadalafil)
    • Levitra (vardenafil)
    • Stendra (avanafil)
  • Antihistamines
  • Haldol (haloperidol)
  • Antiretrovirals used in HIV or AIDS treatment
  • Certain statins 
    • Lipitor (atorvastatin)
    • Zocor (simvastatin)


*This is what happened to Anna- the cannabis interfered with her Klonopin, making the Klonopin build up in her body and making her experience more side effects. 


CYP2D6 metabolizes many antidepressants, so CBD may increase levels of these drugs in your body:

  • SSRI antidepressants
    • Prozac (fluoxetine)
    • Paxil (paroxetine)
    • Zoloft (sertraline)
    • Celexa (citalopram)
    • Lexapro (escitalopram)
  • Tricyclic antidepressants
    • Elavil (amitriptyline)
    • Pamelor (nortriptyline)
  • Antipsychotics
  • Beta blockers 
    • Tenormin (atenolol)
    • Lopressor, Toprol XL (metoprolol)
    • Inderal (propranolol)
    • Zebeta (bisoprolol)
  • Opioids 
    • Forms of oxycodone
    • Forms of codeine
    • Forms of morphine
    • Ultram (tramadol)


Other drug interactions:

  • Medical cannabis may interact with Coumadin (warfarin), a blood thinner that has many drug interactions. THC and CBD increase warfarin levels, making the patient prone to bleeding. 
  • Alcohol may increase levels of THC.
  • Combining cannabis with tobacco can cause increased respiratory symptoms.
  • Many drugs are known as CNS depressants, because they slow down brain activity in the central nervous system (CNS), and are used to treat anxiety, panic, acute stress reactions, and sleep disorders. CNS depressants tend to have an additive effect with other CNS depressants. Cannabis has been shown to have additive CNS depressant effects with alcohol, barbiturates (such as phenobarbital), and benzodiazepines (see list above).


This is not a complete list; other drug interactions may occur. 


The folks over at Leafly remind us that other factors may come into play with cannabis/drug interactions, such as the CBD:THC ratio, and different strain profiles. The article, linked above, provides some more information about cannabis and drug interactions and how cannabis may even be used in conjunction with a certain medication to increase its effect. Due to the versatility of cannabis, Leafly states that “one of the most compelling arguments for cannabis is that it can actually reduce the need to combine multiple medications that have a high risk potential of producing adverse interactions.” Dr. Donald Abrams, chief of hematology-oncology at San Francisco General Hospital and professor of clinical medicine at the University of California, San Francisco, sums it up well: “Why would I write six different prescriptions, all of which may interact with each other, when I could just recommend one medicine [cannabis]?” 


Because data on drug interactions with medical cannabis is still being researched, we do not yet have a full picture of all possible drug interactions. There may be many more that we do not know about yet. Always ask your healthcare professional for advice. 


The pharmacists and doctors at MyCureAll are working on identifying drug interactions for cannabis, as well as working to get cannabis covered and have the best medical protocols for each condition. 


Information in this post is intended to be general information. For personalized advice, always check with your healthcare provider.