Cannabis extracts from four different chemotypes all inhibited the liver enzymes that metabolize warfarin and similar blood thinners, but the degree of inhibition varied dramatically depending on the plant variety.
Read this if you take warfarin or another blood thinner and use cannabis in any form — the interaction risk is real, varies by product, and should be discussed with your prescriber.
What the researchers found
If you take a blood thinner like warfarin and use cannabis, this study has important implications. The researchers tested cannabis extracts from four different chemotypes — varieties with different ratios of THC, CBD, and other cannabinoids — to see how they affected the liver enzymes (CYP2C9 and CYP3A4) responsible for metabolizing common blood-thinning medications.
All four cannabis extract types inhibited these enzymes, meaning all of them could potentially increase blood thinner levels in the body. But the degree of inhibition varied substantially between chemotypes. This variation matters because patients using medical cannabis may switch products or strains without realizing they're changing their drug interaction risk.
The study specifically tested interactions with three coumarin-type anticoagulants: warfarin (most common in the U.S.), phenprocoumon, and acenocoumarol (more common in Europe). Both THC and CBD individually inhibited these pathways, but whole-plant extracts showed interaction profiles that couldn't be predicted simply from their THC and CBD content — suggesting other compounds in the plant contribute to drug interactions.
This is a critical safety finding for the significant number of patients who use both cannabis and anticoagulant medications, particularly elderly patients with atrial fibrillation or mechanical heart valves where anticoagulation must be precisely controlled.
Why it matters
Warfarin has one of the narrowest therapeutic windows of any commonly prescribed drug — too little and blood clots form, too much and dangerous bleeding occurs. If cannabis extracts inhibit the enzymes that metabolize warfarin, patients could unknowingly push their blood levels into the danger zone. This study shows the risk is real and varies by cannabis product type, which is especially concerning because patients rarely consult their anticoagulation clinic about cannabis use.
The numbers in context
Four cannabis chemotypes tested. Both CYP2C9 and CYP3A4 were inhibited by all extract types. Pure THC and CBD both showed inhibitory activity. Three coumarin anticoagulants tested: warfarin, phenprocoumon, acenocoumarol. Inhibition profiles varied between chemotypes, meaning product-switching could change interaction risk.
How the study worked
In vitro study using pooled, mixed-gender human liver microsomes. Cannabis extracts were prepared from four chemotypes, either commercially obtained or prepared via ethanol extraction with overnight decarboxylation. Extracts were characterized for cannabinoid content using NMR and HPLC-PDA-ELSD-ESIMS. CYP inhibition was assessed using tolbutamide (CYP2C9) and testosterone (CYP3A4) as probe substrates, with warfarin, phenprocoumon, and acenocoumarol as clinically relevant model compounds.
Who was studied
In vitro study using human liver microsomes for CYP inhibition assessment.
What this study cannot tell us
In vitro study using liver microsomes — not a clinical trial in patients. Enzyme inhibition in a test tube doesn't always predict clinically significant interactions in living patients. The extracts were tested at concentrations that may or may not reflect what reaches the liver after normal cannabis use. No patient outcomes (bleeding events, INR changes) were measured. The four chemotypes represent a fraction of the enormous variety of cannabis products available.
How to read the evidence
In vitro study using human liver microsomes. Provides mechanistic evidence for a clinically relevant interaction, but the actual clinical significance in patients taking normal cannabis doses has not been established.
When this study was published
Published in 2023. Clinical case reports of cannabis-warfarin interactions continue to accumulate, supporting these in vitro findings.
The bigger picture
This study extends the CYP450 drug interaction findings from RTHC-00091 (CBD inhibiting four enzyme families in a controlled human trial) into a clinically critical medication class. While RTHC-00091 showed the general principle — CBD inhibits drug-metabolizing enzymes — this study applies it specifically to anticoagulants, where the consequences of enzyme inhibition could be life-threatening bleeding. Together with RTHC-00112 (drug-cannabinoid interactions review), these studies build a clear warning: cannabis is not pharmacologically inert, and its interactions with prescription medications deserve the same attention as any other drug-drug interaction.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- At what cannabis dose do clinically significant warfarin interactions begin? Should INR monitoring be increased when anticoagulated patients start, stop, or switch cannabis products? Could cannabis-warfarin interactions explain unexplained bleeding events or unstable INR in patients who don't disclose cannabis use?
Read the original research
Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants.
Medical cannabis and cannabinoids, 6(1), 21-31
Medical Cannabis and Cannabinoids publishes peer-reviewed research on cannabis and its medical applications.
Citation
Treyer, Andrea; Reinhardt, Jakob K; Eigenmann, Daniela Elisabeth; Oufir, Mouhssin; Hamburger, Matthias. (2023). Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants.. Medical cannabis and cannabinoids, 6(1), 21-31. https://doi.org/10.1159/000528465
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