Cannabis Extracts Can Interfere with Blood Thinners Like Warfarin — And Different Strains Vary Widely

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.

Treyer, Andrea et al.·Medical cannabis and cannabinoids·2023·Preliminary EvidenceObservational·1 min read
RTHC-04986ObservationalPreliminary Evidence2023RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Observational
Evidence
Preliminary Evidence
Sample
In vitro study using human liver microsomes for CYP inhibition assessment.
Participants
In vitro study using human liver microsomes for CYP inhibition assessment.

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
Evidence Grade:
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.
Study Age:
Published in 2023. Clinical case reports of cannabis-warfarin interactions continue to accumulate, supporting these in vitro findings.
Original Title:
Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants.
Published In:
Medical cannabis and cannabinoids, 6(1), 21-31 (2023)Medical Cannabis and Cannabinoids publishes peer-reviewed research on cannabis and its medical applications.
Database ID:
RTHC-04986

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

Watches what happens naturally without intervening.

What do these levels mean? →

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Cite This Study

RTHC-04986·https://rethinkthc.com/research/RTHC-04986

APA

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

MLA

Treyer, Andrea, et al. "Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants.." Medical cannabis and cannabinoids, 2023. https://doi.org/10.1159/000528465

RethinkTHC

RethinkTHC Research Database. "Phytochemical Comparison of Medicinal Cannabis Extracts and ..." RTHC-04986. Retrieved from https://rethinkthc.com/research/treyer-2023-phytochemical-comparison-of-medicinal

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.