A CBD-dominant cannabis brownie significantly inhibited four major drug-metabolizing enzymes in healthy adults, meaning CBD could increase blood levels of many common medications — THC alone had minimal effects.
Read this if you take CBD and prescription medications — especially blood thinners, antidepressants, or anti-seizure drugs. This is the human evidence showing those combinations can change how your body processes your medications.
What the researchers found
When you take a medication, your liver enzymes (called cytochrome P450 or CYP enzymes) break it down. If something inhibits those enzymes, the medication stays in your blood longer and at higher levels — potentially causing side effects or toxicity. This study is one of the first controlled human trials to measure exactly how cannabis cannabinoids affect these critical drug-metabolizing enzymes.
Eighteen healthy adults participated in a randomized crossover study. Each person ate, on separate occasions separated by at least one week: a placebo brownie, a CBD-dominant brownie (640 mg CBD + 20 mg THC), or a THC-only brownie (20 mg THC). Thirty minutes after the brownie, they consumed a 'drug cocktail' of five probe medications, each metabolized by a different CYP enzyme: caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A).
The CBD brownie significantly inhibited four of the five enzymes, with CYP2C19 most strongly affected, followed by CYP2C9, CYP3A, and CYP1A2. Only CYP2D6 was spared. The THC-only brownie had minimal effects on any of the enzymes.
This matters because CYP2C19 metabolizes common medications like clopidogrel (blood thinner), some antidepressants, and proton pump inhibitors. CYP2C9 handles warfarin and some anti-inflammatory drugs. CYP3A metabolizes about half of all prescription drugs. If CBD is inhibiting these enzymes, patients taking CBD alongside these medications could be getting higher-than-intended drug levels.
Why it matters
Millions of people use CBD products — often alongside prescription medications — with little awareness of potential drug interactions. This is the first well-controlled human study using actual cannabis extracts (not isolated pharmaceutical CBD) to quantify these interactions. The finding that CBD inhibits four major metabolic pathways has immediate clinical relevance for anyone combining CBD with prescription drugs, particularly blood thinners, antidepressants, anti-seizure medications, and immunosuppressants.
The numbers in context
18 healthy adults in a crossover design. CBD dose: 640 mg (a high but not uncommon supplement dose) + 20 mg THC. CBD brownie inhibited CYP2C19 (strongest), CYP2C9, CYP3A, and CYP1A2. CYP2D6 was not significantly affected. THC-only brownie (20 mg) showed no significant enzyme inhibition. Blood and urine collected over 24 hours.
How the study worked
Randomized, three-way crossover study in 18 healthy adults. Participants received, in random order with ≥1 week washout: (1) placebo brownie, (2) CBD-dominant brownie (640 mg CBD + 20 mg THC), or (3) THC-dominant brownie (20 mg THC). Thirty minutes post-brownie, participants consumed a validated CYP probe drug cocktail (caffeine, losartan, omeprazole, dextromethorphan, midazolam). Plasma and urine were collected over 24 hours to measure enzyme activity through probe drug metabolism.
Who was studied
N=18 healthy adults, aged 18-50, US participants
What this study cannot tell us
Single-dose study in healthy young adults — chronic CBD users or elderly/sick patients may show different interaction profiles. The CBD dose (640 mg) is high compared to typical consumer CBD products (25–100 mg), though some medical uses approach this level. The probe drug cocktail measures enzyme activity, not clinical outcomes — inhibiting an enzyme doesn't automatically mean a dangerous interaction with every drug that enzyme handles. Real-world cannabis products have variable CBD content and additional compounds that could modify these effects.
How to read the evidence
This is a well-designed randomized crossover trial in healthy adults — one of the strongest designs for pharmacokinetic studies. The crossover means each person served as their own control, reducing variability. The evidence for enzyme inhibition is solid; clinical implications need further study.
When this study was published
Published in 2023. This is among the first controlled human studies of cannabis-drug interactions using actual cannabis extracts rather than isolated compounds.
The bigger picture
This study provides the controlled human data that explains mechanisms observed in RTHC-00078 (cannabis users on buprenorphine had 2.7x higher drug levels). It also connects to the drug interaction monitoring in RTHC-00085 (THC/CBD for dementia patients on multiple medications). For the growing population using CBD alongside prescriptions — especially elderly patients on polypharmacy — these enzyme inhibition findings have immediate practical implications.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- At what CBD dose do clinically meaningful drug interactions begin? Do lower CBD doses (50–100 mg, typical supplements) still inhibit these enzymes? Should patients on warfarin, clopidogrel, or immunosuppressants be explicitly warned about CBD products? Can CBD enzyme inhibition be used therapeutically to boost drug levels intentionally (similar to how grapefruit juice interactions are sometimes leveraged)?
Read the original research
Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants.
Clinical pharmacology and therapeutics, 114(3), 693-703
Clinical Pharmacology and Therapeutics is a reputable journal focusing on the science of drug therapy.
Citation
Bansal, Sumit; Zamarripa, C Austin; Spindle, Tory R; Weerts, Elise M; Thummel, Kenneth E; Vandrey, Ryan; Paine, Mary F; Unadkat, Jashvant D. (2023). Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants.. Clinical pharmacology and therapeutics, 114(3), 693-703. https://doi.org/10.1002/cpt.2973
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