# The CBD Drug Interactions That Are Actually Documented, and the Doses at Which They Happen

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/cbd-and-prescription-drug-interactions-evidence/
> **Published:** 2026-09-04T23:13:10-04:00 | **Last Modified / Clinically Audited:** 2026-10-22T13:25:08-04:00
> **Clinical Summary:** CBD and prescription drug interactions with real evidence behind them: clobazam, valproate, warfarin and tacrolimus, and why the dose decides the risk.

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CED Clinical Relevance #44High Clinical RelevanceThis is the cannabis question most likely to cause real harm if answered badly. Patients take over-the-counter cannabidiol alongside anticoagulants, antiepileptics and transplant medications without telling anyone, and several of the documented interactions have a monitoring plan attached.

Cannabidiol interacts with prescription medications, and the sentence stops there in most of what gets written about it. The useful version names the drugs, gives the size of the effect, and states the doses at which those effects were observed, because the dose is doing most of the work.

Clinical Insight | CED Clinic

Four interactions have real human evidence behind them: clobazam, where cannabidiol raises the active metabolite N-desmethylclobazam severalfold; valproate, where the combination raises transaminases without a plasma-level interaction; warfarin, documented in a case report with rising INR; and tacrolimus, documented in a trial participant with roughly threefold higher dose-normalized concentrations.

Every one of those observations came from pharmaceutical-grade cannabidiol at doses between roughly 700 and 2,900 mg per day. Ordinary retail cannabidiol products deliver 10 to 50 mg. Those are not the same exposure, and the interaction literature does not transfer cleanly from one to the other in either direction.

CBD Drug InteractionsClobazamWarfarin and INRLiver MonitoringClinical Pharmacology
AudiencePatients, caregivers, and cliniciansPrimary TopicDocumented cannabidiol interactions with prescription medications and their dose dependenceSource[Read the full source](https://doi.org/10.3390/jcm8070989)
Why This Matters

Patients do not report cannabidiol as a medication. They report it as a supplement, if at all, and often not at all, because it is sold next to vitamins. The result is that a genuine pharmacokinetic perpetrator drug enters a regimen without anyone adjusting monitoring.

The consequences are not theoretical. Sedation on clobazam, transaminase elevation on valproate, an unstable INR on warfarin and a supratherapeutic tacrolimus level are all documented, and all four are manageable if someone knows to look. A smaller human signal involves the antidepressant citalopram; see our review of [CBD and antidepressant interactions](https://cedclinic.com/cannabinoid-interactions-antidepressants-ssris-snris-evidence/).

The Mechanism, and Why Cannabidiol Is Both Target and Cause

Rongrong Jiang and colleagues at Hokuriku University characterized cannabidiol metabolism in human liver microsomes in *Life Sciences* in 2011. Seven of fourteen recombinant cytochrome P450 enzymes tested could metabolize it, and correlation and inhibition work identified CYP3A4 and CYP2C19 as the principal routes, with formation of the active metabolite 7-hydroxy-cannabidiol driven predominantly by CYP2C19.

So cannabidiol is a substrate of the same enzymes that handle a large share of the prescription formulary. It is also an inhibitor of them. Joshua Brown and Almut Winterstein at the University of Florida summarized this in the *Journal of Clinical Medicine* in 2019 with a phrase worth keeping: cannabidiol is implicated as both a victim and a perpetrator of drug interactions.

Sumit Bansal, Mary Paine and Jashvant Unadkat at the University of Washington quantified the inhibition and modeled what it should produce. Publishing in *Drug Metabolism and Disposition* in 2022, they predicted maximum interactions for oral cannabidiol at 700 mg per day against probe drugs, expressed as area under the curve ratios: midazolam 14.8 for CYP3A, diclofenac 9.6 for CYP2C9, omeprazole 7.3 for CYP2C19, theophylline 4.0 for CYP1A2, and smaller ratios for CYP2B6, CYP2D6 and CYP2C8. They also found that the metabolite 7-hydroxy-cannabidiol inhibits most of these enzymes and inactivates CYP2C19 and CYP3A. The authors stated plainly that in vivo studies are needed to verify these predictions, and that caveat should travel with the numbers.

Clobazam: The Best-Characterized Interaction in the Field

Alexandra Geffrey, Elizabeth Thiele and colleagues at Massachusetts General Hospital reported the clinical version first, in *Epilepsia* in 2015. Thirteen children with refractory epilepsy were taking clobazam while receiving cannabidiol under an expanded access protocol. At four weeks, mean clobazam levels had risen 60 percent, and mean N-desmethylclobazam levels, the active metabolite, had risen 500 percent.

The clinical texture of that report is worth repeating. Nine of the thirteen had greater than 50 percent seizure reduction. Ten of thirteen reported side effects. Those side effects were relieved by reducing the clobazam dose, and clobazam doses were in fact reduced in ten of the thirteen patients over the course of treatment. In other words, a substantial part of both the benefit and the toxicity attributed to cannabidiol in that setting was a clobazam interaction.

A controlled healthy-volunteer study confirmed the direction and refined the magnitude. Gilmour Morrison and colleagues ran an open-label fixed-sequence trial published in *Clinical Pharmacology in Drug Development* in 2019. Cannabidiol had little effect on clobazam itself, about 1.2-fold on both peak concentration and area under the curve, while N-desmethylclobazam exposure rose 3.4-fold. Stiripentol exposure rose modestly. Clobazam in turn increased 7-hydroxy-cannabidiol exposure by roughly 1.5 to 1.7-fold, making the interaction bidirectional.

Valproate: A Liver Signal Without a Level Change

This one is easy to get wrong, because the mechanism is not what most people assume. Tyler Gaston, Jerzy Szaflarski and colleagues at the University of Alabama at Birmingham monitored serum levels of 19 antiepileptic drugs in 39 adults and 42 children receiving pharmaceutical cannabidiol titrated from 5 up to 50 mg per kilogram per day, publishing in *Epilepsia* in 2017.

They found significant changes in topiramate, rufinamide and N-desmethylclobazam levels, a decrease in clobazam, and in adults increases in zonisamide and eslicarbazepine. Apart from clobazam and its metabolite, the changes stayed within accepted therapeutic ranges. Separately, aspartate aminotransferase and alanine aminotransferase were significantly higher in participants taking concomitant valproate.

The healthy-volunteer study found no clinically relevant pharmacokinetic interaction between cannabidiol and valproate in either direction. Put those two findings together and the picture is specific: the valproate problem is a hepatic signal, not a plasma-level interaction, which means checking a valproate level will not detect it. Liver function tests will. Orrin Devinsky’s Dravet syndrome trial, published in the *New England Journal of Medicine* in 2017 with 120 participants at 20 mg per kilogram per day, listed abnormal liver-function results among the adverse events more common with cannabidiol than placebo.

Warfarin and Tacrolimus: Small Evidence, Large Consequence

Leslie Grayson, Jerzy Szaflarski and colleagues published a case report in *Epilepsy and Behavior Case Reports* in 2017 describing an interaction between warfarin and cannabidiol, with the practical recommendation that INR be monitored when cannabinoids are introduced. Warfarin’s S-enantiomer is cleared substantially by CYP2C9, which cannabidiol inhibits, so the mechanism is coherent. The evidence is one patient.

The tacrolimus report is similarly small and similarly important. Abbie Leino and colleagues at the University of Cincinnati described in the *American Journal of Transplantation* in 2019 a participant in a cannabidiol epilepsy trial who was also taking tacrolimus and showed an approximately threefold increase in dose-normalized tacrolimus concentrations while receiving 2,000 to 2,900 mg of cannabidiol per day.

A lower-dose counterpoint exists and should be read alongside it. A Uruguayan group led by L. Cunetti gave cannabidiol to seven kidney transplant recipients for [chronic pain](https://cedclinic.com/cbd-gummies-chronic-pain/), escalating from 100 to 300 mg per day, and reported in *Transplantation Proceedings* in 2018 that tacrolimus levels were variable, requiring dose reduction in some patients, while patients on cyclosporine remained stable. Seven patients, three weeks, no control group. The honest summary across both reports is that cannabidiol can raise calcineurin inhibitor concentrations and that nobody has characterized the dose threshold at which it starts to matter.

The Dose Distinction That Keeps Getting Lost

Here are the doses at which the documented interactions were observed. The Dravet trial used 20 mg per kilogram per day, which is 1,400 mg daily for a 70 kilogram adult. The Alabama safety study titrated to as much as 50 mg per kilogram per day. The healthy-volunteer liver study used 1,500 mg per day. The tacrolimus case involved 2,000 to 2,900 mg per day. The interaction modeling was run at 700 mg per day.

A typical retail cannabidiol product delivers 10 to 50 mg per serving. That is one to two orders of magnitude below every figure in the previous paragraph. Treating the trial interaction data as directly applicable to a 25 mg gummy overstates the risk considerably.

The opposite conclusion is equally unsupported. No published human study has characterized interaction risk at consumer doses. The correct statement is that the risk at 25 mg per day is uncharacterized, not that it is zero, and there is a specific reason to withhold reassurance: Marcel Bonn-Miller and colleagues published a research letter in *JAMA* in 2017 comparing label claims against laboratory analysis for cannabidiol extracts sold online, and label accuracy in that market cannot be assumed. A patient taking what they believe is 25 mg may not be.

What the Liver Data Say About Cannabidiol on Its Own

Paul Watkins and colleagues at the University of North Carolina reported something that deserves more attention than it gets, in *Clinical Pharmacology and Therapeutics* in 2021. Sixteen healthy adults with no epilepsy and no concomitant antiepileptic drugs received 1,500 mg of cannabidiol daily for about three and a half weeks as part of a phase 1 interaction study.

Seven of the sixteen, 44 percent, had a peak alanine aminotransferase above the upper limit of normal. In five of them, 31 percent, the value exceeded five times the upper limit, meeting international consensus criteria for drug-induced liver injury. Elevations began within two to four weeks of starting cannabidiol. Six participants were discontinued from the protocol, and some had symptoms consistent with hepatitis or hypersensitivity.

Two features of that result matter clinically. There was no correlation between transaminase elevation and baseline characteristics, CYP2C19 genotype, or cannabidiol plasma concentration, meaning susceptibility could not be predicted in advance. And these were healthy adults, so the liver effect is not solely a consequence of combining cannabidiol with valproate. At pharmaceutical doses, cannabidiol is a drug with a hepatic safety profile, and it should be monitored like one.

Evidence SnapshotClobazam, clinicalN-desmethylclobazam up 500%, clobazam up 60%, in 13 children at 4 weeks. Geffrey AL et al. *Epilepsia* 2015;56(8):1246-51. PMID 26114620Clobazam, controlledN-desmethylclobazam exposure 3.4-fold; clobazam itself 1.2-fold. Morrison G et al. *Clin Pharmacol Drug Dev* 2019;8(8):1009-31. PMID 30791225Antiepileptic panelChanges in topiramate, rufinamide, zonisamide, eslicarbazepine; AST and ALT higher with concomitant valproate. Gaston TE et al. *Epilepsia* 2017;58(9):1586-92. PMID 28782097Valproate levelsNo clinically relevant pharmacokinetic interaction in healthy volunteers, making the valproate issue hepatic rather than a level changeWarfarinCase report of interaction with rising INR; monitoring advised. Grayson L et al. *Epilepsy Behav Case Rep* 2017;9:10-11. PMID 29387536TacrolimusAbout threefold higher dose-normalized concentrations at 2,000 to 2,900 mg/day CBD. Leino AD et al. *Am J Transplant* 2019;19(10):2944-8. PMID 31012522Tacrolimus, lower doseVariable levels in 7 kidney transplant patients at 100 to 300 mg/day; cyclosporine patients stable. Cunetti L et al. *Transplant Proc* 2018;50(2):461-4. PMID 29579828Liver injury in healthy adults7 of 16 (44%) ALT above upper limit of normal; 5 (31%) above 5 times upper limit at 1,500 mg/day. Watkins PB et al. *Clin Pharmacol Ther* 2021;109(5):1224-31. PMID 33022751Enzymes involvedCYP3A4 and CYP2C19 principal for CBD metabolism; 7-OH-CBD inactivates CYP2C19 and CYP3A. Jiang R et al. *Life Sci* 2011, PMID 21704641; Bansal S et al. *Drug Metab Dispos* 2022;50(4):351-60, PMID 35115300Trial doses10 to 50 mg/kg/day pharmaceutical CBD; 20 mg/kg/day in the Dravet trial equals about 1,400 mg for a 70 kg adult. Devinsky O et al. *N Engl J Med* 2017;376(21):2011-20. PMID 28538134Retail product dosesTypically 10 to 50 mg per serving, with interaction risk at that range not characterized in any published human study
How Strong Is This Evidence?

The clobazam interaction is the strongest item here, supported by a clinical cohort and a controlled healthy-volunteer pharmacokinetic study that agree on direction and roughly on magnitude. The liver findings are also strong, coming from a randomized trial program plus a dedicated phase 1 study in healthy adults. Treat both as established at pharmaceutical doses.

The warfarin and tacrolimus evidence is weaker in study design and stronger in consequence. A single case report and a single trial participant are thin, and both involve narrow therapeutic index drugs where a threefold concentration change causes real harm. The correct clinical response to thin evidence about a dangerous interaction is monitoring, not dismissal.

Where This Paper Deserves Skepticism

The interaction magnitudes most often quoted in patient-facing material come from static pharmacokinetic modeling rather than from dosing people. The University of Washington group predicted a nearly fifteenfold increase in midazolam exposure with 700 mg of cannabidiol and explicitly stated that in vivo studies are warranted to verify the predictions. Reproducing that number without the caveat misrepresents the source.

The clinical reports are also small and uncontrolled. Thirteen children on clobazam. One patient on warfarin. One trial participant on tacrolimus. Seven transplant patients over three weeks. These are the right studies to change monitoring practice and the wrong studies to quantify risk for an individual patient.

What This Paper Does Not Show

This literature does not show that low-dose retail cannabidiol causes clinically meaningful interactions. It also does not show that it is safe. No published human study has measured interaction magnitude at 10 to 50 mg per day, which is where most consumer use sits, so both the alarming and the reassuring versions of that claim are unsupported.

The evidence does not identify who is susceptible. In the healthy-adult liver study, transaminase elevation showed no correlation with baseline characteristics, CYP2C19 genotype or cannabidiol plasma concentration. There is currently no way to screen a patient in advance and predict who will have a problem.

How This Fits With the Broader Clinical Conversation

The regulatory situation created this confusion. The same molecule exists as a prescription drug with a full interaction section in its labeling and as a retail supplement with none, at doses differing by a factor of fifty. Patients encounter both under the same three letters and reasonably assume the safety information transfers.

It mostly does not, and the direction of the error runs both ways. People taking 25 mg are frightened by trial-dose warnings, while people taking 1,500 mg of a high-strength oil from an unregulated supplier receive no monitoring at all. The second group is the one clinicians should be looking for.

Dr. Caplan’s Take

The clobazam data changed how I think about this whole subject. When a child on clobazam improves after starting cannabidiol, some meaningful part of that improvement may be the fivefold rise in an active benzodiazepine metabolite, and some meaningful part of the sedation is the same thing. That is not an argument against cannabidiol. It is an argument for knowing what you are actually changing.

In practice my rules are unglamorous. I ask about cannabidiol by name, because patients do not volunteer it. If someone is on warfarin, tacrolimus, cyclosporine, clobazam or valproate, I want to know the milligram dose and the product, and I want baseline labs. And I tell patients on high-dose oils that this is a drug with a liver signal in healthy volunteers, which is usually the first time anyone has framed it that way for them.

Clinical Bottom Line

Cannabidiol inhibits CYP3A4, CYP2C19 and CYP2C9 and has documented interactions with clobazam, warfarin and tacrolimus, plus a transaminase signal with valproate that plasma levels will not detect. Those observations come from doses of roughly 700 to 2,900 mg per day. At retail doses of 10 to 50 mg the risk is uncharacterized rather than absent. Patients on narrow therapeutic index drugs should disclose cannabidiol use and have appropriate monitoring, including liver function tests and INR where relevant.

What a Careful Reader Should Take Away

Carry two things forward. First, the named interactions are real and have specific monitoring attached: clobazam levels and sedation, liver function tests with valproate or high-dose cannabidiol, INR on warfarin, drug levels on calcineurin inhibitors. Second, dose is the variable that determines whether any of this applies, and the doses in the literature are far above what most people are taking. A source that omits the dose is not giving you enough information to act on.

Evidence Interpretation Guide

Table of Contents

- [How to judge whether a CBD interaction warning applies to you](#How_to_judge_whether_a_CBD_interaction_warning_applies_to_you)
- [Cannabidiol Drug Interactions, Seen From Eight Angles](#Cannabidiol_Drug_Interactions_Seen_From_Eight_Angles)[Tell your prescriber, then ask about monitoring](#Tell_your_prescriber_then_ask_about_monitoring)
- [Ask by name and get a number](#Ask_by_name_and_get_a_number)
- [Most quoted numbers are model outputs](#Most_quoted_numbers_are_model_outputs)
- [Case reports are carrying a lot of weight here](#Case_reports_are_carrying_a_lot_of_weight_here)
- [How a supplement became a pharmacokinetic problem](#How_a_supplement_became_a_pharmacokinetic_problem)
- [A workable monitoring plan](#A_workable_monitoring_plan)
- [The missing study is obvious](#The_missing_study_is_obvious)
- [One molecule, two regulatory identities](#One_molecule_two_regulatory_identities)
- [Frequently Asked Questions](#Frequently_Asked_Questions)[Related](#Related)

## How to judge whether a CBD interaction warning applies to you

The Research QuestionWhich cannabidiol interactions with prescription medications have been documented in humans, at what magnitude, and at what dose?The Patient QuestionI take CBD from the pharmacy shelf and I also take prescription medication. Do I need to worry?The Bottom LineDocumented interactions involve clobazam, valproate, warfarin and tacrolimus, at pharmaceutical doses of roughly 700 to 2,900 mg per day. At typical retail doses the risk has not been studied, so disclose use and monitor rather than assume either extreme.
CED Perspective Lens

## Cannabidiol Drug Interactions, Seen From Eight Angles

One interaction literature, read through the lenses that matter in clinical practice.

Lens OverviewCannabidiol inhibits CYP3A4, CYP2C19 and CYP2C9. Documented human interactions involve clobazam, valproate, warfarin and tacrolimus, all observed at doses far above what retail products deliver.

#### Tell your prescriber, then ask about monitoring

The single most useful thing you can do is stop treating cannabidiol as a supplement and start listing it as a medication, with the milligram dose and the product name. Most interactions become manageable the moment someone knows to watch for them.

If you take warfarin, tacrolimus, cyclosporine, clobazam or valproate, this is a conversation to have before your next dose rather than at your next annual visit. For most other medications, and at typical retail doses, disclosure plus ordinary follow-up is a proportionate response.

Lens takeawayReport the milligram dose, not just that you take CBD.

#### Ask by name and get a number

Patients do not report cannabidiol on medication reconciliation, so it has to be asked about directly, and the answer that matters is the daily milligram dose rather than the fact of use. A 25 mg gummy and a 1,500 mg high-strength oil are different clinical objects.

For patients on clobazam, expect the active metabolite rather than the parent drug to rise, and expect sedation to respond to clobazam dose reduction. For patients on valproate, watch transaminases rather than valproate levels, because the healthy-volunteer data show no pharmacokinetic interaction between the two.

Lens takeawayDose in milligrams, then match the monitoring to the drug.

#### Most quoted numbers are model outputs

The dramatic figures circulating in patient-facing material, including a predicted fifteenfold increase in midazolam exposure, come from static pharmacokinetic modeling based on in vitro inhibition constants. The authors of that work explicitly called for in vivo studies to verify the predictions.

Modeled interaction magnitudes are legitimate hazard signals and poor estimates of what happens in a specific patient. When you see a large multiplier quoted, check whether anyone actually dosed a person.

Lens takeawayA predicted interaction and a measured one are not the same evidence.

#### Case reports are carrying a lot of weight here

The warfarin interaction rests on a single published case, and the tacrolimus interaction on a single trial participant. Neither has been reproduced in a controlled study, and both involve drugs where clinicians already monitor closely for other reasons.

That is a defensible basis for heightened vigilance and an indefensible basis for quantifying risk. Saying that cannabidiol triples tacrolimus levels, without saying that the observation comes from one person taking 2,000 to 2,900 mg daily, misleads.

Lens takeawayOne patient is enough to monitor and not enough to quantify.

#### How a supplement became a pharmacokinetic problem

Interaction concerns were largely theoretical until the pediatric epilepsy programs put people on high, sustained, measured doses. The 2015 clobazam report came out of an expanded access protocol, and the systematic antiepileptic panel followed in 2017.

The entire documented interaction literature therefore comes from one clinical setting, refractory childhood epilepsy, which is not where most cannabidiol is consumed. That mismatch between where the evidence was generated and where the product is used explains much of the current confusion.

Lens takeawayThe evidence comes from epilepsy clinics; the use is mostly elsewhere.

#### A workable monitoring plan

For patients starting cannabidiol above roughly 300 mg per day, or at any dose alongside valproate, baseline and follow-up liver function testing is reasonable, with the first recheck inside four weeks given that elevations in the healthy-adult study began within two to four weeks.

For warfarin, increase INR checking frequency around initiation and around any dose change. For calcineurin inhibitors, check levels sooner than the routine interval. For clobazam, anticipate that sedation may require reducing the clobazam rather than the cannabidiol.

Lens takeawayBaseline labs, earlier rechecks, and adjust the interacting drug first.

#### The missing study is obvious

Nobody has run a controlled interaction study at consumer doses. A probe-drug study at 25 to 100 mg of cannabidiol per day would resolve the question that affects the largest number of people, and it would be inexpensive relative to its clinical value.

The second gap is susceptibility. Since the liver signal did not correlate with genotype or plasma concentration, identifying who is at risk will require a different approach than pharmacokinetics alone.

Lens takeawayA probe-drug study at retail doses would answer the common question.

#### One molecule, two regulatory identities

Prescription cannabidiol carries full interaction labeling and monitoring guidance. Retail cannabidiol carries none, and independent laboratory analysis has raised questions about whether the labeled content is what is in the bottle.

That split means the patient bearing the most interaction risk, the one taking a high-strength unregulated oil, is the one receiving the least information. Closing that gap is a labeling and content-verification problem more than a scheduling one.

Lens takeawayThe least regulated products carry the most interaction risk.

 Massachusetts Clinical Care & Certification
 
 Are you a Massachusetts resident seeking physician-supervised cannabinoid therapy? Learn more about scheduling a telehealth consultation with a certified [Massachusetts medical marijuana doctor](https://cedclinic.com/massachusetts-medical-marijuana-doctor/), or read our step-by-step 2026 guide on [how to get a medical marijuana card in Massachusetts](https://cedclinic.com/how-to-get-a-medical-marijuana-card-in-massachusetts/) to save ~20% on state dispensary taxes.
 

Related Reading at CED ClinicContinue exploring the evidence[Two Molecules, Two Routes: How the Body Handles THC and CBD Differently](https://cedclinic.com/thc-and-cbd-metabolism-pathways-compared/)

The enzyme pathways behind every interaction on this page, explained from the metabolism side.

[See the pathways](https://cedclinic.com/thc-and-cbd-metabolism-pathways-compared/)[Running CBD and the Ketogenic Diet Together: A 58-Patient Johns Hopkins Cohort](https://cedclinic.com/cbd-and-ketogenic-diet-for-epilepsy-combination-study/)

A worked example of combining pharmaceutical cannabidiol with another epilepsy treatment and watching what happens.

[Read the cohort data](https://cedclinic.com/cbd-and-ketogenic-diet-for-epilepsy-combination-study/)[Why the Same THC Dose Behaves Differently at 30 and at 70](https://cedclinic.com/cannabis-pharmacokinetics-in-older-adults/)

Older patients carry the most polypharmacy and the most altered cannabinoid handling, which compounds interaction risk.

[See the age effect](https://cedclinic.com/cannabis-pharmacokinetics-in-older-adults/)

Join the Conversation

Have a question about how this applies to your situation? [Ask Dr. Caplan](https://benjamincaplan.com/ask-dr-caplan)

Want to discuss this topic with other patients and caregivers? [Join the forum discussion](https://cedclinic.com/interact/discussion-forums/forum/cannabis-industry/)

## Frequently Asked Questions

Which prescription drugs have documented interactions with CBD?

Four have real human evidence. Clobazam, where cannabidiol raises the active metabolite N-desmethylclobazam by three to five times. Valproate, where the combination raises liver transaminases without changing valproate levels. Warfarin, documented in a case report with rising INR. Tacrolimus, documented in a trial participant with roughly threefold higher dose-normalized concentrations. Changes in topiramate, rufinamide, zonisamide and eslicarbazepine have also been measured.

How does CBD cause drug interactions?

Cannabidiol is metabolized principally by CYP3A4 and CYP2C19, and it also inhibits those enzymes plus CYP2C9. Its circulating metabolite 7-hydroxy-cannabidiol inhibits most major cytochrome P450 enzymes and inactivates CYP2C19 and CYP3A. Because those enzymes clear a large share of prescription medications, inhibiting them raises the concentration of the other drug. Cannabidiol is therefore both a target and a cause of interactions.

Does a 25 mg CBD gummy interact with my medications?

Nobody has studied it properly, which is the honest answer. Every documented interaction was observed at roughly 700 to 2,900 mg of pharmaceutical cannabidiol per day, one to two orders of magnitude above a typical retail serving. The risk at consumer doses is uncharacterized rather than proven absent. Disclose the product and dose to your prescriber, particularly if you take a narrow therapeutic index medication.

What happens when CBD is taken with clobazam?

Clobazam levels rise modestly and N-desmethylclobazam, the active metabolite, rises substantially. A clinical cohort of thirteen children found a 500 percent mean increase in the metabolite at four weeks, and a controlled healthy-volunteer study found a 3.4-fold increase. Sedation is the common consequence, and in the pediatric cohort it was relieved by reducing the clobazam dose rather than by stopping cannabidiol.

Should I have liver tests while taking CBD?

At pharmaceutical doses, yes. In a phase 1 study of sixteen healthy adults taking 1,500 mg daily, seven had alanine aminotransferase above the upper limit of normal and five exceeded five times that limit, meeting criteria for drug-induced liver injury, with elevations beginning within two to four weeks. Anyone on high-dose cannabidiol, or on any dose alongside valproate, warrants baseline and follow-up liver testing.

Can I take CBD with warfarin?

Only with closer INR monitoring and your prescriber’s knowledge. A published case report documented an interaction between cannabidiol and warfarin, and the mechanism is plausible because cannabidiol inhibits CYP2C9, which clears the more potent S-enantiomer of warfarin. The evidence is a single patient, which justifies vigilance rather than prohibition. Check INR more frequently around starting, stopping or changing the cannabidiol dose.

Is CBD safe for transplant patients on tacrolimus?

It requires level monitoring. One trial participant taking 2,000 to 2,900 mg of cannabidiol daily showed approximately threefold higher dose-normalized tacrolimus concentrations. A separate series of seven kidney transplant patients at 100 to 300 mg daily found variable tacrolimus levels requiring dose reduction in some, while patients on cyclosporine remained stable. Discuss with the transplant team before starting, not after.

Why do CBD interaction warnings vary so much between sources?

Because sources rarely state the dose, and the dose determines everything. Some warnings derive from trials at 20 to 50 mg per kilogram per day, some from pharmacokinetic modeling at 700 mg per day, and some are extrapolated to 25 mg products where no data exist. A warning that does not name the dose it came from cannot tell you whether it applies to what you are taking.

 

### Related

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).