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CBD and medicines interactions

CBD and medicines: what the studies say

CBD slows several liver enzymes that clear medicines from the body. This dossier lists 25 interactions, grades each one by strength of evidence and by severity, and links it to the studies behind it.

Interactions listed
25
Rated severe
3
Studies cited
40

Last checked: 20 October 2026

Check a medicine classRead the article on the grapefruit effect
Two reservoirs feed one block and a single outlet: CBD at the back, the chosen medicine in front. The block stands for the cytochrome they both go through. The more the class depends on it, the fuller the medicine's reservoir stays, the emptier the collector at the outlet, and the dial on the block turns to the documented level of vigilance.

The bottleneck

The pink reservoir is the medicine, the block the cytochrome it shares with CBD. The dial has four marks: none, information, moderate, high.

Contents

In brief

  • CBD slows down liver enzymes, mainly CYP2C19 and CYP3A4. A medicine cleared by these enzymes can then build up in the blood[1] source 1.
  • Three interactions are rated severe: medicines cleared by CYP3A4, including two immunosuppressants (everolimus and tacrolimus), lithium and methadone.
  • Most interaction studies give 20 mg of CBD per kilogram per day, about 1,400 mg for a 70 kg adult. Among 1,160 consumers, the median was 41 mg a day[2] source 2. Even so, no study has set a risk-free threshold.
  • If you take a medicine, especially one whose effective dose is close to its toxic dose, talk to your pharmacist or doctor about CBD before you use it. Never stop a treatment on your own.

The mechanism

The liver clears many medicines by changing them chemically. Enzymes do this work, in particular the cytochrome P450 family (CYP). Each one has its own substrates: CYP3A4, CYP2C19 and CYP2C9 do not handle the same molecules.

In the laboratory, CBD blocks several of these enzymes at low concentrations: CYP3A4[3] source 3, CYP2C19[4] source 4, CYP2C9[5] source 5, CYP2D6[6] source 6, and another family of liver enzymes, the UGTs[7] source 7. While the enzyme is occupied, the medicine it should have cleared stays in the blood longer and its concentration rises.

Without CBD
MedicineCYP3A4Cleared
With CBD
MedicineCYP3A4 occupied by CBDStays in the blood

It also works the other way round. CBD is itself cleared by CYP3A4 and CYP2C19[8] source 8, so a medicine that blocks or speeds up these enzymes changes the amount of CBD in the blood[9] source 9.

A modest rise matters little for a medicine whose effective dose is far from its toxic dose. It matters a great deal when that margin is narrow, as with tacrolimus or lithium, where a small change in concentration changes the effect.

The same dose, cleared more slowly

Concentration in the blood

Time after the dose

  • Without CBD
  • With CBD
  • Expected effect range
  • Toxicity threshold
Diagram: when the medicine is cleared more slowly, it climbs higher and comes down later. The curves illustrate the principle and do not reproduce any measurement.

What the studies measure

Three kinds of study fit together. Laboratory tests show which enzymes CBD can block. Trials in volunteers measure the real effect on probe medicines. Case reports describe what happens to patients.

A cocktail of five probe medicines

  1. OmeprazoleCYP2C19+207%
  2. LosartanCYP2C9+77%
  3. MidazolamCYP3A+56%
  4. CaffeineCYP1A2+39%
  5. DextromethorphanCYP2D6No effect
Rise in exposure (area under the curve) to each probe after a single dose of 640 mg of CBD with 20 mg of THC, in 18 adults, compared with placebo. THC alone did not change any enzyme[1] source 1.

CYP2C19 is hit hardest: exposure to omeprazole, which it clears, triples. CYP2D6, very sensitive to CBD in the laboratory[6] source 6, did not move in humans. A block measured in a test tube does not, on its own, tell you what happens in the body.

What CBD changes for the medicines studied

  • N-desmethylclobazam

    active metabolite of clobazam

    ×3.4 Morrison 2019×2.6 VanLandingham 2020

  • Tacrolimus

    ×3 Leino 2019

  • Everolimus

    ×2.5 Wray 2023

  • Stiripentol

    ×1.6 Morrison 2019×1.3 Ben-Menachem 2020

  • Clobazam

    ×1.2 Morrison 2019×1.1 VanLandingham 2020

  • Valproate

    ×0.83 Ben-Menachem 2020

Exposure to each medicine with CBD, relative to exposure without CBD: ×1 means unchanged. One dot per study. Tacrolimus is a single case, measured as concentration adjusted for dose.

When the CBD level is what changes

  • Ketoconazole, blocks CYP3A4

    +89%

  • Omeprazole, blocks CYP2C19

    No significant change

  • Rifampicin, speeds up CYP3A4

    −52%

Peak CBD in the blood (Cmax) after a dose of THC/CBD spray, in 36 volunteers, taken with a medicine that blocks or speeds up the enzymes that clear it[9] source 9.

The interaction map

Each interaction gets two grades. The evidence level says how well established it is; severity says what it can cause. Choose a name to open its entry.

Show

Severe

Moderate

Not established

Evidence level

Probable
Seen in human trials or in several observations that agree.
Possible
Reported in a case report, or inferred from an effect measured in humans.
Theoretical
Inferred from laboratory or animal studies, with no observation in humans.

Severity

Severe
Can lead to serious toxicity or hospitalisation.
Moderate
Can make side effects worse or lead the prescriber to adjust the dose.
Not established
The data are not enough to judge the consequences.

These definitions describe how we read the two grades in this dossier.

Severe interactions

Three interactions can cause serious toxicity. Two of them rest on single cases, which does not make them any less serious.

Medicines cleared by CYP3A4including everolimus and tacrolimus, two immunosuppressantsSeverity: SevereEvidence: Probable

CBD blocks CYP3A4 in the laboratory[3] source 3 and in humans: a 640 mg dose raises exposure to midazolam, the probe for this enzyme, by 56%[1] source 1.

In volunteers, 12.5 mg/kg of CBD twice a day raised the peak and the exposure to everolimus 2.5-fold[10] source 10. In a girl aged six and a half, the everolimus trough level was 4 to 5 µg/L before CBD; six weeks after she started CBD it reached 12.0 µg/L, then 16.0 µg/L even though her everolimus dose had been halved[11] source 11.

In a transplant patient taking 2,000 to 2,900 mg of CBD a day, the tacrolimus concentration adjusted for dose roughly tripled[12] source 12.

Everolimus, trough level, µg/L

  1. 4 to 5before CBD
  2. 12.0after 6 weeks
  3. 16.0dose halved
What changes
The other substance's level rises
Enzymes
CYP3A4
Lithiummood stabiliserSeverity: SevereEvidence: Possible

Only one case has been published. A patient on lithium was admitted to hospital two weeks after starting CBD, shortly after the dose went from 5 to 10 mg/kg a day. The patient's lithium level had reached 2.4 mmol/L, against a usual 1 to 1.3 mmol/L, with excessive drowsiness and balance problems[13] source 13.

The mechanism is unknown. One line of research looks at how CBD acts on sodium channels[14] source 14, but no link with lithium has been shown.

Lithium in the blood, mmol/L

  1. 1 to 1.3usual
  2. 2.4on CBD
  3. 0.6at discharge
What changes
The other substance's level rises
MethadoneopioidSeverity: SevereEvidence: Possible

One case has been published, in a 13-year-old girl with cancer who was taking 7.5 mg of methadone twice a day. Her methadone level was 271 ng/mL on CBD and fell to 125 ng/mL fourteen days after the CBD was stopped. Her drowsiness and fatigue decreased at the same time[15] source 15.

Methadone in the blood, ng/mL

  1. 271on CBD
  2. 12514 days after stopping
What changes
The other substance's level rises

Moderate interactions

These make side effects worse or change exposure by a measurable amount. Many involve antiepileptics, because the large CBD trials were run in patients with epilepsy.

Clobazambenzodiazepine antiepilepticSeverity: ModerateEvidence: Probable

CBD changes clobazam itself very little, but it sharply raises its active metabolite, N-desmethylclobazam. Exposure went up 3.4-fold in volunteers[16] source 16 and 2.6-fold in 20 patients taking 20 mg/kg of CBD a day[17] source 17. The likely cause is the block on CYP2C19, the enzyme that clears this metabolite[18] source 18.

In 13 children, the level of this metabolite rose by an average of 500% in four weeks. Side effects appeared in 10 of them and lessened once their clobazam dose was lowered[19] source 19. In animals, the two molecules together also increase activity at the GABA-A receptor[20] source 20.

What changes
The other substance's level rises
Enzymes
CYP2C19
StiripentolantiepilepticSeverity: ModerateEvidence: Probable

Exposure to stiripentol rises slightly with CBD: 1.6-fold in volunteers[16] source 16, and by 30% in patients taking 20 mg/kg of CBD a day[21] source 21.

What changes
The other substance's level rises
Valproateantiepileptic, valproic acidSeverity: ModerateEvidence: Possible

CBD does not change the valproate level[21] source 21. The risk lies with the liver and the platelets.

In a long-term follow-up, 15% of patients with Lennox-Gastaut syndrome had transaminases (liver enzymes) above three times the upper limit of normal, and 73% of those patients were taking valproate[22] source 22. In Dravet syndrome, all 22 patients affected were taking it[23] source 23. A review of randomised trials links this rise to the combination with valproate[24] source 24, and so does a study of 81 patients[25] source 25.

Among 87 children followed at a single centre, 9 of the 23 who received CBD with valproate saw their platelets fall below 110,000 per µL, against none of the 57 who received CBD without valproate[26] source 26.

Platelets below 110,000 per µL

CBD with valproate 9 of 23

CBD without valproate 0 of 57

Each dot is a child followed after starting CBD; the pink dots are children whose platelets fell[26] source 26.
What changes
The liver and platelets
Sedativessleeping pills, anxiolytics, sedating antihistaminesSeverity: ModerateEvidence: Probable

Drowsiness is among the most common side effects of CBD at the doses used in trials[27] source 27. It affected 29% of patients in a long-term follow-up[22] source 22 and 69% in a small study of 13 people with Parkinson's disease[28] source 28. It can add to the drowsiness caused by another sedative.

What changes
Sedative effects add up
Medicines cleared by CYP2C19such as omeprazole, used as a probeSeverity: ModerateEvidence: Probable

CYP2C19 is the enzyme most sensitive to CBD in humans: exposure to omeprazole tripled (+207%) after 640 mg of CBD[1] source 1. In the laboratory, CBD blocks it at concentrations as low as 2.5 µM[4] source 4. The same enzyme also helps clear CBD itself[8] source 8.

What changes
The other substance's level rises
Enzymes
CYP2C19
Medicines cleared by CYP1A2such as caffeine, used as a probeSeverity: ModerateEvidence: Probable

The effect is weaker here: exposure to caffeine rose by 39% after 640 mg of CBD[1] source 1. CBD also blocks this enzyme in the laboratory[29] source 29.

What changes
The other substance's level rises
Enzymes
CYP1A2
Medicines cleared by CYP2C9such as losartan, used as a probeSeverity: ModerateEvidence: Possible

Exposure to losartan rises by 77% after 640 mg of CBD[1] source 1. In the laboratory, CBD slows the processing of warfarin, an anticoagulant, by this enzyme; the strength of the block varies with test conditions, from 0.95 to 9.9 µM[5] source 5.

What changes
The other substance's level rises
Enzymes
CYP2C9
Medicines that block CYP3A4such as ketoconazole, an antifungalSeverity: ModerateEvidence: Possible

This time CBD is what builds up. With 400 mg of ketoconazole, peak CBD went from 0.66 to 1.25 ng/mL, a rise of 89%[9] source 9. Side effects of CBD such as drowsiness may then increase.

What changes
The CBD level rises
Enzymes
CYP3A4
Medicines that speed up CYP3A4such as rifampicin, an antibioticSeverity: ModerateEvidence: Possible

With 600 mg of rifampicin, peak CBD fell by 52%[9] source 9. The body then clears CBD faster.

What changes
The CBD level falls
Enzymes
CYP3A4
THCcannabis, THC-rich productsSeverity: ModerateEvidence: Probable

Taken with 640 mg of CBD, 20 mg of THC by mouth gave a THC exposure 2.6 times higher (+161%)[1] source 1, with more sedation and more reported memory problems[30] source 30.

The results are mixed. A review of 16 studies found that CBD sometimes dampens the effects of THC, though not consistently[31] source 31, and an inhalation trial with 10 to 30 mg of CBD changed neither THC levels nor THC's effects[32] source 32.

What changes
The other substance's level rises
Enzymes
CYP2C9, CYP3A4

Theoretical interactions

These are inferred from laboratory studies. Two have been checked in humans, and neither was confirmed.

Medicines cleared by CYP2D6such as dextromethorphan, used as a probeSeverity: Not establishedEvidence: Theoretical

In the laboratory, CBD strongly blocks CYP2D6[6 source 629 source 2933] source 33. In humans, a 640 mg dose did not change exposure to dextromethorphan, the probe for this enzyme[1] source 1.

What changes
The other substance's level rises
Enzymes
CYP2D6
Medicines cleared by UGTsUGT1A9, UGT2B4, UGT1A6, UGT2B7Severity: Not establishedEvidence: Theoretical

These enzymes attach a chemical group to molecules, which makes them easier to eliminate. In the laboratory, CBD blocks them at very low concentrations, as low as 0.12 µM for UGT1A9[7] source 7, and it slows the processing of alcohol by UGT1A9 and UGT2B7[34] source 34. There are no data in humans.

What changes
The other substance's level rises
Enzymes
UGT1A9, UGT2B4, UGT1A6, UGT2B7
Medicines that block CYP2C19such as omeprazoleSeverity: Not establishedEvidence: Theoretical

They could slow the clearance of CBD. Yet in volunteers, 40 mg of omeprazole did not significantly change the CBD level[9] source 9.

What changes
The CBD level rises
Enzymes
CYP2C19
Medicines that speed up CYP2C19Severity: Not establishedEvidence: Theoretical

They could speed up the clearance of CBD, which partly runs through this enzyme[8 source 835] source 35. The effect has not been measured.

What changes
The CBD level falls
Enzymes
CYP2C19

In the test tube and in the body

EnzymeBlock in the laboratory, µMIn humans, 640 mg
CYP3A4Ki 1.00 Yamaori 2011+56% (midazolam)
CYP2C19IC50 2.51 Jiang 2013+207% (omeprazole)
CYP2C9Ki 0.954 to 9.88 Yamaori 2012+77% (losartan)
CYP2D6Ki 1.16 to 2.69 Yamaori 2011No effect (dextromethorphan)
UGT1A9IC50 0.12 Nasrin 2021Not tested
UGT2B7IC50 0.82 Nasrin 2021Not tested
In the laboratory, the lower the concentration, the stronger the block. Ki and IC50 are two related measures of that strength and cannot be compared directly. The right-hand column comes from the cocktail study[1] source 1.

Herbs and supplements

The same enzymes clear compounds found in herbs and supplements. Data are scarce and the consequences are not established.

Supplements cleared by CYP2C19Severity: Not establishedEvidence: Probable

The mechanism is the same as for medicines cleared by this enzyme, the one most sensitive to CBD in humans[1] source 1. What it means for a supplement has not been established.

What changes
The other substance's level rises
Enzymes
CYP2C19
Herbs and supplements that block CYP3A4Severity: Not establishedEvidence: Possible

They could raise the CBD level, as ketoconazole does[9] source 9.

What changes
The CBD level rises
Enzymes
CYP3A4
Herbs and supplements that speed up CYP3A4Severity: Not establishedEvidence: Possible

They could lower the CBD level, as rifampicin does[9] source 9.

What changes
The CBD level falls
Enzymes
CYP3A4
KavaPacific plantSeverity: Not establishedEvidence: Theoretical

Kavalactones, the active compounds in kava, block several CYPs themselves[36] source 36. The only data involving CBD concern a different plant, kratom: in rats, CBD raised exposure to its main alkaloid 2.8-fold, at a dose equivalent to 8 mg/kg in humans[37] source 37.

What changes
The other substance's level rises
Enzymes
CYP3A4
Supplements cleared by CYP2D6Severity: Not establishedEvidence: Theoretical

CBD blocks this enzyme in the laboratory[6] source 6, but not in humans at 640 mg of CBD[1] source 1.

What changes
The other substance's level rises
Enzymes
CYP2D6
Supplements that block CYP2C19Severity: Not establishedEvidence: Theoretical

Any effect on the CBD level is theoretical. Omeprazole, which blocks this enzyme, had none[9] source 9.

What changes
The CBD level rises
Enzymes
CYP2C19
Supplements that speed up CYP2C19Severity: Not establishedEvidence: Theoretical

The effect is theoretical: faster clearance of CBD, which partly runs through this enzyme[8] source 8.

What changes
The CBD level falls
Enzymes
CYP2C19
Sedative herbs and supplementsSeverity: Not establishedEvidence: Theoretical

The drowsiness caused by CBD[27] source 27 can add to theirs. No study has tested these combinations.

What changes
Sedative effects add up

The question of dose

The doses studied are usually far above what consumers take. Among 1,160 adults who chose their own dose, the median was 41 mg a day, ranging from 8 to 390 mg depending on the person[2] source 2. In a survey run mostly in the United Kingdom, 54% of users took less than 50 mg a day[38] source 38, as did more than 40% in an online survey of 267 users[39] source 39.

Where the studied doses sit

mg of CBD per day, logarithmic scale

Doses chosen by consumers, 8 to 390 mg

41 mg
Consumer median Kaufmann 2023
≈350 mg
Liver trial, 5 mg/kg Florian 2025
640 mg
Cocktail study, single dose Bansal 2023
≈1,400 mg
Trials in patients with epilepsy, 20 mg/kg VanLandingham 2020
≈1,750 mg
Everolimus study, 25 mg/kg Wray 2023
Values preceded by ≈ are calculated for a 70 kg adult from the mg/kg doses in the studies.

Less evidence does not mean less risk. In 2025, an FDA trial in 201 healthy adults gave 5 mg/kg of CBD a day for 28 days, a dose the authors place within the range consumers use. Of those adults, 5.6% had liver enzymes above three times the upper limit of normal, against none on placebo[40] source 40.

An interaction has also been reported in a child at a dose as low as 200 mg a day[11] source 11. With no studies at common doses, no risk-free threshold has been established.

Liver enzymes above three times the upper limit of normal

  1. Healthy adults, CBD 5 mg/kgFlorian 20255.6%
  2. Same adults, placeboFlorian 20250%
  3. Lennox-Gastaut syndrome, long follow-upPatel 202115%
  4. Dravet syndrome, long follow-upDevinsky 201917.2%
Share of participants affected. In both long follow-ups, most or all of the patients affected were also taking valproate[22 source 2223] source 23.

What you can do

  • Write down the medicines, supplements and herbs you take, CBD included, and show the list to your pharmacist or doctor.
  • If a medicine's leaflet warns against grapefruit, mention CBD: grapefruit slows CYP3A4 too.
  • If a blood test is planned to measure one of your medicines, say that you use CBD.
  • Never stop or change a treatment on your own.

To see the metabolic pathway of a medicine class: CBD and medicines interactions

Method and limits

This dossier starts from the interaction table in Examine.com's entry on cannabidiol, accessed on 20 October 2026. We took its evidence and severity grades, then reread each primary source to pull out the figures. Three rows of that table have neither a public description nor a substance name, so we left them out rather than guess.

The figures come from each article's abstract or, for a few case and dose values, from its full text. Milligram doses preceded by ≈ are calculated for 70 kg.

The data have real limits. Many studies use pure CBD medicines at high doses, in patients who take several medicines. The cocktail study combines CBD with 20 mg of THC. Several interactions rest on a single case. This dossier does not replace your pharmacist, who knows your whole treatment.

If you find an error or a missing study, write to us through the contact page.

Sources

Primary studies, in the order this dossier cites them. Starting point: Examine.com, Cannabidiol (CBD), Interactions section, accessed 20 October 2026.

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