CBD and tacrolimus: why can drug levels rise?

Medicines and the importance of the interaction

From peer-reviewed publications and drug labels: the warning. The same warning also appears in the interaction checker.

How does the interaction happen?

Tacrolimus is broken down in the gut and liver mostly by the CYP3A4 and CYP3A5 enzymes; in the gut it is also carried by P-gp (P-glycoprotein: a transporter that pumps a drug from gut cells back out). Medicines that slow these pathways, or grapefruit juice, can raise the blood level of tacrolimus. (Tacrolimus prescribing information §7.2, PMID 39601108, PMID 27595035)

In the drug-level study, CBD raised the peak level of tacrolimus and its total amount in the blood (AUC) but did not change how fast it is cleared from the body (its half-life). According to the authors, this suggests that CBD slows the breakdown or pumping back out of tacrolimus as it passes from the gut into the blood, rather than its breakdown in the liver; it is not yet known which of CYP3A4, CYP3A5 and P-gp plays a role. Approved CBD had not changed the level of midazolam, which is broken down by CYP3A4. (PMID 39601108, FDA Epidiolex label §12.3 (05/2026))

In a laboratory study, CBD and its active breakdown product 7-OH-CBD slowed the breakdown of tacrolimus; the effect of CBD was more marked on the CYP3A5 enzyme. The breakdown product 7-COOH-CBD, which is found in the blood at about 40 times the level of CBD itself when approved CBD is used regularly, had very little effect on the breakdown of tacrolimus in these experiments. A larger ongoing study is examining whether the size of the interaction differs between people who carry CYP3A5 and those who do not. In another laboratory study with human liver tissue, 7-OH-CBD also inactivated CYP3A, which breaks down tacrolimus, over time; in the same study, 7-OH-CBD slowed all of the CYP enzymes studied except CYP1A2. (PMID 39921332, PMID 35115300, PMID 39601108, FDA Epidiolex label §12.3 (05/2026))

The prescribing information for approved CBD states that, because of the gut P-gp effect of CBD shown with everolimus, the level of tacrolimus taken by mouth may also rise, and it recommends considering drug-level monitoring and a dose reduction. The published studies used high doses of CBD; the size of the effect at the lower doses of over-the-counter products is unknown. (EMA Epidyolex prescribing information 4.5, FDA Epidiolex label §7.2 (05/2026), PMID 39601108)

What do studies and official drug information say?

Each finding shows the type of evidence it rests on. A case report describes a single patient; it does not prove cause and effect.

1. Drug-level study

   Drug-level study: tacrolimus rose about 3-fold (2025)

   12 healthy volunteers first received a single dose of tacrolimus (5 mg). They then took approved CBD for 14 days (starting at 2.5 mg/kg twice a day and increasing to 5 mg/kg) and took the same tacrolimus dose again. With CBD, the peak blood level of tacrolimus rose on average 4.2-fold and its total amount in the blood (AUC) 3.1-fold; its half-life did not change. Side effects were mostly mild. This is an interim analysis of a larger ongoing study; it was not done in transplant patients.

   Source: PMID 39601108

2. Case report

   Level rose 3-fold in a patient taking very high doses of CBD (2019)

   A 32-year-old woman taking tacrolimus for kidney inflammation (interstitial nephritis) started pure CBD in a CBD study for epilepsy. While she was taking 2000–2900 mg of CBD a day, her dose-adjusted tacrolimus blood level rose about 3-fold. As reported in a systematic review, her kidney test value (creatinine) also rose.

   Source: PMID 31012522, PMID 38868665

3. Case series

   Levels varied in kidney transplant patients (2018)

   7 kidney transplant patients who took CBD for pain for 3 weeks (increased from 50 mg to 150 mg twice a day) were followed. Tacrolimus levels varied: in one patient the level was already high before CBD and the dose was reduced several times, in another the dose was reduced on day 21, and in one patient the level dropped and returned to normal a week later. The authors said longer follow-up was needed.

   Source: PMID 29579828

4. Official drug information

   The prescribing information for tacrolimus names CBD (08/2023)

   The US prescribing information for tacrolimus states that the tacrolimus level may rise when it is used with CBD; it recommends closely monitoring the level and side effects that suggest tacrolimus toxicity, and reducing the tacrolimus dose if needed. The patient information also lists CBD among the medicines you should be sure to tell your doctor about.

   Source: Tacrolimus prescribing information §5.17 and §7.3

5. Official drug information

   Prescribing information for approved CBD

   The US (Epidiolex, 05/2026) prescribing information and the European (Epidyolex) product information state that the level of tacrolimus taken by mouth may rise with CBD, and they recommend considering drug-level monitoring and a dose reduction. The patient leaflet of the European product information also lists tacrolimus among the medicines you should tell your doctor about.

   Source: FDA Epidiolex label §7.2 (05/2026), EMA Epidyolex prescribing information 4.5, EMA Epidyolex prescribing information package leaflet section 2

6. Case report

   Levels also rose with THC-containing cannabis (2016, 2019)

   In a 67-year-old man who had had a bone marrow transplant, the tacrolimus level rose to 45.8 ng/mL, far above the target range (8–12 ng/mL), after he used an edible cannabis product containing THC; he developed diarrhea, muscle stiffness, tremor and a change in consciousness and was admitted to intensive care. He was also taking an antifungal medicine (posaconazole) that can raise tacrolimus levels. Tacrolimus toxicity was also reported in another transplant patient who used THC-dominant cannabis lozenges.

   Source: PMID 27595035, PMID 30819507, PMID 38868665

7. Systematic review

   Systematic review: among the most frequently reported (2024)

   In a systematic review of 31 publications reporting cannabinoid interactions with medicines that have a narrow therapeutic range, warfarin, valproate, tacrolimus and sirolimus stood out as the most frequently reported drugs and those that may carry the greatest risk for patients. All publications on tacrolimus were case reports or small case series.

   Source: PMID 38868665

What is monitored?

• Tacrolimus level: it is measured more often when CBD is started, when the amount of CBD changes and when CBD is stopped (in blood drawn just before the next dose). Your transplant team decides how often to measure it. (Tacrolimus prescribing information §2.6 and §7.3, PMID 39601108)
• Kidney function: when the tacrolimus level rises, the risk of kidney damage increases; your doctor monitors your kidneys with blood tests such as creatinine. Approved CBD itself can also raise creatinine by about 10% in the first two weeks without changing the kidneys' filtration rate; it is important that your doctor knows you use CBD when interpreting the results. (Tacrolimus prescribing information §5.5, FDA Epidiolex label §6.1 and §12.2 (05/2026), EMA Epidyolex prescribing information 4.8)
• Signs of side effects: headache, tremor, numbness or tingling, confusion, changes in behavior or vision, seizures; signs of high blood sugar such as frequent urination, excessive thirst and blurred vision. If you notice any of these, tell your doctor right away. (Tacrolimus patient information)
• What is in the product: tacrolimus levels have also been reported to rise with products containing THC; in over-the-counter CBD products, the amount of CBD on the label may not be accurate and the product may contain THC. Check the CBD and THC content of the product you use on its label and its certificate of analysis. (PMID 27595035, NIH NCCIH) How to read a label and certificate of analysis

Frequently asked questions

References

Last reviewed: October 27, 2026. On this date, each source was opened and checked against the related sentence.