CBDPhase 1NCT05490511
Drug-gene-nutraceutical Interactions of Cannabidiol and Tacrolimus
A Phase 1 study testing Tacrolimus single dose, Epidiolex single dose and Epidiolex steady-state and tacrolimus single dose in people with CBD and Transplant Complication, run by Indiana University at 1 site in United States.
Trial summary
The information learned in these studies will help to inform doctors as to how to appropriately adjust doses of cannabidiol and tacrolimus in order to improve health outcomes and long-term treatment success for transplant recipients. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- CBD, Transplant Complication, Kidney Disease, Chronic
- What is being tested?
- Tacrolimus single dose, Epidiolex single dose and Epidiolex steady-state and tacrolimus single dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2022to 31 Aug 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-75
- Are judged healthy enough to participate as determined by and decided from a pre-enrollment screening session that includes medical history and laboratory tests such as blood and urine tests, and electrocardiography (EKG).
- Agree to refrain from taking any prescription medications, over-the-counter medications, and herbal, dietary, and alternative supplements that may interact with the metabolism of the study drugs at least 2 weeks prior to the start of the study and until study completion.
- Are willing to commit the time requested for this study
- Are willing to refrain from smoking or use of tobacco or marijuana for at least two weeks prior to and until the completion of the study (the entire study lasts for approximately 26 days).
- Additional Criteria for the Healthy volunteer study:
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- Have a GFR above 60 ml/min/1.73m2 with proteinuria less than 0.3 grams by urine protein to creatinine ratio or 24 hour urine collection
- Additional Criteria for the CKD study:
- Have either:
- A GFR less than or equal to 60 ml/min/1.73m2 or
- The presence of greater than 0.3 grams of proteinuria by urine protein to creatinine ratio or 24 hour urine collection, but less than 3.5 gm of nephrotic range proteinuria as hypoalbuminemia may impact protein binding.
Who cannot join
- Unable to provide informed consent
- Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (tacrolimus or cannabidiol);
- Are currently taking sedative agents, including agents for insomnia
- Are underweight (body mass index (BMI) less than 18.5) or overweight [body mass index (BMI) greater than 35]
- Have a positive pregnancy serum or urine test obtained just prior to each study, or are breast feeding
- Are night shift workers
Show all 23Show fewer
- Are on dialysis
- Have compromised liver function as defined by pre-screening bilirubin, AST and ALT testing including any elevation of bilirubin or AST/ALT more than 2x the upper limit of normal.
- Are not willing to refrain from smoking or use of marijuana for at least two weeks prior to and until the completion of the study
- Have a Hgb < 10.0 g/dL
- Have gastrointestinal (digestive) disorders such as persistent diarrhea or malabsorption that would interfere with the absorption of orally administered drugs
- Have a history of or current seizure disorder
- Are currently on immunosuppression or are immunosuppressed.
- Are recipients of a current allograft (heart, kidney, pancreas, liver, intestine, lung, stem cell transplant).
- Have baseline EKG readings that are abnormal that could place the patient at the high risk.
- Have alcohol (more than 4 alcoholic drinks per day on a regular basis) or drug abuse, including opioids, or have used tobacco products or marijuana within the past three months, and are unwilling or unable to stop taking these medications two weeks prior to and during the entire study period
- Have participated in a research study involving intensive blood sampling or have donated blood within the past two months
- Had an unplanned hospitalization in the last 6 months or two or more unplanned hospitalizations in the last 2 years.
- Are taking prescription medications, that may interfere with the metabolism of the study drugs (e.g., inhibitors or inducers of CYP3A4/5 or CYP2C19 or those that will displace protein binding of tacrolimus/cannabidiol). Interactions will be screened according to the Flockhart table.
- Are taking over-the-counter medications, herbal or dietary supplements, and alternative medicines that may interfere with the metabolism of the study drugs (e.g., inhibitors or inducers of CYP3A4/5 or CYP2C19 or those that will displace protein binding of tacrolimus/cannabidiol) that the subject is unwilling or unable to stop over the course of the study. Interactions will be screened according to the Flockhart table.
- Are students under supervision of any of the study investigators.
- Cannot commit the time requested for this study.
- Have a known CYP3A4 *22/*22 genotype
Trial locations and contacts
1 site in 1 country.
United States1 site
IU Health University Hospital
Indianapolis, Indiana, 46202
About this study
The information learned in these studies will help to inform doctors as to how to appropriately adjust doses of cannabidiol and tacrolimus in order to improve health outcomes and long-term treatment success for transplant recipients.
Read the detailed description
The commercial availability of cannabidiol, or CBD oil, has increased in the United Stated and this supplement has the potential to cause a variety of drug-drug interactions, including in solid organ transplant recipients who receive tacrolimus to prevent rejection. Through a series of pharmacokinetic and pharmacodynamics assays, this proposal will identify gene-drug and drug-drug interactions (DDI), including those that place transplant recipients at risk for increased toxicity related to their immunosuppression. The information learned in these studies will help to inform practitioners as to whether cannabidiol needs to be avoided in transplant recipients and how to appropriately adjust doses of CBD and immunosuppression in order to improve health outcomes and long-term treatment success in this high-risk population.
- Conditions
- CBD, Transplant Complication, Kidney Disease, Chronic
- Being tested
- Tacrolimus single dose, Epidiolex single dose, Epidiolex steady-state and tacrolimus single dose
- Keywords
- cannabidiol, tacrolimus, CYP3A5
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus single doseDrug
Also called Period 1
5 mg once
Epidiolex single doseDrug
Also called Period 2
Epidiolex 5 mg/kg
Epidiolex steady-state and tacrolimus single doseDrug
Also called Period 3
Epidiolex at up to 5 mg/kg twice daily (for 14 days) and tacrolimus 5 mg once on day 12 of period
| Study group | Role | What they receive |
|---|---|---|
| CYP3A5 expressers without chronic kidney disease | Active comparator | Not described Receives: Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose |
| CYP3A5 non-expressers without chronic kidney disease | Active comparator | Not described Receives: Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose |
| CYP3A5 expressers with chronic kidney disease | Active comparator | Not described Receives: Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose |
| CYP3A5 non-expressers with chronic kidney disease | Active comparator | Not described Receives: Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
The AUC0-Infinity Ratio of Tacrolimus With Cannabidiol Divided by Tacrolimus Alone
The primary outcome is the AUC0-Infinity ratio of tacrolimus with cannabidiol divided by tacrolimus alone between CYP3A5 expressers and non-expressers in subjects with and without chronic kidney disease (CKD). Tacrolimus whole blood concentrations were measured at 0, 20, 40, and 60 minutes and 2, 4, 6, 12, 24, 48, and/or 72 hours.
Measured: 27 days
Secondary outcomes (1)
Cell Viability Ratio
The hypothesis tested is that cannabidiol will reduce immune cell proliferation between Period 1 and Period 3. There is no comparison between CYP3A5 expressor groups intended for this outcome measure. Period 1 (pre-CBD or baseline measurement) and Period 3 (post-CBD or steady-state cannabidiol) will be compared in a subset of individuals undergoing this phenotyping. Cell viability was measured in peripheral blood mononuclear cells using CellTiter-Glo (Promega Corp., catalog G7570) on 96-well plates to quantify cell proliferation by adenosine triphosphate (ATP) detection using a Spectramax M5 system coupled with SoftMax Pro 5.2 (Molecular Devices). Values were calculated as a unitless ratio of luminescence (ATP detection) in the stimulated (CD3/CD28) condition normalized by the non-stimulated (No CD3/CD28) condition.
Measured: 27 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2022
- Study start31 Oct 2022
- Primary completion31 Aug 2025
- Study completion31 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CBDStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Subjects participate in a 3-phase fixed sequence pharmacokinetic study to evaluate the interaction between tacrolimus, cannabidiol, and genotype on tacrolimus AUC and immune system pharmacodynamic outcomes. Subjects with and without CKD will be enrolled in parallel arms.
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Principal investigator, Michael Eadon, Indiana University
- Investigators
- Michael Eadon, MD, Principal investigator, Indiana UniversityZeruesenay Desta, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05490511
- Sponsor's protocol ID
- 12763
- Other IDs
- 5R01AT011463-02
- Status last verified
- Jul 2026
- First submitted
- 3 Aug 2022
- Last updated
- 30 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, Wang D, Vinks AA, He Y, Swen JJ, Leeder JS, van Schaik R, Thummel KE, Klein TE, Caudle KE, MacPhee IA. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015 Jul;98(1):19-24. doi: 10.1002/cpt.113. Epub 2015 Jun 3.
PubMed 25801146Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019 Jul 8;8(7):989. doi: 10.3390/jcm8070989.
PubMed 31288397Gisch DL, Koyama S, Etkins J, So GC, Fehrenbach DJ, Lu JBL, Cheng YH, Ferreira RM, Rajadhyaksha E, McClara K, Asghari M, Sharfuddin AA, Dagher PC, Snell LM, Madhur MS, Polidoro RB, Desta Z, Eadon MT. Cannabidiol exerts antiinflammatory effects but maintains T effector memory cell differentiation in humans. JCI Insight. 2025 Nov 18;11(1):e198590. doi: 10.1172/jci.insight.198590. eCollection 2026 Jan 9.
PubMed 41252210So GC, Lu JBL, Koyama S, Cheng YH, Gisch DL, McClara K, Dexter PR, Sharfuddin AA, Etkins J, Tillman EM, Beamon TR, Cowsert Z, Stuart JS, Desta Z, Eadon MT. A Phase I Trial of the Pharmacokinetic Interaction Between Cannabidiol and Tacrolimus. Clin Pharmacol Ther. 2025 Mar;117(3):716-723. doi: 10.1002/cpt.3504. Epub 2024 Nov 27.
PubMed 39601108
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug-gene-nutraceutical Interactions of Cannabidiol and Tacrolimus
- ClinicalTrials.gov ID
- NCT05490511
- Acronym / sponsor ID
- 12763
- Conditions
- CBD, Transplant Complication, Kidney Disease, Chronic
- Keywords
- cannabidiol, tacrolimus, CYP3A5
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 31 Oct 2022 (actual)
- Primary completion
- 31 Aug 2025 (actual)
- Study completion
- 31 Aug 2025 (actual)
- First posted
- 5 Aug 2022 (actual)
- Results
- Posted 30 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The information learned in these studies will help to inform doctors as to how to appropriately adjust doses of cannabidiol and tacrolimus in order to improve health outcomes and long-term treatment success for transplant recipients.
Detailed description
The commercial availability of cannabidiol, or CBD oil, has increased in the United Stated and this supplement has the potential to cause a variety of drug-drug interactions, including in solid organ transplant recipients who receive tacrolimus to prevent rejection. Through a series of pharmacokinetic and pharmacodynamics assays, this proposal will identify gene-drug and drug-drug interactions (DDI), including those that place transplant recipients at risk for increased toxicity related to their immunosuppression. The information learned in these studies will help to inform practitioners as to whether cannabidiol needs to be avoided in transplant recipients and how to appropriately adjust doses of CBD and immunosuppression in order to improve health outcomes and long-term treatment success in this high-risk population.
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Subjects participate in a 3-phase fixed sequence pharmacokinetic study to evaluate the interaction between tacrolimus, cannabidiol, and genotype on tacrolimus AUC and immune system pharmacodynamic outcomes. Subjects with and without CKD will be enrolled in parallel arms.
| Arm | Type | Receives |
|---|---|---|
| CYP3A5 expressers without chronic kidney disease | Active comparator | Drug: Tacrolimus single dose, Drug: Epidiolex single dose, Drug: Epidiolex steady-state and tacrolimus single dose |
| CYP3A5 non-expressers without chronic kidney disease | Active comparator | Drug: Tacrolimus single dose, Drug: Epidiolex single dose, Drug: Epidiolex steady-state and tacrolimus single dose |
| CYP3A5 expressers with chronic kidney disease | Active comparator | Drug: Tacrolimus single dose, Drug: Epidiolex single dose, Drug: Epidiolex steady-state and tacrolimus single dose |
| CYP3A5 non-expressers with chronic kidney disease | Active comparator | Drug: Tacrolimus single dose, Drug: Epidiolex single dose, Drug: Epidiolex steady-state and tacrolimus single dose |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18-75
- Are judged healthy enough to participate as determined by and decided from a pre-enrollment screening session that includes medical history and laboratory tests such as blood and urine tests, and electrocardiography (EKG).
- Agree to refrain from taking any prescription medications, over-the-counter medications, and herbal, dietary, and alternative supplements that may interact with the metabolism of the study drugs at least 2 weeks prior to the start of the study and until study completion.
- Are willing to commit the time requested for this study
- Are willing to refrain from smoking or use of tobacco or marijuana for at least two weeks prior to and until the completion of the study (the entire study lasts for approximately 26 days).
Key exclusion criteria (23 listed)
- Unable to provide informed consent
- Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (tacrolimus or cannabidiol);
- Are currently taking sedative agents, including agents for insomnia
- Are underweight (body mass index (BMI) less than 18.5) or overweight [body mass index (BMI) greater than 35]
- Have a positive pregnancy serum or urine test obtained just prior to each study, or are breast feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus single doseAlso: Period 15 mg once | Drug | CYP3A5 expressers with chronic kidney disease, CYP3A5 expressers without chronic kidney disease, CYP3A5 non-expressers with chronic kidney disease, CYP3A5 non-expressers without chronic kidney disease |
| Epidiolex single doseAlso: Period 2Epidiolex 5 mg/kg | Drug | CYP3A5 expressers with chronic kidney disease, CYP3A5 expressers without chronic kidney disease, CYP3A5 non-expressers with chronic kidney disease, CYP3A5 non-expressers without chronic kidney disease |
| Epidiolex steady-state and tacrolimus single doseAlso: Period 3Epidiolex at up to 5 mg/kg twice daily (for 14 days) and tacrolimus 5 mg once on day 12 of period | Drug | CYP3A5 expressers with chronic kidney disease, CYP3A5 expressers without chronic kidney disease, CYP3A5 non-expressers with chronic kidney disease, CYP3A5 non-expressers without chronic kidney disease |
Primary outcome
The AUC0-Infinity Ratio of Tacrolimus With Cannabidiol Divided by Tacrolimus Alone
Time frame: 27 days
The primary outcome is the AUC0-Infinity ratio of tacrolimus with cannabidiol divided by tacrolimus alone between CYP3A5 expressers and non-expressers in subjects with and without chronic kidney disease (CKD). Tacrolimus whole blood concentrations were measured at 0, 20, 40, and 60 minutes and 2, 4, 6, 12, 24, 48, and/or 72 hours.
1 secondary outcome
Cell Viability Ratio
Time frame: 27 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25801146Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, Wang D, Vinks AA, He Y, Swen JJ, Leeder JS, van Schaik R, Thummel KE, Klein TE, Caudle KE, MacPhee IA. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015 Jul;98(1):19-24. doi: 10.1002/cpt.113. Epub 2015 Jun 3.
- Background: PubMed 31288397Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019 Jul 8;8(7):989. doi: 10.3390/jcm8070989.
- Derived from this study: PubMed 41252210Gisch DL, Koyama S, Etkins J, So GC, Fehrenbach DJ, Lu JBL, Cheng YH, Ferreira RM, Rajadhyaksha E, McClara K, Asghari M, Sharfuddin AA, Dagher PC, Snell LM, Madhur MS, Polidoro RB, Desta Z, Eadon MT. Cannabidiol exerts antiinflammatory effects but maintains T effector memory cell differentiation in humans. JCI Insight. 2025 Nov 18;11(1):e198590. doi: 10.1172/jci.insight.198590. eCollection 2026 Jan 9.
- Derived from this study: PubMed 39601108So GC, Lu JBL, Koyama S, Cheng YH, Gisch DL, McClara K, Dexter PR, Sharfuddin AA, Etkins J, Tillman EM, Beamon TR, Cowsert Z, Stuart JS, Desta Z, Eadon MT. A Phase I Trial of the Pharmacokinetic Interaction Between Cannabidiol and Tacrolimus. Clin Pharmacol Ther. 2025 Mar;117(3):716-723. doi: 10.1002/cpt.3504. Epub 2024 Nov 27.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Eadon, MD principal investigator
Indiana University
Zeruesenay Desta, PhD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tacrolimus single dose, Epidiolex single dose and Epidiolex steady-state and tacrolimus single dose in people with CBD and Transplant Complication, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The AUC0-Infinity Ratio of Tacrolimus With Cannabidiol Divided by Tacrolimus Alone (time frame: 27 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05490511, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.