INTERVENTIONALCOMPLETEDNCT06192589

Clinical Study to Evaluate Cannabidiol Liver Enzyme Elevations and Drug Interactions

Cannabidiol (CBD) is available as a prescription drug product for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. At labeled doses up to 25 mg/kg/day, an increased risk of liver enzyme elevation and drug-induced liver injury has been observed. However, only limited evaluations of the risk of liver enzyme elevation of daily, lower dose CBD use are available. The potential for liver enzyme elevations with lower CBD doses with unapproved consumer products highlights a need for further research. In addition, CBD has the capacity to inhibit cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases, leading to potential drug-drug interactions with multiple common medications. The clinical significance of many of these interactions is also unclear. Furthermore, nonclinical studies have suggested the potential for CBD to cause reproductive and endocrine effects. As such, additional high-quality clinical pharmacology studies are needed to further characterize CBD's safety profile. The objective of this study is to characterize the effects of daily CBD use at a dose within the range of what consumers are taking as unapproved CBD products on liver enzyme elevations, drug interactions, and endocrine measures.

Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2025-07-31

What this record can show

Registry results are available

Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.

Registry facts

Study at a glance

Phase: PHASE1
Enrollment: 241 (ACTUAL)
Start date: 2024-02-08
Sponsor: Food and Drug Administration (FDA)
Design: RANDOMIZED · PARALLEL · OTHER
Locations: 1
Results record: Present in registry snapshot

The cannabis plant contains bioactive compounds known as cannabinoids; delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent cannabinoids in most varieties of cannabis. The Agricultural Improvement Act (Farm Bill) of 2018 removed hemp, defined as cannabis and derivatives of cannabis with extremely low concentrations of THC, from the definition of marijuana in the Controlled Substances Act. Following this, many CBD products have been made available to consumers. However, hemp products remain subject to regulation under the Federal Food Drug \& Cosmetic Act, when applicable (e.g., as drugs, foods, dietary supplements, cosmetics, veterinary products) and the growing CBD products market raises various safety concerns, especially with long-term use. CBD is available as a prescription drug product for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. At labeled doses up to 25 mg/kg/day, an increased risk of liver enzyme elevation and drug-induced liver injury has been observed. However, only limited evaluations of the risk of liver enzyme elevation of daily, lower dose CBD use are available. The potential for liver enzyme elevations with CBD doses in unapproved consumer products highlights a need for further research to quantify risks at these doses. In addition, CBD has the capacity to inhibit cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases, leading to potential drug-drug interactions with multiple common medications. The clinical significance of many of these interactions is also unclear. Furthermore, nonclinical studies have suggested the potential for CBD to cause reproductive and endocrine effects. As such, additional high-quality clinical pharmacology studies are needed to further characterize CBD's safety profile. This study will be divided into two parts. In Part 1, 200 healthy subjects will be randomized to 5 mg/kg/day of CBD (150 subjects) or placebo (50 subjects) for 4 weeks with weekly laboratory assessments to characterize the percentage of participants with liver enzyme elevation (primary endpoint) or meeting withdrawal criteria for potential drug-induced liver injury (secondary endpoint). Additional secondary endpoints include the change from baseline after 4 weeks of daily CBD dosing for male reproductive (testosterone and inhibin B) and thyroid hormones (thyroid stimulating hormone \[TSH\], triiodothyronine \[T3\] and thyroxine \[T4\]) as secondary endpoints. Exploratory endpoints include additional characterization of liver findings and other blood biomarkers. In Part 2, 40 healthy subjects will receive either oral citalopram (20 subjects) or morphine (20 subjects) at baseline and then again after receiving CBD 5 mg/kg/day to characterize the effect of daily cannabidiol use on the plasma concentration of citalopram and morphine. Citalopram was selected because it is a common prescription medication for depression and anxiety that is metabolized by CYP2C19 and CYP3A4, which CBD inhibits. Morphine was selected because it is a common opioid analgesic that is metabolized by UGT2B7, which CBD inhibits.

Group	N	Value	Spread / interval
Cannabidiol (Part 1)	151	5.6	1.8 to 9.3
Placebo (Part 1)	50	0	0 to 7.6

Group	N	Value	Spread / interval
Part 2: Citalopram	19	1033	26
Part 2: Citalopram and Cannabidiol	19	1475	24

Group	N	Value	Spread / interval
Part 2: Citalopram	19	23	21
Part 2: Citalopram and Cannabidiol	19	26	24

Group	N	Value	Spread / interval
Part 2: Morphine	20	44	45
Part 2: Morphine and Single Dose Cannabidiol	20	47	51
Part 2: Morphine and Multiple Doses of Cannabidiol	18	51	60

Group	N	Value	Spread / interval
Part 2: Morphine	20	8.3	40
Part 2: Morphine and Single Dose Cannabidiol	20	9.9	45
Part 2: Morphine and Multiple Doses of Cannabidiol	18	9.3	31

Group	N	Value	Spread / interval
Cannabidiol (Part 1)	151	4.9	1.3 to 8.4
Placebo (Part 1)	50	0	0 to 7.6

Group	N	Value	Spread / interval
Cannabidiol (Part 1)	77	5.0	-20.0 to 30.0
Placebo (Part 1)	26	-13.6	-57.1 to 29.9

Group	N	Value	Spread / interval
Cannabidiol (Part 1)	77	5.8	0.8 to 10.7
Placebo (Part 1)	26	8.2	-0.0 to 16.5

Group	N	Value	Spread / interval
Cannabidiol (Part 1)	139	0.073	-0.003 to 0.148
Placebo (Part 1)	47	0.005	-0.124 to 0.134

Group	N	Value	Spread / interval
Cannabidiol (Part 1)	139	-0.006	-0.023 to 0.011
Placebo (Part 1)	47	0.014	-0.015 to 0.043

Group	N	Value	Spread / interval
Cannabidiol (Part 1)	139	-0.014	-0.025 to -0.003
Placebo (Part 1)	47	-0.012	-0.031 to 0.006

Group	N	Value	Spread / interval
Part 2: Morphine	20	2416	18
Part 2: Morphine and Single Dose Cannabidiol	20	2450	17
Part 2: Morphine and Multiple Doses of Cannabidiol	18	2382	14

Group	N	Value	Spread / interval
Part 2: Morphine	20	265	21
Part 2: Morphine and Single Dose Cannabidiol	20	296	29
Part 2: Morphine and Multiple Doses of Cannabidiol	18	256	25

Group	N	Value	Spread / interval
Part 2: Morphine	20	327	30
Part 2: Morphine and Single Dose Cannabidiol	20	355	28
Part 2: Morphine and Multiple Doses of Cannabidiol	18	416	27

Group	N	Value	Spread / interval
Part 2: Morphine	20	47	24
Part 2: Morphine and Single Dose Cannabidiol	20	51	28
Part 2: Morphine and Multiple Doses of Cannabidiol	18	52	28

Milestone	Cannabidiol (Part 1)	Placebo (Part 1)	Cannabidiol and Citalopram Drug Interaction (Part 2)	Cannabidiol and Morphine Drug Interaction (Part 2)
STARTED	151	50	20	20
COMPLETED	133	47	20	18
NOT COMPLETED	18	3	0	2

Event	System	Groups: affected / at risk
Anxiety	Psychiatric disorders	Cannabidiol (Part 1): 2 / 151 · Placebo (Part 1): 0 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 0 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 0 / 20
Application Site Irritation	Skin and subcutaneous tissue disorders	Cannabidiol (Part 1): 1 / 151 · Placebo (Part 1): 0 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 0 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 0 / 20
Arthropod Bite	Skin and subcutaneous tissue disorders	Cannabidiol (Part 1): 1 / 151 · Placebo (Part 1): 0 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 0 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 0 / 20
Back Pain	General disorders	Cannabidiol (Part 1): 0 / 151 · Placebo (Part 1): 1 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 0 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 1 / 20
Bacterial Vaginosis	Infections and infestations	Cannabidiol (Part 1): 1 / 151 · Placebo (Part 1): 0 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 0 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 0 / 20
Constipation	Gastrointestinal disorders	Cannabidiol (Part 1): 1 / 151 · Placebo (Part 1): 0 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 0 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 0 / 20
Diarrhea	Gastrointestinal disorders	Cannabidiol (Part 1): 6 / 151 · Placebo (Part 1): 0 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 2 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 1 / 20
Dizziness	Nervous system disorders	Cannabidiol (Part 1): 4 / 151 · Placebo (Part 1): 0 / 50 · Cannabidiol and Citalopram Drug Interaction (Part 2): 0 / 20 · Cannabidiol and Morphine Drug Interaction (Part 2): 1 / 20

Exclusion criteria

1. Abnormal liver labs at screening on check-in (Day -1), defined as any of the following (tests may be repeated once for confirmation at screening and check-in): 1. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 × ULN. (The ULN for ALT will be 33 U/L for males and 25 U/L for females.) 2. Total bilirubin (TBL) \> ULN. 3. International normalized ratio (INR) \> 1.3 2. Use or intend to use any medications/products in the 14 days prior to check-in (Day -1), unless deemed acceptable by the investigator 3. Subject is currently participating in another clinical study of an investigational drug or has been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of dosing for this study. 4. Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, electronic cigarettes) within 6 weeks of Screening. Subjects must refrain from using these throughout the study. 5. Subject has consumed alcohol, xanthine-containing products (e.g., tea, coffee, chocolate, cola), caffeine, kava melatonin, St Johns Wart, grapefruit, or grapefruit juice within 24 hours of check-in. Subjects must refrain from ingesting these throughout the study. 6. Subject is unable to tolerate a controlled, quiet study conduct environment, including avoidance of music, television, movies, games, and activities that may cause excitement, emotional tension, or arousal during the prespecified time points (e.g., before and during CBD dosing). 7. Subject has a history of consuming more than 14 units of alcoholic beverages per week within 6 months before Screening, has a history of alcoholism or drug/chemical/substance abuse within 2 years before Screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine, or 1 ounce of spirits/hard liquor) 8. Subject has a positive test result for alcohol or drugs of misuse (amphetamines, barbiturates, benzodiazepines, cocaine, alcohol, opiates, phencyclidine, propoxyphene, and methadone) at Screening or Check-in (Day -1 \[both Parts\]; Day 10 \[Part 2, morphine DDI\]; Day 12 \[Part 2, citalopram DDI\]). 9. Subject has a positive test result for cannabinoids (THC) at screening or Day -1. 10. Subject has a history of opioid or narcotic misuse. 11. Subject has a history of suicidal ideation or previous suicide attempts 12. Subject has a history or evidence of a clinically significant disorder, condition, or disease (e.g., cancer, human immunodeficiency virus \[HIV\], hepatic or renal impairment) that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. 13. Subject has any signs or symptoms that are consistent with Coronavirus Disease 2019 (COVID-19) per Center for Disease Control (CDC) recommendations at screening or check-in (Day -1). These include subjects with fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea may have COVID-19. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator. 14. Subject has known or suspected allergies or sensitivities to the study drug or placebo components (e.g., sucralose, sesame). 15. Subjects with a documented hypersensitivity reaction to cannabidiol 16. Subjects with a documented medical history of clinical disorders related to mood, anxiety or panic, including diagnosed depression, generalized anxiety disorder or panic attacks. 17. Subject has any condition possibly affecting study drug absorption (e.g., gastrectomy, Crohn's disease, irritable bowel syndrome). Uncomplicated cholecystectomies and appendectomies may be included at the investigator's discretion. 18. Subject has clinical laboratory test results (hematology, serum chemistry and urinalysis) at Screening or Check-In that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator. Tests may be repeated once for confirmation at both Screening and Check-In. 19. Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen. 20. Subject has a mean systolic blood pressure \<85 or \>145 mmHg or a mean diastolic blood pressure \<45 or \>95 mmHg at either Screening or Check-in. Blood pressure will be measured in triplicate after the subject has been resting in a supine position for a minimum of 5 minutes. 21. Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or is unlikely to complete the study due to poor venous access. 22. Female subject is currently pregnant or lactating or was within 3 months of the study. 23. Subject has had any significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days, or donated plasma within 7 days before Check-in. 24. Subject has any other condition that precludes his or her participation in the study (as determined by the investigator).

Registry results are available

Study at a glance

Related local records

Conditions

Cannabinoids and active compounds

Medicines

Researchers and organizations

What was registered

Cannabidiol

Placebo

Citalopram

Morphine

Results posted to the registry

Statistical analyses

Statistical analyses

Statistical analyses

Statistical analyses

Statistical analyses

Statistical analyses

Statistical analyses

Statistical analyses

Overall Study

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Cannabidiol (Part 1)

Placebo (Part 1)

Cannabidiol and Citalopram Drug Interaction (Part 2)

Cannabidiol and Morphine Drug Interaction (Part 2)

Population and criteria

Inclusion criteria

Exclusion criteria

primary measures

Part 1 - Percentage of Participants With an Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Liver Enzyme Elevation Greater Than Three Times the Upper Limit of Normal (> 3 × ULN).

Part 2 - Area Under the Plasma Concentration-time Curve (AUC) of Citalopram When Administered Alone Versus When Co-administered With Cannabidiol After 7 Days of CBD Dosing.

Part 2 - Maximum Concentration (Cmax) of Citalopram When Administered Alone Versus When Co-administered With CBD After 7 Days of Cannabidiol Dosing.

Part 2 - Morphine AUC When Administered Alone Versus When Co-administered With the First Dose of Cannabidiol and After 7 Days of CBD Dosing.

Part 2 - Morphine Cmax When Administered Alone Versus When Co-administered With the First Dose of Cannabidiol and After 7 Days of Cannabidiol Dosing.

secondary measures

Part 1 - Percentage of Participants Meeting Withdrawal Criteria for Potential Drug-induced Liver Injury (DILI).

Part 1 - Change From Baseline in Total Testosterone in Male Participants After Cannabidiol Administration Compared to Placebo.

Part 1 - Change From Baseline in Inhibin B in Male Participants After Cannabidiol Administration Compared to Placebo.

Part 1 - Change From Baseline in Thyroid Stimulating Hormone (TSH) After Cannabidiol Administration Compared to Placebo.

Part 1 - Change From Baseline in Total T3 After Cannabidiol Administration Compared to Placebo.

Part 1 - Change From Baseline in Free T4 After Cannabidiol Administration Compared to Placebo.

Part 2 - Morphine-3-glucuronide (M3G) AUC When Morphine is Administered Alone Versus When Co-administered With Cannabidiol.

Part 2 - M3G Cmax When Morphine is Administered Alone Versus When Co-administered With Cannabidiol.

Part 2 - Morphine-6-glucuronide (M6G) AUC When Morphine is Administered Alone Versus When Co-administered With Cannabidiol.

Part 2 - M6G Cmax When Morphine is Administered Alone Versus When Co-administered With Cannabidiol.

Locally readable linked articles

Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence.

Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial.

Median Body Weight

Median Height

Median Body Mass Index