Study of Cannabidiol (CBD) in Healthy Volunteers

Immune System Diseases Clinical Trial

Official title:

An Open-Label Parallel Phase I Study Evaluating Multiple Ascending Dose Pharmacokinetics and Acute Immunomodulatory Potential of a Novel Oral Cannabidiol (CBD) Formulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06286839
• Other study ID #: AFCRO-150
• Status: Completed
• Phase: N/A
• Start date: May 12, 2022
• Est. completion date: December 14, 2022

Study information

• Verified date: February 2024
• Source: NextEvo Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a prospective, single-centre, open label, randomized, two-arm, parallel design study to evaluate the effect of four-weeks consumption of active study product on primary endpoint in healthy adults

Description:

Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa L., has been purported to have a variety of beneficial physiological effects including but not limited to, pain relief, anti-anxiety, anti-seizure, anti-depressant, anti-oxidant, and anti-inflammatory. Despite the enthusiasm of the CBD industry for these claims, the empirical evidence supporting favourable physiological responses is inconsistent. These discrepancies may in part be explained by differences in CBD bioavailability when administered orally that in turn may be influenced by non-standardized CBD formulation, and/or the body size and composition of the recipient. The purpose of this study was to test the bioavailability of two doses of a novel CBD formation given twice per day for three consecutive days in healthy study subjects and explore their potential acute anti-inflammatory properties as assessed by highly sensitive immunologic assays. The rationale for conducting the study was to evaluate the pharmacokinetic (PK) profile of a novel formulation of CBD designed to improve bioavailability given at two dose levels twice per day for three consecutive days. Although previous studies conducted in healthy study subjects have documented the safety and PK profile for a single dose of the test product, multiple ascending dose studies have not yet been conducted. In addition to evaluating multiple ascending dose PK, the pharmacodynamic properties of the CBD were assessed using ex vivo lipopolysaccharides (LPS) stimulated whole blood assays and high sensitivity serum cytokine assays.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 14, 2022
• Est. primary completion date: October 28, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Be able to give written informed consent.

2. Be between 18 and 45, inclusive.

3. Has a BMI between 18-29.50 kg/m2.

4. Is in general good health, as determined by the investigator.

5. Willing to abstain from consuming tobacco or nicotine- containing products, consuming alcohol, grapefruit, or grapefruit juice, or taking any prescription drugs, dietary supplements, or non-prescription drugs for the periods required by the study protocol.

6. Willing to consume the investigational product daily for the duration of the trial.

7. Willing and able to communicate effectively with the study personnel and willing to comply with all protocol requirements, including visit schedule and oral intake of investigational product

8. Willing to consume the standard meal and an 8oz Boost nutritional drink at visit 2

Exclusion Criteria:

1. Are less than 18 or greater than 45

2. Participants who are pregnant or wish to become pregnant during the trial.

3. Participants who are lactating and/or currently breastfeeding

4. Post-menopausal, defined as one year without menses.

5. Participants currently of childbearing potential but not using an effective method of

contraception, as outlined below:

1. Complete abstinence from intercourse two weeks before administration of the investigational product, throughout the clinical trial, until the completion of follow-up procedures, or for two weeks following discontinuation of the investigational product in cases where the participant discontinues the trial prematurely. (Participants utilizing this method must agree to use an alternate method of contraception if they should become sexually active and will be queried on whether they have been abstinent in the preceding 2 weeks when they present to the clinic for the Final Visit).

2. Has a male sexual partner who is surgically sterilized before the Screening Visit and is the only male sexual partner for that participant.

3. Sexual partner(s) is/are exclusively female.

4. Use of an acceptable method of contraception, such as a spermicide, mechanical barrier (e.g., male condom, female diaphragm), or contraceptive pill. The participant must use this method for at least 1 week before and 1 week following the end of the trial.

5. Use of any intrauterine device (IUD) or contraceptive implant. The participant must have the device inserted at least 2 weeks before the first Screening Visit, throughout the trial, and 2 weeks following the end of the trial.

6. Are hypersensitive to any of the components of the investigational product.

7. Has taken any dietary supplement or non-prescription drugs within 3 days prior to baseline or has taken any prescription drugs within 14 days prior to baseline (antihistamines, acetaminophen, contraception or single- use over-the-counter medications including nonsteroidal anti-inflammatory drugs (NSAIDs) allowed before baseline.

8. Has a self-reported history of drug and/or alcohol abuse at the time of within 6 months before screening or exhibits evidence of drug and/or alcohol abuse at baseline.

9. Has consumed alcohol within 24 hours before screening and baseline.

10. Has consumed grapefruit or grapefruit juice within 3 days before screening or baseline

11. The participant has a current acute or chronic disease, which may, in the opinion of the investigator, impact the outcomes of the study.

12. The participant has clinically significant abnormal findings outside the normal screening ranges.

13. The participant has clinically significant abnormal findings from physical examination at screening and baseline that may, in the investigator's opinion, impact the study's outcomes.

14. The participant has a clinically important history of a medical disorder that may, in the opinion of the investigator, compromise the participant's safety or data quality

15. Current regular tobacco vape or nicotine-containing product use within 60 days prior to screening and between screening and baseline (Occasional use defined as less than 5 cigarettes per week or equivalent nicotine product/vape use)

16. Use of tetrahydrocannabinol (THC)/cannabidiol (CBD) products in within 7 days of screening.

17. The participant has a history of anaphylaxis, a documented hypersensitivity reaction, or a clinically important reaction to any drug which, in the opinion of the investigator, impacts the outcomes of the study.

18. A history of human immunodeficiency virus infection/acquired immune deficiency syndrome or a positive screening assessment for human immunodeficiency virus or viral hepatitis.

19. Evidence of amphetamines, barbiturates, Benzodiazepine (including prescription), cannabinoids, cocaine, opiates, phencyclidine, or ethanol on a urine drug screening at screening.

20. Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial.

21. Participants may not be receiving treatment involving experimental drugs or devices. If the participant has been in a recent experimental trial, these must have been completed at least 30 prior to this trial.

22. Any Participant who is an employee of the investigational site an Atlantia Clinical Trials employee or their close family member, or a member of their household

Related Conditions & MeSH terms

• Immune System and Related Disorders
• Immune System Diseases

Intervention

Dietary Supplement:
• Cannabidiol (CBD)
Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa L.

Locations

Country	Name	City	State
United States	Altantia Clinical Trials	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
NextEvo Inc.	Atlantia Food Clinical Trials

Country where clinical trial is conducted

United States, 

References & Publications (4)

Brunet LR, LaBrie S, Hagemann T. Immune monitoring technology primer: immunoprofiling of antigen-stimulated blood. J Immunother Cancer. 2016 Mar 15;4:18. doi: 10.1186/s40425-016-0122-4. eCollection 2016. No abstract available. — View Citation

Hobbs JM, Vazquez AR, Remijan ND, Trotter RE, McMillan TV, Freedman KE, Wei Y, Woelfel KA, Arnold OR, Wolfe LM, Johnson SA, Weir TL. Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults. Phytother Res. 2020 Jul;34(7):1696-1703. doi: 10.1002/ptr.6651. Epub 2020 Mar 8. — View Citation

Millar SA, Stone NL, Yates AS, O'Sullivan SE. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Front Pharmacol. 2018 Nov 26;9:1365. doi: 10.3389/fphar.2018.01365. eCollection 2018. — View Citation

Williams NNB, Ewell TR, Abbotts KSS, Harms KJ, Woelfel KA, Dooley GP, Weir TL, Bell C. Comparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability. Pharmaceuticals (Basel). 2021 Jan 6;14(1):35. doi: 10.3390/ph14010035. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma CBD pharmacokinetics of twice daily intake of 2 different doses of CBD over three days	Difference in plasma CBD concentration (ng/ml) between groups as measured by total Area Under the Curve (tAUC) derived from plasma	T-30 minutes, T 0 minutes, T30 minutes, T60 minutes, T240 minutes (4 Hours), T480 minutes (8 Hours), and T4320 minutes (72 Hours)
Primary	Evaluate the safety of twice daily intake of 2 different doses of CBD over three 3 days	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	T-30 minutes, T 0 minutes, T30 minutes, T60 minutes, T240 minutes (4 Hours), T480 minutes (8 Hours), and T4320 minutes (72 Hours)
Secondary	Plasma CBD maximal concentration (Cmax, ng/ml)	Difference in plasma Cmax concentration between groups as measured by total Area Under the Curve (tAUC) derived from plasma	T-30 minutes, T 0 minutes, T30 minutes, T60 minutes, T240 minutes (4 Hours), T480 minutes (8 Hours), and T4320 minutes (72 Hours)
Secondary	Plasma CBD time to peak (Tmax, minutes)	Difference in plasma Tmax concentration between groups as measured by total Area Under the Curve (tAUC) derived from plasma	T-30 minutes, T 0 minutes, T30 minutes, T60 minutes, T240 minutes (4 Hours), T480 minutes (8 Hours), and T4320 minutes (72 Hours)
Secondary	Percentage Change between groups on whole blood LPS stimulated cytokines (% change)	Differences between groups for the change from baseline were assessed for whole blood LPS stimulated cytokines	T0 minutes, T4320 minutes(72 Hours)