Cannabidiol and Oral Contraceptive Pills: Exploring a Drug-Drug Interaction

• ClinicalTrials.gov Identifier: NCT04396730
• Recruitment Status: Active, not recruiting
• First Posted: May 21, 2020
• Last Update Posted: September 30, 2022
• Sponsor: Oregon Health and Science University
• Collaborator: Society of Family Planning
• Information provided by (Responsible Party): Shaalini Ramanadhan, Oregon Health and Science University

Study Description

Brief Summary:

The purpose of this study is to assess how Cannabidiol (CBD) impacts the effectiveness of oral contraceptive (birth control) pills and if CBD changes the possible side effects of birth control pills when CBD and birth control pills are taken at the same time.

This study explores the potential interaction between CBD and birth control pills by assessing serum levels of the contraceptive steroid hormones ethinyl estradiol and levonorgestrel in birth control pill users when they also use CBD.

Condition or disease	Intervention/treatment	Phase
Contraception	Drug: Cannabidiol Oil; Drug: Placebo; Drug: Combined oral contraceptive pill	Phase 4

Detailed Description:

Participants will be randomized to either the CBD or placebo for cycle one, followed by a washout cycle. For cycle three, participants will take the opposite of what they received in Cycle one. For example if they received CBD during cycle one they will take placebo for cycle 3.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Cannabidiol and Oral Contraceptive Pills: Exploring a Drug-Drug Interaction
• Actual Study Start Date: April 8, 2020
• Actual Primary Completion Date: March 2, 2022
• Estimated Study Completion Date: March 2, 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo followed by cannabidiol; Oral contraceptives will be taken daily for 24 days along with placebo (oral) once daily for cycle 1. During cycle 3, cannabidiol will be taken once daily along with OCPs.	Drug: Cannabidiol Oil; 400 mg Cannabidiol oil will be administered daily along with oral contraceptives daily for 24 days.; Other Name: Cannabidiol + OCP; Drug: Placebo; Placebo will be administered daily along with oral contraceptives daily for 24 days.; Other Name: Placebo + OCP; Drug: Combined oral contraceptive pill; All participants will receive oral contraceptives
Experimental: Cannabidiol follow Placebo; Oral contraceptives will be taken daily for 24 days along with Cannabidiol 400mg once daily for cycle 1. During cycle 3. placebo will be taken once daily along with OCPs.	Drug: Cannabidiol Oil; 400 mg Cannabidiol oil will be administered daily along with oral contraceptives daily for 24 days.; Other Name: Cannabidiol + OCP; Drug: Placebo; Placebo will be administered daily along with oral contraceptives daily for 24 days.; Other Name: Placebo + OCP; Drug: Combined oral contraceptive pill; All participants will receive oral contraceptives

Outcome Measures

Primary Outcome Measures :

1. Maximum plasma concentration Ethinyl Estradiol [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
   Area under the plasma concentration vs time curve of ethinyl estradiol (EE)
2. Maximum plasma concentration Ethinyl Estradiol [ Time Frame: At the end of Cycle 3 (each cycle is 28 days) ]
   Area under the plasma concentration vs time curve of ethinyl estradiol (EE)
3. Maximum plasma concentration of Levonorgestrel [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
   Area under the plasma concentration vs time curve of levonorgestrel (LNG)
4. Maximum plasma concentration of Levonorgestrel [ Time Frame: At the end of Cycle 3 (each cycle is 28 days) ]
   Area under the plasma concentration vs time curve of levonorgestrel (LNG)

Secondary Outcome Measures :

1. Time to maximum measured plasma concentration (Tmax) [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
   Time to maximum measured plasma concentration of LNG and EE. (Tmax)
2. Time to maximum measured plasma concentration (Tmax) [ Time Frame: At the end of Cycle 3 (each cycle is 28 days) ]
   Time to maximum measured plasma concentration of LNG and EE. (Tmax)
3. Time to maximum measured plasma concentration (Cmax) [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
   Time to maximum measured plasma concentration of LNG and EE (Cmax)
4. Time to maximum measured plasma concentration (Cmax) [ Time Frame: At the end of Cycle 3 (each cycle is 28 days) ]
   Time to maximum measured plasma concentration of LNG and EE (Cmax)
5. Final time taken for plasma concentration to be reduced by half (t1/2) [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
   Final time taken for plasma concentration of LNG and EE to be reduced by half (t1/2)
6. Final time taken for plasma concentration to be reduced by half (t1/2) [ Time Frame: At the end of Cycle 3 (each cycle is 28 days) ]
   Final time taken for plasma concentration of LNG and EE to be reduced by half (t1/2)
7. The area under the plasma concentration of LNG and EE vs. time curve (AUC) [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
   The area under the plasma concentration of LNG and EE vs. time curve (AUC)
8. The area under the plasma concentration of LNG and EE vs. time curve (AUC) [ Time Frame: At the end of Cycle 3 (each cycle is 28 days) ]
   The area under the plasma concentration of LNG and EE vs. time curve (AUC)
9. The first-order final elimination rate constant of EE and LNG [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
   The first-order final elimination rate constant of EE and LNG
10. The first-order final elimination rate constant of EE and LNG [ Time Frame: At the end of Cycle 3 (each cycle is 28 days) ]
    The first-order final elimination rate constant of EE and LNG

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Have regular menses (every 21-35 days)
• Not at risk for pregnancy (not sexually active, using a barrier method of birth control, using a copper IUD for birth control, have a partner with a vasectomy, have had a tubal ligation, or in a same sex relationship)
• Generally healthy women between the age of 18 to 35 years old
• English speaking

Exclusion Criteria:

• Active users of hormonal contraception

  1. For combined methods, if they have recently stopped use, they must have had one normal menstrual cycle
  2. For prior Depo-Medroxyprogesterone Acetate users, they must be off of the medication for 2 months and be having regular menstrual cycles

• Pregnancy (less than 6 weeks prior), breastfeeding (less than 6 weeks prior),

  a. If participants have a normal menstrual cycle after these events, they may be considered for enrollment

• Any absolute/relative contraindications to EE and LNG (MEC category 3 or 4 [12]) including impaired liver function, history of deep venous thrombosis, hypertension (> 140/90), diabetes with vascular changes, migraines with aura or neurological changes, history of myocardial infarction, pulmonary embolus, stroke or breast cancer.
• Use of CBD or THC products / Marijuana in the last 30 days
• Use of a known CYP450 inhibitor or inducer (other medication)
• BMI>25
• Metabolic disorders including uncontrolled thyroid dysfunction and Polycystic Ovarian Syndrome
• Impaired liver or renal function
• Smoking/vaping/e-cigarettes
• Prior bariatric surgery
• Decisional impairment
• Incarceration

Contacts and Locations

Locations

United States, Oregon

OHSU

Portland, Oregon, United States, 97239

Sponsors and Collaborators

Oregon Health and Science University

Society of Family Planning

Investigators

• Principal Investigator: Shaalini Ramanadhan, MD; Oregon Health and Science University

More Information

• Responsible Party: Shaalini Ramanadhan, Clinical Instructor, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT04396730
• Other Study ID Numbers: STUDY00020906
• First Posted: May 21, 2020
• Last Update Posted: September 30, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shaalini Ramanadhan, Oregon Health and Science University:

Cannabidiol; Combined oral contraceptives

Additional relevant MeSH terms:

Cannabidiol; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined; Reproductive Control Agents; Physiological Effects of Drugs; Anticonvulsants; Contraceptive Agents, Female