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

Phase 4

Completed

• Conditions: Contraception
• Interventions: Drug: Cannabidiol Oil; Drug: Placebo; Drug: Combined oral contraceptive pill

• Registration Number: NCT04396730
• Lead Sponsor: Oregon Health and Science University

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.

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 Timeline

• Study Start: 2020-04-08
• Study First Submitted: 2020-04-29
• Study First Submitted QC: 2020-05-15
• Study First Posted: 2020-05-21
• Primary Completion: 2022-03-02
• Study Completion: 2022-03-02
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-07
• Last Update Posted: 2023-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo followed by cannabidiol	Cannabidiol Oil	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.
Placebo followed by cannabidiol	Placebo	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.
Cannabidiol follow Placebo	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.
Cannabidiol follow Placebo	Combined oral contraceptive pill	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.
Placebo followed by cannabidiol	Combined oral contraceptive pill	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.
Cannabidiol follow Placebo	Cannabidiol Oil	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.

Primary Outcome Measures

Name	Time	Method
Maximum plasma concentration Ethinyl Estradiol	At the end of Cycle 3 (each cycle is 28 days)	Area under the plasma concentration vs time curve of ethinyl estradiol (EE)
Maximum plasma concentration of Levonorgestrel	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

Name	Time	Method
Time to maximum measured plasma concentration (Cmax)	At the end of Cycle 3 (each cycle is 28 days)	Time to maximum measured plasma concentration of LNG and EE (Cmax)
The first-order final elimination rate constant of EE and LNG	At the end of Cycle 3 (each cycle is 28 days)	The first-order final elimination rate constant of EE and LNG
The area under the plasma concentration of LNG and EE vs. time curve (AUC)	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)
Time to maximum measured plasma concentration (Tmax)	At the end of Cycle 3 (each cycle is 28 days)	Time to maximum measured plasma concentration of LNG and EE. (Tmax)
Final time taken for plasma concentration to be reduced by half (t1/2)	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)

Trial Locations

Locations (1)

OHSU; 🇺🇸 Portland, Oregon, United States