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

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.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: Cannabidiol Oil; Drug: Placebo; Drug: Combined oral contraceptive pill

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Cannabidiol + OCP; Drug: Placebo; Placebo will be administered daily along with oral contraceptives daily for 24 days.; Other Names: 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 Names: Cannabidiol + OCP; Drug: Placebo; Placebo will be administered daily along with oral contraceptives daily for 24 days.; Other Names: Placebo + OCP; Drug: Combined oral contraceptive pill; All participants will receive oral contraceptives

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration Ethinyl Estradiol	Area under the plasma concentration vs time curve of ethinyl estradiol (EE)	At the end of Cycle 1 (each cycle is 28 days)
Maximum plasma concentration Ethinyl Estradiol	Area under the plasma concentration vs time curve of ethinyl estradiol (EE)	At the end of Cycle 3 (each cycle is 28 days)
Maximum plasma concentration of Levonorgestrel	Area under the plasma concentration vs time curve of levonorgestrel (LNG)	At the end of Cycle 1 (each cycle is 28 days)
Maximum plasma concentration of Levonorgestrel	Area under the plasma concentration vs time curve of levonorgestrel (LNG)	At the end of Cycle 3 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum measured plasma concentration (Tmax)	Time to maximum measured plasma concentration of LNG and EE. (Tmax)	At the end of Cycle 1 (each cycle is 28 days)
Time to maximum measured plasma concentration (Tmax)	Time to maximum measured plasma concentration of LNG and EE. (Tmax)	At the end of Cycle 3 (each cycle is 28 days)
Time to maximum measured plasma concentration (Cmax)	Time to maximum measured plasma concentration of LNG and EE (Cmax)	At the end of Cycle 1 (each cycle is 28 days)
Time to maximum measured plasma concentration (Cmax)	Time to maximum measured plasma concentration of LNG and EE (Cmax)	At the end of Cycle 3 (each cycle is 28 days)
Final time taken for plasma concentration to be reduced by half (t1/2)	Final time taken for plasma concentration of LNG and EE to be reduced by half (t1/2)	At the end of Cycle 1 (each cycle is 28 days)
Final time taken for plasma concentration to be reduced by half (t1/2)	Final time taken for plasma concentration of LNG and EE to be reduced by half (t1/2)	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)	The area under the plasma concentration of LNG and EE vs. time curve (AUC)	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)	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 first-order final elimination rate constant of EE and LNG	The first-order final elimination rate constant of EE and LNG	At the end of Cycle 1 (each cycle is 28 days)
The first-order final elimination rate constant of EE and LNG	The first-order final elimination rate constant of EE and LNG	At the end of Cycle 3 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Society of Family Planning
• Investigators: Principal Investigator: Shaalini Ramanadhan, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): March 2, 2022

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Cannabidiol; Combined oral contraceptives
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anticonvulsants; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined; Cannabidiol
• Other Study ID Numbers: STUDY00020906

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No