Dronabinol Effects on THC Metabolism During Pregnancy

(PrECEPT Trial)

Recruiting at 1 trial location

Overseen By Nina Isoherranen, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Washington

Must not be taking: Anticoagulants, Antipsychotics, Antidepressants, others

Disqualifiers: Diabetes, Cardiac, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Cannabis use is prevalent among pregnant women, but the effects of use on both the developing fetus and pregnant woman are unknown. Importantly, drug exposure could be influenced by the impact of pregnancy-associated hormones on the metabolism of tetrahydrocannabinol (THC), the main psychoactive component of cannabis. The goal of this study is to determine whether cortisol and estradiol - hormones that rise dramatically during pregnancy - increase the clearance of dronabinol (THC) in reproductive age women to simulate the pregnant state. The collected data will then be used to predict the time course and magnitude of changes in THC metabolism in pregnant women, particularly with gradually increasing estradiol and cortisol concentrations that evolve over the course of pregnancy. The overall objective of this study is to better understand the effects of THC use during pregnancy on the health of the pregnant woman and developing fetus.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications or supplements that affect certain liver enzymes (CYP2C9, CYP3A4, or UGT) at least 1 month before participating. If you're on prescription drugs that affect these enzymes, you won't be eligible to join the study.

Is Dronabinol (THC) safe to use during pregnancy?

Research suggests that using THC during pregnancy can have harmful effects on both the mother and the baby, including psychiatric issues for the mother and heart rhythm problems, growth restrictions, and birth defects for the baby. It is important to be cautious and consult with a healthcare provider before using THC during pregnancy. ^{1 2 3 4 5}

How does the drug Dronabinol differ from other treatments for THC metabolism during pregnancy?

Dronabinol, a synthetic form of THC, is unique because it specifically targets the endocannabinoid system, which plays a crucial role in pregnancy. Unlike other treatments, it may alter the expression of enzymes involved in endocannabinoid metabolism, potentially affecting placental development and fetal growth. ^{6 7 8 9 10}

Who Is on the Research Team?

Nina Isoherranen, PhD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for healthy, premenopausal women aged 21-45 with a BMI under 30. Participants should have regular menstrual cycles and agree to use nonhormonal contraception. Exclusions include history of blood clots, cancer, severe hypertriglyceridemia, uncontrolled hypertension, anemia, certain medication use (including hormonal contraceptives), current pregnancy or lactation, allergies to study drugs or sesame oil, psychiatric illness history, systemic diseases like auto-immune disorders or extensive skin disease.

Inclusion Criteria

I am a healthy woman, aged 21-45, and have not gone through menopause.

Body mass index (BMI) <30 kg/m2

Willingness to use nonhormonal methods of contraception during the study period

Exclusion Criteria

Allergy to sesame oil

I am not allergic to dronabinol, synthetic steroids, or similar drugs.

I have a history of seizures or severe mental health issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Estradiol Treatment

Participants receive 0.3 mg/24 hr transdermal estradiol for 1 week

1 week

1 visit (in-person)

Cortisol Treatment

Participants receive 30 mg hydrocortisone daily, administered in 2 divided doses for 1 week

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dronabinol

Trial Overview The study investigates how pregnancy hormones affect the body's processing of THC by using dronabinol as a stand-in for cannabis' active ingredient. It aims to simulate pregnant conditions in reproductive-age women by monitoring changes in THC metabolism influenced by increasing levels of cortisol and estradiol.

How Is the Trial Designed?

Group I: Estradiol Experimental Treatment 1 Intervention

1 week treatment with 0.3 mg/24 hr transdermal estradiol

Group II: Cortisol Experimental Treatment 1 Intervention

1 week treatment with 30 mg hydrocortisone daily, administered in 2 divided doses

Dronabinol is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting
• Sleep apnea

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Studies on the agonistic activity of delta 9-11-tetrahydrocannabinol in mice, dogs and rhesus monkeys and its interactions with delta 9-tetrahydrocannabinol. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Effects of cannabinoids on the development of chick embryos in ovo. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Adverse events of recreational cannabis use during pregnancy reported to the French Addictovigilance Network between 2011 and 2020. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Characterization of cannabinoid plasma concentration, maternal health, and cytokine levels in a rat model of prenatal Cannabis smoke exposure. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover. [2015]

8. Japan pubmed.ncbi.nlm.nih.gov

Comparison of pharmacological effects of tetrahydrocannabinols and their 11-hydroxy-metabolites in mice. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta. [2022]