Dronabinol for Endometriosis

Recruiting at 1 trial location

Overseen By Adetola Vaughan, MA Psychology

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Must not be taking: Cannabinoids, Opioids, Benzodiazepines, others

Disqualifiers: Obesity, Psychiatric illness, Cardiac disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This exploratory, proof-of-concept study is a double-blind (participants and investigators will be blinded), placebo-controlled, randomized, two-arm clinical trial of Marinol \[dronabinol, synthetic Δ9-tetrahydrocannabinol (THC)\] for e endometriosis-associated chronic pelvic pain (endo-CPP) with a 2:1 allocation ratio. Up to 75 subjects will be enrolled in this pilot study and randomized to receive doses of THC (up to 30 mg/day), orally, over 8 weeks. This study will be conducted at a single site; it does not include any stratifications, and there is no interim analysis planned. Notably, the goal is to determine whether there is enough evidence of the safety of THC to support the development of later-phase clinical trials. Thus, detailed developmental plans are contingent on the outcomes of this study.

Will I have to stop taking my current medications?

The trial requires participants to stop using cannabis, marijuana, and any other cannabinoids, including over-the-counter CBD products. Participants using oral contraceptives or vaginal rings for endometriosis must agree to stop these medications and switch to dronabinol as the primary treatment during the study. Additionally, participants must not start new pain medications or increase their current doses during the study.

What data supports the effectiveness of the drug Dronabinol for treating endometriosis?

Dronabinol, which is a form of delta-9-tetrahydrocannabinol, has shown promise in managing pain, as cannabinoids have been effective in treating both inflammatory and neuropathic pain in other conditions. This suggests potential benefits for pain management in endometriosis, although direct evidence for endometriosis is not provided. ^{1 2 3 4 5}

Is dronabinol generally safe for humans?

Dronabinol is generally considered safe for humans, with common side effects including dry mouth, dizziness, and headache, which are usually mild to moderate and temporary. More studies are needed to fully understand its side effect profile, but current data suggest that the benefits may outweigh these risks. ^{6 7 8 9 10}

How does the drug Dronabinol differ from other treatments for endometriosis?

Dronabinol, a synthetic form of THC (the active ingredient in cannabis), is unique because it targets the endocannabinoid system, which is involved in pain management. This approach is different from traditional hormonal or surgical treatments, as it may help manage pain by modulating the body's natural pain-relief pathways. ^{11 12 13 14 15}

Research Team

Christopher Verrico, PhD in Pharmacology

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for up to 75 individuals with chronic pelvic pain due to endometriosis. Participants will be randomly assigned in a 2:1 ratio to receive either the study drug or a placebo, without knowing which one they are getting.

Inclusion Criteria

I am fluent in English.

Stated willingness to comply with all study procedures and availability for the duration of the study

I agree to follow specific lifestyle guidelines during the study.

Exclusion Criteria

Treatment with another investigational drug or other intervention within 3 months of the screening visit

I am allergic to cannabis, CBD, THC, or similar substances.

I currently use cannabis or CBD products and do not want to stop.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dronabinol or placebo capsules, twice per day for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dronabinol

Trial Overview The DARP study tests if dronabinol (synthetic THC) can reduce endometriosis-associated chronic pelvic pain. Participants will take up to 30 mg/day of this oral medication or a placebo over an eight-week period at Texas Children's Hospital.

Participant Groups

Group I: Dronabinol Experimental Treatment 1 Intervention

Dronabinol capsules, over-encapsulated with filler to match the appearance of the placebo capsule, up to 15 mg, twice per day for 8 weeks.

Group II: Placebo Placebo Group 1 Intervention

Capsules with placebo (i.e., cellulose filler), twice per day for 8 weeks.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

In a study of 1,145 patients with refractory chronic pain, adding Δ9-tetrahydrocannabinol (dronabinol) to their treatment significantly reduced average pain intensity from 46.3 to 26.8 mm on a visual analog scale over 12 weeks.

Dronabinol was well tolerated, with 46.8% of patients reporting mild drug-related adverse events, and many patients were able to reduce or stop other pain medications during the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry. Ueberall, MA., Horlemann, J., Schuermann, N., et al.[2022]

In a meta-analysis of 16 trials, nabilone was associated with significantly higher rates of drowsiness, dizziness, and dry mouth compared to placebo, indicating a notable risk of these side effects.

Dronabinol also showed increased occurrences of dry mouth, dizziness, and headache compared to placebo, but the overall severity of adverse events was generally mild-to-moderate, suggesting that the benefits may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Bajtel, Á., Kiss, T., Tóth, B., et al.[2022]

Among older adults, those with chronic obstructive pulmonary disease (COPD) were more likely to use synthetic oral cannabinoids (0.6%) compared to those without COPD (0.3%), indicating a higher prevalence of off-label use in this population.

Older adults with COPD not only used synthetic cannabinoids more frequently but also for longer durations and at higher doses, raising potential safety concerns that warrant further research on the respiratory effects of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Synthetic Oral Cannabinoid use Among Older Adults with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study. Vozoris, NT., Yao, Z., Li, P., et al.[2020]

Cannabis use is increasing due to decriminalization and legalization, but its adverse effects, including cardiovascular and pulmonary issues, as well as links to malignancy and neuropsychiatric disorders, are becoming more evident despite limited research.

The rise in cannabis use among minors has led to more cases of overdose and toxicity, highlighting concerns about its safety, particularly regarding impaired driving and motor vehicle accidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Impact of Cannabis on Human Health. Chandy, M., Nishiga, M., Wei, TT., et al.[2023]

In a study involving 36 female rats with surgically induced endometriosis, a 5 mg/kg dose of cannabidiol (CBD) significantly reduced the surface area of endometriotic implants and lowered levels of inflammatory markers like IL-6 and TNF-α compared to a saline solution.

CBD also improved total antioxidant status in the serum and peritoneal fluid, showing similar efficacy to the standard treatment leuprolide acetate, suggesting that CBD could be a promising therapeutic option for managing endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model. Okten, SB., Cetin, C., Tok, OE., et al.[2023]

The endocannabinoid system (ECS) is identified as a promising target for managing severe pain associated with endometriosis, which is often inadequately addressed by current medical and hormonal therapies.

This review highlights the complex pain mechanisms in endometriosis and suggests that modulating the ECS could provide new strategies for effective pain relief in affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. Bouaziz, J., Bar On, A., Seidman, DS., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Medical Use of Cannabinoids. [2022]

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

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry. [2022]

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

Novel approaches and current challenges with targeting the endocannabinoid system. [2022]

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

Neuropharmacology and therapeutic potential of cannabinoids. [2022]

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

Abuse potential of dronabinol (Marinol). [2013]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers. [2020]

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

Dronabinol Therapy: Central Nervous System Adverse Events in Adults With Primary Brain Tumors. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Prescription Synthetic Oral Cannabinoid use Among Older Adults with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study. [2020]

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

Adverse Impact of Cannabis on Human Health. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model. [2023]

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

The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. [2020]

13. Germany pubmed.ncbi.nlm.nih.gov

Endocannabinoids modulate apoptosis in endometriosis and adenomyosis. [2018]

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

Endometriosis and Cannabis Consumption During the COVID-19 Pandemic: An International Cross-Sectional Survey. [2023]

15. Poland pubmed.ncbi.nlm.nih.gov

Comparison of dienogest effects upon 3,3'-diindolylmethane supplementation in models of endometriosis and clinical cases. [2018]