CBD for Endometriosis Pain

Overseen By Barbara Scheetz

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Milton S. Hershey Medical Center

Must be taking: Norethindrone acetate

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

Disqualifiers: Pregnancy, Liver disease, Obesity, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabidiol (CBD) can aid in pain relief and enhance the quality of life for individuals with endometriosis. Participants will test various doses of CBD combined with norethindrone acetate, a standard hormonal therapy, to determine the most effective combination. The study spans 12 weeks, with regular check-ins and daily pain tracking. Individuals diagnosed with endometriosis who experience moderate to severe pain may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

Yes, if you are using oral contraceptives, vaginal ring, injectable progesterone, or GnRH agonists/antagonists, you must stop them and switch to Norethindrone acetate (NETA) for the study. If you use long-acting reversible contraceptives (LARCs), you must also switch to NETA. Additionally, you must stop using cannabis products, opioids, benzodiazepines, CNS depressants, Clobazam, and Valproate for a washout period and the study duration.

Will I have to stop taking my current medications?

Participants may need to stop their current medications. If you are using oral contraceptives or certain other treatments for endometriosis, you might need to switch to Norethindrone acetate (NETA) during the study. Additionally, if you are taking medications that cause drowsiness or certain other drugs, you may need to stop them for a washout period (time without taking certain medications) and the duration of the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CBD is generally safe for use. Many individuals using CBD for pain relief report positive outcomes. Studies indicate that only a small number of participants discontinue CBD due to side effects. Specifically, about 4.3% of those using low doses and up to 12.9% using high doses of CBD drop out of studies. In comparison, about 3.5% of those taking a placebo stop participating. This suggests that while some may experience side effects, most find them manageable. Overall, CBD is considered safe, with many users experiencing pain relief without major issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using CBD for endometriosis pain because it offers a new approach compared to traditional hormone-based therapies like birth control pills or pain relievers. Unlike these common treatments, CBD utilizes a natural compound derived from the cannabis plant, which may interact with the body's endocannabinoid system to alleviate pain and inflammation differently. This trial explores both low and high doses of CBD combined with norethindrone acetate, providing insights into how varying levels of CBD might impact pain management. By potentially offering a more targeted and natural alternative, CBD could become a promising option for those seeking relief from endometriosis pain.

What evidence suggests that this trial's treatments could be effective for endometriosis pain?

Studies have shown that cannabidiol (CBD) may help relieve pain linked to endometriosis. Surveys from several countries suggest that many people with this condition find cannabis-based products helpful for managing pain. Participants in similar studies reported not only less pain but also better sleep and reduced anxiety and depression. Some research shows that cannabinoids, the active ingredients in cannabis, can provide modest relief from long-term pain. This trial will evaluate the effectiveness of CBD in managing endometriosis pain by administering either a low dose or high dose of CBD combined with Norethindrone acetate, or a placebo combined with Norethindrone acetate. Additionally, people with endometriosis often use cannabis products when traditional pain treatments don't work well enough. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for women aged 18-45 with a surgical diagnosis of endometriosis and moderate to severe pain. Participants must not be planning surgery, agree to use contraception, and can switch to Norethindrone acetate for the study duration. Exclusions include high BMI, liver disease, certain medication use, substance abuse issues, chronic opioid use for other pains, current cannabis product use or recent history thereof.

Inclusion Criteria

I am a woman aged between 18 and 45.

Agrees to use approved contraception during the entire study if not surgically sterile

I agree to switch to NETA for endometriosis treatment during the study.

Exclusion Criteria

I am a woman with liver disease or my liver tests have been high in the past year.

I have had a stroke or heart attack.

I have not had suicidal thoughts or uncontrolled depression in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either placebo, low dose CBD, or high dose CBD for 8 weeks

8 weeks

Several onsite visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Pharmacokinetic Study (optional)

Participants may opt into pharmacokinetic testing with sublingual CBD

24-48 hours

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol (CBD) Extract
• Norethindrone Acetate
• Placebo

Trial Overview The study examines if CBD extract improves pain and quality of life in endometriosis patients over 12 weeks compared to a placebo. It includes onsite visits and daily assessments. Patients may also receive Norethindrone Acetate as part of their treatment regimen during the trial.

How Is the Trial Designed?

Group I: Group B - Low Dose CBD Active Control 2 Interventions

Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)

Group II: Group C - High Dose CBD Active Control 2 Interventions

Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)

Group III: Group A - Placebo Placebo Group 2 Interventions

Norethindrone acetate (5mg daily) + Placebo

Cannabidiol (CBD) Extract is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidyolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Sativex for:

• Symptomatic relief of spasticity in adult patients with multiple sclerosis
• Adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis
• Adjunctive analgesic treatment for moderate to severe pain in adult patients with advanced cancer

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

Ovarian endometriotic lesions express cannabinoid receptors CB1 and CB2, indicating that these lesions may respond to cannabinoid-based pain medications.

This study provides a foundation for future clinical research on the effectiveness of cannabis as an alternative therapy for managing pain associated with endometriosis, especially as current opioid treatments pose risks of addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of Cannabinoid Receptor Expression by Endometriotic Lesions in Women with Endometriosis as an Alternative to Opioid-Based Pain Medication. Allam, S., Paris, E., Lazcano, I., et al.[2022]

Cannabidiol (CBD) has been FDA-approved for treating severe epilepsy syndromes like Dravet and Lennox-Gastaut, demonstrating its therapeutic efficacy, but it is not without risks.

CBD can cause adverse effects such as drug-drug interactions, liver abnormalities, and gastrointestinal issues in humans, and potential developmental toxicity in animals, which clinicians should consider before recommending it for off-label use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Adverse Effects and Toxicity. Huestis, MA., Solimini, R., Pichini, S., 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]

In an in vivo model of endometriosis, daily administration of cannabidiol (CBD) significantly reduced the size and volume of endometriosis lesions, indicating its potential as a therapeutic agent.

CBD demonstrated multiple beneficial effects, including anti-inflammatory, anti-oxidant, and analgesic properties, which contributed to its effectiveness in suppressing endometriosis symptoms and improving lesion morphology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis. Genovese, T., Cordaro, M., Siracusa, R., et al.[2022]

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]

In a case-control study of 23 women with endometriosis and 19 controls, higher levels of the endocannabinoid 2-AG in peritoneal fluid were linked to noncyclic abdominal pain, suggesting a potential role of the endocannabinoid system in managing endometriosis-related pain.

The study also found that women with dysmenorrhea had elevated 2-AG and reduced AEA levels during the proliferative phase of the menstrual cycle, indicating that fluctuations in endocannabinoid levels may be associated with inflammatory pain in endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of endocannabinoids with pain in endometriosis. Andrieu, T., Chicca, A., Pellegata, D., et al.[2023]

In a survey of 213 women with endometriosis, 95.5% reported using cannabis primarily for pain relief and improved sleep, with 81% indicating significant improvement in their pain symptoms.

Over 81% of respondents reported that cannabis use led to a reduction in their regular medication usage, with 59% completely stopping medications, particularly analgesics like opioids, suggesting cannabis may serve as an effective alternative for managing endometriosis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. Armour, M., Sinclair, J., Noller, G., et al.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0165614724002153

Endometriosis: cannabidiol therapy for symptom relief Surveys in several countries (Table 1) suggested that patients find the use of cannabis-derived extracts effective in managing symptoms, including pain and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04527003

Cannabidiol and Management of Endometriosis Pain The investigators are looking to conduct a study looking at the effects of cannabidiol (CBD) in patients with endometriosis. It is believed that CBD will ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40216330/

Cannabidiol Use and Perceptions of Effectiveness in Women ... Participants who reported pain improvement were more likely to report improved sleep (P < 0.001), anxiety (P < 0.001), depression (P = 0.001), ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12472909/

Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse ... Cannabinoids can provide modest but measurable relief in chronic pain, although variability in study design continues to limit interpretation.

5. acog.org acog.org/clinical/clinical-guidance/clinical-consensus/articles/2024/07/the-use-of-cannabis-products-for-the-management-of-pain-associated-with-gynecologic-conditions

The Use of Cannabis Products for the Management of Pain ... Survey data indicate that patients with endometriosis and chronic pelvic pain may use cannabis to manage pain, especially when their pain is not effectively ...

6. trialx.com trialx.com/clinical-trials/listings/242208/cannabidiol-for-the-treatment-of-pelvic-pain-in-endometriosis-dreamland/

Cannabidiol for the Treatment of Pelvic Pain in ... The objective of this work is to conduct a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of ...