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

12 Participants Needed

Trial Summary

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.

What data supports the idea that CBD for Endometriosis Pain is an effective treatment?

The available research shows that CBD may help with endometriosis pain by reducing inflammation and pain. One study found that CBD reduced the size and severity of endometriosis lesions in a rat model, suggesting it could help manage the condition. Another study highlighted CBD's potential to reduce pain by interacting with the body's endocannabinoid system, which is involved in pain regulation. Additionally, CBD might offer a safer alternative to opioids, which are commonly used for pain but can lead to addiction. Overall, these findings suggest that CBD could be an effective option for managing endometriosis pain. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug for endometriosis pain?

Research suggests that cannabidiol (CBD) may help reduce endometriosis pain due to its anti-inflammatory and pain-relieving properties. Studies have shown that CBD can decrease lesion size and inflammation, which are common in endometriosis, and may offer an alternative to traditional pain medications. ^{1 2 3 4 5}

What safety data exists for using CBD to treat endometriosis pain?

CBD has been studied for its potential therapeutic effects in endometriosis, showing anti-inflammatory, antioxidative, and analgesic properties. It has been FDA-approved as Epidiolex for epilepsy, indicating some level of safety in clinical use. However, adverse effects and toxicity have been reported in preclinical and clinical studies. Additionally, a survey in New Zealand found that women using cannabis for endometriosis reported improved pain relief and reduced use of other medications, though adverse events were also noted. ^{1 2 3 6 7}

Is CBD safe for use in humans?

CBD is generally considered safe for use in humans, as evidenced by its FDA approval for treating certain epilepsy syndromes. However, some studies report adverse effects and toxicity, so it's important to consult with a healthcare provider before use. ^{1 2 3 6 7}

Is the drug Cannabidiol (CBD) Extract a promising treatment for endometriosis pain?

Yes, Cannabidiol (CBD) Extract is a promising treatment for endometriosis pain. Research shows that CBD has anti-inflammatory and pain-relieving effects, which can help reduce the pain and inflammation associated with endometriosis. It also has antioxidant properties that can protect cells from damage. Additionally, CBD may help reduce the need for other pain medications, like opioids, which can have serious side effects. ^{1 2 3 4 7}

How does the drug CBD differ from other treatments for endometriosis pain?

CBD is unique because it targets inflammation and oxidative stress, which are key factors in endometriosis, and it may reduce pain by interacting with the body's endocannabinoid system. Unlike traditional pain medications, CBD has anti-inflammatory, antioxidative, and antiangiogenic effects, potentially offering a more comprehensive approach to managing endometriosis symptoms. ^{1 2 3 4 7}

What is the purpose of this trial?

This trial is testing CBD to see if it can help reduce pain and improve the quality of life for patients with endometriosis. The study will compare different doses of CBD over a few months. Researchers believe CBD may work by affecting the body's natural systems that control pain and inflammation. CBD has been shown to significantly improve pain intensity in some studies, although evidence quality is low due to high risk of bias and small sample sizes.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis. [2022]

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

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

4. Egypt 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. [2022]

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

Association of endocannabinoids with pain in endometriosis. [2023]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Cannabidiol Adverse Effects and Toxicity. [2023]

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

Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. [2021]