Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Milton S. Hershey Medical Center
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 4 jurisdictions
Trial Summary
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.
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.
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.
12345What 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.
12367Is 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.
12347Eligibility 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.
+3 more
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.
+12 more
Participant Groups
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.
3Treatment groups
Active Control
Placebo Group
Group I: Group B - Low Dose CBDActive Control2 Interventions
Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)
Group II: Group C - High Dose CBDActive Control2 Interventions
Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)
Group III: Group A - PlaceboPlacebo Group2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Penn State Health Milton S. Hershey Medical CenterHershey, PA
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Who Is Running the Clinical Trial?
Milton S. Hershey Medical CenterLead Sponsor
References
Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model. [2023]Can cannabidiol (CBD) be used in the treatment of endometriosis for its anti-inflammatory, antioxidative and antiangiogenic effects?
Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis. [2022]Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on the anti-inflammatory, anti-oxidant and analgesic effects of cannabidiol (CBD) and on its potential role in endometriosis. We employed an in vivo model of endometriosis and administered CBD daily by gavage. CBD administration strongly reduced lesions diameter, volume and area. In particular, it was able to modify lesion morphology, reducing epithelial glands and stroma. CBD showed anti-oxidant effects reducing lipid peroxidation, the expression of Nox-1 and Nox-4 enzymes. CBD restored the oxidative equilibrium of the endogenous cellular defense as showed by the SOD activity and the GSH levels in the lesions. CBD also showed important antifibrotic effects as showed by the Masson trichrome staining and by downregulated expression of MMP-9, iNOS and TGF-β. CBD was able to reduce inflammation both in the harvested lesions, as showed by the increased Ikb-α and reduced COX2 cytosolic expressions and reduced NFkB nuclear localization, and in the peritoneal fluids as showed by the decreased TNF-α, PGE2 and IL-1α levels. CBD has important analgesic effects as showed by the reduced mast cells recruitment in the spinal cord and the reduced release of neuro-sensitizing and pro-inflammatory mediators. In conclusion, the collected data showed that CBD has an effective and coordinated effects in endometriosis suppression.
The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. [2020]Introduction: Patients with endometriosis often suffer from diffuse and poorly localized severe pain. The current pain management strategies include medical and hormonal therapy, as well as surgery. Medical management of pain is often insufficient and is associated with high rate of recurrence. Better pain management is therefore of urgent need. Methods: Among the various candidates, the endocannabinoid system (ECS) has recently emerged as a relevant pharmacological target for the management of endometriosis-related pain. A computerized literature search was performed to identify relevant studies combining the keywords "endometriosis," "endocannabinoid," "cannabinoid receptor," "THC," and "pain mechanisms." Conclusions: This review describes the multiple and complex pain mechanisms associated with endometriosis. Current data and theories concerning the link between the ECS and pain management for endometriosis patients are presented. Finally, we will discuss which aspects of endometriosis-associated pain can be targeted by modulation of the ECS.
Detection of Cannabinoid Receptor Expression by Endometriotic Lesions in Women with Endometriosis as an Alternative to Opioid-Based Pain Medication. [2022]Emerging information suggests a potential role of medicinal cannabis in pain medication in addition to enhancing immune functions. Endometriosis is a disease of women of reproductive age associated with infertility and reproductive failure as well as chronic pain of varying degrees depending on the stage of the disease. Currently, opioids are being preferred over nonsteroidal anti-inflammatory drugs (NSAID) due to the latter's side effects. However, as the opioids are becoming a source of addiction, additional pain medication is urgently needed. Cannabis offers an alternative therapy for treating the pain associated with endometriosis. Information on the use and effectiveness of cannabis against endometriotic pain is lacking. Moreover, expression of receptors for endocannabinoids by the ovarian endometriotic lesions is not known. The goal of this study was to examine whether cannabinoid receptors 1 and 2 (CB1 and CB2) are expressed by ovarian endometriotic lesions. Archived normal ovarian tissues, ovaries with endometriotic lesions, and normal endometrial tissues were examined for the presence of endometrial stromal cells using CD10 (a marker of endometrial stromal cells). Expression of CB1 and CB2 were determined by immunohistochemistry, immunoblotting, and gene expression studies. Intense expression for CB1 and CB2 was detected in the epithelial cells in ovarian endometriotic lesions. Compared with stroma in ovaries with endometriotic lesions, the expression of CB1 and CB2 was significantly higher in the epithelial cells in endometriotic lesions in the ovary (P < 0.0001 and P < 0.05, respectively). Immunoblotting and gene expression assays showed similar patterns for CB1 and CB2 protein and CNR1 (gene encoding CB1) and CNR2 (gene encoding CB2) gene expression. These results suggest that ovarian endometriotic lesions express CB1 and CB2 receptors, and these lesions may respond to cannabinoids as pain medication. These results will form a foundation for a clinical study with larger cohorts.
Association of endocannabinoids with pain in endometriosis. [2023]Endocannabinoid (eCB) levels fluctuate in inflammatory conditions and as such may take part in endometriosis-associated pain or even in endometriosis pathogenesis. In this case-control (23 cases and 19 controls) study, targeted lipids were measured in the serum and peritoneal fluid collected during laparoscopy. Endometriosis was confirmed histologically. Dysmenorrhea, abdominal pain, and dyspareunia were assessed using the Numeric Rating Scale for pain. Steroids, eCBs, and related lipids were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tumor necrosis factor alpha, IL-8, PAPP-A, PP14, RANTES, OPG, MIDKINE, MCP-1, VEGF, leptin, and defensins were quantified by ELISA. We found that eCB levels were significantly influenced by both noncyclic and cyclic abdominal pain. Specifically, women suffering from noncyclic abdominal pain were characterized by a higher 2-AG level in the peritoneal fluid throughout the menstrual cycle, whereas women suffering from dysmenorrhea had higher 2-AG levels and lower AEA levels during the proliferative phase alone. In addition, 2-AG positively correlated with prostaglandin E2 (PGE2), and the ratio AEA/2-AG positively correlated with defensins, suggesting a possible link between endocannabinoids system and inflammatory pain. The results of the current study indicate that the eCB system may play a role in endometriosis-associated pain, but additional studies are needed to investigate the causal relationship.
Cannabidiol Adverse Effects and Toxicity. [2023]Currently, there is a great interest in the potential medical use of cannabidiol (CBD), a non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred in the 1970s and intensified recently with many discoveries about the endocannabinoid system. Multiple preclinical and clinical studies led to FDA-approval of Epidiolex®, a purified CBD medicine formulated for oral administration for the treatment of infantile refractory epileptic syndromes, by the US Food and Drug Administration in 2018. The World Health Organization considers rescheduling cannabis and cannabinoids. CBD use around the world is expanding for diseases that lack scientific evidence of the drug's efficacy. Preclinical and clinical studies also report adverse effects (AEs) and toxicity following CBD intake.
Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. [2021]Background: Endometriosis affects around 10% of women worldwide. Many women with endometriosis struggle with finding adequate pain management, and data from other countries suggest that women use cannabis, either legal or illicit, to help manage their endometriosis symptoms. The aim of this study was to determine use of cannabis where endometriosis was self-identified as a condition that was being treated with cannabis, as well as the impact of cannabis use on the usage on other pharmaceuticals. Materials and Methods: A cross-sectional online survey of those using cannabis for health-related conditions run between May and July 2019. This article reports on the subset of this larger data set for those reporting they had a diagnosis of endometriosis and/or polycystic ovary syndrome. Data were collected on demographics, modes of cannabis administration, symptoms treated, changes in pharmaceutical usage, and adverse events. Results: Two hundred thirteen valid responses were analyzed. Mean age of respondents was 32 years and 79.8% were current cannabis users. The most common outcomes that cannabis was used for were to improve pain relief (95.5%) and to improve sleep (95.5%). Respondents reported that their symptom was "much better" for pain (81%), sleep (79%), and nausea or vomiting (61%). Over three-quarters (81.4%) indicated cannabis had reduced their normal medication usage. Over half (59%) were able to completely stop a medication, most commonly (66%) analgesics. Opioids (40%) were the most common class of analgesic stopped. Conclusions: Cannabis is reported as an effective intervention for pain and other endometriosis symptoms with potential substitution effects on opioid usage.