Category Archives: Endometriosis

Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis

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“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.”

https://pubmed.ncbi.nlm.nih.gov/35628240/

https://www.mdpi.com/1422-0067/23/10/5427


Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms

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Ostovari, Yu research published in PLOS ONE - Healthcare Ergonomics Analytics Lab - Purdue University“Background: The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain.

Results: A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion.

Conclusions: Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.”

“Recent studies have suggested that a dysfunction in the endocannabinoid system (ECS) is present in endometriosis patients, and that aspects of endometriosis-associated pain may be targeted by modulating the ECS .Previous research on the use of illicit cannabis in women with endometriosis has shown promise in the treatment of endometriosis pain and co-morbid symptoms such as poor sleep, gastrointestinal upset and mood disorders.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258940

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

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ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain.

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“Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment.

Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development.

Here we evaluate the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis.

In this model, female mice develop mechanical hypersensitivity in the caudal abdomen, mild anxiety-like behavior and substantial memory deficits associated with the presence of extrauterine endometrial cysts.

Interestingly, daily treatments with THC (2 mg/kg) alleviate mechanical hypersensitivity and pain unpleasantness, modify uterine innervation and restore cognitive function without altering the anxiogenic phenotype. Strikingly, THC also inhibits the development of endometrial cysts.

These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.”

https://www.ncbi.nlm.nih.gov/pubmed/31931958

https://elifesciences.org/articles/50356

The role of the endocannabinoid system in aetiopathogenesis of endometriosis: A potential therapeutic target.

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European Journal of Obstetrics and Gynecology Home“Endometriosis affects a large proportion of women during their reproductive years and is associated with pain and infertility, also affecting psychological wellbeing and quality of life. The pathogenesis of the disease remains unclear, although it is believed to be multifactorial.

The endocannabinoid system (ECS) consists of a number of ligands, receptors and enzymes, and has gained interests in endometriosis research. This review aims to summarise all available evidence reporting the roles of the ECS in endometriosis.

A literature search of the PubMed, EMBASE, and Web of Science electronic medical databases was performed. Original and review articles published in peer-reviewed journals were included. No publication date or publication status restrictions were imposed.

Significant differences in the concentrations and expressions of the components of the ECS were reported in the eutopic and ectopic endometrium, and the systemic circulation of women with endometriosis compared to controls. Endometriosis appears to be associated with downregulation of CB1 receptors and upregulation of TRPV1 receptors.

The role of CB1 and progesterone in anti-inflammatory action and the role of TRPV1 in inflammation and pain are of particular interests. Furthermore, the ECS has been reported to be involved in processes relevant to endometriosis, including cell migration, cell proliferation, apoptosis, inflammation, and interacts with sex steroid hormones.

The ECS may play a role in disease establishment, progression, and pain in endometriosis. However, reports are based on studies of limited size and there are inconsistencies among the definition of their control groups. There are also conflicting reports regarding precise involvement of the ECS in endometriosis. Future research with larger numbers, strict inclusion and exclusion criteria and detailed clinical information is imperative.”

https://www.ncbi.nlm.nih.gov/pubmed/31785471

https://www.ejog.org/article/S0301-2115(19)30526-3/fulltext

Cannabis Use, a Self-Management Strategy Among Australian Women With Endometriosis: Results From a National Online Survey.

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Journal of Obstetrics and Gynaecology Canada Home“This study sought to determine the prevalence, tolerability, and self-reported effectiveness of cannabis in women with endometriosis.

A total of 484 responses were included for analysis, with 76% of the women reporting the use of general self-management strategies within the last 6 months. Of those using self-management, 13% reported using cannabis for symptom management. Self-reported effectiveness in pain reduction was high (7.6 of 10), with 56% also able to reduce pharmaceutical medications by at least half. Women reported the greatest improvements in sleep and in nausea and vomiting. Adverse effects were infrequent (10%) and minor.

Women report good efficacy of cannabis in reducing pain and other symptoms, with few adverse effects reported.”

https://www.ncbi.nlm.nih.gov/pubmed/31722852

https://www.jogc.com/article/S1701-2163(19)30808-4/fulltext

Expression of Cannabinoid Receptors in Myometrium and its Correlation With Dysmenorrhea in Adenomyosis.

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“The myometrium, especially the junctional zone (JZ), is now well documented to have a role in the pathogenesis of adenomyosis. Cannabinoid receptors have been shown to participate in the establishment of endometriosis and its pain perception. However, its relation to adenomyosis has not been identified yet. The aim of this study was to investigate the expression of cannabinoid receptor type I (CB1) and type II (CB2) in myometrium of uteri with and without adenomyosis and determine the correlation between their levels and clinical parameters of adenomyosis. We collected tissue samples of JZ and the outer myometrium from 45 premenopausal women with adenomyosis and 34 women without adenomyosis. CB1 and CB2 messenger RNA (mRNA) and protein expression levels were evaluated by the use of Western blotting and real-time quantitative polymerase chain reaction from all samples. Clinical information on the severity of dysmenorrhea and other data were collected. We found both CB1 and CB2 mRNA and protein levels in women with adenomyosis were significantly higher than those of controls, and CB1 expression levels in JZ were positively correlated with the severity of dysmenorrhea. These data suggest that cannabinoid receptor CB1 may be involved in the pathogenesis of dysmenorrhea in adenomyosis and may be a potential therapeutic target.”

https://www.ncbi.nlm.nih.gov/pubmed/30832539

https://journals.sagepub.com/doi/abs/10.1177/1933719119833483?journalCode=rsxb

Decreased Expression of Cannabinoid Receptors in the Eutopic and Ectopic Endometrium of Patients with Adenomyosis.

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“Adenomyosis is a common gynecologic benign disease that may have a life-long negative impact on women.

Previous studies have indicated that the endocannabinoid system may participate in the progress of endometriosis.

Our research aims to analyze the expression patterns of the typical cannabinoid receptors (CB1 and CB2), the main constituents of the endocannabinoid system, in endometrial samples derived from patients diagnosed as adenomyosis or not.

RESULTS:

In either the proliferative or the secretory phase, CB1 and CB2 protein and mRNA levels were both significantly lower in the eutopic and ectopic endometrium of adenomyosis when compared with normal endometrium. For women with adenomyosis, CB1 and CB2 protein and mRNA levels were much lower in the ectopic endometrium than the eutopic in both phases of the cycle. Both CB1 and CB2 protein and mRNA levels were increased during the secretory phase in normal endometrium, while CB1 lost its cyclic variation in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis.

CONCLUSION:

The decreased expression of CB1 and CB2 in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis suggests that cannabinoid receptors may participate in the pathogenesis of adenomyosis.”

https://www.ncbi.nlm.nih.gov/pubmed/30800671

“In conclusion, we found a significant decrease in the cannabinoid receptors CB1 and CB2 in the eutopic and ectopic endometrium of patients with adenomyosis, regardless of the menstrual phase, suggesting that CB1 and CB2 participate in the pathogenesis of this condition.”

https://www.hindawi.com/journals/bmri/2019/5468954/

Self-management strategies amongst Australian women with endometriosis: a national online survey.

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“Endometriosis has a significant negative impact on the lives of women, and current medical treatments often do not give sufficient pain relief or have intolerable side effects for many women. The majority of women with primary dysmenorrhea use self-management strategies (including self-care techniques or lifestyle choices) to help manage period related symptoms, but little is known about self-management in women with endometriosis.

The aim of this survey was to determine the prevalence of use, safety, and self-rated effectiveness of common forms of self-management.

Cannabis, heat, hemp/CBD oil, and dietary changes were the most highly rated in terms of self-reported effectiveness in pain reduction. Physical interventions such as yoga/Pilates, stretching, and exercise were rated as being less effective.

Self-management was very commonly used by women with endometriosis and form an important part of self-management.

Women using cannabis reported the highest self-rated effectiveness.”

https://www.ncbi.nlm.nih.gov/pubmed/30646891

https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-019-2431-x

The Clinical Significance of Endocannabinoids in Endometriosis Pain Management.

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“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.”
https://www.ncbi.nlm.nih.gov/pubmed/28861506
http://online.liebertpub.com/doi/10.1089/can.2016.0035
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