In a recently published study, Dr Journal of Clinical Medicine, researchers reviewed the available literature on cannabis as a self-management strategy in the treatment of pain caused by endometriosis. They also investigated the mechanisms by which cannabis treats these conditions with the endocannabinoid system (ECS) and interactions between the gut microbiota and the ECS. Their findings reveal that cannabis-derived endocannabinoids have a protective effect on the gut, reducing intestinal inflammation and improving its permeability. This, in turn, suppresses swelling, the most common symptom of endometriosis. Cannabinoids also naturally suppress pain receptors and act as a natural pain reliever. These findings highlight the gut microbiota and ECS as future clinical trial targets in the fight against endometriosis.
Study: Cannabis and endometriosis: the role of gut microbiota and the endocannabinoid system. Image credit: Rapeepat Pornsipak / Shutterstock
Endometriosis and the benefits of cannabis
Endometriosis is a disease in sexually mature women (between the first period and up to menopause) in which tissue like the lining of the uterus grows outside the boundaries of the uterus. It is a common condition, estimated to affect 10% of all women, resulting in symptoms including severe pelvic pain and difficulty conceiving.
In addition to its direct consequences, endometriosis-related chronic pelvic pain (CPP) has been associated with several comorbidities, including irritable bowel syndrome (IBS), psoriasis, rheumatoid arthritis, mental health problems (depression and anxiety), and chronic fatigue syndrome. The annual economic loss due to the disease is estimated between USD 1,459 and USD 20,239 per woman, which only highlights the socioeconomic burden of the disease, not accounting for its treatment.
Research has identified progesterone as a common feature of endometriosis patients, suggesting a hormonal imbalance that subsequently triggers inflammation due to local infiltration of immune cells. These cells establish new cells, which have been found to activate pathways associated with invasion, proliferation, metastasis, and angiogenesis. Because most hormone resistance arises from an imbalance in the gut microbial system, resulting in changes in the expression levels of estrogen-metabolizing enzymes, recent studies have focused on the relationship between the gut microbiome and disease.
Current treatment for endometriosis involves a combination of surgical intervention and hormonal treatment. Anti-neuropathics, including gabapentin, pregabalin, and amitriptyline, are used to reduce pain and allow normal daily functioning. Unfortunately, these interventions are clinically suboptimal due to reduced women’s access to surgery in developing and underdeveloped countries and the much lower efficacy of anti-neuropathics in pain relief in patients with endometriosis. Studies have shown that patients with endometriosis are four times more likely to overuse painkillers, leading to the development of dependence and abuse conditions.
Metabolism from marijuana The genus gained widespread attention in the 1990s, leading to the discovery of the endocannabinoid system (ECS), a complex signaling system consisting of G-protein-coupled cannabinoid receptors, the ion channel transient potential receptor vanilloid 1, and a complex of enzymes responsible for endocannabinoids. synthesis and catabolism. Cannabidiol (CBD) and tetrahydrocannabinol (THC), the two main active ingredients derived from cannabis consumption, have inherent pain-relieving properties and have been used in other medical studies.
Due to its relative cheapness and availability, cannabis consumption has become a popular self-medication against endometriosis pain despite considerable research on the pathways and mechanisms through which it can affect the ECG, thereby positively- or negatively altering endometriosis outcomes.
The current study is a descriptive review of current scientific knowledge regarding endometriosis, focusing on the effects of endocannabinoids on disease outcomes and the relationships between ECS, gut microbiota, and endometriosis. Although the publication screening method was not reported, the list of citations suggests that more than 140 scientific papers were used during the synthesis of this work.
Research has identified that the ECS is primarily involved in pain modulation and inflammation suppression. Endocannabinoids or exogenous cannabinoids have been shown to activate CB1 and CB2 receptors, important components of the G-protein-coupled system, thereby suppressing nociceptive processing and inducing analgesia.
“In a prospective randomized placebo-controlled trial, smoked marijuana (3.56% delta-9-tetrahydrocannabinol (THC)-competitors smoked three cigarettes per day over a 4-day period) reduced daily pain experienced by adults susceptible to HIV-related neuropathy. “
ECS is further hypothesized to play a central role in endometriosis pathology, with some researchers referring to the disease as “endocannabinoid deficiency”. Strong correlations have been observed between circulating endocannabinoid levels in plasma and the severity of endometriosis, with lower levels of endocannabinoids associated with increased pain. However, other studies have suggested that endometriosis and ECS may have a complex relationship with the former initiating a feedback loop. This indicates that the role of ECS in endometriosis may extend beyond inflammation- and pain-suppression, and allows further research into the mechanisms underlining these interactions.
Can external cannabis use help?
The role of cannabis derivatives in endometriosis, especially with regard to their pain suppressing ability, has encouraged the examination of the use of cannabis as a potential natural alternative to current anti-neuropathic therapies. An ongoing clinical trial is examining the efficacy of CBD isolate oil and vaporized THC in pain modulation for women admitted to hospitals and clinics reporting severe endometrial pain. Murine in vivo models have paved the way for such trials, not only the positive effects of CBD against endometrial pain but also their observed growth inhibitory effects on the surface area of endometriotic implants.
These promising results highlight the potential therapeutic benefits of CBD and THC for endometriosis-related pain, warranting the need for human studies.
What about gut microbiota?
The gut forms a part of the ECS, and enzymes secreted by the gut have been shown to significantly alter ECS hormones, thereby having a regulatory effect on endometriosis. However, research in this area remains in its infancy. Thus far, findings suggest a bidirectional relationship between gut microbiota, ECS, and endometriosis, thereby influencing both disease risk and severity.
“Endocannabinoids and exogenous cannabinoids have opposite effects on intestinal permeability. For example, when examining the decrease in permeability due to inflammation, it was shown that 2-AG and AEA increased permeability, while THC and CBD decreased permeability.”
Although research examining the direct effects of cannabinoids on endometriosis remains scarce, preclinical models have shown positive effects of the former on comorbidities of the latter, particularly irritable bowel disorder (IBD). Importantly, the gut microbiota is involved in these associations Lactobacillus acidophilus Intestinal inoculation of mice results in endogenous upregulation of CB2 expression in intestinal cells, resulting in reduced analgesic effects and visceral pain in mice. Furthermore, studies on athletes have linked cannabinoids to pain relief, anti-inflammatory and improved intestinal absorption.
“Studies have also examined the relationship between ECS and gut microbial metabolism. For example, endocannabinoids have been found to mediate the anti-inflammatory effects of SCFAs. This association was observed in an exercise intervention that increased SCFAs (including butyrate) and SCFA-producing bacteria (such as Bifidobacterium). Proinflammatory cytokines were associated with decreased TNF-α and IL-6.”
The current study combines currently available data on studies of cannabinoids, ECS, gut microbiota and their combined (potentially bidirectional) association with endometriosis. Results are initially positive, with studies confirming beneficial effects of both endogenous and exogenous cannabinoids on endometriosis outcomes and disease comorbidities. However, further research is needed to evaluate the safety of THC and CBD administration in the treatment of endometriosis and the mechanisms underlying these preclinically observed benefits. Fortunately, at least one clinical trial aimed at achieving this is already underway.
- Faruqi, T., Bhuan, D.J., Lowe, M., Sinclair, J., Leonardi, M., and Armor, M. (2022). Cannabis and endometriosis: the role of gut microbiota and the endocannabinoid system. Journal of Clinical Medicine, 12(22), 7071, DOI – https://doi.org/10.3390/jcm12227071, https://www.mdpi.com/2077-0383/12/22/7071