New research suggests that cannabis shows promise in relieving endometriosis pain

From a recent study published in the Journal of Clinical Medicineresearchers examined the available literature on cannabis as a self-management strategy in the treatment of pain due to endometriosis. They further investigated the mechanisms by which cannabis interacts with the endocannabinoid system (ECS) and the interactions of gut microbiota and ECS in the treatment of the condition. Their findings show that cannabis-derived endocannabinoids have a protective effect on the intestines, reducing intestinal inflammation and improving its permeability. This in turn suppresses bloating, the most common symptom of endometriosis. Cannabinoids also inherently suppress pain receptors and serve as a natural painkiller. These results highlight the gut microbiota and ECS as future clinical trial targets in the fight against endometriosis.

Study: Cannabis and endometriosis: the role of the gut microbiota and the endocannabinoid system. Image credits: Rapeepat Pornsipak / Shutterstock

Endometriosis and the benefits of cannabis

Endometriosis is a disease of sexually mature women (between the first menstrual period and up to menopause) characterized by endometrial tissue-like tissue growing beyond the boundaries of the uterus. It is a common condition, estimated to affect 10% of all women, with symptoms including severe pelvic pain and outcomes including difficulty conceiving.

In addition to the immediate results, 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 at between US$1,459 and US$20,239 per woman, highlighting the socio-economic burden of the disease alone and not its treatment.

Research has shown that progesterone is a common feature of endometriosis patients, suggesting that hormonal imbalances then cause inflammation due to the local infiltration of immune cells. These cells establish new cells that have been found to activate pathways related to invasion, proliferation, metastasis and angiogenesis. Because most hormone resistances arise due to imbalances in the gut microbial system, resulting in changes in the expression levels of estrogen-metabolizing enzymes, recent studies have focused on the associations between the gut microbiome and the disease.

Current treatment for endometriosis involves a combination of surgery and hormone treatment. Antineuropathic agents, including gabapentin, pregabalin, and amitriptyline, are used to reduce pain and allow normal daily functioning. Unfortunately, these interventions are medically suboptimal given the reduced access of women in developing and underdeveloped countries to surgery and the greatly reduced efficacy of antineuropathic agents in controlling pain in endometriosis patients. Research has shown that endometriosis patients are four times more likely to overuse painkillers, causing dependence and abuse.

Metabolites from the Hemp gender received extensive attention in the 1990s, resulting in the discovery of the endocannabinoid system (ECS), a complex signaling system consisting of G protein-coupled cannabinoid receptors, ion channel transient receptor potential vanilloid 1, and a cohort of enzymes responsible for endocannabinoid synthesis and catabolism. Cannabidiol (CBD) and tetrahydrocannabinol (THC), the two main active ingredients derived from cannabis consumption, have intrinsic pain-suppressing properties and have been used in other medical research.

Given its relative cheapness and ease of access, cannabis consumption has become a popular self-medication for endometriosis pain, despite ample research into the pathways and mechanisms through which it can affect the ECG, positively or negatively altering endometriosis outcomes.

Findings of the study

The current study is a descriptive review of current scientific knowledge on endometriosis, focusing on the impact of endocannabinoids on disease outcomes and the associations between ECS, gut microbiota and endometriosis. Although no publication screening methodologies were reported, the citation list suggests that more than 140 scientific articles were reviewed during the synthesis of this work.

Research has shown that the ECS is mainly involved in pain modulation and inflammation suppression. Endocannabinoids or exogenous cannabinoids have been shown to activate the CB₁ and C.B₂ receptors, critical components of the G protein-coupled system, suppressing nociceptive processing and inducing analgesia.

“In a prospective randomized, placebo-controlled trial, smoked cannabis (3.56% delta-9-tetrahydrocannabinol (THC) – participants smoked three cigarettes per day for a four-day period) reduced the daily pain experienced by adults with HIV-associated sensory neuropathy .”

ECS is further hypothesized to play a central role in the pathology of endometriosis, with some researchers calling the disease an “endocannabinoid deficiency.” Strong correlations have been observed between circulating plasma endocannabinoid levels and the severity of endometriosis, with lower levels of endocannabinoids being associated with increased pain. However, other studies have suggested that endometriosis and the ECS may have complex associations with the onset of the former, initiating a feedback loop in the latter. This indicates that the role of ECS in endometriosis may extend beyond inflammation and pain suppression and warrants further investigation into the mechanisms underlining these interactions.

Can external cannabis consumption help?

The role of cannabis derivatives in endometriosis, especially regarding their pain-suppressing properties, has led to investigations into cannabis use as a potential natural alternative to current anti-neuropathic therapies. An ongoing clinical trial is testing the efficacy of CBD isolate oil and vaporized THC in pain modulation in women admitted to hospitals and clinics reporting severe endometrial pain. In vivo mouse models have paved the way for these types of studies, given the positive effects of CBD against not only endometrial pain, but also the observed growth-inhibitory effects on the surface of endometrial implants.

These promising findings highlight the potential therapeutic benefits of CBD and THC for endometriosis-associated pain, justifying the need for human studies.

What about the gut microbiota?

The intestines are part of the ECS, and enzymes secreted by the intestines have been shown to significantly alter ECS hormones, potentially having a regulatory effect on endometriosis. However, research in this area is still in its infancy. So far, the findings suggest a bidirectional relationship between the gut microbiota, the ECS and endometriosis, influencing both the risk and severity of the disease.

“Endocannabinoids and exogenous cannabinoids have opposite effects on intestinal permeability. For example, in research on decreased permeability due to inflammation, it was shown that 2-AG and AEA increased permeability, while THC and CBD decreased permeability.”

Although research on the direct effects of cannabinoids on endometriosis remains scarce, preclinical models have demonstrated the positive impact of the former on the comorbidities of the latter, especially irritable bowel disorder (IBD). Interestingly, the gut microbiota has been implicated in these associations Lactobacillus acidophilus intestinal inoculations in mice were shown to result in endogenous upregulation of the CB₂ expression in intestinal cells, resulting in analgesic effects and reduced visceral pain in the mice. Additionally, research in athletes has linked cannabinoids to pain suppression, anti-inflammatory effects, and improved intestinal absorption.

“Studies have also examined the relationship between the ECS and microbial metabolites in the gut. For example, endocannabinoids have been found to mediate the anti-inflammatory effects of SCFAs. This association was observed in an exercise intervention where an increase in SCFAs (including butyrate) and SCFA-producing bacteria (such as Bifidobacterium) was correlated with a decrease in pro-inflammatory cytokines TNF-α and IL-6.”

Conclusions

The current study compiles currently available information on research on cannabinoids, the ECS, the gut microbiota and their collective (potentially bidirectional) association with endometriosis. The findings are largely positive, with research confirming the beneficial effects of cannabinoids, both endogenous and exogenous, on endometriosis outcomes and comorbidities of the disease. However, further research is needed to assess the safety of THC and CBD administrations in the treatment of endometriosis and the mechanisms underlying these preclinically observed benefits. Fortunately, at least one clinical trial is already underway to achieve this.