Endometriosis and the Endocannabinoid System

Understanding Endometriosis 

Endometriosis is a medical condition in which tissue similar to the uterine lining grows outside the uterus. Referred to as endometrial implants, this tissue is often found on various reproductive organs, such as the ovaries, fallopian tubes, the outer surface of the uterus, as well as within the pelvic and abdominal regions. Predominantly affecting women of reproductive age, endometriosis is a prevalent gynaecological disorder.

The presence of endometrial implants can lead to the formation of adhesions, scar tissue, and cysts, causing pain or discomfort, which can potentially impact fertility. Symptoms of endometriosis include pelvic pain, painful menstruation, discomfort during sexual intercourse, painful urination, painful bowel movements and challenges related to fertility. Unfortunately, the anguish doesn’t stop there. The pain can be so severe that the anxiety and fear of the next menstrual cycle often lead to depression. In many cases, personal and professional relationships take a hit when women need to stay at home to deal with the debilitating symptoms that come with endometriosis. 

Pathophysiology of Endometriosis 

Endometriosis manifests through various pathophysiological mechanisms. One prevailing theory, widely accepted in the medical community, is retrograde menstruation. Retrograde menstruation occurs during the menstrual cycle when some of the menstrual blood, carrying endometrial cells, flows backwards through the fallopian tubes into the pelvic cavity. These displaced endometrial cells find fertile ground on the surfaces of pelvic organs and tissues, where they can attach and grow, forming endometrial implants.

Another possible cause is immune system dysfunction. Typically, the immune system functions to recognize and eliminate misplaced cells or abnormal growths. However, in women with endometriosis, there may be abnormalities in immune response, allowing the survival and unchecked growth of endometrial cells outside the uterus. Genetic factors also play a role, with evidence suggesting a genetic predisposition to endometriosis. Women with a family history of the condition may be at a higher risk.

Hormonal influences, particularly related to estrogen, contribute significantly to the pathophysiology of endometriosis. Estrogen, a hormone regulating the menstrual cycle, can stimulate the abnormal growth of endometrial tissue. In women with endometriosis, there is often an abnormal response to oestrogen, leading to excessive growth of endometrial cells outside the uterus. This hormonal imbalance is further characterised by altered progesterone and oestrogen hormone efficiency, resulting in progesterone resistance. Progesterone's primary role is to prepare the lining of the uterus for the potential implantation and growth of a fertilised egg. 

Additionally, inflammation and angiogenesis are associated with endometriosis. In the affected areas, an inflammatory environment promotes the development of new blood vessels (angiogenesis), contributing to the formation of lesions and exacerbating symptoms of pain and discomfort. 

The Role of the Endocannabinoid System on Endometriosis

The Endocannabinoid System (ECS) regulates numerous physiological processes, including influencing inflammation and nociception. Nociception is the body's way of sensing or feeling pain. Recent studies have shown the ECS's involvement in crucial aspects of the female reproductive system. The ECS interacts with the hypothalamic-pituitary-ovarian (HPO) axis, managing and controlling key reproductive processes like helping eggs mature, pain modulation, the development of the uterus lining, implantation, the development of the embryo during pregnancy and more. The HPO serves as a communication pathway that extends from the hypothalamus in the brain to the ovaries. It regulates the menstrual cycle and various reproductive functions in females. The ECS plays a crucial role in safeguarding women against the complications of endometriosis by regulating inflammation, the formation of new blood vessels, cell death and cell growth in the uterine lining, and scarring.

The ECS plays a role throughout female reproductive tissues. In the context of endometriosis, the CB1 receptor, a key cannabinoid receptor, may be impaired during menstruation in individuals with endometriosis. When CB1 is activated, it modulates analgesic activity, reducing the perception of pain; conversely, when CB1 is blocked, pain levels increase. The increased presence of CB1 receptors in nerve fibres and cells within affected endometrial tissue suggests a crucial role of the ECS in managing pain associated with endometriosis.

Another aspect worth considering is the observed endocannabinoid deficiency in endometriosis patients. Studies reveal a scarcity of endocannabinoids, compounds the body produces which activate the ECS, in individuals grappling with this condition. Women experiencing dysmenorrhea and dyspareunia, conditions marked by painful periods and painful intercourse respectively, exhibit elevated plasma levels of endocannabinoids. Additionally, there is a decrease in the expression of CB1 receptors in endometrial stromal cells, cells in the lining of the uterus that play a role in supporting and maintaining the tissue structure.

The promising insight derived from these findings suggests that phytocannabinoids, compounds found in the cannabis plant, could offer relief from the pain associated with endometriosis. By interacting with the ECS, phytocannabinoids may prove a potential avenue for managing and alleviating the challenges faced by women with endometriosis. 

Limitations of Current Treatments

The current medications for endometriosis, while offering relief, come with their share of problems. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as Ibuprofen, effectively address period cramps by inhibiting the COX-2 enzyme responsible for pain and inflammation. However, they also inhibit the COX-1 enzyme, crucial for stomach and intestinal health, leading to potential gastrointestinal (GI) issues, including ulcers. Meftal spas, a popular NSAID, contains mefenamic acid, which can trigger a severe allergic reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome.

Hormonal therapies, like birth control pills, can alleviate menstrual pain by preventing ovulation and reducing prostaglandin production (prostaglandins are natural substances in the body that play a role in inflammation and pain regulation). However, they come with side effects such as headaches, nausea, thrombosis (blood clotting in vessels), bloating, and fatigue. Additionally, they result in a thinner uterine lining, causing scanty flow.

Progestogens, which counteract estrogen and inhibit endometrial growth, have limitations due to virilizing side effects associated with certain steroids like danazol and gestrinone. Virilizing side effects refer to the development of male characteristics in females, such as deepening of the voice or increased body hair. While steroids like dienogest and norethisterone acetate show tentative evidence for pain relief, limited studies hinder a comprehensive understanding of their effectiveness.

Gonadotropin-Releasing Hormone (GnRH) modulators, including agonists and antagonists like leuprorelin and elagolix, work by reducing oestrogen levels. Reviews suggest their effectiveness in pain relief, yet concerns about decreased bone density arise. Surgical intervention, although an option, poses challenges with a high recurrence rate.

Anti-neuropathic drugs like amitriptyline, pregabalin, and gabapentin show limited evidence for their effectiveness in endometriosis. Previous trials indicate gabapentin's efficacy in Chronic Pelvic Pain, but its impact on endometriosis-associated pain, which is not typically neuropathic, remains uncertain. Overall, these limitations highlight the need for continued research and exploration of alternative approaches to enhance endometriosis management.

How Cannabinoids Help

The potential therapeutic benefits of cannabinoids, specifically CBD and THC, in managing endometriosis are gaining attention due to their diverse properties. CBD, known for its anti-inflammatory and anxiolytic (anxiety-reducing) qualities, aligns with a fundamental feature of endometriosis – inflammation. THC, another key cannabinoid, exhibits analgesic (pain-relieving), antispasmodic (spasm-inhibiting), and anti-emetic (anti-vomiting) properties. By targeting various pathways, CBD and THC offer a promising avenue for easing the discomfort associated with endometriosis.

A crucial aspect of the way cannabinoids act involves the modulation of Transient Receptor Potential Vanilloid (TRPV) channels. These channels play a role in transmitting signals related to neuropathic pain. By influencing these channels, cannabinoids have the potential to mitigate the signals contributing to pain in endometriosis. Additionally, CBD's interaction with serotonin receptors (5HT1A) posits further therapeutic potential. This modulation not only enables anxiolytic and antidepressant effects but also aids in pain relief through antinociceptive effects, reducing the perception of pain.

Types of Cannabinoid Medication

Cannabinoid medication comes in various forms tailored to different preferences and needs. Oral formulations, such as oils, capsules or tinctures, offer a straightforward way to incorporate cannabinoids into daily routines. Try Shunyata Calm for an effective oral option. 

Topical formulations, like cannabis-based balms or roll-ons, can be particularly useful for targeted relief. When applied to the lower abdomen during cramping, topical products promote muscle relaxation, providing localised support where it's needed most. We have formulated a topical roll-on called Shunyata Cramp Relief so you can harness the healing potential of cannabinoids on the go. 

Transdermal patches represent an innovative option for sustained cannabinoid delivery and are most effective when worn for 24 hours. These patches are activated by body heat, releasing a controlled amount of CBD through the skin into the bloodstream. Transdermal delivery creates a concentration gradient, ensuring the patch delivers a higher cannabinoid concentration than the skin and penetrates deep below the surface, offering lasting relief.

For a more direct approach, cannabinoid-based vaginal suppositories closely target the female reproductive tract's abundance of cannabinoid receptors. Cannabinoids dissolve quickly and are efficiently absorbed by blood vessels, providing prompt and targeted relief by interacting directly with cannabinoid receptors in the reproductive tract. By bypassing the digestive tract, suppositories and patches prevent gastric inflammation and offer a prolonged release of cannabinoids, ensuring a steady and sustained therapeutic effect.

Understanding endometriosis, from its pathophysiology to the potential therapeutic role of cannabinoids, opens a promising avenue for more targeted and effective interventions. The limitations of current treatments emphasise the need for alternative approaches, and cannabinoid-based therapies emerge as compelling options. Phytocannabinoids provide a potential pathway to alleviate the challenges posed by endometriosis. As research progresses, the intersection of cannabinoids and endometriosis holds the promise of not only managing pain but also improving the overall well-being of those affected by this painful condition.