The Role of the Endocannabinoid System in Dysmenorrhea

What is Dysmenorrhea?

"Dys" means difficult and "rrhea" means discharge or flow. Dysmenorrhea is the medical term referring to painful periods or cramps during menstruation. It can also include other symptoms like nausea, vomiting, fatigue or diarrhoea. Dysmenorrhea impacts nearly half the population of women, and in 10% of cases, symptoms can escalate to the extent of interfering with daily activities. 

Primary Dysmenorrhea

Primary dysmenorrhea is a term often thrown around in discussions about menstrual pain, but what exactly does it entail? Primary dysmenorrhea refers to recurring menstrual pains that occur with each menstrual cycle, unrelated to any other underlying medical condition. Typically, the pain initiates one or two days before the onset of menstruation or when bleeding commences. The discomfort, ranging from mild to severe, is commonly felt in the lower abdomen, back, or thighs. This pain typically diminishes within two or three days. Primary dysmenorrhea stands out as the more prevalent form of dysmenorrhea and simply put, it is the experience of menstrual pain without any discernible underlying physiological changes in the reproductive organs.

Secondary Dysmenorrhea

On the other hand, secondary dysmenorrhea is a condition where menstrual pain is intrinsically linked to an identifiable disease or disorder of structural changes inside or outside the uterus, such as endometriosis, fibroids, or polyps. Typically, the discomfort associated with secondary dysmenorrhea initiates earlier in the menstrual cycle and persists for a more extended period compared to ordinary menstrual cramps. For instance, one might encounter cramping days before the onset of menses, and the pain may endure until the cessation of bleeding. It's worth noting that secondary dysmenorrhea is less prevalent.

Primary Dysmenorrhea Symptoms

Let’s look into the range of symptoms that arise from primary dysmenorrhea. Hallmark features include crampy, colicky spasms of pain concentrated in the suprapubic area. These discomforting sensations typically manifest within a window of 8 to 72 hours from the onset of menstruation, reaching their peak during the initial days as menstrual flow intensifies. Beyond the localised pelvic pain, individuals with primary dysmenorrhea often contend with accompanying backaches and thigh pain, adding layers to the overall discomfort. The ordeal extends further with headaches. Moreover, the spectrum of symptoms broadens to include gastrointestinal disturbances such as diarrhoea, nausea, and vomiting, amplifying the impact severe period cramps can have on a woman's well-being during her menstrual cycle. 

Physiology of Dysmenorrhea

The largest contributing physiological factor in primary dysmenorrhea is increased amounts of prostaglandins present in the menstrual fluid and reduced levels of progesterone. Prostaglandins are hormone-like substances produced in the body that play a key role in causing uterine contractions and inflammation, leading to the pain and discomfort experienced during dysmenorrhea. On the other hand, progesterone is a hormone produced in the ovaries that helps regulate the menstrual cycle and reduce the intensity of uterine contractions, providing relief from the symptoms of primary dysmenorrhea. 

After ovulation when progesterone levels dwindle in the absence of pregnancy, during the second half of one’s menstrual cycle, a series of changes occur as a consequence that make the outer layers of cells in the uterus unstable. A decrease in progesterone destabilises cell membranes in endometrial tissue, leading to the hydrolysis of cell membrane phospholipids, primarily omega-6, in turn resulting in the formation of arachidonic acid. Arachidonic acid is further turned into prostaglandins, namely PGE2 and PGF2a. These excess prostaglandins play a role when the lining of the uterus breaks down during menstruation, releasing a surge that stimulates strong muscle contractions. These contractions, in turn, reduce blood flow to the uterus, leading to low oxygen levels, and causing the painful cramps associated with primary dysmenorrhea.

The Endocannabinoid System’s Role in Dysmenorrhea

The Endocannabinoid System (ECS) has emerged as a promising target for addressing menstrual pain. The ECS regulates various physiological processes including pain modulation, inflammation and homeostasis. Recent studies indicate that the ECS also plays a crucial role in various aspects of the female reproductive system and in hormone release. 

Research illuminates elevated systemic levels of endocannabinoids, such as anandamide and 2-arachidonoyl glycerol (2-AG), in individuals with endometriosis, accompanied by reduced local expression of cannabinoid 1 receptors (CB1). The ECS's role doesn't end there; research suggests that it might play a role in causing dysmenorrhea in people with adenomyosis. Adenomyosis refers to a condition where the tissue lining the uterus grows into the muscular wall of the uterus.

Endocannabinoids help reduce pain by interacting with cells in the nervous system. These compounds, like anandamide and 2-arachidonoyl glycerol (2-AG), are produced in the body when the body senses pain signals. Endocannabinoids act like messengers, attaching to cannabinoid receptors, particularly CB1, on certain nerve cells. This process stops the release of pain signals, helping to ease pain.

The analgesic effect of the endocannabinoid system hinges on the activation of cannabinoid receptors, with CB1 and CB2 playing distinct roles in alleviating pain. CB1 activation helps control the release of neurotransmitters, especially in areas of the body related to pain. This limits the transmission of pain signals and makes it feel like the pain is less. On the flip side, activating CB2 is important for reducing inflammation, a heightened sensitivity to pain, and neuropathic pain. 

Research demonstrates that phytocannabinoids in cannabis activate CB1 and CB2 receptors similar to the body's endocannabinoids. CBD helps alleviate inflammation, pain, and anxiety, while THC helps alleviate pain, muscle spasms, and nausea.

Conclusion

The Endocannabinoid System (ECS) stands out as a promising avenue for addressing dysmenorrhea, with cannabis medicine offering a potential means to manage this often debilitating condition. By engaging cannabinoid receptors, particularly CB1 and CB2, cannabinoids may provide targeted relief by modulating pain pathways and reducing inflammation associated with menstrual discomfort or dysmenorrhea. An expanding understanding of ECS involvement in the female reproductive system, including in the management of conditions like endometriosis and adenomyosis, underscores its significance as a therapeutic target. Harnessing the potential of cannabis medicine opens up new possibilities for innovative treatments, offering renewed optimism for individuals grappling with the challenges of dysmenorrhea via a holistic pathway to improved female reproductive health.

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