Endometriosis is a painful condition where the lining of the uterus grows on other parts of the organ such as the fallopian tubes. The new study, published in eLife, shows initial results from treating endometriosis in mice with cannabinoids – suggesting they can alleviate symptoms of the disease.

The researchers say this new finding will pave the way for further clinical research.

The findings have led to the start of a clinical trial in collaboration with the Gynecology Service of the Hospital Clinic of Barcelona, Spain. The trial will evaluate the possible benefits of the naturally occurring cannabinoid ∆9-tetrahydrocannabinol (THC; the main psychoactive constituent of the cannabis plant) in women with endometriosis.

Endometriosis cannabis treatment

Endometriosis is a common, chronic and painful disease caused when the lining of the womb – the endometrium – grows outside of the womb cavity. These growths affect reproductive organs and can cause pain, infertility, anxiety, depression and result in a considerable impact on quality of life. Treatment options include surgery or hormone therapy, but these are not always effective and often have significant side-effects.

Rafael Maldonado, Professor at the University Pompeu Fabra of Barcelona, Spain, said: “With a lack of effective treatments, women with endometriosis usually rely on self-management strategies like dietary changes or exercise. Although cannabis comes with a large number of potential side effects, its medicinal properties could provide pain relief in endometriosis and other conditions.

“Since medical THC is available in some countries, the findings of our study may be of interest for gynecologists and pain specialists who manage the treatment of women with endometrial pain.”

THC improves symptoms and growths

The team studied mice with endometrial implants in their pelvis to mimic endometriosis in humans. Those with the implants were more sensitive to pain in their pelvis that can also be associated with emotional and cognitive alterations – similar to symptoms seen in some women with endometriosis.

The team next found that mice with endometriosis had similar anxiety-like symptoms experienced by some women with the condition. This was measured by the amount of time the animals spent in open areas of a maze, as those with higher anxiety levels tend not to explore too far. However, their experiments could not reveal whether THC had any significant effects in treating this anxiety.

As endometriosis can be known to impair cognitive function in some women, the team also studied memory performance in the mice. They provided the animals with two identical objects and allowed them to become familiar with them. They then replaced one of the objects and timed how long the mice spent exploring the new versus familiar object, to give an indication of what the animals remembered.

The team found that memory was impaired in the mice with endometriosis compared with those that did not have the condition. However, mice treated with THC did not show this impairment, suggesting that THC may have a protective effect.

Finally, the team studied the effects of THC on the endometrium inside and outside of the womb, and found that mice with endometriosis treated with THC for 32 days had smaller endometrial growths.

First author Alejandra Escudero-Lara, a PhD student at the University Pompeu Fabra of Barcelona, said: “Together, our findings show that THC limits the development and symptoms of endometriosis in an experimental model, and highlight the interest of conducting further research to ensure the safety and beneficial effects of this treatment in women with endometriosis.”

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Endometriosis is a chronic, inflammatory condition where tissue similar to the lining of the uterus is found outside of the womb. It affects around one in ten women of reproductive age, causing pain, infertility and gastrointestinal symptoms.

Women often report difficulty getting their pain and other symptoms under control, despite medication or even surgery.

Our research, published today, found one in ten Australian women with endometriosis reported using cannabis to manage their pain and other symptoms.

What did our study find?

We surveyed 484 women with surgically diagnosed endometriosis about the self-management strategies they used.

Of the respondents, who were aged 18 to 45, 76% reported using self-management techniques in the past six months. This included the use of heat packs (70%), dietary changes (44%), exercise (42%), yoga or pilates (35%) and cannabis (13%).

Out of all of the self-management techniques, cannabis was rated as the most effective for managing pain.

Women who reported higher levels of pain were more likely to use cannabis than those with milder symptoms. This may be because they couldn’t get relief through other measures.

Respondents who used cannabis also reported improvements in other symptoms including gastrointestinal problems, nausea, anxiety, depression and sleep.

One in ten cannabis users reported side effects, which included anxiety, drowsiness and tachycardia (fast heart rate). This is consistent with other research.

How could cannabis help treat endometriosis symptoms?

The endocannabinoid system (ECS) is a complex regulatory system comprised of various receptors, chemicals that bind with these receptors, and enzymes. It helps maintain balance (homeostasis) in our bodies and is important for a wide range of actions, including metabolism, inflammation and immune function.

The ECS is distributed throughout most organs in the human body, but is more abundant in the central nervous, immune and female reproductive systems.

Chemicals from cannabis, including the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD), can interact with the ECS and other receptor types. This suggests a mechanism for how cannabis may alleviate pelvic pain in women with endometriosis.

Emerging research shows medicinal cannabis can help manage a number of conditions, including chronic pain in adults, the spasticity of multiple sclerosis, intractable epilepsy (where seizures can’t be controlled with medication) and chemotherapy-induced nausea and vomiting.

Research is still in its infancy in women with pelvic pain, but one study found women with pelvic pain may benefit from using medicinal cannabis. It may also allow them to reduce their opioid pain-killer intake.

Is it legal?

Medical practitioners in Australia can legally prescribe medicinal cannabis through regulated pathways such as the Special Access Scheme Category B and the Authorised Prescriber Scheme. These pathways are typically used by doctors for unapproved medicines.

According to discussions with prescribing doctors and patients, approvals for medicinal cannabis for pain associated with endometriosis have been successful through these regulated, legal channels.

However, at the time our survey was administered, in late 2017, it’s likely most women who were using cannabis accessed it illicitly. No Special Access Scheme approvals had been granted for endometriosis at the time. Further, most women we surveyed reported smoking cannabis, which is very rarely prescribed by doctors in Australia.

Despite the perception that “natural” equals safe, cannabis use does come with risks. These should be discussed with and monitored by medical professionals.

Why do women resort to cannabis and self care?

Both surgical and pharmaceutical treatments are commonly used for endometriosis.

Surgery can reduce pain, at least in the short to medium term.

Recent reviews have found hormonal treatment options can be effective at managing pain but these are often discontinued or avoided due to significant side effects, such as headaches, mood swings and depression.

Non-steroidal anti-inflammatories (NSAIDs) like ibuprofen don’t seem to be effective at alleviating pain from endometriosis.

In the US, opioids (oxycodone and codeine) are commonly prescribed for endometriosis. Rates of opioid prescription are much lower in Australia but it’s still relatively common among women. This puts women at risk of dependence and potential overdose.

Women with endometriosis report wide-ranging negative impacts on their daily lives, from having to reduce their social activities to problems going to work or studying. It can also cause poor mental and emotional health and affect their sexual and romantic relationships.

So what needs to happen next?

Our survey data shows Australian women are already using cannabis for endometriosis-associated pain, regardless of legality, and with few reported side effects.

However, these survey responses are self-reported so there may be issues such as recall bias. This can lead to over or underestimation of either benefits or harms.

Given women with endometriosis are often suffering without adequate pain control, well designed clinical trials are urgently needed to determine how effective and safe quality-controlled medicinal cannabis might be in treating the symptoms of endometriosis.

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