Medical Cannabis and Endometriosis


Endometriosis is an incurable gynaecological disease in which tissue that is similar to the lining of the womb (the endometrium) grows outside it in other parts of the body.

Whilst endometriosis most often affects the reproductive organs, endometrial tissue can also be found in the bowel and bladder, and more rarely in lungs, heart, and central nervous system. This abnormal growth can cause extreme pain as well as menstrual irregularities and infertility[1].

The impact of endometriosis

Endometriosis remains an underdiagnosed condition, but it is estimated that it affects approximately 10% to 15% of women of reproductive age, whereas this prevalence increases by up to 70% in women with chronic pelvic pain[1]. According to statistics from the Australian Institute of Health and Welfare, in 2016–2017 there were around 34,200 endometriosis-related hospitalisations in Australia[2]. Endometriosis may negatively influence quality of life, daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Such daily challenges may also limit the achievement of life goals over a lifetime[3].

The pain associated with endometriosis varies in many ways. Some women experience pain after or during sexual intercourse, while others may feel increased cramps and abdominal pain before and during their menstrual cycle. Others suffer from pelvic and lower back pain regularly, and many have even reported painful bowel movements. Unfortunately, some women experience all of these in addition to other symptoms such as vomiting, irritability, and fainting.

What causes endometriosis?

The cause of endometriosis remains unknown, and although there are a number of theories, none of these completely explains all different types of endometriosis, which are thought to be influenced by genetics, the immune system and the environment1.  Some women suffering from endometriosis also experience increased sensitivity to pain (hyperalgesia), where they react to a non-painful stimulus as if it were very painful, which is indicative of neuropathic pain. In the case of endometriosis, nerve damage is caused by the invasion of endometrial tissue and by the release of serotonin, histamine, prostaglandins, and nerve growth factor by some types of immune cells[4].

Current treatments

There is no known cure for endometriosis and therefore available treatments only help to alleviate symptoms. First-line pharmacological options include non-steroidal anti-inflammatory drugs, progestins, or combined hormonal contraceptives[5]. Endometriosis surgery options include the removal of lesions via laparoscopy or laparotomy (abdominal keyhole surgery). In some cases, the uterus may be removed (a hysterectomy). In spite of this, symptoms can still reoccur, and treatments can have severe side effects[1, 2]. 

New and potential treatments for endometriosis Australia

New treatments include gonadotropin-releasing hormone (GnRH) analogs which are administered continuously for 3 months and work on the pituitary gland in the brain to stop ovulation and reduce the size of the endometrium[5]. Side effects may involve bone loss, hot flushes, vaginal dryness, and headache[6]. In addition, danazol is a male hormone that results in a reduction of the endometrium by lowering oestrogen levels. The side effect is an increase in the levels of testosterone levels which can lead to excessive hair growth, irreversible deepening of the voice, or acne[5].

A potential treatment under investigation is vagus nerve stimulation. Certain components of the nervous system have been shown to promote the progression of endometriosis. In a study published in 2021, endometriosis patients were found to have reduced vagus nerve activity compared to healthy controls. In mice, vagus nerve stimulation decreased the amount of endometrial tissue, slowed the progression of endometriosis, and improved pain. Clinical trials will be needed to assess whether boosting vagus nerve activity may indeed have therapeutic potential for patients with endometriosis[7].

Current clinical trials in Australia are investigating the efficacy of cognitive behavioural therapy (CBT), mindfulness, hydrotherapy, and a modified traditional Chinese medicine formula called Gynoclear. To learn more about these trials or to see if you are eligible to join one, visit the ANZCTR.

Unfortunately, many current treatments for endometriosis are only partially successful and address the symptoms and not the underlying cause. Cannabis, however, has shown potential in mitigating the development of endometrial cells and tissue outside of the uterus, as well as controlling pain associated with endometriosis.

Could medicinal cannabis help with endometriosis?

The endocannabinoid system (ECS) controls a number of processes in the body and is made up of endocannabinoids (cannabinoids made in the body) which bind to cannabinoid receptors to exercise a number of functions. There are also other components that manufacture, transport, and break down the endocannabinoids[8]. Most of the active components of the ECS are multifunctional and therefore the ECS regulates and is regulated by numerous other signaling pathways in the body[9]. As a result, the ECS plays key roles not just in the central nervous system, but also in a variety of physiological, immune, and cognitive processes[10-21]. For these reasons, the ECS also controls some of the functions within the female reproductive system[22], and dysregulation of the ECS has been associated with some disorders of this system, such as endometriosis[23]. For example, different levels of ECS components have been found in biopsies and blood samples taken from women with endometriosis compared with controls[24].

Other studies have shown that endometriosis is linked with the inhibition of cannabinoid 1 (CB1) receptors which play an anti-inflammatory role, and the activation of TRPV1 receptors which are involved in inflammation and pain. Furthermore, the ECS has been reported to be involved in processes relevant to endometriosis, including cell migration and proliferation, inflammation, as well as interacting with sex steroid hormones. Therefore, the ECS may play a role in endometriosis establishment, progression, and pain[25], and could be targeted with plant cannabinoids such as CBD and/or THC, which can also bind to ECS receptors.

Unfortunately, human studies looking at the efficacy of plant cannabinoids in endometriosis have been few up until now, but a recent study in mice found that daily treatments with moderate doses of THC alleviated pain and modified nerves in the uterus . Importantly, THC also inhibited the development of endometrial cysts[26]. These data highlight the urgent need for clinical trials to examine the possible benefits of plant cannabinoids for women with endometriosis. A current clinical trial in the USA is assessing the use of a CBD extract for endometriosis pain.

Medicinal cannabis and endometriosis pain

The ECS is involved in the regulation of pain[27, 28]. CB1 is involved in controlling nerve signals[28] and the release of neurotransmitters[29, 30]. It is also present in cells of the immune system and when activated produces anti-inflammatory effects[31]. In addition, the cannabinoid 2 (CB2) receptor is present in several types of inflammatory cells, and its activation generates a pain sensing response in situations of inflammatory pain by suppressing the release of inflammatory factors[32, 33]. Plant cannabinoids such as CBD and THC can bind ECS receptors and affect their action.

An Australian study published in 2020, surveyed 484 women with endometriosis[34]. It found that 76% had used general self-management strategies within the last 6 months, including various forms of exercise, rest, heat, meditation, breathing, and dietary changes. Of those using self-management, 13% reported using cannabis for symptom management and of these, most (76%) reported that it was highly effective in reducing pain. More than half of the women using cannabis were also able to reduce pharmaceutical medications by at least half. Women reported the greatest improvements to be in sleep and in nausea and vomiting. Side effects were infrequent (10%) and tolerable[34].

It is important to remember that for medicines containing THC, potential cannabis dependence can occur in 4%−9% of users, as well as possible psychosis, although the latter has been reported in heavy, long-term users of recreational cannabis.  It is unclear whether these issues will apply to medicinal doses[34]. Medicinal cannabis is also contraindicated for people with a hypersensitivity or intolerable adverse reaction to cannabis, unstable cardiovascular disease, severe hepatic impairment, inadequate renal function, substance use disorder, or serious medical or psychiatric conditions.

A current clinical trial in the USA is recruiting women with endometriosis to evaluate the effects of CBD in reducing pain and improving quality of life. There are also a number of clinical studies in Australia and worldwide assessing a range of other different interventions. Continuing medical research will eventually offer new hope in the form of new treatment options for millions of women.

If you have endometriosis, please contact Tetra Health. Our expert nurses and doctors will guide you in the management of your condition and will recommend an appropriate medication based on your symptoms.

[1]Tsamantioti E. Endometriosis: StatPearls; 2021 [Available from:].

[2] Endometriosis in Australia: prevalence and hospitalisations. Canberra: Australian Institute of Health and Welfare (AIHW); 2019.

[3] Missmer SA, Tu FF, Agarwal SK, Chapron C, Soliman AM, Chiuve S, et al. Impact of Endometriosis on Life-Course Potential: A Narrative Review. Int J Gen Med. 2021;14:9-25.

[4] Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261-75.

[5] Kim JH, Han E. Endometriosis and Female Pelvic Pain. Semin Reprod Med. 2018;36(2):143-51.

[6] Magon N. Gonadotropin releasing hormone agonists: Expanding vistas. Indian J Endocrinol Metab. 2011;15(4):261-7.

[7] Hao M, Liu X, Rong P, Li S, Guo SW. Reduced vagal tone in women with endometriosis and auricular vagus nerve stimulation as a potential therapeutic approach. Sci Rep. 2021;11(1):1345.

[8] Reddy V, Grogan D, Ahluwalia M, Salles É L, Ahluwalia P, Khodadadi H, et al. Targeting the endocannabinoid system: a predictive, preventive, and personalized medicine-directed approach to the management of brain pathologies. Epma j. 2020;11(2):217-50.

[9] Lu HC, Mackie K. Review of the Endocannabinoid System. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020.

[10] Donvito G, Nass SR, Wilkerson JL, Curry ZA, Schurman LD, Kinsey SG, et al. The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain. Neuropsychopharmacology. 2017;43:52.

[11] Klein C, Hill MN, Chang SCH, Hillard CJ, Gorzalka BB. Circulating Endocannabinoid Concentrations and Sexual Arousal in Women. The Journal of Sexual Medicine. 2012;9(6):1588-601.

[12] Wang H, Xie H, Dey SK. Endocannabinoid signaling directs periimplantation events. The AAPS Journal. 2006;8(2):E425-E32.

[13] Fride E. The endocannabinoid-CB1 receptor system in pre- and postnatal life. European Journal of Pharmacology. 2004;500(1):289-97.

[14] Di Marzo V, Goparaju SK, Wang L, Liu J, Bátkai S, Járai Z, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410:822.

[15] Gaffuri AL, Ladarre D, Lenkei Z. Type-1 cannabinoid receptor signaling in neuronal development. Pharmacology. 2012;90(1-2):19-39.

[16] Hill MN, McLaughlin RJ, Bingham B, Shrestha L, Lee TTY, Gray JM, et al. Endogenous cannabinoid signaling is essential for stress adaptation. Proceedings of the National Academy of Sciences. 2010;107(20):9406-11.

[17] Ronald M, Winnie H, J PQ, S DJ, A SK. Effects of cannabinoid receptor-2 activation on accelerated gastrointestinal transit in lipopolysaccharide-treated rats. British Journal of Pharmacology. 2004;142(8):1247-54.

[18] Varga K, Wagner JA, Bridgen DT, Kunos G. Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. Faseb j. 1998;12(11):1035-44.

[19] Elphick MR, Egertova M. The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond B Biol Sci. 2001;356(1407):381-408.

[20] Wiskerke J, Pattij T, Schoffelmeer AN, De Vries TJ. The role of CB1 receptors in psychostimulant addiction. Addict Biol. 2008;13(2):225-38.

[21] Barnes MP. The case for medical cannabis-an essay by M P Barnes. BMJ. 2018;362:k3230.

[22] Walker OS, Holloway AC, Raha S. The role of the endocannabinoid system in female reproductive tissues. J Ovarian Res. 2019;12(1):3.

[23] Maia J, Fonseca BM, Teixeira N, Correia-da-Silva G. The fundamental role of the endocannabinoid system in endometrium and placenta: implications in pathophysiological aspects of uterine and pregnancy disorders. Hum Reprod Update. 2020.

[24] Sanchez AM, Cioffi R, Vigano P, Candiani M, Verde R, Piscitelli F, et al. Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis. Reprod Sci. 2016;23(8):1071-9.

[25] Tanaka K, Mayne L, Khalil A, Baartz D, Eriksson L, Mortlock SA, et al. The role of the endocannabinoid system in aetiopathogenesis of endometriosis: A potential therapeutic target. Eur J Obstet Gynecol Reprod Biol. 2020;244:87-94.

[26] Escudero-Lara A, Argerich J, Cabañero D, Maldonado R. Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain. Elife. 2020;9.

[27] Woodhams SG, Sagar DR, Burston JJ, Chapman V. The role of the endocannabinoid system in pain. Handb Exp Pharmacol. 2015;227:119-43.

[28] Manzanares J, Julian M, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4(3):239-57.

[29] Schlicker E, Kathmann M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci. 2001;22(11):565-72.

[30] Maayah ZH, Takahara S, Ferdaoussi M, Dyck JRB. The molecular mechanisms that underpin the biological benefits of full-spectrum cannabis extract in the treatment of neuropathic pain and inflammation. Biochim Biophys Acta Mol Basis Dis. 2020;1866(7):165771.

[31] Small-Howard AL, Shimoda LM, Adra CN, Turner H. Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells. Biochem J. 2005;388(Pt 2):465-73.

I[32] brahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, et al. Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc Natl Acad Sci U S A. 2003;100(18):10529-33.

[33] Rice AS, Farquhar-Smith WP, Nagy I. Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy. Prostaglandins Leukot Essent Fatty Acids. 2002;66(2-3):243-56.

[34]  Sinclair J, Smith CA, Abbott J, Chalmers KJ, Pate DW, Armour M. Cannabis Use, a Self-Management Strategy Among Australian Women With Endometriosis: Results From a National Online Survey. J Obstet Gynaecol Can. 2020;42(3):256-61.

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