Is it the Ideal Time to Start Prescribing Cannabis Derivatives to Treat Endometriosis-associated Pain? - Revista Brasileira de Ginecologia e Obstetrícia
Rev Bras Ginecol Obstet. 2022;44(5):449-451
Endometriosis affects ∼5%-10% of women of reproductive age and is often associated with painful symptoms like dysmenorrhea, dyschezia, dyspareunia, and even non cyclical pain. The disease is diagnosed in at least 20% of women with dysmenorrhea and/or non-menstrual pelvic pain, reaching a prevalence of 50% among adolescents. There is an alignment among international societies that the presumed diagnosis of this disease is enough to start clinical treatment. Moreover, there seems to be a consensus that first-line treatment should be hormonal contraceptives since the efficacy is similar to that of surgery but with lower complication rates and costs. However, these drugs are effective in only approximately two-thirds of patients, have limited long-term efficacy, and may occasionally lead to undesirable side effects. Additionally, there are serious limitations in the interpretation of clinical trials. Accordingly, evidence on the best therapeutic regimens has not yet been established. Other clinical options exist, but the cost, side effects, and similarity of results compared with hormonal contraceptives give them limited utility. Thus, due to the persistence of pain, a significant portion of women undergo surgery, which is obviously capable of eliminating visible endometriotic lesions, but not curing the disease. Despite short-term clinical improvement, postoperative recurrence is common, especially if hormone therapy was not initiated.
Thus, the clear clinical demand for more effective or lasting options for symptomatic relief, together with an increasing recognition of the participation of the central nervous system in the genesis and/or modulation of chronic endometriosis-associated pain, has aroused growing interest in novel therapeutic modalities. Among these treatments, drugs derived from the Cannabis sativa plant, which we will call cannabinoids in the following text, currently seem to be the main topic. In fact, increasing attention has been directed to the potential beneficial effects of these medicines in controlling the symptoms of patients with chronic pain. Cannabis contains over a hundred chemical compounds that act on the endocannabinoid system, yet two are rather distinct, delta-9-tetrahydrocannabinol (THC), which is responsible for the psychoactive effects associated with the use of this plant, and cannabidiol (CBD), which does not produce psychomimetic symptoms. Overall, unlike THC, CBD is not addictive or tolerant and has a very favorable safety and adverse effect profiles. At first, it was believed that cannabinoids produced their analgesic effects by the direct activation of specific receptors (CB1 and CB2). However, it is now known that they can reduce pain by interacting with a wide range of cannabinoid, opioid, vanilloid, serotonergic, and anti-inflammatory receptors. Furthermore, preclinical studies have shown that CBD can interfere with the levels of cytokines potentially involved in the pathophysiology of endometriosis-associated pain; CBD has been shown to decrease the secretion of pro-inflammatory cytokines, including IL-6 and TNF-α, and increase levels of anti-inflammatory cytokines, including IL-10. In addition to these broad potential pain-related mechanisms of action, there is a vast evidence on its anxiolytic, antidepressant, neuroprotective, mood-stabilizing, sleep-modulating effects of cannabinoids, along with many other benefits, which may be useful in the concomitant treatment of non-painful symptoms as the aforementioned comorbidities are also frequent among patients with endometriosis. This makes cannabinoids potentially useful in treating patients with pelvic pain secondary to endometriosis.
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Endometriosis affects ∼5%-10% of women of reproductive age and is often associated with painful symptoms like dysmenorrhea, dyschezia, dyspareunia, and even non cyclical pain. The disease is diagnosed in at least 20% of women with dysmenorrhea and/or non-menstrual pelvic pain, reaching a prevalence of 50% among adolescents. There is an alignment among international societies that the presumed diagnosis of this disease is enough to start clinical treatment. Moreover, there seems to be a consensus that first-line treatment should be hormonal contraceptives since the efficacy is similar to that of surgery but with lower complication rates and costs. However, these drugs are effective in only approximately two-thirds of patients, have limited long-term efficacy, and may occasionally lead to undesirable side effects. Additionally, there are serious limitations in the interpretation of clinical trials. Accordingly, evidence on the best therapeutic regimens has not yet been established. Other clinical options exist, but the cost, side effects, and similarity of results compared with hormonal contraceptives give them limited utility. Thus, due to the persistence of pain, a significant portion of women undergo surgery, which is obviously capable of eliminating visible endometriotic lesions, but not curing the disease. Despite short-term clinical improvement, postoperative recurrence is common, especially if hormone therapy was not initiated.
Thus, the clear clinical demand for more effective or lasting options for symptomatic relief, together with an increasing recognition of the participation of the central nervous system in the genesis and/or modulation of chronic endometriosis-associated pain, has aroused growing interest in novel therapeutic modalities. Among these treatments, drugs derived from the Cannabis sativa plant, which we will call cannabinoids in the following text, currently seem to be the main topic. In fact, increasing attention has been directed to the potential beneficial effects of these medicines in controlling the symptoms of patients with chronic pain. Cannabis contains over a hundred chemical compounds that act on the endocannabinoid system, yet two are rather distinct, delta-9-tetrahydrocannabinol (THC), which is responsible for the psychoactive effects associated with the use of this plant, and cannabidiol (CBD), which does not produce psychomimetic symptoms. Overall, unlike THC, CBD is not addictive or tolerant and has a very favorable safety and adverse effect profiles. At first, it was believed that cannabinoids produced their analgesic effects by the direct activation of specific receptors (CB1 and CB2). However, it is now known that they can reduce pain by interacting with a wide range of cannabinoid, opioid, vanilloid, serotonergic, and anti-inflammatory receptors. Furthermore, preclinical studies have shown that CBD can interfere with the levels of cytokines potentially involved in the pathophysiology of endometriosis-associated pain; CBD has been shown to decrease the secretion of pro-inflammatory cytokines, including IL-6 and TNF-α, and increase levels of anti-inflammatory cytokines, including IL-10. In addition to these broad potential pain-related mechanisms of action, there is a vast evidence on its anxiolytic, antidepressant, neuroprotective, mood-stabilizing, sleep-modulating effects of cannabinoids, along with many other benefits, which may be useful in the concomitant treatment of non-painful symptoms as the aforementioned comorbidities are also frequent among patients with endometriosis. This makes cannabinoids potentially useful in treating patients with pelvic pain secondary to endometriosis.
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