cannabidiol and Endometriosis

To review the available literature on the effect of cannabis-based products on the female reproductive system and establish whether there is any evidence that they benefit or harm patients with endometriosis and, therefore, whether there is sufficient evidence to recommend them.. An electronic-based search was performed in PubMed, Embase, and the Cochrane Database. Reference lists of articles retrieved were reviewed, and a gray literature search was also performed.. The original database search yielded 264 articles from PubMed, Embase, and the Cochrane Database, of which 41 were included. One hundred sixty-one studies relating to gynecologic malignancy, conditions unrelated to endometriosis, or therapies unrelated to cannabis-based products were excluded. Twelve articles were included from a gray literature search and review of references.. Most available evidence is from laboratory studies aiming to simulate the effects of cannabis-based products on preclinical endometriosis models. Some show evidence of benefit with cannabis-based products. However, results are conflicting, and the impact in humans cannot necessarily be extrapolated from these data. Few studies exist looking at the effect of cannabis or its derived products in women with endometriosis; the majority are in the form of surveys and are affected by bias. National guidance was also reviewed: at present, this dictates that cannabis-based products can only be prescribed for conditions in which there is clear published evidence of benefit and only when all other treatment options have been exhausted.. Current treatment options for endometriosis often affect fertility and/or have undesirable side effects that impede long-term management. Cannabis-based products have been suggested as a novel therapeutic option that may circumvent these issues. However, there is a paucity of well-designed, robust studies and randomized controlled trials looking at their use in the treatment of endometriosis. In addition, cannabis use has a potential for harm in the long term, with a possible association with "cannabis use disorder," psychosis, and mood disturbances. At present, national guidance cannot recommend cannabis-based products to patients in the UK owing to lack of clear evidence of benefit. More comprehensive research into the impact of endocannabinoids in the context of endometriosis is required before their use can be recommended or prescribed.

Topics: Cannabidiol; Chronic Pain; Endometriosis; Female; Humans; Pelvic Pain

The discovery of the endocannabinoid system (ECS) dates back only 30 years. Although many research groups have been elucidating its components, location, functions and metabolism, the peculiarities of the compounds considered "neurotransmitters" of ECS generate questions that have not yet been answered or controversies in the literature. In this context, we studied the molecular behaviour of the main endocannabinoid compounds and the main phytocannabinoids in eukaryotic outer and inner model membranes. The high lipophilicity of these compounds gives place to the hypothesis that cannabinoids may reach the molecular targets through the lipid bilayer. This consideration is not only for the cannabinoid receptors but also for other (many) targets that these bioactive molecules modulate (Watkins, 2019; Nelson et al., 2020; Jakowiecki and Filipek, 2016). Given the reported multitarget action of these compounds and the differential behaviour towards the different receptors, studying the properties and dynamics of these cannabinoids in POPC and POPE model membranes become relevant. In this regard, we have studied the differential modulation of the endocannabinoids anandamide and 2-arachidonoyl-glycerol and the phytocannabinoids cannabidiol and trans-Δ

Topics: Cannabidiol; Dronabinol; Endocannabinoids; Endometriosis; Female; Humans; Membranes

Can cannabidiol (CBD) be used in the treatment of endometriosis for its anti-inflammatory, antioxidative and antiangiogenic effects?. Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated.. Significant reductions in the endometriotic implant surface area (P = 0.0213), serum TOS (P = 0.0491), OSI (P = 0.0056), IL-6 (P = 0.0236), TNF-α (P = 0.0083) and peritoneal fluid OSI (P = 0.0401), IL-6 (P = 0.0205) and TNF-α (P = 0.0045) concentrations were observed in the CBD5 group when compared with the saline solution group. Compared with the saline solution group, increased TAS concentrations in serum (P = 0.0012) and peritoneal fluid (P = 0.0145) were found in the CBD5 group. The CBD5 and leuprolide acetate groups were similar regarding inflammatory and oxidative stress parameters of serum and peritoneal fluid samples. The CBD5 group showed significantly lower mean intensity in both surface epithelium and stromal cells for VEGF (both P = 0.002) and only in surface epithelium cells for IL-6 (P = 0.0108), when compared with the leuprolide acetate group.. Due to its anti-inflammatory, antioxidative and antiangiogenic effects, CBD might be a therapeutic agent candidate for endometriosis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cannabidiol; Disease Models, Animal; Endometriosis; Female; Humans; Interleukin-6; Leuprolide; Rats; Rats, Wistar; Saline Solution; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on the anti-inflammatory, anti-oxidant and analgesic effects of cannabidiol (CBD) and on its potential role in endometriosis. We employed an in vivo model of endometriosis and administered CBD daily by gavage. CBD administration strongly reduced lesions diameter, volume and area. In particular, it was able to modify lesion morphology, reducing epithelial glands and stroma. CBD showed anti-oxidant effects reducing lipid peroxidation, the expression of Nox-1 and Nox-4 enzymes. CBD restored the oxidative equilibrium of the endogenous cellular defense as showed by the SOD activity and the GSH levels in the lesions. CBD also showed important antifibrotic effects as showed by the Masson trichrome staining and by downregulated expression of MMP-9, iNOS and TGF-β. CBD was able to reduce inflammation both in the harvested lesions, as showed by the increased Ikb-α and reduced COX2 cytosolic expressions and reduced NFkB nuclear localization, and in the peritoneal fluids as showed by the decreased TNF-α, PGE2 and IL-1α levels. CBD has important analgesic effects as showed by the reduced mast cells recruitment in the spinal cord and the reduced release of neuro-sensitizing and pro-inflammatory mediators. In conclusion, the collected data showed that CBD has an effective and coordinated effects in endometriosis suppression.

Topics: Analgesics; Antioxidants; Cannabidiol; Endometriosis; Female; Humans; Inflammation; Oxidative Stress