Endometriosis

Guideline on evidence collection regarding cannabis use in women; no primary intervention outcomes reported, but recommendations on screening, counselling and treatment.

Canadian guideline (SOGC Guideline No. 425a, Part 1) on cannabis use in women; sections on fertility, contraception, menopause and chronic pelvic pain. Recommends evidence-based, stigma-free counselling; trauma-informed conversation approaches to strengthen the therapeutic alliance. Describes screening methods (Brief Intervention, Referral to Treatment), emphasises the need for informed decision-making given the lack of public funding for cannabis therapy. Systematic literature search (PubMed, EMBASE, grey literature) 01/2018–02/2021; primary evidence base: RCTs, observational studies, systematic reviews on gynaecological indications.

Cannabis-based medicines are recommended as an individual therapeutic trial for chronic endometriosis pain, without a conclusive assessment of efficacy.

S2k guideline 015/045 (DGGG/ÖGGG/SGGG), recommendation 4.E18 (new 2024, expert consensus, consensus strength +++): For endometriosis-associated chronic pain, cannabis-based medicines can be considered as an individual therapeutic trial depending on the pain mechanism. Evidence base: systematic review on medical cannabis in gynecological pain (16 studies) — 61–95,5 % of women reported pain relief; retrospective cohort with 252 endometriosis patients — pain was the most common reason for use (57,3 % lower abdominal pain), inhalation worked better against pain. Not suitable for patients under 25 years.

Survey data showed that most women reported pain relief (61–95,5%), prospective cohort studies and an RCT with PEA combination agents showed significant pain reduction (average 3,35±1,39 on a 10-point scale after 3 months), but one RCT showed no pain reduction and heterogeneous formulations/dosages limit definitive statements.

Systematic review on medical cannabis for gynecological pain syndromes (chronic pelvic pain, vulvodynia, endometriosis, interstitial cystitis, malignancies); k=16 studies (6 prospective cohort studies, 1 RCT on palmitoylethanolamide-PEA combinations, survey data). Cannabis prevalence 13–27%; 61–95,5% of users reported pain reduction. Prospective studies on PEA combinations showed an average VAS reduction of 3,35±1,39 points after 3 months (p<0.05). THC dosages up to 70mg, CBD up to 2.000mg; primary route of administration inhalational/oral, several times weekly. One RCT on a fatty acid amide enzyme inhibitor showed no pain reduction.

Feasibility study with recruitment failure (12 of 63 planned participants randomised, 7 dropouts); primary efficacy outcomes not reported.

Feasibility RCT on cannabis for endometriosis pain (n=12 randomised, planned n=63); 3-arm: inhaled THC (16%) + oral CBD (100mg/mL) vs. CBD alone vs. placebo. Study terminated early due to low recruitment/retention (7 of 12 participants dropped out early, only 4 completed). 10 adverse events (8 possibly cannabis-related), 2 serious adverse events (both not intervention-related). Feasibility and acceptability rated low — primarily due to driving ban requirement and high dropout rate.

Cannabis showed efficacy against endometriosis-related pelvic pain, gastrointestinal symptoms and mood disorders, with varying efficacy depending on the form of application.

n=252 women with endometriosis, prospective online diary on cannabis use and symptoms; self-reported significant reduction in pelvic pain (NRS -7,6 points), nausea, gastrointestinal symptoms and sleep disturbances after cannabis intake (p0,001); no control group, high risk of bias due to self-selection.

Women reported high self-assessed pain reduction (7,6/10) and improvement in sleep as well as nausea/vomiting, with 56% reducing pharmaceuticals by at least half; side effects were rare (10%) and mild.

n=484 Australian women with endometriosis, 13% report cannabis self-medication for pain control; descriptive survey without controlled outcomes, efficacy not quantified.

Cannabis was used by 95,5% for pain relief and sleep improvement; 81% reported that pain became 'much better', and 81,4% reduced their regular medications.

Duplicate: n=484 New Zealand women with endometriosis, online survey on illegal cannabis use; 13% current use, 40% prior use for symptom control; self-reported efficacy for pain reduction in 77% of users, but no objective measurement or control group; descriptive cross-sectional data.

92,3% of cannabis users reported symptom improvement, but 80,7% experienced side effects (dry mouth, drowsiness, feeling of intoxication).

Survey on cannabis use in chronic pelvic pain (CPP); n=122 (113 with CPP diagnosis), 23% reported cannabis use (60% CBD+THC combination). Of the cannabis users (n=26), 92,3% reported symptom improvement (pain, cramps, sleep disturbances, anxiety), 80,7% reported side effects (dry mouth, drowsiness).

96% of cannabis users reported symptom improvement (pain, cramps, muscle spasms, anxiety, depression, sleep disturbances, libido, irritability), but 84% experienced side effects (dry mouth, drowsiness, intoxicating effect).

n=274 women with chronic pelvic pain (incl. endometriosis subgroup), anonymous online survey; 61% report cannabis use for pain self-treatment, subjective symptom relief in dysmenorrhea and dyspareunia; no validated outcome measures, no placebo control.

Narrative review without primary data collection; describes theoretical mechanisms of the endocannabinoid system in endometriosis pain management, without reporting specific intervention outcomes.

Narrative review on the role of the endocannabinoid system in endometriosis pain; discusses CB1/CB2 receptor expression in endometrial lesions, preclinical data on PEA/anandamide effects on inflammation and pain modulation; no RCTs or systematic clinical evidence, primarily a mechanistic-exploratory approach with an outlook on therapeutic potential.

Narrative review without empirical data: endocannabinoids and phytocannabinoids could theoretically offer anti-inflammatory, analgesic and antiproliferative properties for endometriosis management, but no clinical efficacy data are reported.

Narrative review on the role of the endocannabinoid system in endometriosis pathophysiology; discussion of preclinical data on CB1/CB2 receptor expression in ectopic endometrium, inflammation and pain modulation; no systematic data extraction, no clinical intervention studies evaluated; hypothesis-generating.

Narrative review without primary intervention outcomes; ECS shows potential role in endometriosis pathogenesis, but evidence is limited and partly contradictory.

Narrative review on the role of the endocannabinoid system in the etiopathogenesis of endometriosis; discusses CB1/CB2 receptors, anandamide and 2-AG in endometrial tissue as well as potential therapeutic implications of cannabinoids for endometriosis-associated pain.

Preclinical study shows that endocannabinoids can modulate apoptosis in endometriosis and adenomyosis tissue; CB1/CB2 receptor agonists show dose-dependent pro-apoptotic effects in cell lines.

In vitro study on human endometrial stromal cells and epithelial cells from endometriosis and adenomyosis patients; endocannabinoids (anandamide, 2-AG) modulate apoptosis via CB1/CB2 receptors, significant reduction in cell viability at higher concentrations (p0.05), mechanistic evidence for antiproliferative effects.

CB1 receptor agonists reduced endometriosis-associated hyperalgesia in a rat model; CB1 antagonists increased it.

Preclinical study on the endocannabinoid system in endometriosis; evidence of reduced CB1 receptor expression and altered anandamide levels in ectopic endometrium, indications of ECS dysregulation as a pathophysiological factor

THC alleviated mechanical hypersensitivity, pain and memory deficits and inhibited the development of endometrial cysts in the mouse model.

Mouse model of surgically induced endometriosis; daily THC (2 mg/kg) alleviates mechanical hypersensitivity and pain unpleasantness, restores cognitive function and inhibits the development of endometrial cysts. Preclinical translational data without clinical human studies.

Study shows dysregulation of endocannabinoids in endometriosis (increased palmitoylethanolamide levels in lesions, reduced cannabinoid-2-receptor expression), without testing therapeutic intervention or clinical outcomes.

Review on the role of dysregulated endocannabinoid system members (e.g. anandamide, 2-AG) in endometriosis pathophysiology; mechanistic hypotheses, no clinical intervention data.

Study shows increased AEA concentrations in follicular fluid of women with endometriosis and that M1-polarised macrophages increase AEA production by granulosa cells; therapeutic or clinical effects are not investigated.

Measurement of anandamide (AEA) in follicular fluid in women with/without endometriosis; exploratory, mechanistic data on endogenous endocannabinoid status, no intervention with cannabis.