Cannabis Extracts and Women's Health

Introduction

The endocannabinoid system (ECS) is deeply embedded in female reproductive physiology. Cannabinoid receptors CB1 and CB2 are expressed throughout the uterus, ovaries, oviducts, and endometrium, where they participate in regulating processes from folliculogenesis and ovulation to embryo implantation and hormonal signaling. [^1] The endocannabinoid anandamide (AEA) fluctuates across the menstrual cycle, peaking around ovulation, and its levels are tightly regulated by the enzyme FAAH, which is itself modulated by estrogen and progesterone. [^2] This crosstalk between the ECS and the hypothalamic-pituitary-ovarian (HPO) axis provides a compelling biological rationale for investigating cannabinoid therapies in conditions defined by reproductive pain, inflammation, and hormonal transition.

Despite this mechanistic foundation, clinical research targeting women's health applications lags far behind patient demand. Survey data consistently show that women are already using cannabis, often illicitly, to manage menstrual pain, endometriosis symptoms, and menopausal sleep disturbances and mood changes at high rates. What is missing is the controlled trial evidence needed to guide dosing, product selection, and safe integration with existing therapies. This article examines the current evidence base across three major women's health domains, primary dysmenorrhea, endometriosis, and menopause, and identifies the research pathways most likely to produce actionable clinical data.

The Endocannabinoid System in Reproductive Tissues

Understanding why cannabinoid therapies hold promise for women's health conditions requires appreciating the extent to which the ECS is integrated into reproductive biology. The system does not drive hormonal signaling directly but regulates its downstream activity, and when that regulatory function is disrupted by chronic inflammation in endometriosis, prostaglandin surges during menstruation, or estrogen withdrawal during menopause, the resulting symptoms may reflect, at least in part, endocannabinoid dysregulation.

CB1 receptors are expressed in the granulosa cells of ovarian follicles at every developmental stage, in the corpus luteum, and throughout the endometrium and myometrium. CB2 receptors share much of this distribution and are additionally prominent in immune cells within reproductive tissues. [^3][^4] The metabolic enzymes NAPE-PLD (which synthesizes AEA) and FAAH (which degrades it) are also present, creating a complete local signaling apparatus capable of responding to and being modulated by circulating sex hormones. [^5]

Critically, research in a mouse model has demonstrated that ECS component expression in the reproductive tract shifts significantly during reproductive aging, with notable changes in CB1, CB2, and TRPV1 receptor levels between adult, late reproductive, and post-reproductive stages. [^6] This age-dependent modulation suggests that the ECS is not static across a woman's reproductive life but adapts in ways that may influence symptom profiles during perimenopause and menopause.

Endometriosis: The Strongest Signal in the Data

Endometriosis, a chronic inflammatory condition in which endometrial-like tissue grows outside the uterus, affects approximately one in nine women of reproductive age and is frequently associated with severe pelvic pain, dysmenorrhea, gastrointestinal symptoms, and fatigue. [^7] Conventional management options, including hormonal therapies, NSAIDs, and surgery, frequently provide incomplete symptom relief and carry significant side effects, driving many patients toward self-management strategies. Among these, cannabis use has emerged as one of the most commonly reported.

Survey Evidence: High Usage, Reported Efficacy, and Opioid Substitution

The foundational data come from a cross-sectional survey conducted between May and July 2019 among New Zealand residents who self-reported using cannabis therapeutically. Among 213 respondents with endometriosis or polycystic ovary syndrome (PCOS), the most common targets for cannabis use were pain relief and sleep improvement, each reported by 95.5% of respondents. Respondents rated their symptoms as "much better" for pain (81%), sleep (79%), and nausea or vomiting (61%). Notably, 81.4% reported reducing their pharmaceutical medication use after starting cannabis, and 59% were able to stop at least one medication entirely, most commonly analgesics, with opioids being the single most frequently discontinued drug class (40% of those who stopped a medication). [^8]

A subsequent 2022 survey expanded this work to include both Australian and New Zealand cohorts, totaling 237 respondents with a medical diagnosis of endometriosis who reported cannabis use. The study confirmed high rates of illicit access, with 72.0% of Australian respondents and 88.2% of New Zealand respondents self-administering cannabis without a prescription, and identified significant barriers to legal medical cannabis access, including cost, clinician unfamiliarity, and stigma. [^9]

These survey findings are consistent with a broader pattern observed in the gynecological pain literature. A comprehensive review published in 2023 noted that cannabis appears to reduce pain and other endometriosis symptoms, with corresponding reductions in opioid and NSAID use, but emphasized that the safety and effectiveness of cannabis for gynecological pain conditions must still be validated in rigorous clinical trials. [^10]

The 2026 New Zealand Cohort Study: Moving Beyond Surveys

The most significant recent advance is a prospective, mixed-methods cohort study published in January 2026 in BMC Complementary Medicine and Therapies. Conducted in New Zealand, where medically authorized cannabis access has been available since April 2020, this study followed 28 endometriosis patients prescribed either CBD-dominant oil extracts or CBD combined with dried cannabis flower over a 12-week period, as an adjunct to their existing medications. [^11]

Using the validated Endometriosis Health Profile-30 (EHP-30) and weekly numerical pain rating scales, the researchers found meaningful reductions in pelvic pain. "Overall" pain scores decreased from 5.46 (±1.55) at baseline to 3.77 (±2.25) at week 12, and "worst" pain scores fell from 7.62 (±1.51) to 5.38 (±2.69). Health-related quality of life improved across multiple EHP-30 domains, and adverse events were limited. [^12]

While the study was small, uncontrolled, and open-label, limitations the authors acknowledged, it represents a critical step beyond self-report survey data. It used standardized outcome measures, prospective data collection, and medically authorized products with known cannabinoid profiles. The qualitative interview component also highlighted persistent barriers, including stigma and the need for healthcare provider education. [^13]

Research Opportunities for Endometriosis

The progression from survey to prospective cohort establishes a clear pathway for future investigation. The most impactful next steps would include randomized, placebo-controlled trials comparing defined CBD-dominant extracts against placebo or active comparators such as first-line NSAIDs or hormonal therapies, using standardized products with documented cannabinoid and terpene profiles. Specific product types worth investigating include sublingual tinctures for systemic symptom management, topical or transdermal preparations for localized pelvic pain, and vaginal suppositories, a delivery route that targets the pelvic region directly. The opioid substitution signal observed across multiple surveys also warrants formal study, particularly given the public health implications of reducing opioid dependence in chronic pain populations.

Primary Dysmenorrhea: Emerging but Early Evidence

Primary dysmenorrhea, menstrual pain in the absence of underlying structural pathology, affects over 70% of women of reproductive age and is driven primarily by elevated prostaglandin levels in the endometrial lining. [^14] The mechanistic case for cannabinoid therapy here is relatively clear. CBD has been shown to inhibit prostaglandin-producing enzymes through a pathway analogous to NSAIDs, while also engaging anti-inflammatory and analgesic pathways via the ECS. [^15]

Current Data

A Phase II, non-inferiority trial protocol published in 2022 proposed comparing oral CBD directly against ibuprofen in women with primary dysmenorrhea, using the Total Pain Relief (TOTPAR) scale as the primary outcome measure across four menstrual cycles. [^16] This trial design, if successfully completed and reported, would provide the first head-to-head comparison of CBD against a standard-of-care analgesic for menstrual pain.

A separate randomized, single-blinded, placebo-controlled study assessed a CBD-infused tampon in 63 participants and found statistically significant pain reduction compared to placebo, along with high patient acceptance. [^17] While the novel delivery approach raises important pharmacokinetic questions, including whether CBD released from a tampon achieves sufficient local concentration to reach the uterine myometrium and whether absorption competes with menstrual fluid, the study demonstrated that localized vaginal delivery of cannabinoids is feasible and tolerable.

The most substantial real-world evidence to date comes from a 2024 quasi-experimental study published in npj Women's Health. Researchers at McLean Hospital and Harvard Medical School assessed a commercially available high-CBD (100 mg) vaginal suppository in 77 users compared to a treatment-as-usual group of 230 participants over two menstrual cycles. The CBD group showed significantly reduced symptom frequency and severity, decreased impact on daily functioning, and reduced analgesic use (p ≤ 0.032). A dose-dependent response was observed, with increased suppository use associated with greater symptom improvement (p ≤ 0.025). By the second follow-up, 81.1% of CBD participants reported at least moderate improvement. [^18]

Research Opportunities for Dysmenorrhea

This condition is well-suited for clinical trials because it is highly prevalent, cyclically predictable, and has an established standard of care (NSAIDs) against which new therapies can be benchmarked. The CBD-versus-ibuprofen non-inferiority framework represents an optimal design. Beyond oral CBD, the investigation of localized delivery systems such as vaginal suppositories, CBD-infused tampons, and transdermal patches applied to the lower abdomen could help determine whether targeting the pelvic region directly offers advantages over systemic administration. Given that 20 to 25% of dysmenorrhea patients are refractory to NSAIDs, this population represents a particularly compelling cohort for cannabis-focused trials. [^19]

Menopause-Related Symptoms: High Usage, Minimal Clinical Data

The menopausal transition involves declining estrogen production, which disrupts the ECS, a system that estrogen directly modulates through upregulation of AEA synthesis and downregulation of its degradation. [^20] Despite this mechanistic rationale, clinical evidence specific to menopause remains almost entirely limited to survey data.

Survey Evidence

A 2022 survey published in Menopause: The Journal of the North American Menopause Society assessed cannabis use among 258 perimenopausal and postmenopausal participants. The majority (86.1%) were current cannabis users, and 78.7% endorsed using cannabis specifically for menopause-related symptoms. The most common symptom targets were sleep disturbance (67.4%) and mood or anxiety (46.1%). Perimenopausal participants reported significantly worse vasomotor and psychosocial symptomatology compared to postmenopausal participants, including greater burdens of anxiety (p = 0.01) and hot flashes (p = 0.04). [^21]

A separate cross-sectional study from the VA system, presented at the 2020 North American Menopause Society meeting, found that among 231 women veterans with a mean age of approximately 56, roughly 27% reported current or past cannabis use for menopause symptom management, a rate that exceeded the 19% who reported using conventional treatments such as hormone therapy. [^22]

A 2023 Canadian survey of nearly 1,500 women aged 35 and over in Alberta found that one-third were current cannabis users, with the majority using at least once daily. Among current users, cannabis was frequently endorsed for sleep, mood, and pain, all symptoms associated with the menopausal transition. [^23]

Despite this widespread usage, neither the North American Menopause Society nor the Society of Obstetricians and Gynaecologists of Canada has endorsed cannabis for vasomotor symptom management, citing insufficient evidence from controlled trials. Hot flashes, in particular, have not shown the same level of patient-reported improvement as sleep and mood symptoms in survey data, an observation that aligns with the understanding that the hypothalamic thermoregulatory center may not be as directly modulated by cannabinoids as sleep and anxiety circuits. [^24][^25]

The Estrogen-ECS Relationship and Why Menopause Matters

The biological case for investigating cannabinoids during menopause extends beyond symptom management. Estrogen and the ECS are linked in a bidirectional regulatory loop. 17β-estradiol directly stimulates the release of the endocannabinoid anandamide from endothelial cells, upregulates the AEA-synthesizing enzyme NAPE-PLD, and simultaneously downregulates FAAH, the enzyme that degrades AEA. [^26][^27] In effect, estrogen acts as a volume dial for endocannabinoid tone: when estrogen levels are high, anandamide signaling is amplified, and when estrogen declines, as it does during the menopausal transition, endocannabinoid tone may fall with it. The clinical implication is that the regulatory set points for mood, sleep, pain sensitivity, and inflammation may shift as this hormonal input weakens. These mechanistic relationships, however, remain largely untested in human menopausal populations under controlled conditions.

There are also important safety questions that survey data cannot answer. Menopausal symptoms often persist for a decade or more, yet no controlled studies have assessed the long-term effects of sustained cannabis use in middle-aged women on cognitive function, cardiovascular health, or mental health outcomes. This evidence gap is consistent with the conclusion of systematic reviews that the literature on cannabis in menopause remains both sparse and of limited methodological quality. [^28] This is not a reason to dismiss the therapeutic hypothesis, but it underscores the urgency of moving from observational reports to controlled longitudinal research.

Research Opportunities for Menopause

Menopause represents the largest gap between patient usage and clinical evidence in the cannabis and women's health landscape. The priorities for future research include randomized, controlled trials assessing defined CBD and low-dose THC formulations against validated menopause outcome measures such as the Menopause-Specific Quality of Life Questionnaire (MENQOL), polysomnography for sleep, and standardized hot flash diaries. Given that sleep and mood symptoms appear to be the most responsive to cannabinoid use based on current survey data, these should be primary targets for initial trials, with vasomotor symptoms as important but less certain secondary endpoints. Sublingual tinctures and low-dose edibles, already the product types most commonly used by menopausal consumers, represent logical starting points for standardized trial formulations. Future trials should also incorporate cognitive and cardiovascular monitoring as safety endpoints, given the age of the target population and the potential for long-term use.

Overarching Research Challenges

Several challenges cut across all three conditions. Cannabis research has historically underrepresented women, older adults, and racial and ethnic minorities, populations that bear significant burdens of chronic pain, insomnia, and anxiety. The FDA's 2024 guidance on diversity action plans for clinical trials offers a framework for more inclusive recruitment that will be essential for ensuring generalizability. [^29]

Product standardization remains a critical prerequisite. As explored in detail in the companion article Cannabis Product Standardization and Quality: Why Consistency Matters for Research, the majority of commercially available cannabis products fail basic labeling accuracy standards. None of the research described above can advance reliably if the products being tested vary unpredictably from batch to batch. Standardized formulations with documented cannabinoid and terpene profiles are essential for reproducible clinical science.

Hormonal Pharmacokinetics: A Unique Complexity

The hormonal context of women's health conditions introduces pharmacokinetic considerations that have no parallel in most other cannabis research domains. Estrogen modulates the ECS, and the ECS in turn influences hormonal signaling, creating a bidirectional relationship that may cause cannabis to behave differently across the menstrual cycle, during pregnancy, and across the menopausal transition. [^30][^31] A premenopausal woman in the luteal phase of her cycle, when progesterone is high and FAAH activity is upregulated, may metabolize and respond to cannabinoids differently than the same woman in the follicular phase, when estrogen-driven AEA synthesis is at its peak.

This has concrete implications for trial design. Dysmenorrhea trials, for instance, should standardize the timing of intervention relative to cycle day, not just symptom onset. Endometriosis trials involving premenopausal women should consider stratifying or controlling for cycle phase. And menopause trials should differentiate between perimenopausal participants, who still experience hormonal fluctuations, and postmenopausal participants, who have reached a new, lower hormonal baseline, as their ECS environments may differ significantly. The Dahlgren et al. survey already demonstrated this distinction in its finding that perimenopausal participants reported worse symptomatology and higher cannabis use for mood symptoms than their postmenopausal counterparts. [^32]

Bridging Self-Management and Clinical Guidance

A recurring theme across all three conditions is that patients are not waiting for clinical trials to begin using cannabis. They are self-managing with unregulated products, often without disclosing this use to their healthcare providers. The Australia and New Zealand endometriosis survey found that the vast majority of cannabis-using respondents were accessing products illicitly. [^33] The VA menopause study noted that patients may not disclose cannabis use within a federal healthcare system where it remains technically prohibited. [^22] This disconnect between patient behavior and clinical guidance creates real safety risks, particularly when patients independently reduce or discontinue prescribed medications, including opioids and hormonal therapies, without medical supervision.

Closing this gap requires not only clinical trial data but also clinician education. Providers who are aware that their patients with endometriosis, dysmenorrhea, or menopausal symptoms may already be using cannabis are better positioned to monitor for drug interactions, counsel on product quality, and participate in the informed shared decision-making that these complex conditions demand.

Conclusion

The biological foundation for cannabinoid therapy in women's health is substantial. The ECS is not a peripheral player in reproductive physiology but a central regulatory mechanism present in every major tissue of the female reproductive tract, modulated by the very hormones that define menstruation, fertility, and menopause. Patient demand is clear: women are already using cannabis for these conditions at high rates, often without medical guidance and frequently from unregulated sources.

What is needed now is the clinical trial infrastructure to match this demand with evidence. Endometriosis has the strongest preliminary data and the clearest pathway to controlled trials. Dysmenorrhea offers an efficient trial model with a built-in comparator. Menopause represents the widest gap between usage and evidence, but also the largest potential patient population. Across all three domains, the transition from survey data to prospective, controlled, standardized-product trials is the defining challenge, and opportunity, of the next phase of cannabis research in women's health.

Readers interested in the role of product consistency in clinical research may find additional context in Cannabis Product Standardization and Quality: Why Consistency Matters for Research. For a broader exploration of localized ECS engagement through the skin, a delivery mechanism with direct relevance to pelvic pain applications, see the companion article on cannabis topicals.