“A dose of relief?”: Results of an international survey exploring self-reported effectiveness, dose and dosage forms of cannabis for endometriosis pain and related symptoms

“A dose of relief?”: Results of an international survey exploring self-reported effectiveness, dose and dosage forms of cannabis for endometriosis pain and related symptoms | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article “A dose of relief?”: Results of an international survey exploring self-reported effectiveness, dose and dosage forms of cannabis for endometriosis pain and related symptoms Justin Sinclair, Allie Eathorne, Jason Abbott, Jerome Sarris, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6910005/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Endometriosis is a common, chronic inflammatory condition impacting 10–14% of reproductive aged females. Common symptoms include severe dysmenorrhea, pelvic pain and fatigue. Current symptom management options are often unsatisfactory, and new, low risk pain management options urgently needed. Previous research has found people with endometriosis self-reporting either legal or illicit cannabis use to manage the pain and associated symptoms of endometriosis. This international study aims to explore how people with endometriosis access cannabis, and the dosage formats and dose frequency utilised. Respondent self-rated symptomatic effectiveness of medicinal cannabis was also investigated. Methods An online, anonymous, cross-sectional survey was developed in conjunction with endometriosis advocacy groups and patient support networks, and distributed internationally. The survey enquired about legal (medical or adult use/social) versus illicit cannabis consumption for therapeutic purposes, current symptoms, medical and self-management strategies employed, self-rated symptom relief associated with cannabis use, and the dosage format and dose frequency utilised. Results 889 respondents from 28 countries were eligible for data analysis. The average duration respondents had been utilising cannabis to manage their symptoms was 4.4 years. Dried cannabis flower-joints (46.8%) and oral oils (31%) were the highest-rated dosage formats for symptom management. There was evidence that self-rated effectiveness is higher for those using dried cannabis flower as a joint (i.e., inhaled) across numerous symptoms, compared to not utilising cannabis flower as a joint. By contrast, oral oils had a lower self-rated effectiveness. Reasons behind dosage form choices focused on fast onset of action for inhaled formats, and longer duration of effect for orally ingested products. Conclusions Cannabis utilisation for endometriosis symptom management is frequently utilised, and is primarily of illicit origin. Self-reported effectiveness of cannabis is noted across a wide range of symptoms, from chronic pelvic pain and dysmenorrhoea to improving sleep and reducing nausea, and dosage frequency is suggestive of individualised dosing regimens which is consistent with the pharmacological duration of action, and speed of onset, that cannabinoids can provide across different symptom clusters. Whilst such evidence is encouraging, more robust data from clinical trials are needed to fully assess the efficacy of cannabis-based medicinal products. Cannabis Endometriosis Pelvic pain effectiveness dosage forms dose Figures Figure 1 Figure 2 Figure 3 Background Endometriosis is a chronic, systemic, inflammatory gynaecological disease associated with considerable morbidity, including chronic pelvic pain, dysmenorrhoea, fatigue and infertility.( 1 – 3 ) Common co-morbidities include depression, anxiety, sexual dysfunction and fatigue, and often people with the condition report poor quality of life.( 4 – 7 ) Prevalence rates vary depending on country, but current evidence suggests a prevalence rate of between 10–14% of women and those presumed female at birth. ( 8 , 9 ) Over the past 15 years, numerous guidelines ( 10 – 14 ) on endometriosis management have been published and cover the usage of laparoscopic surgery, hormonal agents (combined hormonal contraceptives, progestins, progestogens, gonadotropin hormone-releasing hormone (GnRH) agonists, GnRH antagonists and aromatase inhibitors) and analgesic medications. However, despite the array of treatment options, medical therapy does not provide many women with adequate or continued relief from endometriosis-associated pain,( 15 ) and in Australia, treatment satisfaction for people with endometriosis is low, with over a third of women dissatisfied with their treatment outcomes.( 16 ) In addition, there are women who may not be able to access such management options, due to either socio-economic disadvantage, geographical isolation, or due to the side-effects, addiction potential, or contraindications associated with individual medications.( 15 ) The combination of inadequate pain management, issues with side effects of many medications (particularly hormonal interventions), and concerns around addiction and dependence (e.g., opioids) are not uncommon.( 17 ) This is a key reason many women explore different self-management strategies to assist with pain and other associated endometriosis symptoms.( 17 , 18 ) Among these self-initiated management strategies, the re-emergence of cannabis (i.e., cannabidiol (CBD) and d-9-tetrahydrocannabinol (THC)) as a therapeutic option ( 19 ) is surprisingly common, and provides self-reported relief across not only a wide range of endometriosis-associated symptoms, ( 20 – 25 ) but also other gynaecological conditions such as chronic pelvic pain (CPP),( 26 , 27 ) and primary dysmenorrhoea.( 28 ) In a cohort of Australian endometriosis patients, the cost of legal access and lack of public and private insurance product cost reimbursement was associated with under-dosing of cannabinoids and continued reliance on cheaper illicit sources to ‘bridge the gap’ in order to achieve adequate symptom relief.( 29 ) Whilst preliminary studies have proposed that endocannabinoid system dysfunction may be present in those with endometriosis,( 30 – 32 ) and endometriosis-associated pain may be targeted by modulating this system,( 33 ) more research is necessary to understand these mechanisms more fully. With a growing international trend towards cannabis legalisation across numerous jurisdictions, including both medical and recreational/adult use, researchers need to understand the potential impacts of this growing trend on the endometriosis population, and gather data to assist in the development of robust clinical trials to assess safety, tolerability and efficacy. Given that previous published data on self-reported cannabis consumption in the endometriosis population has primarily focused on the southern hemisphere,( 18 , 22 , 24 , 34 ) this study sought to capture data from the larger international endometriosis community, and investigates the different self-management options being employed by the endometriosis cohort (aside from cannabis), self-rated cannabis effectiveness across symptoms, the different cannabis dosage forms being employed, and cannabis dose frequency. Methods Sample and recruitment : The survey was developed by the research team who have expertise in medicinal cannabis and endometriosis. A copy of the survey can be found in Supplementary File 1. This international survey was approved on the 8th of December, 2020 by the Western Sydney University Human Research Ethics Committee (Approval # H14115). The survey was hosted on the Qualtrics platform (Qualtrics Ltd), was open to people world-wide and required approximately 15–30 minutes to complete. Features were enabled within the Qualtrics platform (i.e., no IP addresses recorded; no cookies being used) to ensure anonymity due to potential disclosure of illegal activities. The survey was open for 12-weeks between mid-January to mid-April 2021, during the then developing COVID-19 pandemic. All research was conducted in compliance with the Helsinki Declaration. People were eligible to participate if they had a medical diagnosis of endometriosis, were aged between 18–55 years, and had used cannabis or phytocannabinoid-based products (e.g., CBD oil, whole cannabis oils, legal dried flowers (“buds”) with known levels of THC and/or CBD, or non-legal forms of cannabis) in the past 3 months specifically for the purpose of managing their endometriosis pain and/or related symptoms. Recruitment was conducted via the social media platforms of Endometriosis New Zealand, Endometriosis Australia, Nancy’s Nook, EndoIreland, Endometriosis UK, The World Endometriosis Society and Endometriosis Network (Canada). Reporting in this paper includes demographic information including age, location, diagnosis (age and type of diagnostic test used) education level, participant numbers by country and classification of cannabis use. Commonly experienced symptoms, medications and non-cannabis self-management strategies were also captured. Self-rated cannabis effectiveness for endometriosis symptoms (combined descriptive data and by most utilised dosage forms) was reported, along with preferred dosage format, reasonings behind dosage format choice, and dose frequency. Data Analysis: Data analyses were conducted using SAS software (Version 9.4). Continuous data were described by means and standard deviations (SD) for parametric data; medians, interquartile ranges and minimum (min) and maximum (max) for non-parametric data, and categorical by counts and proportions expressed as percentages. Comparison of proportions was by Chi square test of independence. Analysis of variance (ANOVA) was used to compare effectiveness, with pairwise comparisons where appropriate. Of the free text responses, initial meaning units were condensed into codes by the first author (JS1). Codes with similar patterns were grouped into categories, with the entire process and categorisation overseen by the senior author (MA). Missing data were not replaced. Values were considered statistically significant if p < 0.05. Results Eligible responses from 28 countries (Prevalence predominantly Western-centric) were received from 889 participants. The mean (SD) age of respondents was 30.3 (6.9) years. Table 1 outlines the demographics, method of diagnosis, years since diagnosis and duration of cannabis utilisation. Figure 1 reports respondent numbers by country, with Appendix 1 providing this information in tabulated format. (Insert Table 1 and Fig. 1 here) Table 1 Demographics Endometriosis diagnosis* N = 889 (%) How were you diagnosed with endometriosis? Surgery (e.g., Laparoscopy) 740 (83.2) Ultrasound 226 (25.4) Magnetic Resonance Imaging (MRI) 108 (12.1) Told by a medical doctor / specialist based on my symptoms 327 (36.8) How long in years since you have been diagnosed with endometriosis? Mean (SD) 6.3 (6.7) Age at diagnosis? (N = 850) 24.8 (6.5) Location A remote area 21 (2.4) A rural area 248 (27.9) An urban area 620 (69.7) Highest level of education Did not finish high school / secondary education 32 (3.6) Completed high school / secondary education 185 (20.8) Diploma / Certificate 234 (26.3) Bachelor’s degree 315 (35.4) Master’s degree 101 (11.4) Doctorate / PhD 21 (2.4) Missing 1 (0.1) Duration of cannabis use How long (in years) have you been using cannabis (whether legal or illegal) to manage the pain and associated symptoms of endometriosis? Mean (SD) 4.4 (5.0) * Multiple choices allowed if applicable Current symptoms, medications, and self-management strategies Respondent were asked to choose the symptoms, medications and self-management strategies they were currently employing as part of their management plan. Fatigue (93.8%) and chronic pelvic pain (93.6%) were the most prevalent symptoms reported, with hip and leg pain, and nerve (i.e., neuropathic) pain, being the most reported free text responses. Non-opioid pain medications (e.g., Non-steroidal anti-inflammatories, acetaminophen) and hormonal medications were the medications of highest prevalence, with heat being the most prevalent self-management strategy employed (92.8%). (Insert Table 2 here) Table 2 Endometriosis symptoms, medications and self-management strategies Current endometriosis symptoms* N/889 (%) Fatigue 834 (93.8) Chronic Pelvic Pain 832 (93.6) Bowel symptoms 777 (87.4) Back pain 772 (86.8) Dysmenorrhoea (Period pain) 738 (83.0) Anxiety 708 (79.6) Difficulties with sleep 675 (75.9) Painful sex (dyspareunia) 659 (74.1) Nausea 644 (72.4) Gastrointestinal symptoms 633 (71.2) Headache or migraine 588 (66.1) Depression 588 (66.1) Bladder symptoms 535 (60.2) Heavy menstrual bleeding 442 (49.7) Other – Free text 122 (13.7) - Hip and leg pain 14 (11.5) - Nerve pain 8 (6.5) - Joint pain 7 (5.7) - Ovarian/ovulation pain 6 (4.9) - Sciatica 5 (4.1) - Brain fog 4 (3.3) - Bloating 4 (3.3) Current medications & treatments* Non-opioid pain medication 662 (74.5) Hormonal treatment 469 (52.7) Opioid-based pain medication 387 (43.5) Antidepressant medications 305 (34.3) Physiotherapy/pelvic exercises 264 (29.7) Antinausea medication 230 (25.8) Anxiolytic medications 200 (22.5) Acupuncture / Traditional Chinese Medicine** 150 (16.8) Herbal Medicine** 125 (14.0) Neuroleptic medication 113 (12.7) Sleeping medications 88 (9.9) Other – Free text 134 (15.0) - Chiropractic** 5 (3.7) - Osteopathy** 3 (2.2) Current self-management strategies* Heat 825 (92.8) Dietary choices 593 (66.7) Breathing exercises 533 (59.9) Dietary supplements or vitamins 485 (54.5) Low intensity exercise 433 (48.7) Massage 404 (45.4) Yoga 347 (39.0) Meditation 335 (37.7) Herbal medicines 271 (30.5) Acupressure 150 (16.8) Moderate to High intensity exercise 139 (15.6) Pilates 61 (6.8) Tai Chi 11 (1.2) Qi Gong 9 (1.0) Other – Free text 75 (8.4) - Transcutaneous electrical nerve stimulation 4 (5.3) - Pelvic floor exercises 4 (5.3) - Weights (i.e. Lifting) 3 (4.0) * Multiple choices allowed if applicable ** Administered by a qualified practitioner Classification of cannabis access Participants were asked to categorise whether their access to cannabis for symptomatic management of their endometriosis symptoms was from medical (under physician supervision/medical prescription), legal (this includes purchasing via dispensaries and other means where products are legally accessible but not under medical supervision) or illicit (i.e., non-legal) pathways. Despite growing regulatory allowances worldwide for medicinal cannabis adoption, with slower adult use/recreational implementation, illicit cannabis is still the predominant access pathway reported by the international endometriosis population (see Fig. 2 ). (Insert Fig. 2 here) Three most effective methods of cannabis administration Respondents were asked to select the three most therapeutically effective methods of cannabis administration (i.e., dosage formats) they had used to manage their endometriosis symptoms. We specifically asked for the three most effective methods of administration as previous research has suggested multi-product use across formats is common, comprising varying cannabinoid ratios, ostensibly to manage the different symptoms of endometriosis.( 23 , 29 , 35 , 36 ) Inhaled formats included joints, bongs (i.e., water pipe), vaporiser, pipes and inhaled oil concentrates ( via dab rigs, a special form of water pipe for heated cannabis concentrates) or hashish/resin ( via pipe). Oral formats included oral oils, edibles (homemade and/or dispensary bought), capsules, infusions (i.e., tea), medicated lozenges, juiced fresh flower or leaf, and oral tinctures. Other methods of administration included topical lotions, pessaries ( per vagina ) and suppositories ( per rectum ). (Insert Table 3 here) Table 3 – Most effective dosage formats for managing endometriosis symptoms Three most effective methods of administration N/889% INHALED - Dried cannabis bud (flower) - joints 416 (46.8) ORAL - Oil (e.g., THC/CBD oil) 276 (31.0) INHALED - Dried cannabis bud (flower) - bong (water pipe) 185 (20.8) ORAL - Cannabis edibles - homemade 181 (20.4) ORAL - Cannabis edibles - dispensary bought 161 (18.1) INHALED - Dried cannabis bud (flower) - vaporiser 145 (16.3) INHALED - Dried cannabis bud (flower) - pipe 108 (12.1) OTHER - Topical cream / lotion 104 (11.7) INHALED - oil concentrate (via "dab rigs" etc.) or hashish /resin (via pipe) 88 (9.9) ORAL - Capsules 53 (6.0) OTHER - Pessary (inserted into the vagina) 38 (4.3) ORAL - Oral tincture (alcohol / glycerin based) 35 (3.9) ORAL - Dried cannabis bud (flower) - infusion / tea 32 (3.6) OTHER - Suppository (inserted into the rectum) 17 (1.9) ORAL - Sublingual sprays 16 (1.8) OTHER - Transdermal patch 11 (1.2) ORAL - Medicated lozenges 6 (0.7) ORAL - Fresh cannabis bud (flower) or leaf - juiced 3 (0.3) ORAL - Dissolvable strips 1 (0.1) Dosage form specifics Of the top two dosage forms utilised, respondents were asked to provide reasoning for why they continued to utilise either inhaled and/or oral dosage forms for their pain and endometriosis-associated symptoms. The time taken for therapeutic onset of effect information and daily dose frequency per dosage format was also captured and is reported in Table 4 . (Insert Table 4 ) Table 4 – Dosage form specifics Reasons for continued utilisation of dosage form N = 889 Inhaled* (N/%) It provides fast relief of symptoms 577 (64.9) Allows tailoring of correct dose 360 (40.5) Side effects are more manageable 263 (29.6) All that is available (illicit sources) 197 (22.1) Recommended by friends/colleagues with endometriosis 79 (8.9) Recommended by my doctor 40 (4.5) Other – Free text 56 (6.3) - Easy/Cheap dosage form to use/more cost effective 6 (10.7) - Most effective format for symptoms 5 (8.9) Oral* (N/%) It provides longer lasting relief of symptoms 424 (47.7) Allows tailoring of correct dose 305 (34.3) Side effects are more manageable 281 (31.6) Recommended by friends/colleagues with endometriosis 123 (13.8) Recommended by my doctor 76 (8.5) Recommended by dispensary worker / pharmacist 37 (4.2) Other – Free text 82 (9.2) - Healthier than inhalation / cannot smoke or inhale 15 (18.3) - Easier method to dose / more convenient 4 (4.9) Inhaled - Time to onset of action (N = 640) (n/%) 5–10 minutes 263 (41.1) Less than 5 minutes 221 (34.5) 11–20 minutes 107 (16.7) 21–30 minutes 36 (5.6) Longer than 30 minutes 13 (2.0) Oral - Time to onset of action (N = 566) (n/%) 21–40 minutes 183 (32.3) 41–60 minutes 139 (24.6) Less than 20 minutes 100 (17.7) 61–90 minutes 96 (17.0) Longer than 90 minutes 48 (8.5) Mean cannabis dosage frequency per day Inhaled (N = 607) (n/%) Two to three times daily 207 (34.1) Don’t need to use every day 155 (25.6) Four or more times daily 141 (23.2) Once daily 104 (17.1) Oral (N-568) Once daily 188 (33.1) Don’t need to use every day 171 (30.1) Two to three times daily 165 (29.0) Four or more times daily 44 (7.7) * Multiple choices allowed if applicable Self-reported symptom effectiveness associated with cannabis consumption Respondents were asked to classify, using a numerical rating scale (0 = no effect and 10 = highly effective), how cannabis consumption has impacted a variety of common endometriosis symptoms. Collective (i.e., all dosage formats) mean, percentiles (25th, 50th and 75th ) and minimum/maximum data across 14 endometriosis symptoms are reported in Fig. 3 . This data is also presented in tabulated form in Supplementary File 2. (Insert Fig. 3 here) Additional analysis was undertaken on the two most effective dosage forms, inhaled dried cannabis flower (joint) and oral oils. Descriptive data along with inferential analysis comparing selected dosage forms is included in Supplementary Files 3 and 4. Inhaled dried cannabis flower (joint) appeared to demonstrate increased benefit for dysmenorrhea (p = 0.0001; 95% CI (-.26 to 0.81)), chronic pelvic pain (p = 0.0005; 95% CI (0.22 to 0.78)), nausea (p = 0.004; 95% CI (0.21 to 1.04)), back pain (p = 0.003; 95% CI (0.17 to 0.80)), headache or migraine (p = 0.004; 95% CI (0.20 to 1.08)), fatigue (p = 0.009; 95% CI (0.15 to 1.07)), depression (p = 0.009; 95% CI (0.16 to 1.10)), difficulties with sleep (p = 0.004; 95% CI (0.15 to 0.77)), and painful sex (dyspareunia) (p = 0.045; 95% CI (0.01 to 1.02)) compared to not using inhaled dried cannabis flower (joint). Evidence of increased benefit for oral oil was lower for back pain (p = 0.04; 95% CI (-0.71 to -0.02)), depression (p = 0.04; 95% CI (-1.06 to -0.02)), and difficulties with sleep (p = 0.04; 95% CI (-0.68 to -0.01)) compared to not using oral oils. Discussion To our knowledge, this study represents the first international survey undertaken to investigate the self-reported effectiveness of cannabis in the endometriosis cohort, along with associated dosage forms utilised, and dose frequency. The five countries with greatest representation were primarily Western-centric, with the USA (27.8%), United Kingdom and Northern Ireland (26.3%), Australia (22.5%), Canada (10.5%) and New Zealand (5.7%) having the largest respondent representation. Respondents reported using cannabis for symptomatic amelioration of symptoms on average for 4 years, with the majority (56.7%) utilising cannabis therapeutically from illicit sources, consistent with previously published literature.( 20 , 22 , 24 , 25 ) The therapeutic effectiveness of cannabis scored high on self-rated assessment across sleep difficulties, dysmenorrhoea, chronic pelvic pain and reducing nausea, which is consistent with previous research.( 23 , 24 ) Additionally, there was evidence of higher self-rated effectiveness for inhaled cannabis (joints) compared to not using joints, and evidence of lower self-rated effectiveness for oral oils versus not using oral oils. Inhalation via joint was the most common method of cannabis administration, followed by oral oils, which is also congruent with previous research.( 23 , 24 ) The main reported driver for cannabis consumption via inhalation was speed of pharmacological onset, whereas for oral oil it was the longer duration of pharmacological effects. Dose frequency across the two most utilised formats appears consistent with the drivers for adoption and pharmacokinetic differences (i.e., specifically absorption) between these two formats,( 37 , 38 ) with greater dose frequency reported for inhaled cannabis versus oral oils. Respondents self-reported that the two most effective dosage formats were inhaled cannabis (primarily joints) and oral oils. These modes of administration are consistent with previous work by this team, including cross-sectional ( 20 , 24 ) , and qualitative research, ( 22 ) as well as a retrospective cohort study,( 23 ) suggesting that these choices are consistent across a range of demographics and geographical locations. Due to the predominance of illicit cannabis being the primary source of access (56.7%), it is perhaps unsurprising that inhaled formats are more favoured, likely due to a lack of sophistication for other dosage forms in non-legal/legacy supply chains.( 23 ) This was demonstrated clearly in this study by the 22.1% that specifically reported that the inhaled route of administration was all that was available to them due to illicit procurement. This could also be exacerbated by the high cost of dried flower vaporisation devices, putting this format outside the reach of many people. Another plausible reason that our team has previously proposed ( 23 ) is that inhaled formats are often chosen due to the fast onset of action comparative to oral products. Inhalation of cannabis leads to rapid absorption and quick onset of pharmacological action, usually within 5–10 minutes,( 38 ) with THC levels detectable after a single inhalation and peaking within 10 minutes,( 39 ) however, it has a shorter duration of effect overall compared to oral intake (i.e., 0.25–3.5 hours).( 40 ) Compared to oral formats, inhaled forms lead to higher plasma levels of cannabinoids, and have greater comparative bioavailability.( 37 ) Our study findings strongly support rapid pharmacological onset being the key driver for inhaled adoption, with almost two thirds (64.9%) utilising inhaled formats due to fast relief of symptoms. This is further supported by the time to onset, with over three quarters (75%) reporting onset of symptom reduction within the first ten minutes, which is consistent with clinician experience and cannabinoid pharmacokinetic research.( 37 , 38 ) This rapid therapeutic onset could be particularly beneficial in breakthrough pain, or ‘endo flares’. Finally, inhaled formats allow for closer control of the level of intoxication/impairment versus symptom relief ( 28 ) (i.e., tailoring of correct dose), and in this study, just under half (40.5%) noted that this was a key reason for choosing this mode of administration, along with side effects being more manageable (29.6%). Compared to inhalation, oral absorption has lower bioavailability (~ 4–20%) due to extensive first-pass liver metabolism, and because of this, the onset of action is much slower, typically in the range of ~ 0.75 to 3 hours.( 40 ) However, oral cannabis-based products exert a substantively longer duration of pharmacological action, lasting between 6–8 hours, compared to the 2–4 hours of inhaled formats.( 24 , 38 ) Just under half (47.7%) of respondents reported that the main reason they chose oral oils was for this longer lasting relief of symptoms, and similar to the inhaled format, oral oils allowed for tailoring of correct dose (34.2%) and more manageable side effects (31.6%) which were the next most prevalent reasons. Of interest, oral time to onset of cannabis-based oral formats typically range between 30–180 minutes.( 37 , 38 ) In this study, 17.7% reported onset of effects within less than 20 minutes, and 32.3% reported time to onset of action between 21–40 minutes. Whilst the authors are uncertain as to why this faster onset of effects was reported compared to published pharmacokinetic literature, potential reasons for this faster onset of action for the oral format being reported in this cohort include (i) taking cannabinoids with a fatty meal increasing absorption,( 41 ) (albeit a recent study reports a delayed T max of THC and enhanced mean levels of THC and 11-OH-THC in the presence of high-fat food),( 42 ) or (ii) self-reported faster onset of oral pharmacological activity being due to subject expectancy effects or positive expectancy, which may be present due to overwhelming media reporting on the topic of cannabis. Dose frequency in previously published cross-sectional literature does not differentiate between dosage forms utilised, but reports that the most prevalent dosage frequency of cannabis for respective endometriosis cohorts was “ two to three times per day ”,( 20 ) or “ daily to multiple times per day. ”( 24 ) This mirrors findings in this study which reports that those utilising the inhaled format had the highest prevalence at “ two to three times per day” (34.1%), with the next highest being “ don’t need to use every day ” at 25.6%, and 23.2% utilising cannabis “ four or more times per day ”. This is suggestive that (i) a proportion of the endometriosis cohort is suffering considerable symptom burden / pain and requires regular consumption of inhaled cannabis due to inhaled formats only having short duration of effect (2–4 hours),( 38 ) and (ii) that a smaller percentage of the endometriosis cohort may only need to utilise inhaled cannabis irregularly for symptom control, which may be focused around the menstrual cycle where pain and other symptoms are intensified. Conversely, respondent data for oral oils tells a different story, with the most prevalent frequency being “ once daily ” (33.1%) or ‘ don’t need to use every day ” (25.6%). Given the longer duration of effects ranging between 6–8 hours for oral formats, women with endometriosis who are utilising oral cannabis may be relying on this longer duration to assist with sleep, or provide analgesic coverage for longer periods of time throughout the day. However, as 29% were utilising oils “ two to three times daily ”, this is suggestive that with a 6–8-hour duration of effect, 24-hour coverage could be possible. This data is suggestive that women are not only adapting the dose frequency, but also the mode of administration to target specific symptoms,( 35 ) and are utilising both inhaled and oral dosage forms, either based off their own product exploratory experience, or guided by medical or dispensary staff who are likely more knowledgeable about the pharmacokinetic implications of varied dosage formats in symptom management. To this point, previous research has demonstrated that the endometriosis cohort are utilising multiple cannabis dosage formats for symptom control,( 20 , 23 , 24 ) with findings from this study adding to this body of research. Self-reported effectiveness of cannabis (inclusive of all dosage forms) across a range of endometriosis-related symptoms were described, including difficulties with sleep, nausea, chronic pelvic pain, dysmenorrhoea (i.e., period pain), and mental health (anxiety and depression) according to reported medians. These results are consistent with previous literature on cannabis use in the endometriosis, dysmenorrhea, and pelvic pain cohorts.( 18 , 23 , 24 , 27 , 34 , 43 , 44 ) Given the pharmacological effects of THC on various receptor targets in the Endocannabinoid System (i.e., CB1 and CB2 receptors), and CBD’s effect on numerous other pharmacological targets such as Transient Receptor Potential Vanilloid 1 (TRPV1) and Serotonin (5HT1A) receptors, the role of cannabis and its major cannabinoids as an analgesic, sedative/hypnotic, anxiolytic, anti-depressant, anti-inflammatory and as an anti-emetic/anti-nauseant demonstrate plausible mechanisms for such clinical indications. ( 45 – 48 ) Conversely, cannabis utilisation demonstrated minimal impact on bladder symptoms, menorrhagia (i.e., heavy menstrual bleeding), or reducing gastrointestinal (GIT) or bowel symptoms associated with endometriosis, which is somewhat surprising given the anti-inflammatory activities of both major cannabinoids. However, potential causations of such symptoms could be of a structural (i.e., adhesions) nature that only surgery might address, or cannabis may negatively impact the microbiome of the GIT given the antimicrobial impact of cannabinoids such as CBD,( 49 ) or the known antibacterial nature of various cannabis terpenes/terpenoids.( 50 ) Significant associations between higher self-rated effectiveness and use of dried cannabis flower as a joint (inhaled) compared to not using dried cannabis flower as a joint, were seen for symptoms of period pain, chronic pelvic pain, nausea, back pain, headache or migraine, fatigue, depression, difficulties with sleep and painful sex. However, this is unlikely to be overly clinically relevant due to factors such as: (i) self-reported preference bias (i.e., belief joints work better due to ritual, faster onset or familiarity rather than actual measurable improvement), (ii) Increased risk of combustion byproducts causing pulmonary side effects, (iii) confounding due to comorbid symptom clustering (e.g., Those choosing joints may have more severe symptoms, greater cannabis tolerance or different usage patterns such as longer history of MC utilisation or multiple dosage form usage). Conversely, evidence of lower self-rated effectiveness for those using oral oil compared to not using oil, was seen for symptoms of back pain, depression and difficulties with sleep. Whilst such data represents real-world evidence, it does not fill the void of more rigorous clinical research, which is still recommended to determine cannabis and cannabinoid safety, tolerability and efficacy in this cohort. There are several limitations to this study which are important to outline. Whilst international in scope (albeit mainly Western-centric), limited participation was noted compared to our teams’ previous study,( 21 ) with lower than anticipated participation. This in part could be due to the survey running amid the global COVID-19 pandemic, however, could also be a result of survey fatigue, as this method of scientific inquiry was all that was available to many research teams during this time, and results may therefore not be generalisable to the wider endometriosis population. Recall bias( 51 ) and non-response bias( 52 ) which can influence responses, and skew the sample towards those that are either more severe in their symptom expression, or more favorable towards cannabis, are respective limitations. So too is sampling bias,( 53 ) due to the survey being advertised through the use of social media to endometriosis advocacy and support groups, potentially skewing results to include people more negatively impacted by their endometriosis compared to the general population. Notwithstanding, data from this paper is consistent with previous studies of similar scope and design.( 18 , 21 , 24 , 25 , 34 ) Conclusion Endometriosis is an oestrogen-dependent, systemic, chronic inflammatory condition for which many women experience sub-optimal symptom management from surgical or pharmaceutical options. Cannabis utilisation for symptom management is frequently being utilised by this cohort, primarily of illicit origin. Self-reported effectiveness of cannabis is noted across a wide range of symptoms, from chronic pelvic pain and dysmenorrhoea to improving sleep and reducing nausea, and dosage frequency is suggestive of higher dosing regimens which is consistent with the pharmacological duration of action, and speed of onset, that cannabinoids can provide across different symptom clusters. Whilst such evidence is encouraging, more robust data from clinical trials are needed to fully assess the efficacy of cannabis-based medicinal products. Abbreviations 5HT1A Serotonin 1A receptor 11-OH-THC 11-Hydroxy-THC ANOVA Analysis of Variance CB1 Cannabinoid 1 receptor CB2 Cannabinoid 2 receptor CBD Cannabidiol CPP Chronic Pelvic Pain ECS Endocannabinoid System GIT Gastrointestinal Tract GnRH Gonadotropin hormone-releasing hormone MC Medicinal Cannabis MRI Magnetic Resonance Imaging NSAID(s) Non-Steroidal Anti-inflammatory Drug(s) NZ New Zealand SD Standard Deviation THC Delta-9-tetrahydrocannabinol T max Time to reach peak plasma concentration TRPV1 Transient Receptor Potential Vanilloid 1 receptor UK United Kingdom Declarations Acknowledgements The authors wish to thank Endometriosis New Zealand, Endometriosis Australia, Nancy’s Nook, EndoIreland, Endometriosis UK, The World Endometriosis Society, Endometriosis Network (Canada), and the participants of this survey, for their support of this project. Funding information No specific funding was received for this research which forms part of a PhD research project for J. Sinclair. Competing interests JS1, AP and MA: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals and industry. Sponsors and donors also provide untied funding for work to advance the vision and mission of the Institute. JS1 is the recipient of a Western Sydney University Postgraduate Research Scholarship and is employed by Australian Natural Therapeutics Group. JS1 also sits on the board of the Australian Medicinal Cannabis Association ( pro bono ), the steering committee of Cannabis Clinicians Australia ( pro bono ) and the scientific advisory board of United in Compassion ( pro bono ). MA has previously been an advisory board member for Evolv Therapeutics, is currently an advisory board member for Nectar Brands, both of which sell medicinal cannabis products. He has previously received funding from Canopy Growth, OzMediCann Group and Cannim to run clinical studies on medicinal cannabis for women’s health conditions, outside the submitted work. JS2 is an Executive Director of Neurala Biosciences and the connected not-for-profit Psyche Institute, which are both involved with psychedelics research and the development of these agents as registered medicines. He is employed and holds equity with Neurala Biosciences. He is also an advisory board representative for HedoniaUSA, which formulates and sells nutraceutical products. He also has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, Noetic Foundry, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Global Pharma Group, Australian Natural Therapeutics Group (a cannabis growing and manufacturing company; as a previous scientific advisor), Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship, Medical Research Futures Fund, CSIRO Australia, Launch Victoria, Genesis Fund, Tin Alley Ventures. Ethics approval and consent to participate. All participants provided informed consent (extended) prior to participating in this survey. The study design was reviewed and approved by the Western Sydney University Human Research Ethics Committee (Approval # H14115). Participation was voluntary, and all participants were informed of their right to withdraw at any time without consequence. Clinical trial number: not applicable. hD research project for J. Sinclair. Author Contribution JS1 and MA conceived the study. JS1, MA and AE analysed survey data. JS1, MA, AE and AP wrote the paper. AP, JS2, JA and MA provided critical subject matter expertise and revisions. Data Availability The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Files. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request. References Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789-99. Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32(2):315-24. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268-79. Facchin F, Barbara G, Saita E, Mosconi P, Roberto A, Fedele L, et al. Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference. J Psychosom Obstet Gynaecol. 2015;36(4):135-41. Barbara G, Facchin F, Meschia M, Berlanda N, Frattaruolo MP, Vercellin IP. When love hurts. A systematic review on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning. Acta Obstet Gynecol Scand. 2017;96(6):668-87. Gambadauro P, Carli V, Hadlaczky G. Depressive symptoms among women with endometriosis: a systematic review and meta-analysis. Am J Obstet Gynecol. 2019;220(3):230-41. Barbara G, Buggio L, Facchin F, Vercellini P. Medical Treatment for Endometriosis: Tolerability, Quality of Life and Adherence. Front Glob Womens Health. 2021;2:729601. Australian Institute of Health & Welfare. Endometriosis 2023 [Available from: https://www.aihw.gov.au/reports/chronic-disease/endometriosis-in-australia/contents/summary#. Rowlands IJ, Abbott JA, Montgomery GW, Hockey R, Rogers P, Mishra GD. Prevalence and incidence of endometriosis in Australian women: a data linkage cohort study. BJOG. 2021;128(4):657-65. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):hoac009. Practice Committee of the American Society for Reproductive M. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril. 2014;101(4):927-35. Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D'Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400-12. Practice Bulletin No. 114: Management of Endometriosis. Obstetrics & Gynecology. 2010;116(1):223-36. Leyland N, Casper R, Laberge P, Singh SS, Sogc. Endometriosis: diagnosis and management. J Obstet Gynaecol Can. 2010;32(7 Suppl 2):S1-32. Becker CM, Gattrell WT, Gude K, Singh SS. Reevaluating response and failure of medical treatment of endometriosis: a systematic review. Fertil Steril. 2017;108(1):125-36. Evans S, Villegas V, Dowding C, Druitt M, O'Hara R, Mikocka-Walus A. Treatment use and satisfaction in Australian women with endometriosis: A mixed-methods study. Intern Med J. 2021. Giese N, Gilbert E, Hawkey A, Armour M. Unmet Needs of Australians in Endometriosis Research: A Qualitative Study of Research Priorities, Drivers, and Barriers to Participation in People with Endometriosis. Medicina (Kaunas). 2023;59(9):1655. Armour M, Sinclair J, Chalmers KJ, Smith CA. Self-management strategies amongst Australian women with endometriosis: a national online survey. BMC Complement Altern Med. 2019;19(1):17. Russo EB. Cannabis treatments in obstetrics and gynecology: a historical review. Journal of Cannabis Therapeutics. 2002;2(3-4):5-35. Armour M, Sinclair J, Noller G, Girling J, Larcombe M, Al-Dabbas MA, et al. Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. Journal of women's health (2002). 2020;30(10):1-8. Armour M, Sinclair J, Cheng J, Davis P, Hameed A, Meegahapola H, et al. Endometriosis and Cannabis Consumption During the COVID-19 Pandemic: An International Cross-Sectional Survey. Cannabis Cannabinoid Res. 2022;7(4):1-9. Sinclair J, Abbott J, Mikocka-Walus A, Ng CHM, Sarris J, Evans S, et al. "A glimmer of hope" - Perceptions, barriers, and drivers for medicinal cannabis use amongst Australian and New Zealand people with endometriosis. Reprod Fertil. 2023;4(4):1-15. Sinclair J, Collett L, Abbott J, Pate DW, Sarris J, Armour M. Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms. PLoS One. 2021;16(10):1-12. 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. 2019;42(3):256-61. Sinclair J, Toufaili Y, Gock S, Pegorer AG, Wattle J, Franke M, et al. Cannabis Use for Endometriosis: Clinical and Legal Challenges in Australia and New Zealand. Cannabis Cannabinoid Res. 2021;7(4):1-9. Carrubba A, Spaulding, AC., Ebbert, JO, DeStephano, CC. Patient-reported Use of Medical Cannabis for management of Chronic Pelvic Pain. Obstetrics & Gynecology. 2020;135:84S. Carrubba AR, Ebbert JO, Spaulding AC, DeStephano D, DeStephano CC. Use of Cannabis for Self-Management of Chronic Pelvic Pain. J Womens Health (Larchmt). 2021;30(9):1344-51. Sinclair J, Armour S, Akowuah JA, Proudfoot A, Armour M. "Should I Inhale?"-Perceptions, Barriers, and Drivers for Medicinal Cannabis Use amongst Australian Women with Primary Dysmenorrhoea: A Qualitative Study. Int J Environ Res Public Health. 2022;19(3):1-11. Proudfoot A, Duffy S, Sinclair J, Abbott J, Armour M. A survey of cost, access and outcomes for cannabinoid-based medicinal product use by Australians with endometriosis. Australian and New Zealand Journal of Obstetrics and Gynaecology. 2024;64(4):411-5. Bilgic E, Guzel E, Kose S, Aydin MC, Karaismailoglu E, Akar I, et al. Endocannabinoids modulate apoptosis in endometriosis and adenomyosis. Acta Histochem. 2017;119(5):523-32. 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. Sanchez AM, Quattrone F, Pannese M, Ulisse A, Candiani M, Diaz-Alonso J, et al. The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis. Hum Reprod. 2017;32(1):175-84. Bouaziz J, Bar On A, Seidman DS, Soriano D. The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. Cannabis Cannabinoid Res. 2017;2(1):72-80. Armour M, Sinclair J, Noller G, Girling J, Larcombe M, Al-Dabbas MA, et al. Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. J Womens Health (Larchmt). 2021;30(10):1485-92. Sinclair J, Abbott J, Proudfoot A, Armour M. The Place of Cannabinoids in the Treatment of Gynecological Pain. Drugs. 2023;83(17):1571-9. Farooqi T, Bhuyan DJ, Low M, Sinclair J, Leonardi M, Armour M. Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System. J Clin Med. 2023;12(22). Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327-60. MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12-9. Foster BC, Abramovici H, Harris CS. Cannabis and Cannabinoids: Kinetics and Interactions. Am J Med. 2019;132(11):1266-70. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-804. Saals B, De Bie TH, Osmanoglou E, van de Laar T, Tuin AW, van Orten-Luiten ACB, et al. A high-fat meal significantly impacts the bioavailability and biphasic absorption of cannabidiol (CBD) from a CBD-rich extract in men and women. Sci Rep. 2025;15(1):3678. Lunn S, Diaz P, O'Hearn S, Cahill SP, Blake A, Narine K, et al. Human Pharmacokinetic Parameters of Orally Administered Delta(9)-Tetrahydrocannabinol Capsules Are Altered by Fed Versus Fasted Conditions and Sex Differences. Cannabis Cannabinoid Res. 2019;4(4):255-64. Yang EC, Koenig NA, Gong M, Brotto LA, Barr AM, Lee T, et al. Cannabis use preferences in women with myofascial pelvic pain: A cross-sectional study. Eur J Obstet Gynecol Reprod Biol X. 2023;18:100192. Liang AL, Gingher EL, Coleman JS. Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review. Obstet Gynecol. 2022;139(2):287-96. Aggarwal SK. Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. Clin J Pain. 2013;29(2):162-71. National Academies of Sciences, Engineering and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington DC: The National Academies Press.; 2017. Machado Rocha FC, Stefano SC, De Cassia Haiek R, Rosa Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl). 2008;17(5):431-43. Upton R, ElSohly, M., Romm, A., Russo, E., Sexton, M, editor. Cannabis inflorescence. Scotts Valley, California: American Herbal Pharmacopoeia; 2013. Blaskovich MAT, Kavanagh AM, Elliott AG, Zhang B, Ramu S, Amado M, et al. The antimicrobial potential of cannabidiol. Commun Biol. 2021;4(1):7. Masyita A, Mustika Sari R, Dwi Astuti A, Yasir B, Rahma Rumata N, Emran TB, et al. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chem X. 2022;13:100217. Pannucci CJ, Wilkins EG. Identifying and avoiding bias in research. Plast Reconstr Surg. 2010;126(2):619-25. Berg N. Non-Resonse Bias. In: Kempf-Leonard K, editor. Encyclopedia of Social Measurement. 2. London: Academic Press; 2005. p. 865-73. Benedict C, Hahn AL, Diefenbach MA, Ford JS. Recruitment via social media: advantages and potential biases. Digit Health. 2019;5:2055207619867223. Additional Declarations Competing interest reported. JS1, AP and MA: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals and industry. Sponsors and donors also provide untied funding for work to advance the vision and mission of the Institute. JS1 is the recipient of a Western Sydney University Postgraduate Research Scholarship and is employed by Australian Natural Therapeutics Group. JS1 also sits on the board of the Australian Medicinal Cannabis Association (pro bono), the steering committee of Cannabis Clinicians Australia (pro bono) and the scientific advisory board of United in Compassion (pro bono). MA has previously been an advisory board member for Evolv Therapeutics, is currently an advisory board member for Nectar Brands, both of which sell medicinal cannabis products. He has previously received funding from Canopy Growth, OzMediCann Group and Cannim to run clinical studies on medicinal cannabis for women’s health conditions, outside the submitted work. JS2 is an Executive Director of Neurala Biosciences and the connected not-for-profit Psychae Institute, which are both involved with psychedelics research and the development of these agents as registered medicines. He is employed and holds equity with Neurala Biosciences. He is also an advisory board representative for HedoniaUSA, which formulates and sells nutraceutical products. He also has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, Noetic Foundry, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Global Pharma Group, Australian Natural Therapeutics Group (a cannabis growing and manufacturing company; as a previous scientific advisor), Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship, Medical Research Futures Fund, CSIRO Australia, Launch Victoria, Genesis Fund, Tin Alley Ventures. 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JS1, AP and MA: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals and industry. Sponsors and donors also provide untied funding for work to advance the vision and mission of the Institute. JS1 is the recipient of a Western Sydney University Postgraduate Research Scholarship and is employed by Australian Natural Therapeutics Group. JS1 also sits on the board of the Australian Medicinal Cannabis Association (pro bono), the steering committee of Cannabis Clinicians Australia (pro bono) and the scientific advisory board of United in Compassion (pro bono). MA has previously been an advisory board member for Evolv Therapeutics, is currently an advisory board member for Nectar Brands, both of which sell medicinal cannabis products. He has previously received funding from Canopy Growth, OzMediCann Group and Cannim to run clinical studies on medicinal cannabis for women’s health conditions, outside the submitted work. JS2 is an Executive Director of Neurala Biosciences and the connected not-for-profit Psychae Institute, which are both involved with psychedelics research and the development of these agents as registered medicines. He is employed and holds equity with Neurala Biosciences. He is also an advisory board representative for HedoniaUSA, which formulates and sells nutraceutical products. He also has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Integria Healthcare \u0026 MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, Noetic Foundry, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Global Pharma Group, Australian Natural Therapeutics Group (a cannabis growing and manufacturing company; as a previous scientific advisor), Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship, Medical Research Futures Fund, CSIRO Australia, Launch Victoria, Genesis Fund, Tin Alley Ventures.","formattedTitle":"“A dose of relief?”: Results of an international survey exploring self-reported effectiveness, dose and dosage forms of cannabis for endometriosis pain and related symptoms","fulltext":[{"header":"Background","content":"\u003cp\u003eEndometriosis is a chronic, systemic, inflammatory gynaecological disease associated with considerable morbidity, including chronic pelvic pain, dysmenorrhoea, fatigue and infertility.(\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Common co-morbidities include depression, anxiety, sexual dysfunction and fatigue, and often people with the condition report poor quality of life.(\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Prevalence rates vary depending on country, but current evidence suggests a prevalence rate of between 10–14% of women and those presumed female at birth. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eOver the past 15 years, numerous guidelines (\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e–\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) on endometriosis management have been published and cover the usage of laparoscopic surgery, hormonal agents (combined hormonal contraceptives, progestins, progestogens, gonadotropin hormone-releasing hormone (GnRH) agonists, GnRH antagonists and aromatase inhibitors) and analgesic medications. However, despite the array of treatment options, medical therapy does not provide many women with adequate or continued relief from endometriosis-associated pain,(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) and in Australia, treatment satisfaction for people with endometriosis is low, with over a third of women dissatisfied with their treatment outcomes.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) In addition, there are women who may not be able to access such management options, due to either socio-economic disadvantage, geographical isolation, or due to the side-effects, addiction potential, or contraindications associated with individual medications.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThe combination of inadequate pain management, issues with side effects of many medications (particularly hormonal interventions), and concerns around addiction and dependence (e.g., opioids) are not uncommon.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) This is a key reason many women explore different self-management strategies to assist with pain and other associated endometriosis symptoms.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) Among these self-initiated management strategies, the re-emergence of cannabis (i.e., cannabidiol (CBD) and d-9-tetrahydrocannabinol (THC)) as a therapeutic option (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) is surprisingly common, and provides self-reported relief across not only a wide range of endometriosis-associated symptoms, (\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e–\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) but also other gynaecological conditions such as chronic pelvic pain (CPP),(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) and primary dysmenorrhoea.(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) In a cohort of Australian endometriosis patients, the cost of legal access and lack of public and private insurance product cost reimbursement was associated with under-dosing of cannabinoids and continued reliance on cheaper illicit sources to ‘bridge the gap’ in order to achieve adequate symptom relief.(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) Whilst preliminary studies have proposed that endocannabinoid system dysfunction may be present in those with endometriosis,(\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e–\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) and endometriosis-associated pain may be targeted by modulating this system,(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) more research is necessary to understand these mechanisms more fully.\u003c/p\u003e\u003cp\u003eWith a growing international trend towards cannabis legalisation across numerous jurisdictions, including both medical and recreational/adult use, researchers need to understand the potential impacts of this growing trend on the endometriosis population, and gather data to assist in the development of robust clinical trials to assess safety, tolerability and efficacy. Given that previous published data on self-reported cannabis consumption in the endometriosis population has primarily focused on the southern hemisphere,(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e) this study sought to capture data from the larger international endometriosis community, and investigates the different self-management options being employed by the endometriosis cohort (aside from cannabis), self-rated cannabis effectiveness across symptoms, the different cannabis dosage forms being employed, and cannabis dose frequency.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eSample and recruitment\u003c/em\u003e:\u003c/p\u003e\u003cp\u003eThe survey was developed by the research team who have expertise in medicinal cannabis and endometriosis. A copy of the survey can be found in Supplementary File 1. This international survey was approved on the 8th of December, 2020 by the Western Sydney University Human Research Ethics Committee (Approval # H14115). The survey was hosted on the Qualtrics platform (Qualtrics Ltd), was open to people world-wide and required approximately 15–30 minutes to complete. Features were enabled within the Qualtrics platform (i.e., no IP addresses recorded; no cookies being used) to ensure anonymity due to potential disclosure of illegal activities. The survey was open for 12-weeks between mid-January to mid-April 2021, during the then developing COVID-19 pandemic. All research was conducted in compliance with the Helsinki Declaration.\u003c/p\u003e\u003cp\u003ePeople were eligible to participate if they had a medical diagnosis of endometriosis, were aged between 18–55 years, and had used cannabis or phytocannabinoid-based products (e.g., CBD oil, whole cannabis oils, legal dried flowers (“buds”) with known levels of THC and/or CBD, or non-legal forms of cannabis) in the past 3 months specifically for the purpose of managing their endometriosis pain and/or related symptoms. Recruitment was conducted \u003cem\u003evia\u003c/em\u003e the social media platforms of Endometriosis New Zealand, Endometriosis Australia, Nancy’s Nook, EndoIreland, Endometriosis UK, The World Endometriosis Society and Endometriosis Network (Canada).\u003c/p\u003e\u003cp\u003eReporting in this paper includes demographic information including age, location, diagnosis (age and type of diagnostic test used) education level, participant numbers by country and classification of cannabis use. Commonly experienced symptoms, medications and non-cannabis self-management strategies were also captured. Self-rated cannabis effectiveness for endometriosis symptoms (combined descriptive data and by most utilised dosage forms) was reported, along with preferred dosage format, reasonings behind dosage format choice, and dose frequency.\u003c/p\u003e\u003ch2\u003eData Analysis:\u003c/h2\u003e\u003cp\u003eData analyses were conducted using SAS software (Version 9.4). Continuous data were described by means and standard deviations (SD) for parametric data; medians, interquartile ranges and minimum (min) and maximum (max) for non-parametric data, and categorical by counts and proportions expressed as percentages. Comparison of proportions was by Chi square test of independence. Analysis of variance (ANOVA) was used to compare effectiveness, with pairwise comparisons where appropriate. Of the free text responses, initial meaning units were condensed into codes by the first author (JS1). Codes with similar patterns were grouped into categories, with the entire process and categorisation overseen by the senior author (MA). Missing data were not replaced. Values were considered statistically significant if p \u0026lt; 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eEligible responses from 28 countries (Prevalence predominantly Western-centric) were received from 889 participants. The mean (SD) age of respondents was 30.3 (6.9) years. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e outlines the demographics, method of diagnosis, years since diagnosis and duration of cannabis utilisation. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e reports respondent numbers by country, with \u003cspan refid=\"Sec6\" class=\"InternalRef\"\u003eAppendix\u003c/span\u003e 1 providing this information in tabulated format. (Insert Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndometriosis diagnosis*\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;889 (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHow were you diagnosed with endometriosis?\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery (e.g., Laparoscopy)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e740 (83.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasound\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e226 (25.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnetic Resonance Imaging (MRI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e108 (12.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTold by a medical doctor / specialist based on my symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e327 (36.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHow long in years since you have been diagnosed with endometriosis?\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMean (SD)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e6.3 (6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge at diagnosis? (N\u0026thinsp;=\u0026thinsp;850)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.8 (6.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLocation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA remote area\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (2.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA rural area\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e248 (27.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAn urban area\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e620 (69.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHighest level of education\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDid not finish high school / secondary education\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (3.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCompleted high school / secondary education\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e185 (20.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiploma / Certificate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e234 (26.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBachelor\u0026rsquo;s degree\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e315 (35.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaster\u0026rsquo;s degree\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e101 (11.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDoctorate / PhD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (2.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMissing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDuration of cannabis use\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHow long (in years) have you been using cannabis (whether legal or illegal) to manage the pain and associated symptoms of endometriosis?\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMean (SD)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e4.4 (5.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e* Multiple choices allowed if applicable\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eCurrent symptoms, medications, and self-management strategies\u003c/em\u003e\u003c/p\u003e\u003cp\u003eRespondent were asked to choose the symptoms, medications and self-management strategies they were currently employing as part of their management plan. Fatigue (93.8%) and chronic pelvic pain (93.6%) were the most prevalent symptoms reported, with hip and leg pain, and nerve (i.e., neuropathic) pain, being the most reported free text responses. Non-opioid pain medications (e.g., Non-steroidal anti-inflammatories, acetaminophen) and hormonal medications were the medications of highest prevalence, with heat being the most prevalent self-management strategy employed (92.8%). (Insert Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEndometriosis symptoms, medications and self-management strategies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCurrent endometriosis symptoms*\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN/889 (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFatigue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e834 (93.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic Pelvic Pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e832 (93.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBowel symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e777 (87.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBack pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e772 (86.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDysmenorrhoea (Period pain)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e738 (83.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e708 (79.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDifficulties with sleep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e675 (75.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePainful sex (dyspareunia)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e659 (74.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e644 (72.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e633 (71.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeadache or migraine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e588 (66.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDepression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e588 (66.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBladder symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e535 (60.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeavy menstrual bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e442 (49.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther \u0026ndash; Free text\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e122 (13.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Hip and leg pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (11.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Nerve pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8 (6.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Joint pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7 (5.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Ovarian/ovulation pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (4.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Sciatica\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (4.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Brain fog\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (3.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Bloating\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (3.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCurrent medications \u0026amp; treatments*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-opioid pain medication\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e662 (74.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHormonal treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e469 (52.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOpioid-based pain medication\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e387 (43.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntidepressant medications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e305 (34.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhysiotherapy/pelvic exercises\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e264 (29.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntinausea medication\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e230 (25.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnxiolytic medications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e200 (22.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcupuncture / Traditional Chinese Medicine**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e150 (16.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHerbal Medicine**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e125 (14.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuroleptic medication\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e113 (12.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleeping medications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e88 (9.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther \u0026ndash; Free text\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e134 (15.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Chiropractic**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (3.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Osteopathy**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (2.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCurrent self-management strategies*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeat\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e825 (92.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDietary choices\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e593 (66.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBreathing exercises\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e533 (59.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDietary supplements or vitamins\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e485 (54.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow intensity exercise\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e433 (48.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMassage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e404 (45.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYoga\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e347 (39.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeditation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e335 (37.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHerbal medicines\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e271 (30.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcupressure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e150 (16.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate to High intensity exercise\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e139 (15.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePilates\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e61 (6.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTai Chi\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (1.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQi Gong\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (1.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther \u0026ndash; Free text\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e75 (8.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Transcutaneous electrical nerve stimulation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (5.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Pelvic floor exercises\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (5.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Weights (i.e. Lifting)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (4.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e* Multiple choices allowed if applicable ** Administered by a qualified practitioner\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cem\u003eClassification of cannabis access\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eParticipants were asked to categorise whether their access to cannabis for symptomatic management of their endometriosis symptoms was from medical (under physician supervision/medical prescription), legal (this includes purchasing \u003cem\u003evia\u003c/em\u003e dispensaries and other means where products are legally accessible but not under medical supervision) or illicit (i.e., non-legal) pathways. Despite growing regulatory allowances worldwide for medicinal cannabis adoption, with slower adult use/recreational implementation, illicit cannabis is still the predominant access pathway reported by the international endometriosis population (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). (Insert Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eThree most effective methods of cannabis administration\u003c/em\u003e\u003c/p\u003e\u003cp\u003eRespondents were asked to select the three most therapeutically effective methods of cannabis administration (i.e., dosage formats) they had used to manage their endometriosis symptoms. We specifically asked for the three most effective methods of administration as previous research has suggested multi-product use across formats is common, comprising varying cannabinoid ratios, ostensibly to manage the different symptoms of endometriosis.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) Inhaled formats included joints, bongs (i.e., water pipe), vaporiser, pipes and inhaled oil concentrates (\u003cem\u003evia\u003c/em\u003e dab rigs, a special form of water pipe for heated cannabis concentrates) or hashish/resin (\u003cem\u003evia\u003c/em\u003e pipe). Oral formats included oral oils, edibles (homemade and/or dispensary bought), capsules, infusions (i.e., tea), medicated lozenges, juiced fresh flower or leaf, and oral tinctures. Other methods of administration included topical lotions, pessaries (\u003cem\u003eper vagina\u003c/em\u003e) and suppositories (\u003cem\u003eper rectum\u003c/em\u003e). (Insert Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u0026ndash; Most effective dosage formats for managing endometriosis symptoms\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThree most effective methods of administration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN/889%\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINHALED - Dried cannabis bud (flower) - joints\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e416 (46.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Oil (e.g., THC/CBD oil)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e276 (31.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINHALED - Dried cannabis bud (flower) - bong (water pipe)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e185 (20.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Cannabis edibles - homemade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e181 (20.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Cannabis edibles - dispensary bought\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e161 (18.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINHALED - Dried cannabis bud (flower) - vaporiser\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e145 (16.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINHALED - Dried cannabis bud (flower) - pipe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e108 (12.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOTHER - Topical cream / lotion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e104 (11.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINHALED - oil concentrate (via \"dab rigs\" etc.) or hashish /resin (via pipe)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e88 (9.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Capsules\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e53 (6.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOTHER - Pessary (inserted into the vagina)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e38 (4.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Oral tincture (alcohol / glycerin based)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35 (3.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Dried cannabis bud (flower) - infusion / tea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e32 (3.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOTHER - Suppository (inserted into the rectum)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17 (1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Sublingual sprays\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (1.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOTHER - Transdermal patch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (1.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Medicated lozenges\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (0.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Fresh cannabis bud (flower) or leaf - juiced\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (0.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eORAL - Dissolvable strips\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (0.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eDosage form specifics\u003c/em\u003e\u003c/p\u003e\u003cp\u003eOf the top two dosage forms utilised, respondents were asked to provide reasoning for why they continued to utilise either inhaled and/or oral dosage forms for their pain and endometriosis-associated symptoms. The time taken for therapeutic onset of effect information and daily dose frequency per dosage format was also captured and is reported in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. (Insert Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u0026ndash; Dosage form specifics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReasons for continued utilisation of dosage form\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;889\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInhaled*\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(N/%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIt provides fast relief of symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e577 (64.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAllows tailoring of correct dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e360 (40.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSide effects are more manageable\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e263 (29.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAll that is available (illicit sources)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e197 (22.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecommended by friends/colleagues with endometriosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79 (8.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecommended by my doctor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40 (4.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther \u0026ndash; Free text\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (6.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Easy/Cheap dosage form to use/more cost effective\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (10.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Most effective format for symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (8.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOral*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e(N/%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIt provides longer lasting relief of symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e424 (47.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAllows tailoring of correct dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e305 (34.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSide effects are more manageable\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e281 (31.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecommended by friends/colleagues with endometriosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e123 (13.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecommended by my doctor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e76 (8.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecommended by dispensary worker / pharmacist\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (4.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther \u0026ndash; Free text\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82 (9.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Healthier than inhalation / cannot smoke or inhale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (18.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Easier method to dose / more convenient\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (4.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInhaled - Time to onset of action (N\u0026thinsp;=\u0026thinsp;640)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e(n/%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u0026ndash;10 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e263 (41.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLess than 5 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e221 (34.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u0026ndash;20 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e107 (16.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e21\u0026ndash;30 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (5.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLonger than 30 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (2.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOral - Time to onset of action (N\u0026thinsp;=\u0026thinsp;566)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e(n/%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e21\u0026ndash;40 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e183 (32.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e41\u0026ndash;60 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e139 (24.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLess than 20 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e100 (17.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e61\u0026ndash;90 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96 (17.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLonger than 90 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (8.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean cannabis dosage frequency per day\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInhaled (N\u0026thinsp;=\u0026thinsp;607)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e(n/%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTwo to three times daily\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e207 (34.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDon\u0026rsquo;t need to use every day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155 (25.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFour or more times daily\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e141 (23.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce daily\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e104 (17.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOral (N-568)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnce daily\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e188 (33.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDon\u0026rsquo;t need to use every day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e171 (30.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTwo to three times daily\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165 (29.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFour or more times daily\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44 (7.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e* Multiple choices allowed if applicable\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003ch2\u003e\u003cem\u003eSelf-reported symptom effectiveness associated with cannabis consumption\u003c/em\u003e\u003c/h2\u003e\u003cp\u003eRespondents were asked to classify, using a numerical rating scale (0\u0026thinsp;=\u0026thinsp;no effect and 10\u0026thinsp;=\u0026thinsp;highly effective), how cannabis consumption has impacted a variety of common endometriosis symptoms. Collective (i.e., all dosage formats) mean, percentiles (25th, 50th and 75th ) and minimum/maximum data across 14 endometriosis symptoms are reported in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. This data is also presented in tabulated form in Supplementary File 2. (Insert Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003eAdditional analysis was undertaken on the two most effective dosage forms, inhaled dried cannabis flower (joint) and oral oils. Descriptive data along with inferential analysis comparing selected dosage forms is included in Supplementary Files 3 and 4. Inhaled dried cannabis flower (joint) appeared to demonstrate increased benefit for dysmenorrhea (p\u0026thinsp;=\u0026thinsp;0.0001; 95% CI (-.26 to 0.81)), chronic pelvic pain (p\u0026thinsp;=\u0026thinsp;0.0005; 95% CI (0.22 to 0.78)), nausea (p\u0026thinsp;=\u0026thinsp;0.004; 95% CI (0.21 to 1.04)), back pain (p\u0026thinsp;=\u0026thinsp;0.003; 95% CI (0.17 to 0.80)), headache or migraine (p\u0026thinsp;=\u0026thinsp;0.004; 95% CI (0.20 to 1.08)), fatigue (p\u0026thinsp;=\u0026thinsp;0.009; 95% CI (0.15 to 1.07)), depression (p\u0026thinsp;=\u0026thinsp;0.009; 95% CI (0.16 to 1.10)), difficulties with sleep (p\u0026thinsp;=\u0026thinsp;0.004; 95% CI (0.15 to 0.77)), and painful sex (dyspareunia) (p\u0026thinsp;=\u0026thinsp;0.045; 95% CI (0.01 to 1.02)) compared to not using inhaled dried cannabis flower (joint). Evidence of increased benefit for oral oil was lower for back pain (p\u0026thinsp;=\u0026thinsp;0.04; 95% CI (-0.71 to -0.02)), depression (p\u0026thinsp;=\u0026thinsp;0.04; 95% CI (-1.06 to -0.02)), and difficulties with sleep (p\u0026thinsp;=\u0026thinsp;0.04; 95% CI (-0.68 to -0.01)) compared to not using oral oils.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this study represents the first international survey undertaken to investigate the self-reported effectiveness of cannabis in the endometriosis cohort, along with associated dosage forms utilised, and dose frequency. The five countries with greatest representation were primarily Western-centric, with the USA (27.8%), United Kingdom and Northern Ireland (26.3%), Australia (22.5%), Canada (10.5%) and New Zealand (5.7%) having the largest respondent representation. Respondents reported using cannabis for symptomatic amelioration of symptoms on average for 4 years, with the majority (56.7%) utilising cannabis therapeutically from illicit sources, consistent with previously published literature.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) The therapeutic effectiveness of cannabis scored high on self-rated assessment across sleep difficulties, dysmenorrhoea, chronic pelvic pain and reducing nausea, which is consistent with previous research.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) Additionally, there was evidence of higher self-rated effectiveness for inhaled cannabis (joints) compared to not using joints, and evidence of lower self-rated effectiveness for oral oils \u003cem\u003eversus\u003c/em\u003e not using oral oils. Inhalation \u003cem\u003evia\u003c/em\u003e joint was the most common method of cannabis administration, followed by oral oils, which is also congruent with previous research.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) The main reported driver for cannabis consumption \u003cem\u003evia\u003c/em\u003e inhalation was speed of pharmacological onset, whereas for oral oil it was the longer duration of pharmacological effects. Dose frequency across the two most utilised formats appears consistent with the drivers for adoption and pharmacokinetic differences (i.e., specifically absorption) between these two formats,(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) with greater dose frequency reported for inhaled cannabis \u003cem\u003eversus\u003c/em\u003e oral oils.\u003c/p\u003e\u003cp\u003eRespondents self-reported that the two most effective dosage formats were inhaled cannabis (primarily joints) and oral oils. These modes of administration are consistent with previous work by this team, including cross-sectional (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e and qualitative research, (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) as well as a retrospective cohort study,(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) suggesting that these choices are consistent across a range of demographics and geographical locations. Due to the predominance of illicit cannabis being the primary source of access (56.7%), it is perhaps unsurprising that inhaled formats are more favoured, likely due to a lack of sophistication for other dosage forms in non-legal/legacy supply chains.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) This was demonstrated clearly in this study by the 22.1% that specifically reported that the inhaled route of administration was all that was available to them due to illicit procurement. This could also be exacerbated by the high cost of dried flower vaporisation devices, putting this format outside the reach of many people. Another plausible reason that our team has previously proposed (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) is that inhaled formats are often chosen due to the fast onset of action comparative to oral products. Inhalation of cannabis leads to rapid absorption and quick onset of pharmacological action, usually within 5\u0026ndash;10 minutes,(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) with THC levels detectable after a single inhalation and peaking within 10 minutes,(\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e) however, it has a shorter duration of effect overall compared to oral intake (i.e., 0.25\u0026ndash;3.5 hours).(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eCompared to oral formats, inhaled forms lead to higher plasma levels of cannabinoids, and have greater comparative bioavailability.(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) Our study findings strongly support rapid pharmacological onset being the key driver for inhaled adoption, with almost two thirds (64.9%) utilising inhaled formats due to fast relief of symptoms. This is further supported by the time to onset, with over three quarters (75%) reporting onset of symptom reduction within the first ten minutes, which is consistent with clinician experience and cannabinoid pharmacokinetic research.(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) This rapid therapeutic onset could be particularly beneficial in breakthrough pain, or \u0026lsquo;endo flares\u0026rsquo;. Finally, inhaled formats allow for closer control of the level of intoxication/impairment \u003cem\u003eversus\u003c/em\u003e symptom relief (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) (i.e., tailoring of correct dose), and in this study, just under half (40.5%) noted that this was a key reason for choosing this mode of administration, along with side effects being more manageable (29.6%).\u003c/p\u003e\u003cp\u003eCompared to inhalation, oral absorption has lower bioavailability (~\u0026thinsp;4\u0026ndash;20%) due to extensive first-pass liver metabolism, and because of this, the onset of action is much slower, typically in the range of ~\u0026thinsp;0.75 to 3 hours.(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e) However, oral cannabis-based products exert a substantively longer duration of pharmacological action, lasting between 6\u0026ndash;8 hours, compared to the 2\u0026ndash;4 hours of inhaled formats.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) Just under half (47.7%) of respondents reported that the main reason they chose oral oils was for this longer lasting relief of symptoms, and similar to the inhaled format, oral oils allowed for tailoring of correct dose (34.2%) and more manageable side effects (31.6%) which were the next most prevalent reasons. Of interest, oral time to onset of cannabis-based oral formats typically range between 30\u0026ndash;180 minutes.(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) In this study, 17.7% reported onset of effects within less than 20 minutes, and 32.3% reported time to onset of action between 21\u0026ndash;40 minutes. Whilst the authors are uncertain as to why this faster onset of effects was reported compared to published pharmacokinetic literature, potential reasons for this faster onset of action for the oral format being reported in this cohort include (i) taking cannabinoids with a fatty meal increasing absorption,(\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e) (albeit a recent study reports a delayed T\u003csub\u003emax\u003c/sub\u003e of THC and enhanced mean levels of THC and 11-OH-THC in the presence of high-fat food),(\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) or (ii) self-reported faster onset of oral pharmacological activity being due to subject expectancy effects or positive expectancy, which may be present due to overwhelming media reporting on the topic of cannabis.\u003c/p\u003e\u003cp\u003eDose frequency in previously published cross-sectional literature does not differentiate between dosage forms utilised, but reports that the most prevalent dosage frequency of cannabis for respective endometriosis cohorts was \u0026ldquo;\u003cem\u003etwo to three times per day\u003c/em\u003e\u0026rdquo;,(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) or \u0026ldquo;\u003cem\u003edaily to multiple times per day.\u003c/em\u003e\u0026rdquo;(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) This mirrors findings in this study which reports that those utilising the inhaled format had the highest prevalence at \u0026ldquo;\u003cem\u003etwo to three times per day\u0026rdquo;\u003c/em\u003e (34.1%), with the next highest being \u0026ldquo;\u003cem\u003edon\u0026rsquo;t need to use every day\u003c/em\u003e\u0026rdquo; at 25.6%, and 23.2% utilising cannabis \u0026ldquo;\u003cem\u003efour or more times per day\u003c/em\u003e\u0026rdquo;. This is suggestive that (i) a proportion of the endometriosis cohort is suffering considerable symptom burden / pain and requires regular consumption of inhaled cannabis due to inhaled formats only having short duration of effect (2\u0026ndash;4 hours),(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) and (ii) that a smaller percentage of the endometriosis cohort may only need to utilise inhaled cannabis irregularly for symptom control, which may be focused around the menstrual cycle where pain and other symptoms are intensified.\u003c/p\u003e\u003cp\u003eConversely, respondent data for oral oils tells a different story, with the most prevalent frequency being \u0026ldquo;\u003cem\u003eonce daily\u003c/em\u003e\u0026rdquo; (33.1%) or \u0026lsquo;\u003cem\u003edon\u0026rsquo;t need to use every day\u003c/em\u003e\u0026rdquo; (25.6%). Given the longer duration of effects ranging between 6\u0026ndash;8 hours for oral formats, women with endometriosis who are utilising oral cannabis may be relying on this longer duration to assist with sleep, or provide analgesic coverage for longer periods of time throughout the day. However, as 29% were utilising oils \u0026ldquo;\u003cem\u003etwo to three times daily\u003c/em\u003e\u0026rdquo;, this is suggestive that with a 6\u0026ndash;8-hour duration of effect, 24-hour coverage could be possible. This data is suggestive that women are not only adapting the dose frequency, but also the mode of administration to target specific symptoms,(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e) and are utilising both inhaled and oral dosage forms, either based off their own product exploratory experience, or guided by medical or dispensary staff who are likely more knowledgeable about the pharmacokinetic implications of varied dosage formats in symptom management. To this point, previous research has demonstrated that the endometriosis cohort are utilising multiple cannabis dosage formats for symptom control,(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) with findings from this study adding to this body of research.\u003c/p\u003e\u003cp\u003eSelf-reported effectiveness of cannabis (inclusive of all dosage forms) across a range of endometriosis-related symptoms were described, including difficulties with sleep, nausea, chronic pelvic pain, dysmenorrhoea (i.e., period pain), and mental health (anxiety and depression) according to reported medians. These results are consistent with previous literature on cannabis use in the endometriosis, dysmenorrhea, and pelvic pain cohorts.(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e) Given the pharmacological effects of THC on various receptor targets in the Endocannabinoid System (i.e., CB1 and CB2 receptors), and CBD\u0026rsquo;s effect on numerous other pharmacological targets such as Transient Receptor Potential Vanilloid 1 (TRPV1) and Serotonin (5HT1A) receptors, the role of cannabis and its major cannabinoids as an analgesic, sedative/hypnotic, anxiolytic, anti-depressant, anti-inflammatory and as an anti-emetic/anti-nauseant demonstrate plausible mechanisms for such clinical indications. (\u003cspan additionalcitationids=\"CR46 CR47\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e) Conversely, cannabis utilisation demonstrated minimal impact on bladder symptoms, menorrhagia (i.e., heavy menstrual bleeding), or reducing gastrointestinal (GIT) or bowel symptoms associated with endometriosis, which is somewhat surprising given the anti-inflammatory activities of both major cannabinoids. However, potential causations of such symptoms could be of a structural (i.e., adhesions) nature that only surgery might address, or cannabis may negatively impact the microbiome of the GIT given the antimicrobial impact of cannabinoids such as CBD,(\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e) or the known antibacterial nature of various cannabis terpenes/terpenoids.(\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eSignificant associations between higher self-rated effectiveness and use of dried cannabis flower as a joint (inhaled) compared to not using dried cannabis flower as a joint, were seen for symptoms of period pain, chronic pelvic pain, nausea, back pain, headache or migraine, fatigue, depression, difficulties with sleep and painful sex. However, this is unlikely to be overly clinically relevant due to factors such as: (i) self-reported preference bias (i.e., belief joints work better due to ritual, faster onset or familiarity rather than actual measurable improvement), (ii) Increased risk of combustion byproducts causing pulmonary side effects, (iii) confounding due to comorbid symptom clustering (e.g., Those choosing joints may have more severe symptoms, greater cannabis tolerance or different usage patterns such as longer history of MC utilisation or multiple dosage form usage). Conversely, evidence of lower self-rated effectiveness for those using oral oil compared to not using oil, was seen for symptoms of back pain, depression and difficulties with sleep. Whilst such data represents real-world evidence, it does not fill the void of more rigorous clinical research, which is still recommended to determine cannabis and cannabinoid safety, tolerability and efficacy in this cohort.\u003c/p\u003e\u003cp\u003eThere are several limitations to this study which are important to outline. Whilst international in scope (albeit mainly Western-centric), limited participation was noted compared to our teams\u0026rsquo; previous study,(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) with lower than anticipated participation. This in part could be due to the survey running amid the global COVID-19 pandemic, however, could also be a result of survey fatigue, as this method of scientific inquiry was all that was available to many research teams during this time, and results may therefore not be generalisable to the wider endometriosis population. Recall bias(\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e) and non-response bias(\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e) which can influence responses, and skew the sample towards those that are either more severe in their symptom expression, or more favorable towards cannabis, are respective limitations. So too is sampling bias,(\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e) due to the survey being advertised through the use of social media to endometriosis advocacy and support groups, potentially skewing results to include people more negatively impacted by their endometriosis compared to the general population. Notwithstanding, data from this paper is consistent with previous studies of similar scope and design.(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eEndometriosis is an oestrogen-dependent, systemic, chronic inflammatory condition for which many women experience sub-optimal symptom management from surgical or pharmaceutical options. Cannabis utilisation for symptom management is frequently being utilised by this cohort, primarily of illicit origin. Self-reported effectiveness of cannabis is noted across a wide range of symptoms, from chronic pelvic pain and dysmenorrhoea to improving sleep and reducing nausea, and dosage frequency is suggestive of higher dosing regimens which is consistent with the pharmacological duration of action, and speed of onset, that cannabinoids can provide across different symptom clusters. Whilst such evidence is encouraging, more robust data from clinical trials are needed to fully assess the efficacy of cannabis-based medicinal products.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e5HT1A\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Serotonin 1A receptor\u003c/p\u003e\n\u003cp\u003e11-OH-THC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;11-Hydroxy-THC\u003c/p\u003e\n\u003cp\u003eANOVA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Analysis of Variance\u003c/p\u003e\n\u003cp\u003eCB1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cannabinoid 1 receptor\u003c/p\u003e\n\u003cp\u003eCB2\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cannabinoid 2 receptor\u003c/p\u003e\n\u003cp\u003eCBD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Cannabidiol\u003c/p\u003e\n\u003cp\u003eCPP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Chronic Pelvic Pain\u003c/p\u003e\n\u003cp\u003eECS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Endocannabinoid System\u003c/p\u003e\n\u003cp\u003eGIT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Gastrointestinal Tract\u003c/p\u003e\n\u003cp\u003eGnRH\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Gonadotropin hormone-releasing hormone\u003c/p\u003e\n\u003cp\u003eMC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Medicinal Cannabis\u003c/p\u003e\n\u003cp\u003eMRI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eNSAID(s)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Non-Steroidal Anti-inflammatory Drug(s)\u003c/p\u003e\n\u003cp\u003eNZ\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;New Zealand\u003c/p\u003e\n\u003cp\u003eSD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Standard Deviation\u003c/p\u003e\n\u003cp\u003eTHC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Delta-9-tetrahydrocannabinol\u003c/p\u003e\n\u003cp\u003eT\u003csub\u003emax\u003c/sub\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Time to reach peak plasma concentration\u003c/p\u003e\n\u003cp\u003eTRPV1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Transient Receptor Potential Vanilloid 1 receptor\u003c/p\u003e\n\u003cp\u003eUK \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; United Kingdom\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to thank Endometriosis New Zealand, Endometriosis Australia, Nancy\u0026rsquo;s Nook, EndoIreland, Endometriosis UK, The World Endometriosis Society, Endometriosis Network (Canada), and the participants of this survey, for their support of this project.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for this research which forms part of a PhD research project for J. Sinclair.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJS1, AP and MA: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals and industry. Sponsors and donors also provide untied funding for work to advance the vision and mission of the Institute. JS1 is the recipient of a Western Sydney University Postgraduate Research Scholarship and is employed by Australian Natural Therapeutics Group. JS1 also sits on the board of the Australian Medicinal Cannabis Association (\u003cem\u003epro bono\u003c/em\u003e), the steering committee of Cannabis Clinicians Australia (\u003cem\u003epro bono\u003c/em\u003e) and the scientific advisory board of United in Compassion (\u003cem\u003epro bono\u003c/em\u003e). MA has previously been an advisory board member for Evolv Therapeutics, is currently an advisory board member for Nectar Brands, both of which sell medicinal cannabis products. He has previously received funding from Canopy Growth, OzMediCann Group and Cannim to run clinical studies on medicinal cannabis for women\u0026rsquo;s health conditions, outside the submitted work.\u003c/p\u003e\n\u003cp\u003eJS2 is an Executive Director of Neurala Biosciences and the connected not-for-profit Psyche Institute, which are both involved with psychedelics research and the development of these agents as registered medicines. He is employed and holds equity with Neurala Biosciences. He is also an\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eadvisory board representative for HedoniaUSA, which formulates and sells nutraceutical products. He also has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent\u0026nbsp;consultancy payments from: Integria Healthcare \u0026amp; MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, Noetic Foundry, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Global Pharma Group, Australian Natural Therapeutics Group (a cannabis growing and manufacturing company; as a previous scientific advisor), Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship, Medical Research Futures Fund, CSIRO Australia, Launch Victoria, Genesis Fund, Tin Alley Ventures.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided informed consent (extended) prior to participating in this survey. The study design was reviewed and approved by the Western Sydney University Human Research Ethics Committee\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(Approval # H14115). Participation was voluntary, and all participants were informed of their right to withdraw at any time without consequence. Clinical trial number: not applicable.\u003c/p\u003ehD research project for J. Sinclair.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJS1 and MA conceived the study. JS1, MA and AE analysed survey data. JS1, MA, AE and AP wrote the paper. AP, JS2, JA and MA provided critical subject matter expertise and revisions.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Files. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGiudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789-99.\u003c/li\u003e\n\u003cli\u003eJohnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32(2):315-24.\u003c/li\u003e\n\u003cli\u003eBulun SE. Endometriosis. N Engl J Med. 2009;360(3):268-79.\u003c/li\u003e\n\u003cli\u003eFacchin F, Barbara G, Saita E, Mosconi P, Roberto A, Fedele L, et al. Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference. J Psychosom Obstet Gynaecol. 2015;36(4):135-41.\u003c/li\u003e\n\u003cli\u003eBarbara G, Facchin F, Meschia M, Berlanda N, Frattaruolo MP, Vercellin IP. When love hurts. A systematic review on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning. Acta Obstet Gynecol Scand. 2017;96(6):668-87.\u003c/li\u003e\n\u003cli\u003eGambadauro P, Carli V, Hadlaczky G. Depressive symptoms among women with endometriosis: a systematic review and meta-analysis. Am J Obstet Gynecol. 2019;220(3):230-41.\u003c/li\u003e\n\u003cli\u003eBarbara G, Buggio L, Facchin F, Vercellini P. Medical Treatment for Endometriosis: Tolerability, Quality of Life and Adherence. Front Glob Womens Health. 2021;2:729601.\u003c/li\u003e\n\u003cli\u003eAustralian Institute of Health \u0026amp; Welfare. Endometriosis 2023 [Available from: https://www.aihw.gov.au/reports/chronic-disease/endometriosis-in-australia/contents/summary#.\u003c/li\u003e\n\u003cli\u003eRowlands IJ, Abbott JA, Montgomery GW, Hockey R, Rogers P, Mishra GD. Prevalence and incidence of endometriosis in Australian women: a data linkage cohort study. BJOG. 2021;128(4):657-65.\u003c/li\u003e\n\u003cli\u003eBecker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):hoac009.\u003c/li\u003e\n\u003cli\u003ePractice Committee of the American Society for Reproductive M. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril. 2014;101(4):927-35.\u003c/li\u003e\n\u003cli\u003eDunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D\u0026apos;Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400-12.\u003c/li\u003e\n\u003cli\u003ePractice Bulletin No. 114: Management of Endometriosis. Obstetrics \u0026amp; Gynecology. 2010;116(1):223-36.\u003c/li\u003e\n\u003cli\u003eLeyland N, Casper R, Laberge P, Singh SS, Sogc. Endometriosis: diagnosis and management. J Obstet Gynaecol Can. 2010;32(7 Suppl 2):S1-32.\u003c/li\u003e\n\u003cli\u003eBecker CM, Gattrell WT, Gude K, Singh SS. 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Journal of Cannabis Therapeutics. 2002;2(3-4):5-35.\u003c/li\u003e\n\u003cli\u003eArmour M, Sinclair J, Noller G, Girling J, Larcombe M, Al-Dabbas MA, et al. Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. Journal of women\u0026apos;s health (2002). 2020;30(10):1-8.\u003c/li\u003e\n\u003cli\u003eArmour M, Sinclair J, Cheng J, Davis P, Hameed A, Meegahapola H, et al. Endometriosis and Cannabis Consumption During the COVID-19 Pandemic: An International Cross-Sectional Survey. Cannabis Cannabinoid Res. 2022;7(4):1-9.\u003c/li\u003e\n\u003cli\u003eSinclair J, Abbott J, Mikocka-Walus A, Ng CHM, Sarris J, Evans S, et al. \u0026quot;A glimmer of hope\u0026quot; - Perceptions, barriers, and drivers for medicinal cannabis use amongst Australian and New Zealand people with endometriosis. Reprod Fertil. 2023;4(4):1-15.\u003c/li\u003e\n\u003cli\u003eSinclair J, Collett L, Abbott J, Pate DW, Sarris J, Armour M. Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms. PLoS One. 2021;16(10):1-12.\u003c/li\u003e\n\u003cli\u003eSinclair 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. 2019;42(3):256-61.\u003c/li\u003e\n\u003cli\u003eSinclair J, Toufaili Y, Gock S, Pegorer AG, Wattle J, Franke M, et al. Cannabis Use for Endometriosis: Clinical and Legal Challenges in Australia and New Zealand. Cannabis Cannabinoid Res. 2021;7(4):1-9.\u003c/li\u003e\n\u003cli\u003eCarrubba A, Spaulding, AC., Ebbert, JO, DeStephano, CC. Patient-reported Use of Medical Cannabis for management of Chronic Pelvic Pain. Obstetrics \u0026amp; Gynecology. 2020;135:84S.\u003c/li\u003e\n\u003cli\u003eCarrubba AR, Ebbert JO, Spaulding AC, DeStephano D, DeStephano CC. Use of Cannabis for Self-Management of Chronic Pelvic Pain. 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Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis. Reprod Sci. 2016;23(8):1071-9.\u003c/li\u003e\n\u003cli\u003eSanchez AM, Quattrone F, Pannese M, Ulisse A, Candiani M, Diaz-Alonso J, et al. The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis. Hum Reprod. 2017;32(1):175-84.\u003c/li\u003e\n\u003cli\u003eBouaziz J, Bar On A, Seidman DS, Soriano D. The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. Cannabis Cannabinoid Res. 2017;2(1):72-80.\u003c/li\u003e\n\u003cli\u003eArmour M, Sinclair J, Noller G, Girling J, Larcombe M, Al-Dabbas MA, et al. Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. J Womens Health (Larchmt). 2021;30(10):1485-92.\u003c/li\u003e\n\u003cli\u003eSinclair J, Abbott J, Proudfoot A, Armour M. The Place of Cannabinoids in the Treatment of Gynecological Pain. Drugs. 2023;83(17):1571-9.\u003c/li\u003e\n\u003cli\u003eFarooqi T, Bhuyan DJ, Low M, Sinclair J, Leonardi M, Armour M. Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System. J Clin Med. 2023;12(22).\u003c/li\u003e\n\u003cli\u003eGrotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327-60.\u003c/li\u003e\n\u003cli\u003eMacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12-9.\u003c/li\u003e\n\u003cli\u003eFoster BC, Abramovici H, Harris CS. Cannabis and Cannabinoids: Kinetics and Interactions. Am J Med. 2019;132(11):1266-70.\u003c/li\u003e\n\u003cli\u003eHuestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-804.\u003c/li\u003e\n\u003cli\u003eSaals B, De Bie TH, Osmanoglou E, van de Laar T, Tuin AW, van Orten-Luiten ACB, et al. 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Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. Clin J Pain. 2013;29(2):162-71.\u003c/li\u003e\n\u003cli\u003eNational Academies of Sciences, Engineering and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington DC: The National Academies Press.; 2017.\u003c/li\u003e\n\u003cli\u003eMachado Rocha FC, Stefano SC, De Cassia Haiek R, Rosa Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl). 2008;17(5):431-43.\u003c/li\u003e\n\u003cli\u003eUpton R, ElSohly, M., Romm, A., Russo, E., Sexton, M, editor. Cannabis inflorescence. Scotts Valley, California: American Herbal Pharmacopoeia; 2013.\u003c/li\u003e\n\u003cli\u003eBlaskovich MAT, Kavanagh AM, Elliott AG, Zhang B, Ramu S, Amado M, et al. The antimicrobial potential of cannabidiol. Commun Biol. 2021;4(1):7.\u003c/li\u003e\n\u003cli\u003eMasyita A, Mustika Sari R, Dwi Astuti A, Yasir B, Rahma Rumata N, Emran TB, et al. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chem X. 2022;13:100217.\u003c/li\u003e\n\u003cli\u003ePannucci CJ, Wilkins EG. Identifying and avoiding bias in research. Plast Reconstr Surg. 2010;126(2):619-25.\u003c/li\u003e\n\u003cli\u003eBerg N. Non-Resonse Bias. In: Kempf-Leonard K, editor. Encyclopedia of Social Measurement. 2. London: Academic Press; 2005. p. 865-73.\u003c/li\u003e\n\u003cli\u003eBenedict C, Hahn AL, Diefenbach MA, Ford JS. Recruitment via social media: advantages and potential biases. Digit Health. 2019;5:2055207619867223.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cannabis, Endometriosis, Pelvic pain, effectiveness, dosage forms, dose","lastPublishedDoi":"10.21203/rs.3.rs-6910005/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6910005/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eEndometriosis is a common, chronic inflammatory condition impacting 10\u0026ndash;14% of reproductive aged females. Common symptoms include severe dysmenorrhea, pelvic pain and fatigue. Current symptom management options are often unsatisfactory, and new, low risk pain management options urgently needed. Previous research has found people with endometriosis self-reporting either legal or illicit cannabis use to manage the pain and associated symptoms of endometriosis. This international study aims to explore how people with endometriosis access cannabis, and the dosage formats and dose frequency utilised. Respondent self-rated symptomatic effectiveness of medicinal cannabis was also investigated.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eAn online, anonymous, cross-sectional survey was developed in conjunction with endometriosis advocacy groups and patient support networks, and distributed internationally. The survey enquired about legal (medical or adult use/social) \u003cem\u003eversus\u003c/em\u003e illicit cannabis consumption for therapeutic purposes, current symptoms, medical and self-management strategies employed, self-rated symptom relief associated with cannabis use, and the dosage format and dose frequency utilised.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003e889 respondents from 28 countries were eligible for data analysis. The average duration respondents had been utilising cannabis to manage their symptoms was 4.4 years. Dried cannabis flower-joints (46.8%) and oral oils (31%) were the highest-rated dosage formats for symptom management. There was evidence that self-rated effectiveness is higher for those using dried cannabis flower as a joint (i.e., inhaled) across numerous symptoms, compared to not utilising cannabis flower as a joint. By contrast, oral oils had a lower self-rated effectiveness. Reasons behind dosage form choices focused on fast onset of action for inhaled formats, and longer duration of effect for orally ingested products.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eCannabis utilisation for endometriosis symptom management is frequently utilised, and is primarily of illicit origin. Self-reported effectiveness of cannabis is noted across a wide range of symptoms, from chronic pelvic pain and dysmenorrhoea to improving sleep and reducing nausea, and dosage frequency is suggestive of individualised dosing regimens which is consistent with the pharmacological duration of action, and speed of onset, that cannabinoids can provide across different symptom clusters. Whilst such evidence is encouraging, more robust data from clinical trials are needed to fully assess the efficacy of cannabis-based medicinal products.\u003c/p\u003e","manuscriptTitle":"“A dose of relief?”: Results of an international survey exploring self-reported effectiveness, dose and dosage forms of cannabis for endometriosis pain and related symptoms","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-25 11:38:22","doi":"10.21203/rs.3.rs-6910005/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-07-30T22:52:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"44962735803549299023898244999945419911","date":"2025-07-27T23:15:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-22T09:14:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-22T05:54:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-17T03:03:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Complementary Medicine and Therapies","date":"2025-07-17T02:58:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"763d5e9a-9119-446f-af49-95120772af1f","owner":[],"postedDate":"July 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-25T11:38:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-25 11:38:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6910005","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6910005","identity":"rs-6910005","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}