Believing women: a qualitative exploration of provider disbelief and pain dismissal among women with interstitial cystitis/bladder pain syndrome from the MAPP research network.

INTRODUCTION AND HYPOTHESIS: Although allusions to the importance of a good physician-patient relationship are present throughout the interstitial cystitis/bladder pain syndrome (IC/BPS) literature, qualitative analysis of patients' perspectives on the clinical encounter is lacking, particularly among women who are most commonly affected by IC/BPS. Therefore, we adopted a patient-centered experiential approach to understanding female patients' perception of clinical encounters. METHODS: We re-analyzed previously collected data from a qualitative study on patient flare experiences including eight focus groups of female IC/BPS patients (n = 57, mean = 7/group). Qualitative analysis applied grounded theory to index all physician-patient interactions, then thematically coded these interactions to elucidate common experiences of clinical encounters. RESULTS: Women with IC/BPS shared common experiences of provider disbelief and pain dismissal. Discussions with participants demonstrated the extent to which these negative encounters shape patients' health care-seeking behavior, outlook, and psychosocial well-being. Appearing in more than one guise, provider disbelief and dismissal occurred as tacit insinuations, explicit statements, silence, oversimplification, and an unwillingness to listen and discuss alternative treatment. As a result, women adopted several strategies including: rotating specialists; "testing" physicians; self-advocacy; self-management; avoiding the stigma of chronic pain; crying; and opting for alternative medicine over biomedicine. CONCLUSIONS: The prevalence of provider disbelief and pain dismissal among women with IC/BPS indicates a need to improve physician-patient communication, informed by the struggles, anxieties, and gendered inequities that female patients with chronic pain experience in their diagnostic journey. Results suggest that further investigation into the power dynamics of clinical encounters might be required.

Study protocol of a multicentre double-blind RCT, comparing a traditional RCT with an aggregated N-of-1 trial: GAG therapy Efficacy Trial Solution for Bladder pain syndrome/Interstitial cystitis (GETSBI study).

INTRODUCTION: Obtaining level 1 evidence on efficacy of glycosaminoglycan (GAG) therapy is difficult, due to low incidence of bladder pain syndrome/interstitial cystitis (BPS/IC) and heterogeneous symptoms experienced by patients with BPS/IC. Currently, because of a lack of high-grade evidence, the recommendation for applying GAG therapy in most guidelines is 'low grade'. An aggregated N-of-1 trial is a multicrossover design that yields similar level 1 evidence as a traditional randomised controlled trial (RCT), while requiring far less patients. The goal of this study is to investigate the efficacy of intravesical GAG therapy (Ialuril) for patients with BPS/IC with Hunner lesions using a dual RCT and aggregated N-of-1 trial design to obtain level 1 evidence. METHODS AND ANALYSIS: The GETSBI study is a double-blind multidesign multicentre randomised placebo-controlled study to assess the short-term and long-term efficacy of hyaluronic acid (1.6%) + chondroitin sulfate (2%) therapy (Ialuril Prefill, IBSA, Goodlife) in patients with symptomatic BPS/IC with Hunner lesions. It starts as a standard RCT (n=80), but continues as an aggregated N-of-1 trial. There are three parallel arms, receiving blinded treatment for three periods (1 x/week for 6 weeks, ratio placebo to intervention in periods of 2:1). Followed by an open prospective part for the long-term efficacy. The primary study outcome is the maximum bladder pain experienced in the last 3 days measured using the visual analogue pain scale (0-10).This study is a collaboration with the Dutch government and will deliver evidence for the decision to reimburse the therapy. Furthermore, this multidesign study will allow us to compare the two main methods to evaluate applicability for future study designs for BPS/IC research. ETHICS AND DISSEMINATION: Ethical approval was given by METC Oost-Nederland, file number: 2020-7265, NL-number: NL76290.091.20. Findings from this study will be disseminated via publication, reports and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier (NCT number): NCT05518864.

Choreito, a Kampo medicine attenuates detrusor overactivity and bladder pain symptoms in rat tranilast-induced interstitial cystitis/bladder pain syndrome-like model.

AIMS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory condition of the bladder. However, there are only a few medicines that are of pharmaceutical grade and reliably effective for IC/BPS symptoms. Choreito (CRT) is a pharmaceutical-grade Kampo medicine and has been widely prescribed for patients of lower urinary tract symptoms (LUTS) and BPS in Japan. In this study, we exploratory investigated the effects of CRT on the IC/BPS-like symptoms induced by tranilast. METHODS: The rat IC/BPS-like model was induced by feeding administration with 0.4% tranilast. The rats were divided into the three following treatment groups: normal diet (Normal), tranilast treatment (Control), and the groups of 1% CRT (CRT) treatment for IC/BPS-like model. After 4 weeks, continuous cystmetry, locomotor, and vascular permeability was assessed. Furthermore, the cytokine levels in bladder were analyzed by the Bio-Plex suspension array system and plasma monoamine were measured. RESULTS: Control group exhibited 14.3% decrease of locomotor activity in the dark period, and which were 20.3% increase by 1%CRT treatment. The voiding interval was shorter in control than in other groups. 1%CRT suppressed the shortening of voiding interval. Evans blue leakage of bladder wall observed 44.8% higher in control group than in the normal group. The leakage of 1%CRT group was 33.3% less than in the control group. The cytokine level of IFNγ and VEGF were elevated in the control, and CRT treatment suppressed the elevation of IFNγ in the bladder. Plasma noradrenaline was significantly reduced by CRT treatment compared normal group. CONCLUSION: These results suggest that CRT can be an effective therapeutic agent for the treatment of IC/BPS-like symptoms.

[Protective properties of urothelium and possibilities of targeted pathogenetic therapy of chronic pelvic pain: sodium pentosan polysulfate].

The review article is devoted to the possibilities of using targeted therapy for urothelial diseases, namely painful bladder syndrome (BPS). The protective structural components of the bladder mucosa, as well as their chemical features, are described in detail. Pentosanpolysulfate (PPS), being an oral heparinoid, can be used as part of pathogenetic therapy to restore the mucous membrane of the bladder. The efficacy and safety of this drug has been proven by us in a multicenter, randomized, double-blind, placebo-controlled trial. An additional assessment of the effectiveness and safety of the use of PPS in BPS was confirmed as part of our systematic review and meta-analysis. Thus, PPS is a pathogenetically sound tool in the treatment of patients with painful bladder syndrome.

Association of physical therapy techniques can improve pain and urinary symptoms outcomes in women with bladder pain syndrome. A randomized controlled trial.

PURPOSE: to verify the effects of biofeedback (BF) and manual therapy (MT) associated with transcutaneous electrical nerve stimulation (TENS) or postural exercises (PE) in the treatment of bladder pain syndrome (BPS) in women regarding pain and urinary symptoms. MATERIALS AND METHODS: a parallel-randomized controlled trial was conducted in BPS patients diagnosed according to NIH clinical criteria. Two specialized physiotherapists applied demographic and validated questionnaires of perineal and suprapubic pain (VAS), urinary symptoms and problems (ICSI and ICPI) and sexual function (FSFI) and a physical assessment was made to identify myofascial trigger points. Thirty-one women, mean age 51.8 ± 10.9 were randomized in three groups of treatment consisting of ten weekly sessions of BF and MT (Conventional group); BF, MT, and TENS (TENS group); and BF, MT, and PE (Postural group). RESULTS: Postural group improved perineal and suprapubic pain after treatment (p<0.001 and p=0.001, respectively), and the suprapubic pain improvement remained persistent at 3 months of follow up (p=0.001). Postural group improved urinary symptoms and problems after treatment (p<0.001 and p=0.005, respectively) and during follow up (p<0.001 and p=0.001). CONCLUSIONS: Biofeedback and manual therapy associated with postural exercises showed a significant improvement in perineal and suprapubic pain and urinary symptoms after treatment and during follow-up. Both results suggest a possible role for the use of this physiotherapy technique to treat BPS patients. Longer follow-up and a larger number of patients are necessary to confirm these conclusions.

Analysis of ginseng in the treatment of Interstitial Cystitis/Bladder Pain Syndrome based on network pharmacology.

OBJECTIVE: The network pharmacology is adopted in the paper to elaborate the active components, targets, and pathways of ginseng in the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). MATERIALS AND METHODS: The active components and potential targets of ginseng were obtained through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). The OMIM, Disgenet, and Genecards databases for IC/BPS targets, and the STRING11.0 database were used for the protein-protein interaction (PPI) network. Meanwhile, the latter covers R language was used for the target of ginseng for IC/BPS, Bioconductor bioinformatics software for GO and KEGG functional enrichment analysis of key target genes, and the Cytoscape 3.8.2 software for constructing the "component-target" network and the "component-target-pathway" network map. RESULTS: The results are categorized into three camps: components, targets, and pathways. As for components, 22 active components of ginseng that perform biological activities in the cell membrane, cytoplasm, and nucleus were observed, among which kaempferol, girinimbin, suchilacton, arachidonate, and gomisin B are the main active ones. 650 targets were found, mainly represented by PTGS2, PTGS1, AR, SLC6A4, and CHRM2, 134 of which (especially AKT1, TNF, VEGFA, TP53, EGFR, STAT3, IL-1ß, ESR1, and JUN) contribute to the treatment of IC/BPS. Moreover, the pathways that serve as major contributors are the PI3K-Akt signaling pathway, the HIF-1 signaling pathway, the STAT3 signaling pathway, the MAPK signaling pathway, the NF-κB signaling pathway, and the apoptosis-related pathway. CONCLUSIONS: Ginseng can exert anti-inflammatory, anti-oxidative stress and anti-apoptotic effects on IC/BPS thanks to its multi-component, multi-target and multi-way functions.

The Japanese Herbal Medicine Yokukansan Exerted Antioxidant and Analgesic Effects in an Experimental Rat Model of Hunner-Type Interstitial Cystitis.

Background and Objectives: The Japanese herbal medicine Yokukansan (YKS) has analgesic properties and is used for various pain disorders. The purpose of the present study was to investigate the effects of YKS in Hunner-type interstitial cystitis (HIC) using an experimental rat model of HIC and to explore its antioxidant activity and role as the underlying mechanism of action. Materials and Methods: The antioxidant capacity of YKS was evaluated by determining its hydroxyl radical (·OH) scavenging capacity using electron spin resonance (ESR). Next, the effects of YKS administration were explored using a toll-like receptor-7 agonist-induced rat model of HIC. The von Frey test was performed to assess bladder pain. Three days after HIC induction, the bladder was removed, and the expression of oxidative stress parameters in the bladder wall was investigated (reactive oxygen metabolites (ROMs), ·OH, and 8-hydroxy-2'-deoxyguanosine (8-OhdG)). Results: YKS had a ·OH scavenging capacity according to the ESR study. In the von Frey test, a significant decrease in the withdrawal threshold was observed in the HIC group compared with the control group; however, the decrease was ameliorated by the administration of YKS. Oxidative stress parameters showed increasing tendencies (ROMs test and 8-OHdG) or a significant increase (·OH) in the HIC group compared with the control group; however, the increase was significantly suppressed by the administration of YKS. Conclusions: These findings suggest that YKS is effective against HIC and that its antioxidant activity is involved in the mechanism of action.

Pentosan polysulfate for the treatment of hemorrhagic cystitis after allogeneic hematopoietic cell transplant.

INTRODUCTION: Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms. METHODS AND RESULTS: This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10). CONCLUSION: Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.

[Oral therapy for interstitial cystitis: pentosan polysulfate sodium]. / Orale Therapie der Interstitiellen Zystitis: Pentosanpolysulfat-Natrium.

INTRODUCTION: It is currently assumed that interstitial cystitis/bladder pain syndrome is caused by damage to the glycosaminoglycane layer on the urothelium of the urinary bladder. This layer can be repaired by oral therapy with pentosan polysulfate sodium. The focus of this article is on the history of this drug, its efficacy, its valuation in guidelines and especially the possible correlation with maculopathy. METHODS: Literature research in PubMed and Embase. RESULTS: PPS has a US and European approval for the therapy of IC characterised by glomerulations or a Hunner lesion detected by endoscopy and bladder distension. Its efficacy was proven in randomised trials. This led to a recommendation as a basic pharmaceutical therapy (in addition to behavioural intervention, dietary therapy or other drug treatments such as pain therapy). After a treatment period of six months, efficacy should be re-evaluated. Side-effects include mild haemodilution, nausea and loss of hair. Two publications of a US eye clinic have recently postulated a correlation between prolonged high-dose therapy with PPS and a special kind of maculopathy. Although this correlation was rejected in a large-scale health service study in Germany, a "red-hand-letter" led to the recommendation to perform an ophthalmologic examination before and during the treatment with PPS. Due to a pending litigation between payers and the distributor, PPS is currently out of trade in Germany. However, PPS can still be prescribed but must be imported from adjacent European countries. Unfortunately, these modalities have led to a significant undersupply of patients with IC/BPS. It is feared that this undersupply will increase further as the litigation is ongoing. CONCLUSION: Being the only causally acting compound in the therapy of IC/BPS, PPS has an exceptional status. Although an ongoing litigation is pending in Germany and the correlation with maculopathy is still unclear, PPS must remain part of the current and future therapy of IC/BPS.

Therapeutic effect of modulating the NLRP3-regulated transforming growth factor-ß signaling pathway on interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder with complex pathogenesis and lacks effective treatment. Chronic inflammation is the main pathogenesis of Hunner-type IC/BPS. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome-related transforming growth factor-ß (TGF-ß)/Smad signaling pathway plays a crucial role in inflammation-related tissue fibrosis. Lipopolysaccharide (LPS) and protamine sulfate (LPS/PS) were instilled into the mouse bladder twice a week for 5 consecutive weeks to establish a chronic inflammation-induced IC/BPS model (LPS/PS model). Following LPS/PS treatment, curcumin (oral, 100 mg/kg; a potent NLRP3 modulator) was administered for 2 weeks in the curcumin treatment group, and normal saline was used for the sham group. Bladder function was evaluated by performing the voiding spot assay and examining the status of urothelial denudation and fibrosis in bladder tissues. The expression of NLRP3 inflammasome, interleukin-1ß, TGF-ß, Smad, vimentin, and E-cadherin in bladder tissues was evaluated through immunohistochemistry staining. Results revealed that the repeated instillation of LPS/PS leads to voiding dysfunction, bladder urothelium denudation, and detrusor muscle fibrosis through the upregulation of the NLRP3 inflammasome/IL-1ß-related TGF-ß/Smad pathway and the increased epithelial-mesenchymal transition process in bladder tissues. The downregulation of the NLRP3 inflammasome/IL-1ß-related TGF-ß/Smad pathway in bladder tissues through curcumin effectively mitigated bladder injury in the LPS/PS model. In conclusion, the NLRP3 inflammasome/IL-1ß-related TGF-ß/Smad pathway plays a crucial role in bladder injury in the LPS/PS model, and modulation of this pathway, such as by using curcumin, can effectively mitigate the sequelae of chronic inflammation-induced IC/BPS.

Beneficial effect of Bletilla striata extract solution on zymosan-induced interstitial cystitis in rat.

AIMS: Interstitial cystitis (IC) is a chronic pain syndrome that is characterized by suprapubic pain upon bladder filling. Bletilla striata, a well-known traditional Chinese herb with established efficacy in wound healing and anti-inflammation, was hypothesized to improve the symptoms of IC possibly though forming a physical barrier that could isolate the bladder tissue from irritants. This study was conducted to evaluate the beneficial effects of intravesical treatment with B. striata extract solution (BSES) on visceral pain and bladder function of rats with zymosan-induced IC. METHODS: Thirty female rats were randomly divided into control group, zymosan-induced cystitis rats treated with normal saline (Z + NS), and zymosan-induced cystitis rats treated with BSES (Z + BSES). All rats underwent evaluation for abdominal withdrawal reflex (AWR) scores to assess visceral hypersensitivity, cystometrography, and electromyogram (EMG) of both external urethral sphincter and bladder detrusor. Data were analyzed by one way analysis of variance. RESULTS: The Z + NS group had an increased visceral hypersensitivity as compared to control group. Rats treated with BSES (Z + BSES group) had decreased AWR scores and amplitude of bladder detrusor-EMG. Besides, BSES treatment improved overactive bladder with significant effects on the extend of micturition interval and increase of storage of urine. CONCLUSIONS: Intravesical instillation of BSES can significantly alleviate zymosan-induced visceral hypersensitivity and bladder overactivity associated with IC. This study suggested that intravesical instillation with BSES might be a promising treatment for IC.

Evaluation of the efficacy of Chinese herbal medicine and acupuncture for the prevention of mental disorders in interstitial cystitis patients: A nationwide population-based study.

Traditional Chinese medicine (TCM) is commonly used for urinary symptoms in Eastern countries. Since there are few effective treatments available for patients with interstitial cystitis/bladder pain syndrome (IC/BPS), the psychological burden leads to increased healthcare-seeking behavior. Some patients may therefore seek TCM treatment for related urinary symptoms. Due to limited clinical research evaluating the effects of TCM on IC/BPS, we conducted a nationwide population-based cohort study to investigate the relationship between TCM and mental disorders among these patients. The IC/BPS cohort and its matched non-IC/BPS comparison cohort were recruited from the National Health Insurance (NHI) Research Database between 2000 and 2011. Patients with the use of Chinese herbal medicine (CHM) granules or acupuncture over 90 days per year were enrolled as the TCM users. Multivariable Cox proportional hazards models were used to evaluate the hazard ratio (HR) of mental disorders related to interstitial cystitis. The incidence of mental disorders in the 2 cohorts was assessed with Kaplan-Meier curves. A total of 1123 patients with IC/BPS and 4492 matched non-IC/BPS subjects were included in this study. The IC/BPS cohort demonstrated higher incidence rate of mental disorders than the cohort without IC/BPS (adjusted HR: 2.21, 95% confidence interval [CI]: 1.73-2.81). There was no statistically significant difference in the risk of mental disorders between IC/BPS patients with and without CHM granules or acupuncture treatment (adjusted HR: 0.99, 95% CI: 0.58-1.68). Our results indicated that CHM and acupuncture showed insignificant efficacy in the prevention of mental disorders in IC/BPS patients.

Efficacy of Frankincense and Myrrha in Treatment of Acute Interstitial Cystitis/Painful Bladder Syndrome.

OBJECTIVE: To investigate the efficacy of frankincense and myrrha in the treatment of acute interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: The effects of frankincense and myrrha on the proliferation and migration of primary human urothelial cells (HUCs) were assessed in vitro. In the animal study, 48 virgin female rats were randomized into 4 groups (12 in each group): (1) control group (saline-injected control); (2) cyclophosphamide (CYP) group (intraperitoneal injected 150 mg/kg CYP); (3) CYP + pentosan polysulfate sodium group (orally received 50 mg/kg pentosan polysulfate sodium); and (4) CYP + frankincense and myrrha group [orally received frankincense (200 mg/kg) and myrrha (200 mg/kg)]. Rats orally received pentosan polysulfate sodium or frankincense and myrrha on day 1, 2, and 3. The experiments were performed on day 4. Pain and cystometry assessment behavior test were performed. Voiding interval values were assessed in rats under anesthesia. Finally, immunohistochemistry and Western blot were used to confirm the location and level, respectively, of cell junction-associated protein zonula occludens-2 (ZO-2) expression. RESULTS: Low dose frankincense and myrrha increased cell proliferation and migration in HUCs compared with control (P<0.05). Rats with acute IC/PBS rats exhibited lower voiding interval values, pain tolerance, and ZO-2 expression (P<0.05). Voiding interval values and pain tolerance were higher in the frankincense and myrrha group than CYP group (P<0.05). ZO-2 expression in the bladder was increased in the CYP + pentosan polysulfate and frankincense + myrrha groups compared with the CYP-induced acute IC/PBS group (P<0.05). CONCLUSION: frankincense and myrrha modulate urothelial wound healing, which ameliorates typical features of acute IC/PBS in rats.

The clinical effect of traditional chinese medicine on middle-aged women with Interstitial Cystitis: Protocol for a randomized controlled trial.

INTRODUCTION: Interstitial cystitis (IC), as a common disease in urology, is prolonged and repeated. IC has caused great harm to the patient's physical and psychological. Traditional Chinese medicine (TCM) is characterized by overall concepts and dialectical treatment. It provides clinicians with safer and more reliable alternatives in terms of clinical prescriptions and prepared medicines, and also improves the quality of life of patients with IC. Therefore, in this study, we will use the research method of randomized controlled trials to explore the effects of TCM combined with western medicine on renal function and urine metabolism on middle-aged women with IC. METHODS/DESIGN: Use randomized controlled trials. According to the proposed diagnostic, inclusion, and exclusion criteria. Sixty patients with interstitial bladder inflammation that met the criteria were randomized into a treatment group and a control group of 30 cases each. The intervention group was treated with integrated traditional Chinese and western medicine. The control group was given conventional Western medicine treatment. The course of treatment is 8 weeks. Interstitial bladder inflammation symptoms score (ICS worker), problem score (worker CPI), pelvic pain and urinary urgency symptoms, and urodynamics were used as the evaluation criteria. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of TCM for patients with IC. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029971, Registered on 17 February 2020.

Efficacy of combination therapy with pentosan polysulfate sodium and adipose tissue-derived stem cells for the management of interstitial cystitis in a rat model.

We evaluated the synergistic effects of pentosan polysulfate sodium (PPS) and mesenchymal stem cells (MSCs) in an interstitial cystitis (IC) rat model. After generation of the IC rat model, the rats were divided into 4 groups according to the treatment they received: phosphate-buffered saline injection into bladder submucosa, daily oral PPS feeding, MSC injection into bladder submucosa, or MSC injection into bladder submucosa with daily oral PPS feeding. After treatment, conscious cystometry and pain scale measurement were performed and their bladders were obtained for histological and proinflammatory-related gene expression analysis. On cystometric analysis, all treatment groups showed significantly increased intercontraction intervals and lower pain scores compared to those of the control group. Histological analysis revealed regenerated urothelium, less fibrosis, and decreased mast cell infiltration in all treatment groups compared to the control group. Significantly lower expression of TNF-α, IFN-γ, MCP, IL-6, TLR2, and TLR11 was observed in the PPS with MSC group compared to the other groups. Combination therapy with PPS and MSCs showed histological and functional effects in an IC rat model, including synergistic effects leading to increased intercontraction interval and decreased inflammatory reactions.

Marijuana, Lower Urinary Tract Symptoms, and Pain in the Urologic Patient.

OBJECTIVE: To describe marijuana's clinical role for urologic symptoms. METHODS: Studies related to marijuana, voiding dysfunction, lower urinary tract symptoms (LUTS), and pain through January 2019 from PubMed were evaluated for relevance and quality. RESULTS: Forty-eight studies were reviewed. Cannabinoids have mixed efficacy for neurogenic LUTS and little evidence for non-neurogenic LUTS, chronic non-cancer-related and perioperative pain. For cancer-related pain, high-level studies demonstrate cannabinoids are well-tolerated with unclear benefit. CONCLUSION: Cannabinoids appear well-tolerated in the short-term, but their efficacy and long-term impact is unproven and unknown in urologic discomfort. Cannabinoids for urologic symptoms should be further explored with well-designed randomized controlled trials.