High cannabigerol hemp extract moderates colitis and modulates the microbiome in an inflammatory bowel disease model.

Cannabis sativa L. has a long history of medicinal use, particularly for gastrointestinal diseases. Patients with inflammatory bowel disease (IBD) report using cannabis to manage their symptoms, despite little data to support the use of cannabis or cannabis products to treat the disease. In this study, we utilize the well-described dextran sodium sulfate (DSS) model of colitis in mice to assess the impact of commercially available, non-euphorigenic, high cannabigerol (CBG) hemp extract (20 mg/mL cannabigerol, 20.7 mg/mL cannabidiol, 1 mg/mL cannabichromene) on IBD activity and the colonic microbiome. Mice were given 2% DSS in drinking water for 5 days, followed by 2 days of regular drinking water. Over the 7 days, mice were dosed daily with either high CBG hemp extract or matched vehicle control. Daily treatment with high CBG hemp extract dramatically reduces the severity of disease at the histological and organismal levels as measured by decreased disease activity index, increased colon length, and decreases in percent colon tissue damage. 16S rRNA gene sequencing of the fecal microbiota reveals high CBG hemp extract treatment results in alterations in the microbiota, that may be beneficial for colitis. Finally, using metabolomic analysis of fecal pellets, we find that mice treated with high CBG hemp extract have a normalization of several metabolic pathways, including those involved in inflammation. Taken together these data suggest that high CBG hemp extracts may offer a novel treatment option for patients. Significance Statement Using the DSS model of colitis, we show that treatment with high CBG hemp extract reduces the severity of symptoms associated with colitis. Additionally, we show that treatment modulates both the fecal microbiota and metabolome with potential functional significance.

Abdominal pain is associated with an increased risk of future healthcare resource utilization in inflammatory bowel disease.

BACKGROUND: Numerous factors influence healthcare resource utilization (HRU) in inflammatory bowel disease (IBD). We previously demonstrated an association between the presence of certain IBD-related symptoms and HRU. We conducted a longitudinal study to identify the clinical variables and IBD-related symptoms predictive of HRU. METHODS: This investigation utilized clinical encounters at an IBD center within a tertiary care referral center between 10/29/2015-12/31/2019. Participants were assessed over two time points (index and follow-up office visits) separated by a minimum of 6 months. Demographics, endoscopic disease severity, totals and sub-scores of surveys assessing for IBD-related symptoms, HRU, and substance use, and IBD-related medications. HRU was defined as any IBD-related emergency room visit, hospitalization, or surgery during the 6 months prior to follow-up appointment. We identified patients exhibiting HRU (at follow-up) and computed descriptive statistics and contingency table analyses of index appointment clinical data to identify predictors of HRU. Multivariable logistic regression models were fit incorporating significant demographic and clinical factors. RESULTS: 162 consecutively enrolled IBD patients (mean age 44.0 years; 99f:63 m; 115 Crohn's disease [CD], 45 ulcerative colitis [UC], 2 indeterminate colitis) were included. 121 patients (74.7%) exhibited HRU (mean age 43.6 years; 73f:48 m; 84 CD, 36 UC, 1 IC) preceding follow-up appointment. Abdominal pain (OR = 2.18, 95% CI 1.04-4.35, p = 0.04) at the index appointment was the only study variable significantly associated with HRU on bivariate analysis (Table 1). However, none of the clinical factors evaluated in this study were independently associated with HRU in our multivariable logistic regression model. CONCLUSIONS: In this longitudinal study, abdominal pain was the only clinical variable that demonstrated an association with future HRU (even when considering other symptoms and key variables such as disease activity, IBD-medications, and psychiatric comorbidities (i.e., anxious or depressed state). These findings reinforce the importance of regularly screening for and effectively treating abdominal pain in IBD.

Lifestyle Factors Associated with Abdominal Pain in Quiescent Inflammatory Bowel Disease.

BACKGROUND: Lifestyle factors, including diet, exercise, substance use, and sexual activity, have been shown to influence risk of inflammation and complications in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Little is known about their potential role in abdominal pain generation in IBD. AIMS: We performed this study to evaluate for relationships between lifestyle factors and abdominal pain in quiescent IBD (QP-IBD). METHODS: We performed a retrospective analysis utilizing data from our institution's IBD Natural History Registry (January 1, 2017-December 31, 2022). Endoscopic evaluation, concurrent laboratory studies and surveys were completed by participants. Demographic and clinical data were also abstracted. RESULTS: We identified 177 consecutive patients with quiescent disease (105 females:72 males; 121 with CD:56 with UC) for participation in this study, 93 (52.5%) had QP-IBD. Compared to patients with quiescent IBD without pain (QNP-IBD, patients with QP-IBD exhibited no significant differences in IBD type, location, severity or complication rate. Patients with QP-IBD were more likely to have anxiety/depression (55.9% vs. 32.1%, p = 0.002) and to use antidepressants/anxiolytics (49.5% vs. 21.4%, p < 0.001). They were also less likely to engage in exercise at least three times per week (39.8% vs. 54.8%, p = 0.05) or participate in sexual activity at least monthly (53.8% vs. 69.1%, p = 0.04). On logistic regression analysis, antidepressant and/or anxiolytic use was independently associated with QP-IBD [2.72(1.32-5.62)], while monthly sexual activity was inversely associated [0.48(0.24-0.96)]. CONCLUSION: Lifestyle factors, including the lack of sexual activity and exercise, are significantly associated with QP-IBD. Further study is warranted to clarify the relationships between these factors and the development of abdominal pain in quiescent IBD.

Abdominal pain in quiescent inflammatory bowel disease.

OBJECTIVES: Inflammation is an important driver of abdominal pain in inflammatory bowel disease (IBD). However, some patients in remission still experience pain. We aimed to identify risk factors associated with abdominal pain in quiescent IBD (QP-IBD) and to characterize differences from patients with active disease experiencing pain (AP-IBD). METHODS: We performed a retrospective analysis utilizing data from our institution's IBD Natural History Registry (January 1, 2015-August 31, 2018). Endoscopic evaluation, concurrent laboratory studies, and validated surveys were completed by participants. Demographic and clinical data were also abstracted. RESULTS: We recruited 122 patients with quiescent disease (65f:57 m; 93CD:26UC:3Indeterminate) for participation in this study, 74 (60.7%) had QP-IBD. QP-IBD patients were more likely to have anxiety/depression (71.6% vs. 25.0%, p < 0.001) or to use antidepressants (47.3% vs. 22.9%, p < 0.010), opiates (18.9% vs. 2.1%, p < 0.010), other pain medications (50.0% vs. 18.8%, p < 0.010), or corticosteroids (18.9% vs. 2.1%, p < 0.010). On logistic regression analysis, corticosteroid use, anxious/depressed state, and female gender were each independently associated with QP-IBD (p < 0.050 or less). Compared with AP-IBD patients (n = 110, 59f:51 m; 69CD:38UC:3Indeterminate), QP-IBD patients were more likely to use antidepressants (45.6% vs. 26.4%, p < 0.010). Platelet, white blood cell, C-reactive protein, and sedimentation rate levels were all less likely to be elevated in QP-IBD (all p < 0.050), though 44% exhibited pathological elevation in at least one. DISCUSSION: QP-IBD was independently associated with corticosteroid use, anxiety/depression, and female gender. Compared with AP-IBD, QP-IBD patients were more likely to use antidepressants and less likely to exhibit elevated inflammatory markers. However, many QP-IBD patients still demonstrated pathological elevation of these tests, demonstrating the need to develop new noninvasive screening methods for this condition.

Impact of the NaV1.8 variant, A1073V, on post-sigmoidectomy pain and electrophysiological function in rat sympathetic neurons.

NaV1.8 channels play a crucial role in regulating the action potential in nociceptive neurons. A single nucleotide polymorphism in the human NaV1.8 gene SCN10A, A1073V (rs6795970, G>A), has been linked to the diminution of mechanical pain sensation as well as cardiac conduction abnormalities. Furthermore, studies have suggested that this polymorphism may result in a "loss-of-function" phenotype. In the present study, we performed genomic analysis of A1073V polymorphism presence in a cohort of patients undergoing sigmoid colectomy who provided information regarding perioperative pain and analgesic use. Homozygous carriers reported significantly reduced severity in postoperative abdominal pain compared with heterozygous and wild-type carriers. Homozygotes also trended toward using less analgesic/opiates during the postoperative period. We also heterologously expressed the wild-type and A1073V variant in rat superior cervical ganglion neurons. Electrophysiological testing demonstrated that the mutant NaV1.8 channels activated at more depolarized potentials compared with wild-type channels. Our study revealed that postoperative abdominal pain is diminished in homozygous carriers of A1073V and that this is likely due to reduced transmission of action potentials in nociceptive neurons. Our findings reinforce the importance of NaV1.8 and the A1073V polymorphism to pain perception. This information could be used to develop new predictive tools to optimize patient pain experience and analgesic use in the perioperative setting.NEW & NOTEWORTHY We present evidence that in a cohort of patients undergoing sigmoid colectomy, those homozygous for the NaV1.8 polymorphism (rs6795970) reported significantly lower abdominal pain scores than individuals with the homozygous wild-type or heterozygous genotype. In vitro electrophysiological recordings also suggest that the mutant NaV1.8 channel activates at more depolarizing potentials than the wild-type Na+ channel, characteristic of hypoactivity. This is the first report linking the rs6795970 mutation with postoperative abdominal pain in humans.

Anxiety, depression, and inflammation after restorative proctocolectomy.

PURPOSE: Anxiety and depression (A&D) are more common in inflammatory bowel disease (IBD) and in IBD patients who undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA). Our aim was to test the hypothesis that chronic inflammatory conditions in IPAA are associated with increased incidence of A&D. METHODS: Retrospective cohort study at a single tertiary care referral center using a consented IBD and colon cancer natural history registry. Demographic and clinical factors, including surgical and psychiatric history, were abstracted. RESULTS: We compared A&D rate in three cohorts: (1) ulcerative proctocolitis with IPAA (UC) (n = 353), (2) Crohn's disease/indeterminate proctocolitis with IPAA (CDIC) (n = 49), and (3) familial adenomatous polyposis with IPAA (FAP) (n = 33). Forty-six CDIC patients (93.9%) demonstrated pouch-related inflammation, while 126 UC patients (35.7%) and 2 FAP patients (6.1%) developed pouchitis. CDIC had a higher rate of A&D co-diagnosis compared to UC and FAP (20.4 vs.12.7 vs.12.1% respectively; p < 0.05). UC patients with pouchitis also exhibited a higher rate of A&D than UC without pouchitis (19.8 vs.8.8%; p < 0.05). Multivariable analysis demonstrated that pre-operative corticosteroid use (OR = 4.46, CI = 1.34-14.87, p < 0.05), female gender (OR = 2.19, CI = 1.22-3.95, p < 0.01), tobacco use (OR = 2.92, CI = 1.57 = 5.41, p < 0.001), and pouch inflammation (OR = 2.37, CI = 1.28-4.39, p < 0.05) were each independently associated with A&D in these patients. CONCLUSIONS: Anxiety and depression were more common in patients experiencing inflammatory conditions of the pouch. UC without pouchitis and FAP patients demonstrated lower rates of A&D (that were comparable to the general population), implying that having an IPAA alone was not enough to increase risk for A&D. Factors independently associated with A&D in IPAA included an inflamed pouch, corticosteroid use, smoking, and female gender.

Clinical outcomes associated with antidepressant use in inflammatory bowel disease patients and a matched control cohort.

Antidepressant medications (AMs) are frequently used in inflammatory bowel disease (IBD). Many AMs enhance serotonin (5-HT) availability, but this phenomenon may actually worsen IBD. We hypothesized that use of 5-HT-enhancing AMs would be associated with poor clinical outcomes in these disorders. We performed a retrospective cohort study using the Merative Health Marketscan® commercial claims database between 1/1/05 and 12/31/14. Participants (18-63 years) were either controls or had ≥ 2 ICD-9 diagnoses for IBD with ≥ 1 year of continuous insurance enrollment before index diagnosis and 2 years after. We identified new AM prescriptions using the medication possession ratio. Primary outcomes were corticosteroid use (IBD-only), IBD-related complication (IBD-only), IBD-related surgery (IBD-only), hospitalization, and emergency department (ED) visit(s) within 2 years of diagnosis or starting AM. We calculated adjusted hazard ratios (aHRs) in IBD AM users (for each outcome). We also performed subgroup analyses considering IBD and AM subtype. In the IBD cohort (n = 29,393, 41.4% female; 42.2%CD), 5.2% used AMs. In IBD, AM use was independently associated with corticosteroid use, ED visits, and hospitalizations, but not IBD-related complications. AM use was associated with a decreased risk of surgery. In the control cohort (n = 29,393, 41.4% female), AM use was also independently associated with ED visits and hospitalizations, and there was an increased likelihood of these two outcomes compared to the IBD cohort. In conclusion, while AM use was independently associated with an increased risk of ED visits and hospitalization in IBD, these risks were statistically more common in a matched control cohort. Additionally, AM use was associated with reduced risk of surgery in IBD, demonstrating a potential protective role in this setting.

Heterologous expression of the human wild-type and variant NaV 1.8 (A1073V) in rat sensory neurons.

BACKGROUND: Silent inflammatory bowel disease (IBD) is a condition in which individuals with the active disease experience minor to no pain. Voltage-gated Na+ (NaV ) channels expressed in sensory neurons play a major role in pain perception. Previously, we reported that a NaV 1.8 genetic polymorphism (A1073V, rs6795970) was more common in a cohort of silent IBD patients. The expression of this variant (1073V) in rat sympathetic neurons activated at more depolarized potentials when compared to the more common variant (1073A). In this study, we investigated whether expression of either NaV 1.8 variant in rat sensory neurons would exhibit different biophysical characteristics than previously observed in sympathetic neurons. METHODS: Endogenous NaV 1.8 channels were first silenced in DRG neurons and then either 1073A or 1073V human NaV 1.8 cDNA constructs were transfected. NaV 1.8 currents were recorded with the whole-cell patch-clamp technique. KEY RESULTS: The results indicate that 1073A and 1073V NaV 1.8 channels exhibited similar activation values. However, the slope factor (k) for activation determined for this same group of neurons decreased by 5 mV, suggesting an increase in voltage sensitivity. Comparison of inactivation parameters indicated that 1073V channels were shifted to more depolarized potentials than 1073A-expressing neurons, imparting a proexcitatory characteristic. CONCLUSIONS AND INFERENCES: These findings differ from previous observations in other expression models and underscore the challenges with heterologous expression systems. Therefore, the use of human sensory neurons derived from induced pluripotent stem cells may help address these inconsistencies and better determine the effect of the polymorphism present in IBD patients.

Insights into the voltage-gated sodium channel, NaV1.8, and its role in visceral pain perception.

Pain is a major issue in healthcare throughout the world. It remains one of the major clinical issues of our time because it is a common sequela of numerous conditions, has a tremendous impact on individual quality of life, and is one of the top drivers of cost in medicine, due to its influence on healthcare expenditures and lost productivity in those affected by it. Patients and healthcare providers remain desperate to find new, safer and more effective analgesics. Growing evidence indicates that the voltage-gated sodium channel Nav1.8 plays a critical role in transmission of pain-related signals throughout the body. For that reason, this channel appears to have strong potential to help develop novel, more selective, safer, and efficacious analgesics. However, many questions related to the physiology, function, and clinical utility of Nav1.8 remain to be answered. In this article, we discuss the latest studies evaluating the role of Nav1.8 in pain, with a particular focus on visceral pain, as well as the steps taken thus far to evaluate its potential as an analgesic target. We also review the limitations of currently available studies related to this topic, and describe the next scientific steps that have already been undertaken, or that will need to be pursued, to fully unlock the capabilities of this potential therapeutic target.

Identification of Arginine-Vasopressin Receptor 1a (Avpr1a/Avpr1a) as a Novel Candidate Gene for Chronic Visceral Pain Sheds Light on the Potential Role of Enteric Neurons in the Development of Visceral Hypersensitivity.

Chronic abdominal pain in the absence of ongoing disease is the hallmark of disorders of gut-brain interaction (DGBIs), including irritable bowel syndrome (IBS). While the etiology of DGBIs remains poorly understood, there is evidence that both genetic and environmental factors play a role. In this study, we report the identification and validation of arginine-vasopressin receptor 1A (Avpr1a) as a novel candidate gene for visceral hypersensitivity (VH), a primary peripheral mechanism underlying abdominal pain in DGBI/IBS. Comparing 2 C57BL/6 (BL/6) substrains (C57BL/6NTac and C57BL/6J) revealed differential susceptibility to the development of chronic VH following intrarectal zymosan instillation, a validated preclinical model for postinflammatory IBS. Using whole-genome sequencing, we identified a single-nucleotide polymorphism differentiating the 2 strains in the 5' intergenic region upstream of Avpr1a, encoding the protein Avpr1a. We used behavioral, histological, and molecular approaches to identify distal colon-specific gene expression and neuronal hyperresponsiveness covarying with Avpr1a genotype and VH susceptibility. While the 2 BL/6 substrains did not differ across other gastrointestinal phenotypes (eg, fecal water retention), VH-susceptible BL/6NTac mice had higher colonic Avpr1a mRNA and protein expression. These results parallel findings that patients' colonic Avpr1a mRNA expression corresponded to higher pain ratings. Moreover, neurons of the enteric nervous system were hyperresponsive to the Avpr1a agonist arginine-vasopressin, suggesting a role for enteric neurons in the pathology underlying VH. Taken together, these findings implicate differential regulation of Avpr1a as a novel mechanism of VH susceptibility as well as a potential therapeutic target specific to VH. PERSPECTIVE: This article presents evidence of Avpr1a as a novel candidate gene for VH in a mouse model of IBS. Avpr1a genotype and/or tissue-specific expression represents a potential biomarker for chronic abdominal pain susceptibility.

The Impact of Cannabis Use on Clinical Outcomes in Inflammatory Bowel Disease: A Population-based Longitudinal Cohort Study.

BACKGROUND: Cannabis use is common in inflammatory bowel disease (IBD). Recent studies demonstrated that use of cannabis may relieve symptoms; however, it is still unclear how safe cannabis and its derivatives are for IBD patients. We performed this study to evaluate the impact of cannabis use on several key clinical outcomes in IBD. METHODS: We performed a retrospective study using the TriNetX Diamond Network. Cannabis use and noncannabis use subcohorts were identified for 3 patient groups: (1) IBD, (2) Crohn's disease (CD), and (3) ulcerative colitis (UC). Baseline differences between subcohorts for each group were controlled by propensity score matching. In each group, we compared relative incidence of emergency department (ED) visits, hospitalization, corticosteroid use, opioid use, IBD-related surgery, and death between cannabis users and noncannabis users. RESULTS: Inflammatory bowel disease cannabis users demonstrated an increased risk for corticosteroid use (risk ratios [R],1.095; 95% CI, 1.021-1.174; P = .011), ED visits (RR, 2.143; 95% CI, 2.034-2.257; P < .001), hospitalizations (RR, 1.925; 95% CI, 1.783-2.079; P < .001) and opioid use (RR, 1.35; 95% CI, 1.14-1.6); P < .001), but not an increased risk of IBD-related surgery or death. The CD and UC groups exhibited similar outcomes, except only CD demonstrated an increased risk for corticosteroid and opioid use. CONCLUSIONS: Cannabis use in IBD patients is associated with several poor clinical outcomes, including increased risk of corticosteroid and opioid use, ED visits and hospitalization, though not IBD-related surgery or death. It is not clear what drives these risks or whether they are directly related to IBD-associated disease activity or other factors. Further prospective studies are warranted to more carefully investigate these relationships.

Lifestyle Factors and Silent Inflammatory Bowel Disease.

Introduction: Hypoalgesic or silent inflammatory bowel disease (IBD) is a poorly understood condition that has been associated with poor clinical outcomes. There is evidence that lifestyle factors, including diet, exercise, and substance use can influence inflammatory activity and symptoms in IBD. It is unclear, though, whether these issues impact pain experience in IBD. We performed this study to evaluate the potential relationship between several key lifestyle factors and silent IBD. Methods: We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in 2 patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: (a) active IBD without pain (silent IBD) and (b) active IBD with pain. We also evaluated the relative incidence of characteristics related to diet, exercise, sexual activity, and substance abuse. Results: One hundred and eighty IBD patients had active disease and 69 (38.3%) exhibited silent IBD. Silent IBD patients exhibited incidences of disease type, location, and severity as pain-perceiving IBD patients. Silent IBD patients were more likely to be male and less likely to exhibit anxiety and/or depression or to use cannabis, analgesic medication, or corticosteroids. There were no significant differences in dietary, exercise-related, or sexual activities between silent and pain-perceiving IBD patients. Conclusions: Silent IBD was associated with reduced incidence of substance and analgesic medication use. No relationships were found between silent IBD and diet, exercise, or sexual activity, though specific elements of each require further dedicated study.

Polysubstance use in inflammatory bowel disease is associated with increased risk of emergency department visits: a longitudinal study.

Background: Polysubstance use (PSU), the simultaneous use of 2 or more substances of abuse, is common in inflammatory bowel disease (IBD). Preliminary studies suggest it may be associated with poor outcomes. This prospective study evaluated the impact of PSU on disease activity and healthcare resource utilization in IBD. Methods: This study was conducted in a tertiary IBD center between October 29, 2015, and December 31, 2019. Participants were assessed over 2 time points (index and follow-up outpatient appointments) separated by a minimum of 6 months. Demographics, endoscopic disease activity, and surveys assessing symptoms, healthcare resource utilization and substance use (tobacco, alcohol, marijuana, cocaine, methamphetamine, heroin, opioid, or benzodiazepine) were abstracted. We identified PSU during the index appointment and computed descriptive statistics and contingency table analyses, and multivariate logistic regression models at follow up to evaluate outcomes. Results: 162 consecutively enrolled IBD patients were included. Seventy-five patients (46%) were polysubstance users at the index appointment. The most common cohorts were utilizing tobacco and alcohol (n=40) or tobacco and opioids (n=13). On bivariate and multivariate analyses, PSU during the index visit was positively associated with emergency department (ED) visits (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.24-5.07; P=0.01) and negatively associated with extraintestinal manifestations (OR 0.37, 95%CI 0.18-0.74; P=0.005). Age, sex, disease activity, disease subtype and IBD-related symptoms were not associated with PSU. Conclusions: IBD patients exhibiting PSU had increased risk of future ED visits. This study highlights the risks of PSU and reinforces the importance of appropriate substance use screening.

Abdominal Pain in Inflammatory Bowel Disease: An Evidence-Based, Multidisciplinary Review.

Abdominal pain is one of the most common and impactful symptoms associated with inflammatory bowel disease (IBD), including both Crohn's disease and ulcerative colitis. A great deal of research has been undertaken over the past several years to improve our understanding and to optimize management of this issue. Unfortunately, there is still significant confusion about the underlying pathophysiology of abdominal pain in these conditions and the evidence underlying treatment options in this context. There is also a relative paucity of comprehensive reviews on this topic, including those that simultaneously evaluate pharmacological and nonpharmacological therapeutic options. In this review, our multidisciplinary team examines evidence for various currently available medical, surgical, and other analgesic options to manage abdominal pain in IBD.

Revisiting the Association Between Inflammatory Bowel Disease and Parkinson's Disease.

BACKGROUND: Several studies have reported an association between inflammatory bowel disease (IBD) and Parkinson's disease (PD). The aim of this study is to re-evaluate for an association between IBD and PD while controlling for potential socioeconomic and environmental confounders. METHODS: We performed a retrospective cohort study using the Truven Health Marketscan database between January 1, 2005, and December 31, 2014. Individuals with IBD and household age-matched controls were identified. Adjusted hazard ratios (HRs) were calculated for the development of incident PD, adjusting for age, sex, residence type, US region, comorbidities, and behavior. RESULTS: In all, 154 051 subjects with IBD and an equal number of controls were identified. During a mean (SD) follow-up of 3.8 (2.2) years, 132 incident PD cases were identified. There was no significant association between IBD and PD (adjusted HR, 1.01; 0.72-1.42) when adjusting for the confounders previously mentioned. CONCLUSIONS: We found no statistically significant association between these disorders. It is possible that previous associations identified between these disorders were confounded by environmental and socioeconomic factors.

Symptoms and Extraintestinal Manifestations in Active Cannabis Users with Inflammatory Bowel Disease.

Introduction: Cannabis use is common in the setting of inflammatory bowel disease (IBD). Patients frequently use cannabis to treat IBD-associated symptoms, and there is evidence that cannabis and its derivatives are helpful for this purpose. However, it is unclear how the symptom profiles of active IBD cannabis users and nonusers compare and how these symptoms may relate to their underlying disease state and/or complications. Materials and Methods: We performed a retrospective cohort study using a consented IBD natural history registry from a single tertiary care referral center between January 1, 2015 and August 31, 2020. We asked patients about current cannabis use and frequency. We also abstracted demographic and clinical characteristic information, including endoscopic severity, and totals and subscores of surveys assessing IBD characteristics, presence of anxiety/depression, and IBD-associated symptoms. We compared clinical and demographic factors of cannabis users and nonusers and developed a logistic regression model to evaluate for independent associations with cannabis use. Results: Three hundred eighty-three IBD patients met the inclusion criteria (206 females, 177 males; 258 Crohn's disease [CD], 118 ulcerative colitis, and 7 indeterminate colitis). Thirty patients (7.8%) were active cannabis users, consuming it for an average of 2.7 times per week. Cannabis users were more likely to report abdominal pain (83.3% vs. 61.7%), gas (66.7% vs. 45.6%), tenesmus (70.0% vs. 47.6%), and arthralgias (53.3% vs. 20.3%) compared to those that did not use cannabis (p<0.05 for each). Incidence of moderate-severe endoscopic inflammation was similar between cannabis users and nonusers, while CD-associated complications were more common in nonusers (39.1% vs. 69.7%, p<0.05). The only factor that demonstrated a significant association with cannabis use on multivariable analysis was arthralgia (p<0.01). Discussion: Active IBD cannabis users were more likely to report a variety of symptoms, including abdominal pain, gas, tenesmus, and arthralgias. However, they did not demonstrate more frequent active disease or IBD-associated complications, suggesting that other nonluminal factors influence their symptoms and/or decision to use cannabis. These findings demonstrate the importance of evaluating for extraintestinal contributors to symptom burden in IBD cannabis users, as well as the ongoing need to develop safer and more effective methods for recognizing and managing abdominal pain and other symptoms in this setting.

Dedicated Psychiatry Clinic for Inflammatory Bowel Disease Patients Has a Positive Impact on Depression Scores.

Background: Psychiatric disorders, including anxiety and depression, are significantly more common in patients with inflammatory bowel disease (IBD). We established an integrated psychiatry clinic for IBD patients at our tertiary center IBD clinic to provide patients with critical, but frequently unavailable, coordinated mental health services. We undertook this study to evaluate the impact of this service on psychiatric outcomes, quality of life, and symptom experience. Methods: We performed a longitudinal prospective study comparing patients who had been cared for at our integrated IBD-psychiatry clinic to those who had not. We abstracted demographic and clinical information as well as contemporaneous responses to validated surveys. Results: Thirty-six patients cared for in the IBD psychiatry clinic were compared to a control cohort of 35 IBD patients. There was a significant reduction in the Hospital Anxiety and Depression Scale (HADS) depression score over time in the study cohort (p = 0.001), though not in the HADS anxiety score. When compared to the control group, the study cohort showed a significant reduction in the HADS depression score. No significant differences were observed in the Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, or Short IBD Questionnaire. Conclusions: This is the first study to evaluate the impact of an integrated psychiatry clinic for IBD patients. Unlike their control counterparts, individuals treated in this clinic had a significant reduction in the mean HADS depression score. Larger scale studies are necessary to verify these findings. However, this study suggests that use of an integrated psychiatry IBD clinic model can result in improvement in mental health outcomes, even in the absence of significant changes in IBD activity.

Symptoms associated with healthcare resource utilization in the setting of inflammatory bowel disease.

Several symptoms have been connected to increased healthcare resource utilization (HRU) in the context of inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC). This study was designed to investigate the prevalence of IBD-associated symptoms and to determine whether any are independently associated with HRU. We undertook a retrospective analysis of data related to consecutive IBD patient encounters from a tertiary care referral center between 1/1/2015 and 8/31/2019. Demographics, clinical activity, endoscopic severity, IBD-related symptom scores, anxiety and depression scores, and other key clinical data were abstracted. Four hundred sixty-seven IBD patients [247f.: 220 m; 315 CD, 142 UC and 11 indeterminate colitis] were included in this study. The most common symptoms were fatigue (83.6%), fecal urgency (68.2%) and abdominal pain (63.5%). Fatigue, abdominal pain, anxiety or depression, corticosteroids, and opioids were each positively associated with HRU, while NSAID and mesalamine use were inversely associated on bivariate analysis. The only factor that demonstrated a statistically significant association with HRU in the whole cohort on multivariable analysis was abdominal pain. Abdominal pain is independently associated with HRU and should be specifically screened for in IBD patients to identify individuals at risk of undergoing expensive interventions. This study also reinforces the importance of optimizing diagnostic and therapeutic management of abdominal pain in IBD.

Silent Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is frequently associated with a variety of problematic symptoms, including abdominal pain and bowel habit changes, which are associated with poor patient quality of life and significant healthcare expenditure. Interestingly, silent IBD, a condition where patients demonstrate reduced perception and/or reporting of symptoms in the setting of active inflammation, may be as clinically consequential. This condition has been associated with serious complications leading to more costly interventions. It is by its nature an under-recognized phenomenon that affects substantial portions of patients with either Crohn's disease or ulcerative colitis. At the present time, although there are a variety of theories relating to the underlying causes and contributors, little is known about why this phenomenon occurs. As a result, there is a lack of cost-effective, reliable diagnostic methods to identify and manage "at-risk" patients. However, it is significantly likely that further study and an improved understanding of this condition will lead to improved approaches for the diagnosis and treatment of patients with silent IBD as well as other gastrointestinal disorders associated with alterations in symptomatic perception. In this article, we critically review studies that have investigated silent IBD. Specifically, we discuss the following: (1) the methods for defining silent IBD, (2) the known epidemiology of silent IBD, (3) potential causes of and contributors to this clinical entity, (4) current diagnostic modalities available to identify it, and (5) gaps in our understanding as well as potential novel diagnostic and therapeutic applications that could be developed with further study of this condition.