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Vaid R, Fareed A, Qader R, Hussain A, Shaikh W, Zameer U, Ochani S. Cannabis use in Crohn's disease: a systematic review and meta-analysis of randomized controlled trials (RCTs). Ir J Med Sci 2025; 194:439-446. [PMID: 39821383 DOI: 10.1007/s11845-024-03844-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 11/19/2024] [Indexed: 01/19/2025]
Abstract
OBJECTIVE This meta-analysis aims to systematically evaluate the efficacy and safety of cannabis in the management of Crohn's disease (CD) by synthesizing evidence from randomized controlled trials (RCTs). By adhering to the 2020 PRISMA guidelines and registering the study protocol with PROSPERO, this research intends to offer robust, evidence-based recommendations for healthcare practitioners on the therapeutic potential and clinical implications of cannabis use in CD management. METHODS A literature search encompassing PubMed, Google Scholar, and the Cochrane Library was conducted to identify relevant RCTs comparing cannabis to placebo or standard therapy in CD patients. Inclusion criteria focused on outcomes such as remission rates, C-reactive protein (CRP) levels, quality of life (QoL), and adverse events (AEs). Statistical analysis using RevMan 5.3 involved weighted mean differences (MD) and 95% confidence intervals to compare outcomes between the cannabis and control groups. RESULTS The meta-analysis revealed significant findings regarding the impact of cannabis on CD management. The cannabis group exhibited significantly higher clinical remission rates at 8 weeks compared to the control group, with low heterogeneity [MD = - 67.98; 95% CI: (- 100.68, - 35.29)]. However, a statistically significant improvement in QoL was observed in the placebo group compared to the cannabis-treated group [MD = 19.62; 95% CI (14.24 to 25.00)]. There was a non-significant lowering in serum CRP levels compared to the placebo group [MD: - 0.51; 95% CI: (- 1.05, 0.02)]. CONCLUSION The study concludes that cannabis shows promise as a therapeutic option for CD, demonstrating higher remission rates and potential benefits for disease management. However, it also highlights the need for larger, standardized research studies to solidify conclusions regarding efficacy, safety, and biomarker responses in CD patients.
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Affiliation(s)
- Rayyan Vaid
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan.
| | - Areeba Fareed
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan
| | - Rabia Qader
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan
| | - Aariz Hussain
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan
| | - Wajiha Shaikh
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan
| | - Ushna Zameer
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan
| | - Sidhant Ochani
- Department of Medicine, Khairpur Medical College, Khairpur Mir's, Pakistan
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Brodaric A, Polikarpova A, Hong J. Cannabinoids for Inflammatory Bowel Disease: A Scoping Review. Cannabis Cannabinoid Res 2025; 10:18-27. [PMID: 39029906 DOI: 10.1089/can.2024.0061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2024] Open
Abstract
Purpose: Inflammatory bowel disease (IBD) has two main variants, ulcerative colitis (UC) and Crohn's disease (CD), which are characterized by a cycle of remission and relapse. The aim of this scoping review is to understand the landscape of unprescribed and prescribed cannabis use among patients with IBD and investigate objective clinical benefits. Methodology: A literature search was performed across Medline, Embase via Ovid, Scopus, and Cochrane Library databases. We included 40 studies (14 abstracts/letters, 7 randomized controlled trials [RCTs], 6 cohort studies [2 case-matched], 10 cross-sectional surveys, and 3 meta-analyses) in the review. Results: Between 11% and 17.6% of surveyed patients used cannabis for symptom control with a lifetime prevalence of 39.8-78.2%. Patients reported reduced abdominal pain, emotional distress, stool frequency, and anorexia. There was a higher rate of depression, tobacco, and alcohol use among patients with IBD who used cannabis. Individual studies showed patients who were prescribed cannabis were more likely to have had surgery for IBD (14.5% vs. 4.7%, p = 0.0008), require future abdominal surgery (odds ratio = 5.03), report a lower quality of life (p = 0.0001), currently be on corticosteroids (18.1% vs. 10.4%, p = 0.04) and opioids (27.7% vs. 6.4%, p = 0.0001). RCTs of cannabinoids reported mild reductions in disease activity and variable endoscopic inflammation improvement. Conclusions: Patients who use cannabis for IBD are a cohort with refractory disease and lower quality of life who report improvements in symptom management. However, the ability to reduce underlying disease activity appears very modest. Further trials using refined cannabinoid formulations may define a use in IBD.
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Affiliation(s)
- Alen Brodaric
- Colorectal Surgery, Royal Prince Alfred Hospital, Camperdown, Australia
- Faculty of Medicine & Health, The University of Sydney, Camperdown, Australia
- RPA Institute of Academic Surgery, Camperdown, Australia
| | - Aleksandra Polikarpova
- Colorectal Surgery, Royal Prince Alfred Hospital, Camperdown, Australia
- Faculty of Medicine & Health, The University of Sydney, Camperdown, Australia
| | - Jonathan Hong
- Colorectal Surgery, Royal Prince Alfred Hospital, Camperdown, Australia
- Faculty of Medicine & Health, The University of Sydney, Camperdown, Australia
- RPA Institute of Academic Surgery, Camperdown, Australia
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3
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Dzwonkowski M, Bahirwani J, Rollins S, Muratore A, Christian V, Schneider Y. Selected Use of Complementary and Alternative Medicine (CAM) Agents in IBD. Curr Gastroenterol Rep 2025; 27:1. [PMID: 39821707 DOI: 10.1007/s11894-025-00960-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2025] [Indexed: 01/19/2025]
Abstract
PURPOSE OF REVIEW Inflammatory bowel disease (IBD) can cause significant psychological, physical, and economic burdens on patients and healthcare systems. Studies show over one-fifth of patients will seek nontraditional methods of treatment for managing their symptoms. Understanding the benefits - and potential harms - of these therapies is important to provide holistic and evidence-based care to our IBD patients. RECENT FINDINGS In this review, we present several studied herbal therapies for the management of both Crohn's disease and ulcerative colitis. These include cannabinoids, Tripterygium wilfordii, Chios mastic gum, Boswellia serrata, Indigo Naturalis, curcumin, resveratrol, and Zingiber officinale. While these herbal remedies have been shown to have anti-inflammatory effects and positive outcomes in IBD patients, larger scale studies are lacking and the use may be limited by bioavailability, lack of standardization of formulations, and adverse reactions. In reviewing the literature, we discuss the current data available including benefits, adverse reactions, and considerations for use surrounding several of the more common herbal remedies used for IBD.
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Affiliation(s)
- Monica Dzwonkowski
- Department of Gastroenterology, St. Luke's University Health Network, Bethlehem, PA, USA
| | - Janak Bahirwani
- Department of Gastroenterology, Kadlec Clinic, Richland, WA, USA
| | - Samantha Rollins
- Department of Gastroenterology, St. Luke's University Health Network, Bethlehem, PA, USA
| | - Alicia Muratore
- Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA
| | - Vikram Christian
- Department of Pediatric Gastroenterology, M Health Fairview, Minneapolis, MN, USA
| | - Yecheskel Schneider
- Department of Gastroenterology, St. Luke's University Health Network, Bethlehem, PA, USA.
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Summersett Williams F, Zaniletti I, Masonbrink AR, Garofalo R, Rahmandar M, Karnik NS, Donenberg G, Kuhns L. Substance Use Emergency Department Visits Among Youths With Chronic Conditions During COVID-19. JAMA Netw Open 2024; 7:e2435059. [PMID: 39365582 PMCID: PMC11581538 DOI: 10.1001/jamanetworkopen.2024.35059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 07/29/2024] [Indexed: 10/05/2024] Open
Abstract
Importance Pediatric emergency department (ED) visits for substance use (SU) increased during COVID-19. Better understanding of trends associated with SU ED visits among youths with a chronic medical condition (CMC) is needed to target SU screening, prevention, and intervention efforts in this population. Objective To describe trends in pediatric SU ED visits before and during COVID-19 among youths in the US with and without CMCs and by race and ethnicity. Design, Setting, and Participants In this cohort study, data were obtained from 47 US children's hospital EDs in the Pediatric Health Information System (PHIS) between March 1, 2018, and March 1, 2022. The cohort included patients aged 10 to 18 years. Data analysis occurred from November 2022 to February 2023. Exposures ED visit occurrence before or during the COVID-19 pandemic and with or without the presence of a CMC. CMCs included chronic conditions (CCs) and complex CCs (CCCs). Main Outcomes and Measures The primary outcome was the number of visits for an SU diagnosis based on diagnostic codes for youths with and without CMCs. Trends were assessed using logistic regression, adjusting for covariates and center effect. Results The sample included 3 722 553 ED visits from March 1, 2018, to March 1, 2022 (1 932 258 aged 14-18 years [51.9%]; 1 969 718 female [52.9%]; 961 121 Hispanic [25.8%]; 977 097 non-Hispanic Black [26.2%]; 1 473 656 non-Hispanic White [39.6%]). Of all visits, 1 016 913 (27.3%) were youths with CCs and 367 934 (9.9%) were youths with CCCs. Youth SU ED visits increased for all groups during COVID-19. The SU ED visits increased by 23% for youths with CCs (21 357 visits [4.0%] to 23 606 visits [4.9%]), by 26% for youths with CCCs (3594 visits [1.9%] to 4244 visits [2.4%]), and by 50% for youths without CCs (4997 visits [0.4%] to 5607 visits [0.6%]). Furthermore, compared with youths without CCs, youths with CCs had consistently larger odds of SU than the other groups before COVID-19 (adjusted odds ratio, 9.74; 99% CI, 9.35-10.15) and during COVID-19 (adjusted odds ratio, 8.58; 99% CI, 8.25-8.92). The interaction between race and ethnicity and CMCs was significant (P for interaction < .001). Conclusions and Relevance The findings of this cohort study suggest that providing SU services to all youths during times of societal crises is critical, but particularly for youths with CMCs who experience higher potential health impacts from SU given their medical concerns.
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Affiliation(s)
- Faith Summersett Williams
- Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital, Chicago, Illinois
| | | | - Abbey R. Masonbrink
- Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Children’s Mercy Kansas City
| | - Robert Garofalo
- Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital, Chicago, Illinois
| | - Maria Rahmandar
- Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital, Chicago, Illinois
| | - Niranjan S. Karnik
- Institute for Juvenile Research, Department of Psychiatry, College of Medicine, University of Illinois at Chicago
| | - Geri Donenberg
- Department of Medicine, University of Illinois at Chicago, Center for Dissemination and Implementation Science
| | - Lisa Kuhns
- Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital, Chicago, Illinois
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Alshaarawy O, Balasubramanian G, Venkatesan T. Cannabis use in the United States and its impact on gastrointestinal health. Nutr Clin Pract 2024; 39:281-292. [PMID: 38142306 DOI: 10.1002/ncp.11111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 09/13/2023] [Accepted: 11/17/2023] [Indexed: 12/25/2023] Open
Abstract
In recent years, the legalization and social acceptability of cannabis use have increased in the United States. Concurrently, the prevalence of cannabis use has continued to rise, and cannabis products have diversified. There are growing concerns regarding the health effects of regular and high-potency cannabis use, and new research has shed light on its potentially negative effects. Here, we review evidence of the gastrointestinal (GI) effects of cannabis and cannabinoids. Dysregulation of the endocannabinoid system might contribute to various GI disorders, including irritable bowel syndrome and cyclic vomiting syndrome, and endocannabinoids have been found to regulate visceral sensation, nausea, vomiting, and the gut microbiome. Cannabis has been shown to have antiemetic properties, and the US Food and Drug Administration has approved cannabis-based medications for treating chemotherapy-induced nausea and vomiting. Yet, chronic heavy cannabis use has been linked to recurrent episodes of severe nausea and intractable vomiting (cannabinoid hyperemesis syndrome). Given the considerable heterogeneity in the scientific literature, it is unclear if cannabinoid hyperemesis syndrome is truly a distinct entity or a subtype of cyclic vomiting that is unmasked by heavy cannabis use and the associated dysregulation of the endocannabinoid system. The changes in cannabis legalization, availability, and public risk perceptions have outpaced research in this area and there is a need for robust, prospective, large-scale studies to understand the effects of cannabis use on GI health.
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Affiliation(s)
- Omayma Alshaarawy
- Department of Family Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Gokulakrishnan Balasubramanian
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Thangam Venkatesan
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA
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Erridge S, Sodergren MH. Cannabis Use: A Marker of Clinical Severity in Inflammatory Bowel Disease? Inflamm Bowel Dis 2024; 30:322-323. [PMID: 37738592 DOI: 10.1093/ibd/izad221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/24/2023]
Affiliation(s)
- Simon Erridge
- Imperial College Medical Cannabis Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
- Sapphire Medical Clinics, London, UK
| | - Mikael H Sodergren
- Imperial College Medical Cannabis Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
- Sapphire Medical Clinics, London, UK
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Fliss Isakov N, Seidenberg C, Meiri D, Yackobovitch-Gavan M, Maharshak N, Hirsch A. Medical Cannabis Increases Appetite but Not Body Weight in Patients with Inflammatory Bowel Diseases. Nutrients 2023; 16:78. [PMID: 38201908 PMCID: PMC10781068 DOI: 10.3390/nu16010078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/15/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
We aimed to elucidate the effect of Medical Cannabis (MC) on appetite and nutritional status among patients with inflammatory bowel disease (IBD). A case series of patients with IBD were initiating treatment with MC for disease-related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometrics, medical history and treatment and MC use were systematically recorded. An appetite and food frequency questionnaire (SNAQ and FFQ) were filled before, and at 3 and 6 months of treatment. Patients with IBD initiating MC were enrolled (n = 149, age 39.0 ± 14.1 years, 42.3% female), and 33.6% (n = 50) were treated for improvement of nutritional status. A modest increase in appetite after 3 months was detected among all patients enrolled (Pv = 0.08), but there were no significant differences in energy or macronutrient intake, and in patients' body mass index (BMI). A significant appetite improvement after 3 months was detected among 34.0% (n = 17) of patients, but this was not associated with increased caloric intake or BMI at 3 or 6 months. Among patients without increased appetite after 3 months of MC therapy, BMI decreased at 6 months (24.1 ± 3.7 vs. 23.4 ± 3.6, Pv = 0.010). MC may be a potential strategy to improve appetite among some patients with IBD, but not caloric intake or BMI.
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Affiliation(s)
- Naomi Fliss Isakov
- Department of Health Promotion, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; (N.M.); (A.H.)
| | - Chen Seidenberg
- School of Pharmacy, Hebrew University of Jerusalem, Jerusalem 9112002, Israel;
| | - David Meiri
- The Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion—Israel Institute of Technology, Haifa 3200003, Israel;
| | - Michal Yackobovitch-Gavan
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;
| | - Nitsan Maharshak
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; (N.M.); (A.H.)
| | - Ayal Hirsch
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; (N.M.); (A.H.)
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Baillie S, Norton C, Saxena S, Pollok R. Chronic abdominal pain in inflammatory bowel disease: a practical guide. Frontline Gastroenterol 2023; 15:144-153. [PMID: 38420131 PMCID: PMC10897648 DOI: 10.1136/flgastro-2023-102471] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/12/2023] [Indexed: 03/02/2024] Open
Abstract
Pain is common in inflammatory bowel disease (IBD), yet many patients feel their pain is not addressed by healthcare professionals. Listening to a patient's concerns about pain, assessing symptoms and acknowledging the impact these have on daily life remain crucial steps in addressing pain in IBD. While acute pain may be effectively controlled by pain medication, chronic pain is more complex and often pharmacological therapies, particularly opioids, are ineffective. Low-dose tricyclic antidepressants and psychological approaches, including cognitive-behavioural therapy, have shown some promise in offering effective pain management while lifestyle changes such as a trial of low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet in those with overlapping irritable bowel syndrome may also reduce pain. Patients benefit from a long-term, trusting relationship with their healthcare professional to allow a holistic approach combining pharmacological, psychological, lifestyle and dietary approaches to chronic pain. We present a practical review to facilitate management of chronic abdominal pain in IBD.
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Affiliation(s)
- Samantha Baillie
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Christine Norton
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK
| | - Sonia Saxena
- Primary Care and Public Health, Imperial College London, London, UK
| | - Richard Pollok
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
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Coates MD, Clarke K, Williams E, Jeganathan N, Yadav S, Giampetro D, Gordin V, Smith S, Vrana K, Bobb A, Gazzio TT, Tressler H, Dalessio S. Abdominal Pain in Inflammatory Bowel Disease: An Evidence-Based, Multidisciplinary Review. CROHN'S & COLITIS 360 2023; 5:otad055. [PMID: 37867930 PMCID: PMC10588456 DOI: 10.1093/crocol/otad055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Indexed: 10/24/2023] Open
Abstract
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.
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Affiliation(s)
- Matthew D Coates
- Department of Medicine, Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, USA
- Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA
| | - Kofi Clarke
- Department of Medicine, Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, USA
| | - Emmanuelle Williams
- Department of Medicine, Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, USA
| | - Nimalan Jeganathan
- Department of Surgery, Division of Colorectal Surgery, Penn State College of Medicine, Hershey, PA, USA
| | - Sanjay Yadav
- Department of Psychiatry, Penn State College of Medicine, Hershey, PA, USA
| | - David Giampetro
- Department of Anesthesia & Perioperative Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Vitaly Gordin
- Department of Anesthesia & Perioperative Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Sadie Smith
- Department of Anesthesia & Perioperative Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Kent Vrana
- Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA
| | - Anne Bobb
- Department of Surgery, Division of Colorectal Surgery, Penn State College of Medicine, Hershey, PA, USA
| | - Thu Thi Gazzio
- Department of Surgery, Division of Colorectal Surgery, Penn State College of Medicine, Hershey, PA, USA
| | - Heather Tressler
- Department of Medicine, Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, USA
| | - Shannon Dalessio
- Department of Medicine, Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, USA
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Thapa D, Warne LN, Falasca M. Pharmacohistory of Cannabis Use-A New Possibility in Future Drug Development for Gastrointestinal Diseases. Int J Mol Sci 2023; 24:14677. [PMID: 37834122 PMCID: PMC10572150 DOI: 10.3390/ijms241914677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Revised: 09/21/2023] [Accepted: 09/25/2023] [Indexed: 10/15/2023] Open
Abstract
Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.
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Affiliation(s)
- Dinesh Thapa
- Metabolic Signalling Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia; (D.T.); (L.N.W.)
| | - Leon N. Warne
- Metabolic Signalling Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia; (D.T.); (L.N.W.)
- Little Green Pharma, West Perth, WA 6872, Australia
| | - Marco Falasca
- Metabolic Signalling Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia; (D.T.); (L.N.W.)
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11
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Tait MA, Costa DS, Campbell R, Norman R, Warne LN, Schug S, Rutherford C. Health-related quality of life in patients accessing medicinal cannabis in Australia: The QUEST initiative results of a 3-month follow-up observational study. PLoS One 2023; 18:e0290549. [PMID: 37672515 PMCID: PMC10482296 DOI: 10.1371/journal.pone.0290549] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 08/09/2023] [Indexed: 09/08/2023] Open
Abstract
AIMS Patients with chronic health conditions not responding to conventional treatment can access medicinal cannabis (MC) prescriptions from clinicians in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, and depression in a large real-world sample of patients accessing prescribed medicinal cannabis. We hypothesized that all patient-reported outcomes (PROs) would improve from baseline to 3-months. METHODS The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Eligible patients were identified by 120 clinicians at medical centers across six Australian states. Consenting participants completed the EuroQol Group EQ-5D-5L health status questionnaire; European Organization for Research & Treatment of Cancer Quality of Life questionnaire (QLQ-C30); Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms in Fatigue and Sleep Disturbance, and the Depression Anxiety Stress Scale (DASS-21) before starting therapy, at 2-weeks titration, then monthly for 3-months. RESULTS Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18-97 years (mean 51y; SD = 15.4), 62.8% were female. The most commonly treated conditions were chronic pain (n = 1598/2327; 68.7%), insomnia (n = 534/2327; 22.9%), generalized anxiety (n = 508/2327; 21.5%), and mixed anxiety and depression (n = 259/2327; 11%). Across the whole cohort both EQ-5D-5L utility scores and QLQ-C30 summary scores showed clinically meaningful improvement in HRQL from baseline to mean follow-up with d = 0.54 (95%CI:0.47 to 0.59) and d = 0.64 (95%CI:0.58 to 0.70) respectively; and clinically meaningful improvement in fatigue (d = 0.54; 95%CI:0.48 to 0.59). There was clinically meaningful reduction of pain for those with chronic pain (d = 0.65; 95%CI:0.57 to 0.72); significant improvements for those with moderate to extremely severe anxiety (X2 = 383; df = 4; p<0.001) and depression (X2 = 395; df = 4; p<0.001); and no changes in sleep disturbance. CONCLUSIONS We observed statistically significant, clinically meaningful improvements in overall HRQL and fatigue over the first 3-months in patients with chronic health conditions accessing prescribed medical cannabis. Anxiety, depression, and pain also improved over time, particularly for those with corresponding health conditions. The study continues to follow-up patients until 12-months to determine whether improvements in PROs are maintained long-term. TRAIL REGISTRATION Study registration - Australian New Zealand Clinical Trials Registry: ACTRN12621000063819. https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12621000063819.
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Affiliation(s)
- Margaret-Ann Tait
- Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, Sydney Nursing School, The University of Sydney, Sydney, New South Wales, Australia
| | - Daniel S.J. Costa
- Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
| | - Rachel Campbell
- Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
| | - Richard Norman
- School of Population Health, Curtin University, Perth, Australia
| | - Leon N. Warne
- Little Green Pharma, West Perth, Western Australia, Australia
- College of Science, Health, Engineering and Education, Murdoch University, Perth, Western Australia, Australia
- School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
| | - Stephan Schug
- School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
| | - Claudia Rutherford
- Faculty of Medicine and Health, Sydney Nursing School, The University of Sydney, Sydney, New South Wales, Australia
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12
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Greywoode R, Cunningham C, Hollins M, Aroniadis O. Medical Cannabis Use Patterns and Adverse Effects in Inflammatory Bowel Disease. J Clin Gastroenterol 2023; 57:824-829. [PMID: 36227025 PMCID: PMC10102249 DOI: 10.1097/mcg.0000000000001782] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 09/15/2022] [Indexed: 12/10/2022]
Abstract
GOALS To investigate medical cannabis (MC) use patterns and adverse effects in patients with inflammatory bowel disease (IBD). BACKGROUND MC is now legal in many states. Although previous studies suggest improvement in disease activity among IBD patients using MC, use patterns and adverse effects are unclear. STUDY A cross-sectional anonymous survey was conducted (October 23, 2020 to January 24, 2021) among patients accessing MC dispensaries in New York and Minnesota. Eligibility criteria: age 18 years or older, selfreported IBD diagnosis, MC dispensary purchase. Survey questions included IBD characteristics, MC and healthcare utilization, and MC effects/adverse events. Participant characteristics were analyzed with descriptive statistics. Utilization patterns and symptoms before and after MC use were compared using the Stuart Maxwell test. RESULTS Of 236 respondents, overall IBD disease activity was mild-to-moderate. Most respondents (61.0%) took a biological. Median frequency of MC use was at least once within the past week. Most respondents used products with high Δ9-tetrahydrocannabinol content (87.5%) through vape pens/cartridges (78.6%). Respondents reported fewer emergency room visits in the 12 months after versus before MC use (35.2 vs 41.5%, P <0.01) and less impact of symptoms on daily life. Most respondents reported euphoria with MC use (75.4%). The other common side effects were feeling drowsy, groggy, or with memory lapses (4.2%), dry mouth/eyes (3.4%), and anxiety/depression or paranoia (3.4%). Few respondents reported MC diversion (1.3%). CONCLUSIONS MC users with IBD perceive symptom benefits and report decreased emergency room visits without serious adverse effects. Further studies are needed to confirm these results with objective measures of healthcare utilization and disease activity.
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Affiliation(s)
- Ruby Greywoode
- Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
| | - Chinazo Cunningham
- Family and Social Medicine, Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY
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13
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Samuel S, Michael M, Tadros M. Should gastroenterologists prescribe cannabis? The highs, the lows and the unknowns. World J Clin Cases 2023; 11:4210-4230. [PMID: 37449231 PMCID: PMC10336994 DOI: 10.12998/wjcc.v11.i18.4210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 03/31/2023] [Accepted: 04/14/2023] [Indexed: 06/26/2023] Open
Abstract
Cannabis, commonly known as marijuana, is a drug extracted from the Cannabis plant known for its psychotropic and medicinal properties. It has been used for healing purposes during ancient times, although its psychoactive components led to its restricted use in medicine. Nonetheless, cannabis is found to have modulatory effects on the endocannabinoid system exhibiting its medicinal role in the gastrointestinal (GI) system. Emerging animal and human studies demonstrate the influential effects of cannabis on a variety of GI diseases including inflammatory bowel disease, motility disorders and GI malignancies. It also has a regulatory role in GI symptoms including nausea and vomiting, anorexia, weight gain, abdominal pain, among others. However, both its acute and chronic use can lead to undesirable side effects such as dependency and addiction, cognitive impairment and cannabinoid hyperemesis syndrome. We will discuss the role of cannabis in the GI system as well as dosing strategies to help guide gastroenterologists to assess its efficacy and provide patient counseling before prescription of medical marijuana.
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Affiliation(s)
- Sonia Samuel
- Department of Internal Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Mark Michael
- Department of Internal Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Micheal Tadros
- Department of Gastroenterology and Hepatology, Albany Medical Center, Albany, NY 12208, United States
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14
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Tsampoula I, Zartaloudi A, Dousis E, Koutelekos I, Pavlatou N, Toulia G, Kalogianni A, Polikandrioti M. Quality of Life in Patients Receiving Medical Cannabis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1425:401-415. [PMID: 37581814 DOI: 10.1007/978-3-031-31986-0_39] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Abstract
INTRODUCTION Medical cannabis has been used to relieve the symptoms of people with various chronic diseases. Despite of this, it has been stigmatized, even after its legalization in many countries. AIM The purpose of this study was to investigate the quality of life of patients receiving medical cannabis. MATERIAL AND METHOD One hundred patients receiving medical cannabis were given (a) a socio-demographic and clinical questionnaire, and (b) the SF-36 Health Survey scale for assessing quality of life. RESULTS The majority of our patients who received medical cannabis to treat their neurological disorders (58%) reported decrease in their symptoms (96%), better energy and vitality (68%), ability to perform their professional duties (88%), and an improvement in sleeping and appetite (79% and 71%, respectively) after receiving medical cannabis. Our participants exhibited very few restrictions in activities due to emotional difficulties, a moderate general health status as well as moderate vitality and energy. Participants, who reported a longer period of receiving medical cannabis, reported statistically significant more energy and vitality (p = 0.000), but also better mental (p = 0.000) and general health status (p = 0.001). Furthermore, the majority of patients have disclosed medical cannabis use to their family members (85%) and enjoyed their support (93%), but they haven't revealed their medication treatment to their social environment (81%). CONCLUSIONS Appropriate knowledge could significantly help health professionals in the field of planning and implementation of personalized nursing care in order to achieve optimal therapeutic outcomes.
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Affiliation(s)
- Iliana Tsampoula
- Department of Nursing, University of West Attica, Athens, Greece
| | | | - Evangelos Dousis
- Department of Nursing, University of West Attica, Athens, Greece
| | | | - Niki Pavlatou
- Department of Nursing, University of West Attica, Athens, Greece
| | - Georgia Toulia
- Department of Nursing, University of West Attica, Athens, Greece
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15
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Huang W, Czuba LC, Manuzak JA, Martin JN, Hunt PW, Klatt NR, Isoherranen N. Objective Identification of Cannabis Use Levels in Clinical Populations Is Critical for Detecting Pharmacological Outcomes. Cannabis Cannabinoid Res 2022; 7:852-864. [PMID: 34793254 PMCID: PMC9784609 DOI: 10.1089/can.2021.0068] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Introduction: Cannabis is widely used for recreational and medical purposes, but its therapeutic efficacy remains unresolved for many applications as data from retrospective studies show dramatic discrepancy. We hypothesized that false self-reporting of cannabis use and lack of differentiation of heavy users from light or occasional users contribute to the conflicting outcomes. Objective: The goal of this study was to develop an objective biomarker of cannabis use and test how application of such biomarker impacts clinical study outcomes and dose-response measures. Methods and Analysis: Population pharmacokinetic (PK) models of (-)-trans-Δ9-tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC) were developed based on published studies reporting cannabinoid disposition in individual subjects following intravenous administration or smoking of cannabis. Plasma 11-COOH-THC concentration distributions in different cannabis user groups smoking cannabis were generated via Monte Carlo simulations, and plasma concentration cutoff values of 11-COOH-THC were developed to differentiate light and heavy daily cannabis users in clinical studies. The developed cutoff value was then applied to a retrospective study that assessed the impact of cannabis use on T cell activation in subjects with HIV who self-reported as either nonuser or daily user of cannabis. Results: The developed population PK models established plasma 11-COOH-THC concentration of 73.1 μg/L as a cutoff value to identify heavy daily users, with a positive predictive value of 80% in a mixed population of equal proportions of once daily and three times a day users. The stratification allowed detection of changes in T cell activation in heavy users which was not detected based on self-reporting or detectability of plasma cannabinoids. A proof-of-concept power analysis demonstrated that implementation of such cutoff value greatly increases study power and sensitivity to detect pharmacological effects of cannabis use. Conclusions: This study shows that the use of plasma 11-COOH-THC concentration cutoff value as an objective measure to classify cannabis use in target populations is critical for study sensitivity and specificity and provides much needed clarity for addressing dose-response relationships and therapeutic effects of cannabis.
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Affiliation(s)
- Weize Huang
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
| | - Lindsay C. Czuba
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
| | - Jennifer A. Manuzak
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
- Division of Immunology, Tulane National Primate Research Center, Covington, Louisiana, USA
| | - Jeffrey N. Martin
- Department of Medicine and University of California San Francisco, San Francisco, California, USA
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
| | - Peter W. Hunt
- Department of Medicine and University of California San Francisco, San Francisco, California, USA
| | - Nichole R. Klatt
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Nina Isoherranen
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
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16
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Yin J, Li Y, Chen Y, Wang C, Song X. Adalimumab for induction of remission in patients with Crohn's disease: a systematic review and meta-analysis. Eur J Med Res 2022; 27:190. [PMID: 36175983 PMCID: PMC9523983 DOI: 10.1186/s40001-022-00817-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 09/12/2022] [Indexed: 11/17/2022] Open
Abstract
Purpose A large number of people with Crohn's disease (CD) fail to recover from conventional therapy or biological therapy. Some studies showed that adalimumab (ADA) may be an effective alternative therapy for these patients. The aim of this study was to evaluate the efficacy and safety of ADA in inducing CD remission. Methods We performed search of Pubmed/MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register, and several other databases. Randomized controlled trials (RCTs) comparing any dose of ADA with controls (placebo or active) in participants with active CD were included. The primary outcome was the failure to achieve clinical response/remission at 4 weeks. Several subgroup and sensitivity analyses were performed. Review Manager Software v5.3 was used. Results Four RCTs were included (n = 919), in which 553 participants received ADA and 366 participants received placebo. A meta-analysis of four studies showed that at 4 weeks, there were more people in the ADA group with clinical response/remission or symptom improvement compared with the placebo group. The rates of side effects, serious side effects, and study withdrawals due to side effects were lower in ADA participants than placebo ones. Conclusion This meta-analysis shows that ADA is superior to placebo in induction of clinical response/remission of CD patients, but no firm conclusions can be drawn on the safety of ADA in CD due to the low number of events. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s40001-022-00817-6.
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Affiliation(s)
- Juntao Yin
- Department of Pharmacy, Huaihe Hospital, Henan University, Kaifeng, Henan, China. .,Department of Pharmaceutics, School of Pharmacy, Henan University, Zhengzhou, 450000, Henan, China.
| | - Yang Li
- Department of Pharmacy, Huaihe Hospital, Henan University, Kaifeng, Henan, China
| | - Yangyang Chen
- Cardiology, Huaihe Hospital, Henan University, Kaifeng, Henan, China
| | - Chaoyang Wang
- General Surgery, Huaihe Hospital, Henan University, Kaifeng, 475000, Henan, China.
| | - Xiaoyong Song
- Department of Pharmaceutics, School of Pharmacy, Henan University, Zhengzhou, 450000, Henan, China
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17
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Coates MD, Dalessio S, Walter V, Stuart A, Bernasko N, Tinsley A, Razeghi S, Williams ED, Clarke K, Vrana K. Symptoms and Extraintestinal Manifestations in Active Cannabis Users with Inflammatory Bowel Disease. Cannabis Cannabinoid Res 2022; 7:445-450. [PMID: 33998892 PMCID: PMC9418352 DOI: 10.1089/can.2020.0155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
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.
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Affiliation(s)
- Matthew D. Coates
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Shannon Dalessio
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Vonn Walter
- Department of Public Health Sciences, and Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
- Department of Biochemistry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - August Stuart
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Nana Bernasko
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Andrew Tinsley
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Sanam Razeghi
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Emmanuelle D. Williams
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Kofi Clarke
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Kent Vrana
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
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18
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Spagnuolo R, Basile A, Corea A, Iaquinta FS, Milić N, Doldo P, Luzza F, Abenavoli L. Measuring Mood and Anxiety Disorders by Patient Reported Outcomes in Inflammatory Bowel Disease: A Literature Review Update. Rev Recent Clin Trials 2022; 17:RRCT-EPUB-124855. [PMID: 35770406 DOI: 10.2174/1574887117666220628151256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 04/17/2022] [Accepted: 04/19/2022] [Indexed: 06/15/2023]
Abstract
Background Anxiety and depression are the most common psychological disorders found in Inflammatory Bowel Disease (IBD) patients. Accurate measuring of these disorders should be proposed for a prompt management. Patient-reported outcome measurements (PROMs) allow patients to self-report their psychological symptoms. Objective To highlight the presence of PROMs measuring anxiety and depression in IBD setting evaluating the most used psychometric tools. Methods We reviewed the literature from 2010 up to September 2021. Articles on adult IBD patients assessing depression and anxiety by PROMs in English language were included. Results Thirty-six studies, including 11 psychometric tools were found. Hospital Anxiety and Depression Scale (21 studies), Beck Depression Inventory II (5 studies), Spielberg State-Trait Anxiety Inventory (3 studies), Patient-Reported Outcomes Measurement Information System (3 studies), Symptom Checklist-90 (2 studies), Euro Quality of Life (2 studies) mostly used psychometric tools for anxiety and depression in IBD settings. Conclusion Our review analyzed psychometric tools used for PROMs evaluating anxiety and depression in IBD setting. No chronological differences have emerged, all have been used in the last ten years, highlighting a lack of specificity. The strong association between IBD and mood disorders suggests that clinicians should consider the evaluation of depression and anxiety as integral parts of IBD clinical care. It is essential to identify tools enabling these items to be detected better. A global view of IBD patients, accounting not only for physical but also for psychical symptoms with an early and feasible assessment of unrecognized psychiatric disorders, can have a strong impact on their management strategy.
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Affiliation(s)
- Rocco Spagnuolo
- Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Calabria, Catanzaro, Italy
| | - Antonio Basile
- Department of Health Sciences, Magna Graecia University of Catanzaro, Calabria, Catanzaro, Italy
| | - Alessandro Corea
- Department of Health Sciences, Magna Graecia University of Catanzaro, Calabria, Catanzaro, Italy
| | | | - Nataša Milić
- Department of Pharmacy, University of Novi Sad, Novi Sad, Serbia
| | - Patrizia Doldo
- Department of Health Sciences, Magna Graecia University of Catanzaro, Calabria, Catanzaro, Italy
| | - Francesco Luzza
- Department of Health Sciences, Magna Graecia University of Catanzaro, Calabria, Catanzaro, Italy
| | - Ludovico Abenavoli
- Department of Health Sciences, Magna Graecia University of Catanzaro, Calabria, Catanzaro, Italy
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19
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Cannabis sativa L. Bioactive Compounds and Their Protective Role in Oxidative Stress and Inflammation. Antioxidants (Basel) 2022; 11:antiox11040660. [PMID: 35453344 PMCID: PMC9030479 DOI: 10.3390/antiox11040660] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/24/2022] [Accepted: 03/28/2022] [Indexed: 12/27/2022] Open
Abstract
Cannabis (Cannabis sativa L.) plants from the family Cannabidaceae have been used since ancient times, to produce fibers, oil, and for medicinal purposes. Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) are the main pharmacologically active compounds of Cannabis sativa. These compounds have, for a long time, been under extensive investigation, and their potent antioxidant and inflammatory properties have been reported, although the detailed mechanisms of their actions have not been fully clarified. CB1 receptors are suggested to be responsible for the analgesic effect of THC, while CB2 receptors may account for its immunomodulatory properties. Unlike THC, CBD has a very low affinity for both CB1 and CB2 receptors, and behaves as their negative allosteric modulator. CBD activity, as a CB2 receptor inverse agonist, could be important for CBD anti-inflammatory properties. In this review, we discuss the chemical properties and bioavailability of THC and CBD, their main mechanisms of action, and their role in oxidative stress and inflammation.
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20
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Bogale K, Raup-Konsavage W, Dalessio S, Vrana K, Coates MD. Cannabis and Cannabis Derivatives for Abdominal Pain Management in Inflammatory Bowel Disease. Med Cannabis Cannabinoids 2022; 4:97-106. [PMID: 35224429 DOI: 10.1159/000517425] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 05/22/2021] [Indexed: 12/15/2022] Open
Abstract
For centuries, cannabis and its components have been used to manage a wide variety of symptoms associated with many illnesses. Gastrointestinal (GI) diseases are no exception in this regard. Individuals suffering from inflammatory bowel disease (IBD) are among those who have sought out the ameliorating properties of this plant. As legal limitations of its use have eased, interest has grown from both patients and their providers regarding the potential of cannabis to be used in the clinical setting. Similarly, a growing number of animal and human studies have been undertaken to evaluate the impact of cannabis and cannabinoid signaling elements on the natural history of IBD and its associated complications. There is little clinical evidence supporting the ability of cannabis or related products to treat the GI inflammation underlying these disorders. However, 1 recurring theme from both animal and human studies is that these agents have a significant impact on several IBD-related symptoms, including abdominal pain. In this review, we discuss the role of cannabis and cannabinoid signaling in visceral pain perception, what is currently known regarding the efficacy of cannabis and its derivatives for managing pain, related symptoms and inflammation in IBD, and what work remains to effectively utilize cannabis and its derivatives in the clinical setting.
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Affiliation(s)
- Kaleb Bogale
- Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Wesley Raup-Konsavage
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Shannon Dalessio
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Kent Vrana
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
| | - Matthew D Coates
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.,Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
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21
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Wynne J, Kozuch P. Medical marijuana for inflammatory bowel disease: the highs and lows. Scand J Gastroenterol 2022; 57:197-205. [PMID: 34919496 DOI: 10.1080/00365521.2021.1998604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Increased interest in cannabis as a potential treatment and/or adjuvant therapy for inflammatory bowel disease (IBD) has been driven by patients with refractory disease seeking relief as well those who desire alternatives to conventional therapies. Available data have shown a potential role of cannabis as a supportive medication, particularly in pain reduction; however, it remains unknown whether cannabis has any impact on the underlying inflammatory process of IBD. The purpose of this review article is to summarize the available literature concerning the use of cannabis for the treatment of IBD and highlight potential areas for future study.
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Affiliation(s)
- Joshua Wynne
- Internal Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Patricia Kozuch
- Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
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22
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Lian J, Casari I, Falasca M. Modulatory role of the endocannabinoidome in the pathophysiology of the gastrointestinal tract. Pharmacol Res 2021; 175:106025. [PMID: 34883211 DOI: 10.1016/j.phrs.2021.106025] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/29/2021] [Accepted: 12/05/2021] [Indexed: 12/13/2022]
Abstract
Originating from Eastern Asia, the plant Cannabis sativa has been used for centuries as a medicinal treatment. The unwanted psychotropic effects of one of its major components, Δ9-tetrahydrocannabinol, discouraged its therapeutic employment until, recently, the discovery of cannabinoids receptors and their endogenous ligands endocannabinoids reignited the interest. The endocannabinoid system has lately been found to play an important role in the maintenance of human health, both centrally and peripherally. However, the initial idea of the endocannabinoid system structure has been quickly understood to be too simplistic and, as new receptors, mediators, and enzymes have been discovered to participate in a complex relationship, the new, more comprehensive term "expanded endocannabinoid system" or "endocannabinoidome", has taken over. The discovery of other endocannabinoid-like receptors, such as the G protein-coupled receptor 119 and G protein-coupled receptor 55, has opened the way to the development of potential therapeutic targets for the treatment of various metabolic disorders. In addition, recent findings have also provided evidence suggesting the potential therapeutic link between the endocannabinoidome and various inflammatory-based gut diseases, such as inflammatory bowel disease and cancer. This review will provide an introduction to the endocannabinoidome, focusing on its modulatory role in the gastrointestinal tract and on the interest generated by the link between gut microbiota, the endocannabinoid system and metabolic diseases such as inflammatory bowel disease, type-2 diabetes and obesity. In addition, we will look at the potential novel aspects and benefits of drugs targeting the endocannabinoid system.
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Affiliation(s)
- Jerome Lian
- Metabolic Signalling Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia
| | - Ilaria Casari
- Metabolic Signalling Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia
| | - Marco Falasca
- Metabolic Signalling Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia.
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23
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Nso N, Nyabera A, Nassar M, Alshamam MS, Sumbly V, Vest M, Patel N, Ojong G, Rizzo V. Cannabis and Its Potential Protective Role Against Inflammatory Bowel Disease: A Scoping Review. Cureus 2021; 13:e18841. [PMID: 34804696 PMCID: PMC8597664 DOI: 10.7759/cureus.18841] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/07/2021] [Indexed: 01/08/2023] Open
Abstract
Globally, around 15%-40% of patients suffering from inflammatory bowel disease (IBD) use Cannabis for pain reduction, increased appetite, and reduced need for other medications. Although many patients report having benefited by using Cannabis in IBD, there is still a lack of consensus regarding the use of Cannabis in IBD. The aim is to identify, explore and map literature on the potential protective role of Cannabis against IBD through this scoping review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed during the search to answer the focal question: (1) Does Cannabis play a protective role against IBD as assessed by clinical remission; (2) If yes, what is the mechanism of action for this protective role. There were only three randomized controlled trials (RCTs) and three observational studies that satisfied the selection criteria of this scoping review. Although promising results including the improvement in general well-being/ Harvey-Bradshaw Index, health perception enhancement [4.1±1.43 to 7±1.42 (p = 0.0002)], weight gain, Crohn's Disease Activity Index (CDAI) score<150, Mayo scores (4-10), and reduction in clinical complications have been found in some studies, its medical use in IBD is still questionable due to the lack of high-quality evidence. Future RCTs studies should determine the cannabis treatment parameters and validate its safety and effectiveness in the IBD setting. The highlights include: the current literature provides inconclusive evidence concerning the protective role of cannabis for IBD patients; limited research evidence regarding the therapeutic use of cannabinoids for IBD warrants future investigation via RCTs; cannabis provides some benefits to IBD patients by improving their general well-being perceptions, Harvey-Bradshaw Index, Mayo scores, and minimizing their clinical complications.
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Affiliation(s)
- Nso Nso
- Internal Medicine, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, USA
| | - Akwe Nyabera
- Internal Medicine, New York City Health and Hospitals/Queens, New York, USA
| | - Mahmoud Nassar
- Internal Medicine, Icahn School of Medicine at Mount Sinai, New York City Health and Hospitals/Queens, New York, USA
| | - Mohsen S Alshamam
- Internal Medicine, Icahn School of Medicine at Mount Sinai, New York City Health and Hospitals/Queens, New York, USA
| | - Vikram Sumbly
- Internal Medicine, Icahn School of Medicine at Mount Sinai, New York City Health and Hospitals/Queens, New York, USA
| | - Mallorie Vest
- Internal Medicine, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, USA
| | - Nehal Patel
- Internal Medicine, Chicago Medical School, Chicago, USA
| | - Gilbert Ojong
- Internal Medicine, La Magna Health/United Regional Hospital, Atlanta, USA
| | - Vincent Rizzo
- Internal Medicine, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, USA
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24
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Doeve BH, van de Meeberg MM, van Schaik FDM, Fidder HH. A Systematic Review With Meta-Analysis of the Efficacy of Cannabis and Cannabinoids for Inflammatory Bowel Disease: What Can We Learn From Randomized and Nonrandomized Studies? J Clin Gastroenterol 2021; 55:798-809. [PMID: 32675631 DOI: 10.1097/mcg.0000000000001393] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 06/07/2020] [Indexed: 12/20/2022]
Abstract
GOAL AND BACKGROUND A number of studies have investigated the effectiveness of cannabis or cannabinoids for treatment of inflammatory bowel diseases (IBD). We aimed to systematically analyze their effect in in the treatment of IBD patients. STUDY We included randomized controlled trials and nonrandomized studies analyzing IBD patients of any age using cannabi(noid)s. Two reviewers searched 3 databases until August 13, 2019. Primary outcome was clinical remission and secondary outcomes included inflammatory biomarkers, symptom improvement, quality of life (QoL) scores, and hospital outcomes. Risk of bias was assessed according to study type. The meta-analyses were performed using a random-effects model with subgroup analyses based on study type. RESULTS The search identified 682 records of which 15 nonrandomized studies and 5 randomized controlled trials were eligible for inclusion. The meta-analysis of the primary outcome included 146 randomized participants, all 18 years of age or older. Risk of bias was moderate. Cannabi(noid)s were not effective at inducing remission (risk ratio=1.56, 95% confidence interval=0.99-2.46). No effect on inflammatory biomarkers was observed. However, clinical symptoms (abdominal pain, general well-being, nausea, diarrhea, and poor appetite) all improved with cannabi(noid)s on Likert-scales. Baseline QoL scores were lower in patients using cannabis among cohort studies but improved significantly with cannabi(noid)s. Although length of hospital stay was shorter and risk of parenteral nutrition was lower in patients using cannabis, there was no effect on other IBD complications. CONCLUSIONS Cannabi(noid)s do not induce clinical remission or affect inflammation in IBD patients. However, cannabi(noid)s significantly improve patient-reported symptoms and QoL.
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Affiliation(s)
| | - Maartje M van de Meeberg
- Departments of Gastroenterology and Hepatology
- Clinical Pharmacology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
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25
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Graczyk M, Lewandowska AA, Dzierżanowski T. The Therapeutic Potential of Cannabis in Counteracting Oxidative Stress and Inflammation. Molecules 2021; 26:molecules26154551. [PMID: 34361704 PMCID: PMC8347461 DOI: 10.3390/molecules26154551] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/25/2021] [Accepted: 07/26/2021] [Indexed: 12/26/2022] Open
Abstract
Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids published in the last five years. Multimodal properties of cannabinoids include their involvement in immunological processes, anti-inflammatory, and antioxidative effects. Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions.
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Affiliation(s)
- Michał Graczyk
- Department of Palliative Care, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland;
| | | | - Tomasz Dzierżanowski
- Laboratory of Palliative Medicine, Department of Social Medicine and Public Health, Medical University of Warsaw, 02-007 Warsaw, Poland
- Correspondence:
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26
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Inflammatory Bowel Disease and Cannabis: A Practical Approach for Clinicians. Adv Ther 2021; 38:4152-4161. [PMID: 34110607 PMCID: PMC8279986 DOI: 10.1007/s12325-021-01805-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 05/24/2021] [Indexed: 12/11/2022]
Abstract
Although still not approved at the federal level for medical or adult recreational use, cannabis has been approved in the United States (USA) by individual states for both of these purposes. A total of 15 states now regulate cannabis for adult use and 36 states for medical use. In more recent years, cannabis has gained popularity for the treatment of chronic conditions, inflammatory bowel disease (IBD) being one of them. However, the exact role of cannabis in the treatment of IBD remains uncertain. While cannabis may help in some instances with symptom management, it has not been proven to help with inflammation or to fundamentally correct underlying disease processes. Additionally, along with the perceived symptom benefits of cannabis come concerning issues like dosing inconsistencies, dependence, and cannabinoid hyperemesis syndrome. In this review article, we explore the nuanced relationship between cannabis and the treatment of IBD by summarizing the current research. We also use clinical vignettes to discuss the more practical considerations surrounding its use.
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Neufeld T, Pfuhlmann K, Stock-Schröer B, Kairey L, Bauer N, Häuser W, Langhorst J. Cannabis use of patients with inflammatory bowel disease in Germany: a cross-sectional survey. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1068-1077. [PMID: 34157755 DOI: 10.1055/a-1400-2768] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND AIMS Progressive legalization and increasing utilization of medical cannabis open up potential new applications, including for inflammatory bowel disease (IBD). This study aimed to collect current figures on the use of and experience with cannabis among IBD patients in Germany. METHODS A 71-item questionnaire was mailed to a randomly selected representative sample of 1000 IBD patients. RESULTS Questionnaires were returned by 417 patients (mean age 49.1 ± 17.0 years; 55.8 % women; 43.4 % ulcerative colitis and 54.7 % Crohn's disease). Seventy-three respondents (17.5 %) stated past cannabis use for recreational purposes, while 12 users mentioned usage at the time the questionnaire was completed (2.9 %). Seventeen patients (4.1 %) indicated past use of cannabis, and 18 participants (4.3 %) reported current use of cannabis to treat IBD. Perceived benefits of cannabis use by its users included reduced abdominal pain, improved sleep quality, and relief of unease and worry. They reported lower quality of life and higher levels of anxiety or depression than non-users. Of notice, 52.9 % of cannabis users obtained their cannabis from the black market. A total of 76.5 % of former and 50 % of current users did not report their cannabis use to the physician. CONCLUSION This survey reveals the largest data set on cannabis use among IBD patients in Germany, with the potential for further research. Cannabis is mainly procured from the black market, with unknown quality.
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Affiliation(s)
- Tanja Neufeld
- Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Chair for Integrative Medicine, University of Duisburg-Essen, Bamberg, Germany
| | - Katrin Pfuhlmann
- Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Chair for Integrative Medicine, University of Duisburg-Essen, Bamberg, Germany
| | - Beate Stock-Schröer
- University of Witten/Herdecke, Faculty of Health/Department of Human Medicine, Witten/Herdecke, Germany
| | - Lana Kairey
- Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
| | - Nina Bauer
- Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Chair for Integrative Medicine, University of Duisburg-Essen, Bamberg, Germany
| | - Winfried Häuser
- Department for Internal Medicine, Klinikum Saarbruecken, Saarbruecken, Germany
| | - Jost Langhorst
- Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Chair for Integrative Medicine, University of Duisburg-Essen, Bamberg, Germany
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Ahmed I, Rehman SU, Shahmohamadnejad S, Zia MA, Ahmad M, Saeed MM, Akram Z, Iqbal HMN, Liu Q. Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders. Molecules 2021; 26:3389. [PMID: 34205169 PMCID: PMC8199938 DOI: 10.3390/molecules26113389] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/11/2021] [Accepted: 05/29/2021] [Indexed: 02/05/2023] Open
Abstract
In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.
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Affiliation(s)
- Ishtiaq Ahmed
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China;
- School of Medical Science, Gold Coast Campus, Griffith University, Southport, QLD 4222, Australia;
| | - Saif Ur Rehman
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China;
| | - Shiva Shahmohamadnejad
- Department of Clinical Biochemistry, School of medicine, Tehran University of Medical Sciences, Tehran 14176-13151, Iran;
| | - Muhammad Anjum Zia
- Enzyme Biotechnology Laboratory, Department of Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan; (M.A.Z.); (M.M.S.)
| | - Muhammad Ahmad
- Faculty of Veterinary Sciences, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences (SBBUVAS), Sakrand 67210, Pakistan;
| | - Muhammad Muzammal Saeed
- Enzyme Biotechnology Laboratory, Department of Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan; (M.A.Z.); (M.M.S.)
| | - Zain Akram
- School of Medical Science, Gold Coast Campus, Griffith University, Southport, QLD 4222, Australia;
| | - Hafiz M. N. Iqbal
- Tecnologico de Monterrey, School of Engineering and Sciences, 64849 Monterrey, Mexico;
| | - Qingyou Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China;
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van der Sloot KWJ, Geertsema P, Rijkmans HC, Voskuil MD, van Dullemen HM, Visschedijk MC, Festen EAM, Weersma RK, Alizadeh BZ, Dijkstra G. Environmental factors associated with biological use and surgery in inflammatory bowel disease. J Gastroenterol Hepatol 2021; 36:1022-1034. [PMID: 32839987 PMCID: PMC8247347 DOI: 10.1111/jgh.15223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/30/2020] [Accepted: 08/16/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM While major efforts were made studying the complex etiology of inflammatory bowel disease (IBD) including environmental factors, less is known about underlying causes leading to the heterogeneous and highly variable course of disease. As cigarette smoking cessation is the best-known environmental factor with beneficial effect in Crohn's disease (CD), more exposome factors are likely involved. Further insights into the role of the exposome in heterogeneity of disease might not only further knowledge of underlying pathways, but also allow for better risk stratification. METHODS Seven hundred twenty-eight IBD patients completed the validated Groningen IBD Environmental Questionnaire, collecting exposome data for 93 exposome factors. Associations with disease course, that is, for need for surgery or biological therapy, were evaluated using univariate and multivariate-adjusted logistic regression modeling. RESULTS No significant associations were seen after Bonferroni correction. However, 11 novel exposome factors were identified with P < 0.05. Two factors were associated with course of CD and ulcerative colitis (UC): beer (CD OR0.3/UC OR0.3) and cannabis (0.5/2.2). While in CD, carpet flooring (0.5) was associated with biological use, and four factors were associated with surgery: working shifts (1.8), appendectomy (2.4), frequent tooth brushing (2.8), and large household size (0.1). For UC, migrants more often required biologicals (10.2). Childhood underweight (3.4), amphetamine use (6.2), and cocaine use (4.8) were associated with surgery. Five factors were replicated. CONCLUSIONS We identified 16 environmental factors nominally associated with biological use and surgery in established IBD. These new insights form an important stepping stone to guide research on biological pathways involved, risk stratification, tailor-made interventions, and preventive strategies in IBD.
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Affiliation(s)
- Kimberley W J van der Sloot
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands,Department of Epidemiology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Paul Geertsema
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Hanneke C Rijkmans
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Michiel D Voskuil
- Department of Epidemiology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Hendrik M van Dullemen
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Marijn C Visschedijk
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Behrooz Z Alizadeh
- Department of Epidemiology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
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Koslowsky B, Mazuz B, Ben-Ya'acov A, Neumark A, Bar-Gil Shitrit A, Goldin E. Gastroenterologists' Attitude Regarding Medical Cannabis for Inflammatory Bowel Diseases in Israel. Dig Dis 2021; 39:502-507. [PMID: 33503640 DOI: 10.1159/000514776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 01/22/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND The use of medical cannabis (MC) for inflammatory bowel diseases (IBDs) is expanding. Current evidence does not support the efficacy of MC for reducing inflammation in IBD patients. Even so, many gastroenterologists encounter the issue of recommending use of MC to IBD patients. METHODS A Web-based survey was completed by 84 (34%) gastroenterologists in Israel. RESULTS Out of 84 physicians whom completed the questionnaire, 59 (70%) were male, 34 (40%) were under age 50 years, 71 (85%) were adult gastroenterologists, and 53 (63%) work mainly in a hospital. Of them, 15, 41, and 44% of physicians think that MC is very effective, mildly effective, and not effective at all, respectively. Physicians will commonly, rarely, and never recommend MC in 31, 47, and 22%, respectively. Older physicians (above age 50 years) were significantly more likely to have a positive attitude towards MC in both questions. When presented with a clinical scenario of a patient in deep remission, requesting to increase the dose, 32% would increase, 49% would maintain, and only 18% would stop prescribing MC altogether; 48% of physicians did not know the recommended initial dose for MC. Only 2 (2.5%) physicians initiated the use of MC to all patients. Female gastroenterologists were significantly more likely to initiate MC, p = 0.048. CONCLUSION The use of MC for IBD patients is commonly encountered. Completely different attitudes regarding this treatment were seen. Age above 50 years and female physicians generally had a more positive attitude towards the use of MC. Guidelines and clear recommendations are needed.
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Abstract
In traditional medicine, Cannabis sativa has been prescribed for a variety of diseases. Today, the plant is largely known for its recreational purpose, but it may find a way back to what it was originally known for: a herbal remedy. Most of the plant's ingredients, such as Δ-tetrahydrocannabinol, cannabidiol, cannabigerol, and others, have demonstrated beneficial effects in preclinical models of intestinal inflammation. Endogenous cannabinoids (endocannabinoids) have shown a regulatory role in inflammation and mucosal permeability of the gastrointestinal tract where they likely interact with the gut microbiome. Anecdotal reports suggest that in humans, Cannabis exerts antinociceptive, anti-inflammatory, and antidiarrheal properties. Despite these reports, strong evidence on beneficial effects of Cannabis in human gastrointestinal diseases is lacking. Clinical trials with Cannabis in patients suffering from inflammatory bowel disease (IBD) have shown improvement in quality of life but failed to provide evidence for a reduction of inflammation markers. Within the endogenous opioid system, mu opioid receptors may be involved in anti-inflammation of the gut. Opioids are frequently used to treat abdominal pain in IBD; however, heavy opioid use in IBD is associated with opioid dependency and higher mortality. This review highlights latest advances in the potential treatment of IBD using Cannabis/cannabinoids or opioids.
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Aviram J, Pud D, Gershoni T, Schiff-Keren B, Ogintz M, Vulfsons S, Yashar T, Adahan HM, Brill S, Amital H, Goor-Aryeh I, Robinson D, Green L, Segal R, Fogelman Y, Tsvieli O, Yellin B, Vysotski Y, Morag O, Tashlykov V, Sheinfeld R, Goor R, Meiri D, Eisenberg E. Medical cannabis treatment for chronic pain: Outcomes and prediction of response. Eur J Pain 2020; 25:359-374. [PMID: 33065768 DOI: 10.1002/ejp.1675] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 07/21/2020] [Accepted: 10/10/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success. METHODS Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity). RESULTS A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12-month follow-up. At 1 year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI = -2.13 to -1.81; p < 0.001)]. All other parameters improved by 10%-30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = -34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite. CONCLUSIONS This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild-to-modest long-term improvement of the tested measures and identifying possible predictors for treatment success.
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Affiliation(s)
- Joshua Aviram
- Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.,Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel
| | - Dorit Pud
- Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
| | - Tamar Gershoni
- Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
| | | | - Miriam Ogintz
- Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel
| | - Simon Vulfsons
- Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel
| | | | - Haim-Moshe Adahan
- Pain Rehabilitation Unit, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Silviu Brill
- Institute for Pain Medicine, Sourasky Medical Center, Tel Aviv, Israel
| | - Howard Amital
- Department of Internal Medicine B, Sheba Medical Center, Tel-Hashomer, Ramat-Gan & Zabludowicz Center for Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Itay Goor-Aryeh
- Institute for Pain Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Dror Robinson
- Orthopedic Research Department, Hasharon Hospital, Rabin Medical Center, Petach Tikva, Israel
| | | | - Refael Segal
- Long Term Care Department, Geriatric Medicine Center "Shmuel Harofeh", Be'er Ya'akov, Israel
| | - Yacov Fogelman
- Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel
| | - Oren Tsvieli
- Shoulder and Elbow Surgery unit Mayanei HaYeshua Medical Center, Bnei Brak, Israel
| | - Ben Yellin
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel
| | - Yelena Vysotski
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ofir Morag
- Institute for Pain Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Vadim Tashlykov
- Institute for Pain Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Roee Sheinfeld
- Institute for Pain Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Ruth Goor
- Institute for Pain Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - David Meiri
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel
| | - Elon Eisenberg
- Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine-Technion, Israel Institute of Technology, Haifa, Israel
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Abstract
Cannabinoids have been known as the primary component of cannabis for decades, but the characterization of the endocannabinoid system (ECS) in the 1990s opened the doors for cannabis' use in modern medicine. The 2 main receptors of this system, cannabinoid receptors 1 and 2, are found on cells of various tissues, with significant expression in the gastrointestinal (GI) tract. The characterization of the ECS also heralded the understanding of endocannabinoids, naturally occurring compounds synthesized in the human body. Via secondary signaling pathways acting on vagal nerves, nociceptors, and immune cells, cannabinoids have been shown to have both palliative and detrimental effects on the pathophysiology of GI disorders. Although research on the effects of both endogenous and exogenous cannabinoids has been slow due to the complicated legal history of cannabis, discoveries of cannabinoids' treatment potential have been found in various fields of medicine, including the GI world. Medical cannabis has since been offered as a treatment for a myriad of conditions and malignancies, including cancer, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis, chronic pain, nausea, posttraumatic stress disorder, amyotrophic lateral sclerosis, cachexia, glaucoma, and epilepsy. This article hopes to create an overview of current research on cannabinoids and the ECS, detail the potential advantages and pitfalls of their use in GI diseases, and explore possible future developments in this field.
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Becker W, Alrafas HR, Wilson K, Miranda K, Culpepper C, Chatzistamou I, Cai G, Nagarkatti M, Nagarkatti PS. Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer through Myeloid Cell De-activation Upstream of IL-22 Production. iScience 2020; 23:101504. [PMID: 32942172 PMCID: PMC7501437 DOI: 10.1016/j.isci.2020.101504] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 07/20/2020] [Accepted: 08/24/2020] [Indexed: 12/17/2022] Open
Abstract
Intestinal disequilibrium leads to inflammatory bowel disease (IBD), and chronic inflammation predisposes to oncogenesis. Antigen-presenting dendritic cells (DCs) and macrophages can tip the equilibrium toward tolerance or pathology. Here we show that delta-9-tetrahydrocannabinol (THC) attenuates colitis-associated colon cancer and colitis induced by anti-CD40. Working through cannabinoid receptor 2 (CB2), THC increases CD103 expression on DCs and macrophages and upregulates TGF-β1 to increase T regulatory cells (Tregs). THC-induced Tregs are necessary to remedy systemic IFNγ and TNFα caused by anti-CD40, but CB2-mediated suppression of APCs by THC quenches pathogenic release of IL-22 and IL-17A in the colon. By examining tissues from multiple sites, we confirmed that THC affects DCs, especially in mucosal barrier sites in the colon and lungs, to reduce DC CD86. Using models of colitis and systemic inflammation we show that THC, through CB2, is a potent suppressor of aberrant immune responses by provoking coordination between APCs and Tregs.
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Affiliation(s)
- William Becker
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
| | - Haider Rasheed Alrafas
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
| | - Kiesha Wilson
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
| | - Kathryn Miranda
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
| | - Courtney Culpepper
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
| | - Ioulia Chatzistamou
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
| | - Guoshuai Cai
- Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
| | - Mitzi Nagarkatti
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
| | - Prakash S. Nagarkatti
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
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Szczepaniak A, Fichna J. What role do cannabinoids have in modern medicine as gastrointestinal anti-inflammatory drugs? Expert Opin Pharmacother 2020; 21:1931-1934. [DOI: 10.1080/14656566.2020.1795129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Adrian Szczepaniak
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
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Inglet S, Winter B, Yost SE, Entringer S, Lian A, Biksacky M, Pitt RD, Mortensen W. Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature. Ann Pharmacother 2020; 54:1109-1143. [DOI: 10.1177/1060028020930189] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective: To compile and synthesize the available literature describing medical cannabis use across various disease states. Data Sources: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. Study Selection and Data Extraction: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. Data Synthesis: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. Relevance to Patient Care and Clinical Practice: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. Conclusions: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.
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Affiliation(s)
| | | | | | | | - Anh Lian
- Intermountain Healthcare, Taylorsville, UT, USA
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de Carvalho ACA, de Souza GA, de Marqui SV, Guiguer ÉL, Araújo AC, Rubira CJ, Goulart RDA, Flato UAP, Bueno PCDS, Buchaim RL, Barbalho SM. Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse. Int J Mol Sci 2020; 21:2940. [PMID: 32331305 PMCID: PMC7215817 DOI: 10.3390/ijms21082940] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/07/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn's disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.
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Affiliation(s)
- Antonelly Cassio Alves de Carvalho
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525902, São Paulo, Brazil; (A.C.A.d.C.); (É.L.G.); (A.C.A.); (R.d.A.G.); (U.A.P.F.); (R.L.B.)
| | - Gabriela Achete de Souza
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
| | - Samylla Vaz de Marqui
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
| | - Élen Landgraf Guiguer
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525902, São Paulo, Brazil; (A.C.A.d.C.); (É.L.G.); (A.C.A.); (R.d.A.G.); (U.A.P.F.); (R.L.B.)
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
- Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília, Marília 17525902, São Paulo, Brazil
| | - Adriano Cressoni Araújo
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525902, São Paulo, Brazil; (A.C.A.d.C.); (É.L.G.); (A.C.A.); (R.d.A.G.); (U.A.P.F.); (R.L.B.)
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
| | - Claudio José Rubira
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
| | - Ricardo de Alvares Goulart
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525902, São Paulo, Brazil; (A.C.A.d.C.); (É.L.G.); (A.C.A.); (R.d.A.G.); (U.A.P.F.); (R.L.B.)
| | - Uri Adrian Prync Flato
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525902, São Paulo, Brazil; (A.C.A.d.C.); (É.L.G.); (A.C.A.); (R.d.A.G.); (U.A.P.F.); (R.L.B.)
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
| | - Patricia Cincotto dos Santos Bueno
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
- Department of Animal Sciences, School of Veterinary Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil
| | - Rogério Leone Buchaim
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525902, São Paulo, Brazil; (A.C.A.d.C.); (É.L.G.); (A.C.A.); (R.d.A.G.); (U.A.P.F.); (R.L.B.)
- Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo (FOB–USP), Alameda Doutor Octávio Pinheiro Brisolla, 9-75, Bauru 17040, São Paulo, Brazil
| | - Sandra M. Barbalho
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525902, São Paulo, Brazil; (A.C.A.d.C.); (É.L.G.); (A.C.A.); (R.d.A.G.); (U.A.P.F.); (R.L.B.)
- School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17525902, São Paulo, Brazil; (G.A.d.S.); (S.V.d.M.); (C.J.R.); (P.C.d.S.B.)
- Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília, Marília 17525902, São Paulo, Brazil
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Scott FI. Marijuana Use in Inflammatory Bowel Disease: Understanding the Prevalence and the Potential Pitfalls. CROHN'S & COLITIS 360 2020; 2:otaa016. [PMID: 32363340 PMCID: PMC7182098 DOI: 10.1093/crocol/otaa016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Indexed: 11/13/2022] Open
Abstract
Many patients with inflammatory bowel disease experiment with marijuana for symptom control. Marijuana may help reduce abdominal pain but does not control inflammatory bowel disease related inflammation. Patients should discuss their marijuana use with their providers and continue appropriate medications if considering marijuana.
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Affiliation(s)
- Frank I Scott
- Crohn’s and Colitis Center, Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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Zeng Z, Mukherjee A, Varghese AP, Yang XL, Chen S, Zhang H. Roles of G protein-coupled receptors in inflammatory bowel disease. World J Gastroenterol 2020; 26:1242-1261. [PMID: 32256014 PMCID: PMC7109274 DOI: 10.3748/wjg.v26.i12.1242] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 01/18/2020] [Accepted: 03/05/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a complex disease with multiple pathogenic factors. Although the pathogenesis of IBD is still unclear, a current hypothesis suggests that genetic susceptibility, environmental factors, a dysfunctional immune system, the microbiome, and the interactions of these factors substantially contribute to the occurrence and development of IBD. Although existing and emerging drugs have been proven to be effective in treating IBD, none can cure IBD permanently. G protein-coupled receptors (GPCRs) are critical signaling molecules implicated in the immune response, cell proliferation, inflammation regulation and intestinal barrier maintenance. Breakthroughs in the understanding of the structures and functions of GPCRs have provided a driving force for exploring the roles of GPCRs in the pathogenesis of diseases, thereby leading to the development of GPCR-targeted medication. To date, a number of GPCRs have been shown to be associated with IBD, significantly advancing the drug discovery process for IBD. The associations between GPCRs and disease activity, disease severity, and disease phenotypes have also paved new avenues for the precise management of patients with IBD. In this review, we mainly focus on the roles of the most studied proton-sensing GPCRs, cannabinoid receptors, and estrogen-related GPCRs in the pathogenesis of IBD and their potential clinical values in IBD and some other diseases.
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Affiliation(s)
- Zhen Zeng
- Department of Gastroenterology, Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 410061, Sichuan Province, China
| | - Arjudeb Mukherjee
- West China School of Medicine, Sichuan University, Chengdu 410061, Sichuan Province, China
| | | | - Xiao-Li Yang
- Department of Gastroenterology, Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 410061, Sichuan Province, China
| | - Sha Chen
- Department of Gastroenterology, Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 410061, Sichuan Province, China
| | - Hu Zhang
- Department of Gastroenterology, Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 410061, Sichuan Province, China
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Perisetti A, Rimu AH, Khan SA, Bansal P, Goyal H. Role of cannabis in inflammatory bowel diseases. Ann Gastroenterol 2020; 33:134-144. [PMID: 32127734 PMCID: PMC7049239 DOI: 10.20524/aog.2020.0452] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 11/26/2019] [Indexed: 12/12/2022] Open
Abstract
For many centuries, cannabis (marijuana) has been used for both recreational and medicinal purposes. Currently, there are about 192 million cannabis users worldwide, constituting approximately 3.9% of the global population. Cannabis comprises more than 70 aromatic hydrocarbon compounds known as cannabinoids. Endogenous circulating cannabinoids, or endocannabinoids, such as anandamide and 2-arachidonoyl-glycerol, their metabolizing enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) and 2 G-protein coupled cannabinoid receptors, CB1 and CB2, together represent the endocannabinoid system and are present throughout the human body. In the gastrointestinal (GI) tract, the activated endocannabinoid system reduces gut motility, intestinal secretion and epithelial permeability, and induces inflammatory leukocyte recruitment and immune modulation through the cannabinoid receptors present in the enteric nervous and immune systems. Because of the effects of cannabinoids on the GI tract, attempts have been made to investigate their medicinal properties, particularly for GI disorders such as pancreatitis, hepatitis, and inflammatory bowel diseases (IBD). The effects of cannabis on IBD have been elucidated in several small observational and placebo-controlled studies, but with varied results. The small sample size and short follow-up duration in these studies make it difficult to show the clear benefits of cannabis in IBD. However, cannabis is now being considered as a potential drug for inflammatory GI conditions, particularly IBD, because of its spreading legalization in the United States and other countries and the growing trend in its use. More high-quality controlled studies are warranted to elucidate the mechanism and benefits of cannabis use as a possible option in IBD management.
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Affiliation(s)
- Abhilash Perisetti
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences (Abhilash Perisetti)
| | - Afrina Hossain Rimu
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX (Afrina Hossain Rimu)
| | - Salman Ali Khan
- University of Arkansas for Medical Sciences, AR (Salman Ali Khan)
| | - Pardeep Bansal
- Department of Gastroenterology, Regional Hospital and Moses Taylor Hospital, PA (Pardeep Bansal)
| | - Hemant Goyal
- Department of Medicine, The Wright Center for Graduate Medical Education (Hemant Goyal), USA
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Black N, Stockings E, Campbell G, Tran LT, Zagic D, Hall WD, Farrell M, Degenhardt L. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry 2019; 6:995-1010. [PMID: 31672337 PMCID: PMC6949116 DOI: 10.1016/s2215-0366(19)30401-8] [Citation(s) in RCA: 283] [Impact Index Per Article: 47.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 08/30/2019] [Accepted: 08/30/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders. METHODS For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977). FINDINGS 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis. INTERPRETATION There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed. FUNDING Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.
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Affiliation(s)
- Nicola Black
- National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia
| | - Emily Stockings
- National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia
| | - Gabrielle Campbell
- National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia
| | - Lucy T Tran
- National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia
| | - Dino Zagic
- National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia
| | - Wayne D Hall
- Centre for Youth Substance Abuse Research, University of Queensland, Brisbane QLD, Australia; National Addiction Centre, Kings College London, London, UK
| | - Michael Farrell
- National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia
| | - Louisa Degenhardt
- National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia.
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Magen R, Shaoul R. Alternative & complementary treatment for pediatric inflammatory bowel disease. Transl Pediatr 2019; 8:428-435. [PMID: 31993357 PMCID: PMC6970111 DOI: 10.21037/tp.2019.09.02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Alternative medicine includes treatments that are not considered mainstream and is suggested to replace the accepted treatment, while complementary treatment is added to the conventional treatment. The estimated prevalence of their use in patients with inflammatory bowel disease (IBD) is high, ranging between 21-60%. This review summarizes the data on these treatments and their efficacy in the setting of IBD.
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Affiliation(s)
- Ramit Magen
- Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel
| | - Ron Shaoul
- Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel
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Pagano E, Romano B, Iannotti FA, Parisi OA, D'Armiento M, Pignatiello S, Coretti L, Lucafò M, Venneri T, Stocco G, Lembo F, Orlando P, Capasso R, Di Marzo V, Izzo AA, Borrelli F. The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients. Pharmacol Res 2019; 149:104464. [PMID: 31553934 DOI: 10.1016/j.phrs.2019.104464] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 09/18/2019] [Accepted: 09/20/2019] [Indexed: 01/27/2023]
Abstract
Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1β, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.
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Affiliation(s)
- E Pagano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - B Romano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - F A Iannotti
- Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Pozzuoli, Italy
| | - O A Parisi
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - M D'Armiento
- Department of Biomorphological and Functional Science, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - S Pignatiello
- Department of Biomorphological and Functional Science, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - L Coretti
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy; Department of Physiology and Biochemistry, Faculty of medicine and Surgery, University of Malta, Msida, Malta
| | - M Lucafò
- Department of Life Science, University of Trieste, Italy
| | - T Venneri
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - G Stocco
- Department of Life Science, University of Trieste, Italy
| | - F Lembo
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - P Orlando
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy; Institute of Protein Biochemistry, National Research Council, Naples, Italy; Institute of Applied Sciences and Intelligent Systems, National Research Council, Naples, Italy
| | - R Capasso
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
| | - V Di Marzo
- Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Pozzuoli, Italy; Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Centre de Recherche de l'Institut Universitaire de Cardiologie et Pneumologie de Quèbec, Québec City, Canada; et Institut sur la Nutrition et les Aliments Fonctionnels, Québec City, Université Laval, Canada
| | - A A Izzo
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
| | - F Borrelli
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
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Anticipatory care of children and adolescents with inflammatory bowel disease: a primer for primary care providers. Curr Opin Pediatr 2019; 31:654-660. [PMID: 31205126 DOI: 10.1097/mop.0000000000000795] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW About 10-20% of patients with newly diagnosed inflammatory bowel disease (IBD) are under 18 years of age, with incidence increasing in young children. Children with IBD have unique healthcare needs, which require coordination between primary care providers and pediatric gastroenterologists to provide appropriate care. This review highlights some key elements of anticipatory care in pediatric IBD, including vaccination, risk of serious infection and malignancy, psychosocial and educational needs, and cannabis use. RECENT FINDINGS Therapies for IBD that include anti-tumor necrosis factor medications, especially when combined with corticosteroids are associated with higher risks of serious infections. Vaccination remains the best way to prevent infections. Live vaccinations should be avoided during immunosuppression, but the schedule should be otherwise completed, including vaccination for influenza, pneumococcus and meningococcus, and human papillomavirus. Malignancy risk is increased in IBD patients, both because of disease factors and resulting from immunomodulatory medications. Children with IBD are at risk for mental health disorders and negative educational outcomes, so identification of at-risk children and early intervention are important. SUMMARY High-quality care in pediatric IBD requires coordination between pediatric gastroenterologists and primary care providers, with careful attention paid to the specific needs of children with IBD.
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Picardo S, Kaplan GG, Sharkey KA, Seow CH. Insights into the role of cannabis in the management of inflammatory bowel disease. Therap Adv Gastroenterol 2019; 12:1756284819870977. [PMID: 31523278 PMCID: PMC6727090 DOI: 10.1177/1756284819870977] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 07/26/2019] [Indexed: 02/04/2023] Open
Abstract
Over the last decade, interest in the therapeutic potential of cannabis and its constituents (e.g. cannabidiol) in the management of inflammatory bowel diseases (IBD) has escalated. Cannabis has been increasingly approved for a variety of medical conditions in several jurisdictions around the world. In animal models, cannabinoids have been shown to improve intestinal inflammation in experimental models of IBD through their interaction with the endocannabinoid system. However, the few randomized controlled trials of cannabis or cannabidiol in patients with IBD have not demonstrated efficacy in modulating inflammatory disease activity. Cannabis may be effective in the symptomatic management of IBD. Given the increasing utilization and cultural acceptance of cannabis, physicians need to be aware of its safety and efficacy in order to better counsel patients. The aim of this review is to provide an overview of the role of cannabis in the management of patients with IBD.
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Affiliation(s)
- Sherman Picardo
- Inflammatory Bowel Disease Unit, Department of Gastroenterology, Cumming School of Medicine, University of Calgary, AB, Canada
| | - Gilaad G. Kaplan
- Inflammatory Bowel Disease Unit, Department of Gastroenterology, Cumming School of Medicine, University of Calgary, AB, Canada,Department of Community Health Sciences, University of Calgary, AB, Canada
| | - Keith A. Sharkey
- Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, AB, Canada
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Mbachi C, Attar B, Oyenubi O, Yuchen W, Efesomwan A, Paintsil I, Madhu M, Ajiboye O, Roberto SLC, Trick WE, Kotwal V. Association between cannabis use and complications related to ulcerative colitis in hospitalized patients: A propensity matched retrospective cohort study. Medicine (Baltimore) 2019; 98:e16551. [PMID: 31393356 PMCID: PMC6708902 DOI: 10.1097/md.0000000000016551] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory process that is occasionally associated with complications that cause significant morbidity and mortality. Studies in experimental animal models have demonstrated a beneficial effect of cannabis on intestinal inflammation. It is however unknown if this corresponds to fewer complications for patients with Ulcerative Colitis.We aimed to compare the prevalence of UC related complications and certain key clinical endpoints among cannabis users and nonusers hospitalized with a primary diagnosis of UC, or primary diagnosis of a UC-related complication with a secondary diagnosis of UC.Using data from the Healthcare Cost and Utilization Project-National Inpatient Sample (NIS) during 2010-2014, a total of 298 cannabis users with UC were compared to a propensity score matched group of nonusers with UC. We evaluated several UC-related complications and clinical endpoints.Within our matched cohort, prevalence of partial or total colectomy was lower in cannabis users compared to nonusers (4.4% vs 9.7%, P = .010) and there was a trend toward a lower prevalence of bowel obstruction (6.4% vs 10.7%, P = .057). Cannabis users had shorter hospital length-of-stay (4.5 vs 5.7 days P < .007) compared to their nonuser counterparts.Cannabis use may mitigate some of the well described complications of UC among hospitalized patients. Our findings need further evaluation, ideally through more rigorous clinical trials.
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Affiliation(s)
| | - Bashar Attar
- John H Stroger Hospital of Cook County, Chicago IL
| | - Olamide Oyenubi
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Wang Yuchen
- John H Stroger Hospital of Cook County, Chicago IL
| | | | | | - Mathew Madhu
- John H Stroger Hospital of Cook County, Chicago IL
| | | | - Simons-Linares C. Roberto
- Digestive Disease Institute, Gastroenterology and Hepatology Department, Cleveland Clinic, Cleveland, OH
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Wahby S, Karnik V, Brobbey A, Wiebe S, Sajobi T, Josephson CB. Cannabis use is both independently associated with and mediates worse psychosocial health in patients with epilepsy. J Neurol Neurosurg Psychiatry 2019; 90:945-951. [PMID: 30826738 DOI: 10.1136/jnnp-2018-319780] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 02/01/2019] [Accepted: 02/09/2019] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To examine whether cannabis use is associated with or mediates psychosocial health in people with epilepsy. METHODS Consecutive adult epilepsy patients visiting the Calgary Comprehensive Epilepsy Programme clinic were administered validated patient-reported outcome measures (PROMs) including the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Quality of Life in Epilepsy (QOLIE-10-P), EuroQOL five dimensions five level scale (EQ-5D-5L), Global Assessment of Severity of Epilepsy Scale, Global Assessment of Disability Associated with Seizures Scale and the Treatment Satisfaction Questionnaire for Medication scale. We used multiple regression analyses to investigate associations between cannabis use and PROMs. Mediation analyses were performed to determine the degree to which cannabis modulated the associations between current or past psychiatric disorders, monthly seizure frequency, and 1-year seizure freedom on psychosocial health. RESULTS Of 337 consecutive patients, 71 (21%) reported cannabis use. Cannabis use was independently associated with depression (NDDI-E score≥14; OR 3.90; 95% CI 2.01 to 7.59; p<0.001), lower quality of life (β=-16.73, 95% CI - 26.26 to - 7.20; p=0.001), worse epilepsy-related disability (OR 2.23, 95% CI 1.19 to 4.17; p=0.01) and lower satisfaction with antiepileptic medication (OR 0.41, 95% CI 0.23 to 0.72; p=0.002). Cannabis use mediates 7%-12% of the effect of a psychiatric history on depression, worse quality of life and worse health valuation. CONCLUSIONS There is a strong and independent association between cannabis use and poor psychosocial health, and it partially mediates the deleterious effect of a psychiatric history on these same outcomes. Inclusion of PROMs in future cannabis trials is warranted.
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Affiliation(s)
- Sandra Wahby
- Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Vikram Karnik
- Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Anita Brobbey
- Community Health Sciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Samuel Wiebe
- Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Tolulope Sajobi
- Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.,Community Health Sciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Colin Bruce Josephson
- Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada .,Community Health Sciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
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Ambrose T, Simmons A. Cannabis, Cannabinoids, and the Endocannabinoid System-Is there Therapeutic Potential for Inflammatory Bowel Disease? J Crohns Colitis 2019; 13:525-535. [PMID: 30418525 PMCID: PMC6441301 DOI: 10.1093/ecco-jcc/jjy185] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Cannabis sativa and its extracts have been used for centuries, both medicinally and recreationally. There is accumulating evidence that exogenous cannabis and related cannabinoids improve symptoms associated with inflammatory bowel disease [IBD], such as pain, loss of appetite, and diarrhoea. In vivo, exocannabinoids have been demonstrated to improve colitis, mainly in chemical models. Exocannabinoids signal through the endocannabinoid system, an increasingly understood network of endogenous lipid ligands and their receptors, together with a number of synthetic and degradative enzymes and the resulting products. Modulating the endocannabinoid system using pharmacological receptor agonists, genetic knockout models, or inhibition of degradative enzymes have largely shown improvements in colitis in vivo. Despite these promising experimental results, this has not translated into meaningful benefits for human IBD in the few clinical trials which have been conducted to date, the largest study being limited by poor medication tolerance due to the Δ9-tetrahydrocannabinol component. This review article synthesises the current literature surrounding the modulation of the endocannabinoid system and administration of exocannabinoids in experimental and human IBD. Findings of clinical surveys and studies of cannabis use in IBD are summarised. Discrepancies in the literature are highlighted together with identifying novel areas of interest.
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Affiliation(s)
- Tim Ambrose
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK,MRC Human Immunology Unit, John Radcliffe Hospital, Oxford, UK,Corresponding author: Dr Tim Ambrose, BSc (Hons), MBChB, MRCP (UK) (Gastroenterology), c/o Prof. Alison Simmons, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headley Way, Oxford OX3 9DS, UK. Tel.: 01865 222628;
| | - Alison Simmons
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK,MRC Human Immunology Unit, John Radcliffe Hospital, Oxford, UK
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Salaga M, Binienda A, Piscitelli F, Mokrowiecka A, Cygankiewicz AI, Verde R, Malecka-Panas E, Kordek R, Krajewska WM, Di Marzo V, Fichna J. Systemic administration of serotonin exacerbates abdominal pain and colitis via interaction with the endocannabinoid system. Biochem Pharmacol 2019; 161:37-51. [DOI: 10.1016/j.bcp.2019.01.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 01/02/2019] [Indexed: 12/24/2022]
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Halbmeijer N, Groeneweg M, De Ridder L. Cannabis, a potential treatment option in pediatric IBD? Still a long way to go. Expert Rev Clin Pharmacol 2019; 12:355-361. [PMID: 30767696 DOI: 10.1080/17512433.2019.1582330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The onset of inflammatory bowel disease (IBD) in children is rising. Current treatment options are based on immunomodulatory therapy. Alternative treatment options are upcoming since they appear to be effective in individual patients. Cannabis might relief IBD symptoms in these cases and improve quality of life. Recent evidence suggests a potential anti-inflammatory effect of cannabis. Areas covered: This review presents an overview of recent literature on the use of cannabis in IBD focussing on pediatric IBD patients. Background information on the role of the endocannabinoid system within the gastrointestinal tract is presented. Other modalities of cannabis and its purified ingredients will be discussed as well, with attention to its applicability in children with IBD. Expert opinion: More research is needed on the efficacy and safety of cannabis in pediatric IBD. Studies are well underway, but until then the use of cannabis in pediatric IBD cannot be recommended.
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Affiliation(s)
- Nienke Halbmeijer
- a Department of Pediatrics , Maasstad Hospital , Rotterdam , The Netherlands
| | - Michael Groeneweg
- a Department of Pediatrics , Maasstad Hospital , Rotterdam , The Netherlands
| | - Lissy De Ridder
- b Department of Paediatric Gastroenterology , Erasmus MC-Sophia Children's Hospital , Rotterdam , The Netherlands
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