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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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Niu X, Zhu L, Xu Y, Zhang M, Hao Y, Ma L, Li Y, Xing H. Global prevalence, incidence, and outcomes of alcohol related liver diseases: a systematic review and meta-analysis. BMC Public Health 2023; 23:859. [PMID: 37170239 PMCID: PMC10173666 DOI: 10.1186/s12889-023-15749-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/25/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Alcohol related liver disease (ARLD) is one of the major chronic liver diseases worldwide. This review aimed to describe the global prevalence, incidence, and outcomes of ARLD. METHODS Medline, Embase, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to May 31, 2022. The language was restricted to English or Chinese. According to the criteria, articles describing the basic characteristics of the population were selected. Two reviewers extracted the data independently. RESULTS A total of 372 studies were identified: 353 were used for prevalence analysis, 7 were used for incidence analysis, and 114 were used to for outcome analysis. The prevalence of ARLD worldwide was 4.8%. The prevalence in males was 2.9%, which was higher than female (0.5%). Among the ethnic groups, the percentage was highest in Caucasians (68.9%). Alcoholic liver cirrhosis comprised the highest proportion in the disease spectrum of ARLD at 32.9%. The prevalence of ascites in ARLD population was highest (25.1%). The ARLD population who drinking for > 20 years accounted for 54.8%, and the average daily alcohol intake was 146.6 g/d. About 59.5% of ARLD patients were current or former smokers, and 18.7% were complicated with hepatitis virus infection. The incidence was 0.208/1000 person-years. The overall mortality was 23.9%, and the liver-related mortality was 21.6%. CONCLUSION The global prevalence of ARLD was 4.8% and was affected by sex, region, drinking years, and other factors. Therefore, removing the factors causing a high disease prevalence is an urgent requisite. TRIAL REGISTRATION PROSPERO Nr: CRD42021286192.
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Affiliation(s)
- Xuanxuan Niu
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
| | - Lin Zhu
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
| | - Yifan Xu
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
| | - Menghan Zhang
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
| | - Yanxu Hao
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
| | - Lei Ma
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
| | - Yan Li
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
| | - Huichun Xing
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015 China
- Peking University Ditan Teaching Hospital, Beijing, 100015 China
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Du R, Tang XY, Yang C, Gao WH, Gao SJ, Xiang HJ, Yang L. Marijuana use is inversely associated with liver steatosis detected by transient elastography in the general United States population in NHANES 2017-2018: A cross-sectional study. PLoS One 2023; 18:e0284859. [PMID: 37200309 DOI: 10.1371/journal.pone.0284859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 04/09/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND The impact of marijuana on the general population is largely unknown. The present study aimed to assess the association between marijuana use and liver steatosis and fibrosis in the general United States population utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS This cross-sectional study was performed with data from the 2017-2018 cycle of NHANES. The target population comprised adults in the NHANES database with reliable vibration controlled transient elastography (VCTE) results. The median values of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate liver steatosis and fibrosis, respectively. After adjusting for relevant confounders, a logistic regression analysis was used to assess the association between marijuana use and liver steatosis and fibrosis. RESULTS A total of 2622 participants were included in this study. The proportions of never marijuana users, past users, and current users were 45.9%, 35.0%, and 19.1%, respectively. Compared to never marijuana users, past and current users had a lower prevalence of liver steatosis (P = 0.184 and P = 0.048, respectively). In the alcohol intake-adjusted model, current marijuana use was an independent predictor of a low prevalence of liver steatosis in people with non-heavy alcohol intake. The association between marijuana use and liver fibrosis was not significant in univariate and multivariate regression. CONCLUSION In this nationally representative sample, current marijuana use is inversely associated with steatosis. The pathophysiology is unclear and needs further study. No significant association was established between marijuana use and liver fibrosis, irrespective of past or current use.
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Affiliation(s)
- Rui Du
- Department of Ultrasound, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China
| | - Xiao-Yan Tang
- Department of Cardiology, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China
| | - Cheng Yang
- Department of Radiology, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China
| | - Wen-Hong Gao
- Department of Ultrasound, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China
| | - Shun-Ji Gao
- Department of Ultrasound, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China
| | - Hui-Juan Xiang
- Department of Ultrasound, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China
| | - Li Yang
- Department of Ultrasound, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China
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Bailey MM, Emily Mills MC, Haas AE, Bailey K, Kaufmann RC. The effects of subacute exposure to a water-soluble cannabinol compound in male mice. J Cannabis Res 2022; 4:44. [PMID: 35897117 PMCID: PMC9327251 DOI: 10.1186/s42238-022-00153-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/08/2022] [Indexed: 01/05/2023] Open
Abstract
Background Cannabinol (CBN) is one of the many cannabinoids present in Cannabis sativa and has been explored as a potential treatment for sleeplessness. The purpose of this study was to determine the physiological and behavioral effects of subacute exposure to therapeutic and low pharmacological levels of a mechanically formed, stabilized water-soluble cannabinol nano-emulsion (CBNight™). Methods Sixty-two male mice were randomly assigned to one of six treatment groups given CBNight™ at dosages designed to deliver 0mg (control) to 4 mg/kg of CBN daily via oral gavage for 14 days. In-cage behavior was observed at 30 minutes and at 2, 4, 8, and 16 hours after each dose. After 14 days, the mice were sacrificed and necropsied. Organs were weighed and inspected for gross abnormalities, and blood was collected via cardiac puncture for clinical chemistry. Results No dosage-dependent adverse effects on behavior, body mass, or blood chemistry were observed, except that the highest doses of CBNight™ were associated with significantly lower eosinophil counts. Conclusions The commercially available, water-soluble CBN compound employed in this study does not appear to cause adverse effects in mice; rather, it appears to be well tolerated at pharmacological levels. The findings of eosinopenia at higher doses of CBN and lack of hepatotoxicity at any dosage employed in this study have not been reported to date. Supplementary Information The online version contains supplementary material available at 10.1186/s42238-022-00153-w.
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Desai R, Jain A, Sultan W, Gandhi Z, Raju AR, Varughese VJ, Jnaneswaran G, Agarwal C, Rizvi B, Mansuri Z, Gupta P, Kumar G, Sachdeva R. Hypertensive Crisis-Related Hospitalizations and Subsequent Major Adverse Cardiac Events in Young Adults with Cannabis Use Disorder: A Nationwide Analysis. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58101465. [PMID: 36295625 PMCID: PMC9609556 DOI: 10.3390/medicina58101465] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/11/2022] [Accepted: 10/13/2022] [Indexed: 11/07/2022]
Abstract
Background and Objectives: With the growing recreational cannabis use and recent reports linking it to hypertension, we sought to determine the risk of hypertensive crisis (HC) hospitalizations and major adverse cardiac and cerebrovascular events (MACCE) in young adults with cannabis use disorder (CUD+). Material and Methods: Young adult hospitalizations (18−44 years) with HC and CUD+ were identified from National Inpatient Sample (October 2015−December 2017). Primary outcomes included prevalence and odds of HC with CUD. Co-primary (in-hospital MACCE) and secondary outcomes (resource utilization) were compared between propensity-matched CUD+ and CUD- cohorts in HC admissions. Results: Young CUD+ had higher prevalence of HC (0.7%, n = 4675) than CUD- (0.5%, n = 92,755), with higher odds when adjusted for patient/hospital-characteristics, comorbidities, alcohol and tobacco use disorder, cocaine and stimulant use (aOR 1.15, 95%CI:1.06−1.24, p = 0.001). CUD+ had significantly increased adjusted odds of HC (for sociodemographic, hospital-level characteristics, comorbidities, tobacco use disorder, and alcohol abuse) (aOR 1.17, 95%CI:1.01−1.36, p = 0.034) among young with benign hypertension, but failed to reach significance when additionally adjusted for cocaine/stimulant use (aOR 1.12, p = 0.154). Propensity-matched CUD+ cohort (n = 4440, median age 36 years, 64.2% male, 64.4% blacks) showed higher rates of substance abuse, depression, psychosis, previous myocardial infarction, valvular heart disease, chronic pulmonary disease, pulmonary circulation disease, and liver disease. CUD+ had higher odds of all-cause mortality (aOR 5.74, 95%CI:2.55−12.91, p < 0.001), arrhythmia (aOR 1.73, 95%CI:1.38−2.17, p < 0.001) and stroke (aOR 1.46, 95%CI:1.02−2.10, p = 0.040). CUD+ cohort had fewer routine discharges with comparable in-hospital stay and cost. Conclusions: Young CUD+ cohort had higher rate and odds of HC admissions than CUD-, with prevalent disparities and higher subsequent risk of all-cause mortality, arrhythmia and stroke.
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Affiliation(s)
- Rupak Desai
- Division of Cardiology, Atlanta VA Medical Center, 1670 Clairmont Rd., Decatur, GA 30033, USA
- Correspondence: or
| | - Akhil Jain
- Department of Internal Medicine, Mercy Catholic Medical Center, Darby, PA 19153, USA
| | - Waleed Sultan
- Department of Family Medicine, Conemaugh Memorial Medical Center, Johnstown, PA 15905, USA
| | - Zainab Gandhi
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA
| | - Athul Raj Raju
- Department of Medicine, Karuna Medical College, Chittur-Thathamangalam 678103, Kerala, India
| | - Vivek Joseph Varughese
- Department of Internal Medicine, Government Medical College, Thiruvananthapuram 695011, Kerala, India
| | - Geethu Jnaneswaran
- Department of Medicine, SUT Academy of Medical Sciences, Thiruvananthapuram 695028, Kerala, India
| | - Charu Agarwal
- Department of Medicine, Sri Siddhartha Medical College, Tumakuru 572107, Karnataka, India
| | - Bisharah Rizvi
- Department of Internal Medicine, Saint Agnes Medical Center, Fresno, CA 93720, USA
| | - Zeeshan Mansuri
- Department of Psychiatry, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Puneet Gupta
- Department of Cardiology, Baptist Health Deaconess Madisonville, Madisonville, KY 42431, USA
| | - Gautam Kumar
- Division of Cardiology, Atlanta VA Medical Center, 1670 Clairmont Rd., Decatur, GA 30033, USA
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30307, USA
| | - Rajesh Sachdeva
- Division of Cardiology, Atlanta VA Medical Center, 1670 Clairmont Rd., Decatur, GA 30033, USA
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Cannabinoids and Chronic Liver Diseases. Int J Mol Sci 2022; 23:ijms23169423. [PMID: 36012687 PMCID: PMC9408890 DOI: 10.3390/ijms23169423] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/13/2022] [Accepted: 08/17/2022] [Indexed: 11/19/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders.
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Courtney JB, Russell MA, Conroy DE. Tobacco and cannabis use as moderators of the association between physical activity and alcohol use across the adult lifespan in the United States: NHANES, 2005-2016. Prev Med 2022; 155:106931. [PMID: 34954238 PMCID: PMC8886825 DOI: 10.1016/j.ypmed.2021.106931] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 12/14/2021] [Accepted: 12/19/2021] [Indexed: 02/03/2023]
Abstract
Physically-active adults are more likely to consume alcohol, but this association may vary if adults also use other substances (i.e., tobacco and/or cannabis), which could increase substance-use related harms. This study examined whether tobacco and/or cannabis use moderated the associations between physical activity, odds of drinking and alcohol drinks/week. We used cross-sectional 2005-2016 National Health and Nutrition Examination Survey data (United States of America). Physical activity was assessed using device-based and self-reported moderate-to-vigorous physical activity (MVPA) and total physical activity hours/week. Individuals were categorized into one of four (poly)substance use categories, no tobacco/no cannabis, tobacco, cannabis, or tobacco/cannabis use. Regression models examined substance use as a moderator of the association between physical activity and the odds of drinking versus not drinking and alcohol drinks/week among light/moderate/heavy drinkers (≥12 drinks/year). Using cannabis or tobacco weakened the significant positive associations between total physical activity and self-reported recreational MVPA hours/week on odds of drinking (ORs = 0.978 and 0.967, respectively), such that the effect was negative or null when using cannabis or tobacco, respectively. Greater total physical activity and device-based MVPA hours/week was associated with consuming greater drinks/week (IRRs = 1.003 and 1.035, respectively). Using tobacco weakened the association between device-based MVPA and alcohol drinks/week (IRR = 0.934, 95% CI: [0.888, 0.982]). Cannabis and tobacco use weakened the association between physical activity and alcohol use. The positive association between physical activity and alcohol use may be limited to single substance users of alcohol and could reflect shared reasons for engaging in these behaviors, such as stress management or social motives.
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Affiliation(s)
- J B Courtney
- College of Health and Human Development, Pennsylvania State University, 320 Biobehavioral Health Building, University Park, PA 16802, USA.
| | - M A Russell
- College of Health and Human Development, Pennsylvania State University, 219 Biobehavioral Health Building, University Park, PA 16802, USA
| | - D E Conroy
- College of Health and Human Development, Pennsylvania State University, 266 Recreation Hall, University Park, PA 16802, USA
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Yang K, Choi SE, Jeong WI. Hepatic Cannabinoid Signaling in the Regulation of Alcohol-Associated Liver Disease. Alcohol Res 2021; 41:12. [PMID: 34646717 PMCID: PMC8496755 DOI: 10.35946/arcr.v41.1.12] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
PURPOSE The endocannabinoid system has emerged as a key regulatory signaling pathway in the pathophysiology of alcohol-associated liver disease (ALD). More than 30 years of research have established different roles of endocannabinoids and their receptors in various aspects of liver diseases, such as steatosis, inflammation, and fibrosis. However, pharmacological applications of the endocannabinoid system for the treatment of ALD have not been successful because of psychoactive side effects, despite some beneficial effects. Thus, a more delicate and detailed elucidation of the mechanism linking the endocannabinoid system and ALD may be of paramount significance in efforts to apply the system to the treatment of ALD. SEARCH METHODS Three electronic databases (PubMed, MEDLINE, and Cochrane Library) were used for literature search from November 1988 to April 2021. Major keywords used for literature searches were “cannabinoid,” “cannabinoid receptor,” “ALD,” “steatosis,” and “fibrosis.” SEARCH RESULTS According to the inclusion and exclusion criteria, the authors selected 47 eligible full-text articles out of 2,691 searched initially. Studies in the past 3 decades revealed the opposite effects of cannabinoid receptors CB1R and CB2R on steatosis, inflammation, and fibrosis in ALD. DISCUSSION AND CONCLUSIONS This review summarizes the endocannabinoid signaling in the general physiology of the liver, the pathogenesis of ALD, and some of the potential therapeutic implications of cannabinoid-based treatments for ALD.
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Affiliation(s)
- Keungmo Yang
- Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
| | - Sung Eun Choi
- Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
| | - Won-Il Jeong
- Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.,Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
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Morgan MY, Sharma M, Atkinson SR. Genetic and Environmental Susceptibility to Alcoholic Hepatitis. Clin Liver Dis 2021; 25:517-535. [PMID: 34229837 DOI: 10.1016/j.cld.2021.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Constitutional, environmental, and genetic risk factors influence the development of alcohol-related cirrhosis. The amount of alcohol consumed and whether excessive drinking continues after the identification of pre-cirrhotic liver damage are key risk factors. Female sex, ethnicity, obesity, coffee consumption, cigarette smoking, and exposure to other causes of liver injury also influence the risk of disease development. More recently several genetic loci have been robustly associated with the risk for developing significant alcohol-related liver disease. It remains unclear whether additional risk factors are involved in the development of the clinical syndrome of alcoholic hepatitis, but the genetic evidence is suggestive.
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Affiliation(s)
- Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College, Rowland Hill Street, Hampstead, London NW3 2PF, UK.
| | - Moksh Sharma
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College, Rowland Hill Street, Hampstead, London NW3 2PF, UK
| | - Stephen R Atkinson
- Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
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Jugl S, Okpeku A, Costales B, Morris EJ, Alipour-Haris G, Hincapie-Castillo JM, Stetten NE, Sajdeya R, Keshwani S, Joseph V, Zhang Y, Shen Y, Adkins L, Winterstein AG, Goodin A. A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019. Med Cannabis Cannabinoids 2021; 4:21-42. [PMID: 34676348 PMCID: PMC8525213 DOI: 10.1159/000515069] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 02/03/2021] [Indexed: 12/15/2022] Open
Abstract
In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016-2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn's disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson's disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.
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Affiliation(s)
- Sebastian Jugl
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Aimalohi Okpeku
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Brianna Costales
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Earl J. Morris
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Golnoosh Alipour-Haris
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Juan M. Hincapie-Castillo
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | | | - Ruba Sajdeya
- Epidemiology, University of Florida, Gainesville, Florida, USA
| | - Shailina Keshwani
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Verlin Joseph
- Epidemiology, University of Florida, Gainesville, Florida, USA
| | - Yahan Zhang
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Yun Shen
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Lauren Adkins
- Health Sciences Center Libraries, University of Florida, Gainesville, Florida, USA
| | - Almut G. Winterstein
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
| | - Amie Goodin
- Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, Florida, USA
- Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, Florida, USA
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Kaminski NE, Kaplan BLF. Immunomodulation by cannabinoids: Current uses, mechanisms, and identification of data gaps to be addressed for additional therapeutic application. ADVANCES IN PHARMACOLOGY 2021; 91:1-59. [PMID: 34099105 DOI: 10.1016/bs.apha.2021.01.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The endocannabinoid system plays a critical role in immunity and therefore its components, including cannabinoid receptors 1 and 2 (CB1 and CB2), are putative druggable targets for immune-mediated diseases. Whether modulating endogenous cannabinoid levels or interacting with CB1 or CB2 receptors directly, cannabinoids or cannabinoid-based therapeutics (CBTs) show promise as anti-inflammatory or immune suppressive agents. Herein we provide an overview of cannabinoid effects in animals and humans that provide support for the use of CBTs in immune-mediated disease such as multiple sclerosis (MS), inflammatory bowel disease (IBD), asthma, arthritis, diabetes, human immunodeficiency virus (HIV), and HIV-associated neurocognitive disorder (HAND). This is not an exhaustive review of cannabinoid effects on immune responses, but rather provides: (1) key studies in which initial and/or novel observations were made in animal studies; (2) critical human studies including meta-analyses and randomized clinical trials (RCTs) in which CBTs have been assessed; and (3) evidence for the role of CB1 or CB2 receptors in immune-mediated diseases through genetic analyses of single nucleotide polymorphisms (SNPs) in the CNR1 and CNR2 genes that encode CB1 or CB2 receptors, respectively. Perhaps most importantly, we provide our view of data gaps that exist, which if addressed, would allow for more rigorous evaluation of the efficacy and risk to benefit ratio of the use of cannabinoids and/or CBTs for immune-mediated diseases.
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Affiliation(s)
- Norbert E Kaminski
- Institute for Integrative Toxicology, Center for Research on Ingredient Safety, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
| | - Barbara L F Kaplan
- Center for Environmental Health Sciences, Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
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Adejumo AC, Akanbi O, Alayo Q, Ejigah V, Onyeakusi NE, Omede OF, Pani L, Omole O. Predictors, rates, and trends of opioid use disorder among patients hospitalized with chronic pancreatitis. Ann Gastroenterol 2021; 34:262-272. [PMID: 33654369 PMCID: PMC7903576 DOI: 10.20524/aog.2021.0579] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 09/23/2020] [Indexed: 12/15/2022] Open
Abstract
Background Patients with chronic pancreatitis (CP) suffer from pain and receive increased opioid prescriptions with a high risk of opioid use disorder (OUD). We studied the predictors, trends and outcomes of OUD among patients hospitalized with CP. Methods Records with CP (with/without OUD) were extracted from the Nationwide Inpatient Sample (NIS) 2012-2014, and the association of OUD with the burden of CP was calculated. We then charted the trends of OUD and its interaction with concomitant CP from NIS 2007-2014 (SAS 9.4). Results In the period 2012-2014, 4349 (4.99%) of the 87,068 CP patients had concomitant OUD, with higher risk among patients who were young, females, white vs. Hispanics, and individuals with chronic back pain, arthritis, non-opioid substance use, mental health disorders, and those hospitalized in urban centers. OUD was associated with a longer hospital stay (6.9 vs. 6.5 days, P=0.0015) but no significant difference in charges ($47,151 vs. $49,017, P=0.0598) or mortality (1.64% vs. 0.74%, P=0.0506). From 2007-2014, the average yearly rate of OUD was 174 cases per 10,000 hospitalizations (174/10,000), almost 3 times higher among CP vs. non-CP (479/10,000 vs. 173/10,000, P<0.001), and it increased from 2007 to 2014 (135/10,000 to 216/10,000, P<0.001). The yearly increase was 2.7 times higher among patients with CP vs. non-CP (29.9/10,000 vs. 11.3/10,000 hospitalizations/year, P<0.001). Conclusions CP is associated with higher rates and trends of OUD. Patients with CP at high risk of OUD may benefit from alternate analgesic regimens or surveillance for OUD when they are prescribed opioids.
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Affiliation(s)
- Adeyinka Charles Adejumo
- Department of Medicine, North Shore Medical Center, Salem, Massachusetts (Adeyinka Charles Adejumo, Ogorchukwu Faith Omede, Lydie Pani).,Department of Medicine, Tufts University Medical School, Boston, Massachusetts (Adeyinka Charles Adejumo, Ogorchukwu Faith Omede, Lydie Pani)
| | - Olalekan Akanbi
- Department of Medicine, University of Kentucky College of Medicine, Lexington Kentucky (Olalekan Akanbi)
| | - Quazim Alayo
- Department of Medicine, St. Luke's Hospital, Chesterfield, Missouri (Quazim Alayo)
| | - Victor Ejigah
- Department of Pharmaceutical Sciences, University of Massachusetts Lowell, Lowell, Massachusetts (Victor Ejigah)
| | - Nnaemeka Egbuna Onyeakusi
- Department of Anesthesiology, Case Western - MetroHealth campus, Cleveland, Ohio (Nnaemeka Egbuna Onyeakusi)
| | - Ogorchukwu Faith Omede
- Department of Medicine, North Shore Medical Center, Salem, Massachusetts (Adeyinka Charles Adejumo, Ogorchukwu Faith Omede, Lydie Pani).,Department of Medicine, Tufts University Medical School, Boston, Massachusetts (Adeyinka Charles Adejumo, Ogorchukwu Faith Omede, Lydie Pani)
| | - Lydie Pani
- Department of Medicine, North Shore Medical Center, Salem, Massachusetts (Adeyinka Charles Adejumo, Ogorchukwu Faith Omede, Lydie Pani).,Department of Medicine, Tufts University Medical School, Boston, Massachusetts (Adeyinka Charles Adejumo, Ogorchukwu Faith Omede, Lydie Pani)
| | - Oluwatosin Omole
- Department of Family Medicine, University Health System, San Antonio, Texas (Oluwatosin Omole), USA
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Li HY, Gan RY, Shang A, Mao QQ, Sun QC, Wu DT, Geng F, He XQ, Li HB. Plant-Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:6621644. [PMID: 33728021 PMCID: PMC7939748 DOI: 10.1155/2021/6621644] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/04/2021] [Accepted: 02/19/2021] [Indexed: 02/07/2023]
Abstract
Fatty liver disease (FLD), including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), is a serious chronic metabolic disease that affects a wide range of people. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of FLD. The plant-based, high-fiber, and low-fat diet has been recommended to manage FLD for a long time. This review discusses the current state of the art into the effects, mechanisms, and clinical application of plant-based foods in NAFLD and AFLD, with highlighting related molecular mechanisms. Epidemiological evidence revealed that the consumption of several plant-based foods was beneficial to alleviating FLD. Further experimental studies found out that fruits, spices, teas, coffee, and other plants, as well as their bioactive compounds, such as resveratrol, anthocyanin, curcumin, and tea polyphenols, could alleviate FLD by ameliorating hepatic steatosis, oxidative stress, inflammation, gut dysbiosis, and apoptosis, as well as regulating autophagy and ethanol metabolism. More importantly, clinical trials confirmed the beneficial effects of plant-based foods on patients with fatty liver. However, several issues need to be further studied especially the safety and effective doses of plant-based foods and their bioactive compounds. Overall, certain plant-based foods are promising natural sources of bioactive compounds to prevent and alleviate fatty liver disease.
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Affiliation(s)
- Hang-Yu Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Ren-You Gan
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China
| | - Ao Shang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Qian-Qian Mao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Quan-Cai Sun
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212001, China
| | - Ding-Tao Wu
- Institute of Food Processing and Safety, College of Food Science, Sichuan Agricultural University, Ya'an, China
| | - Fang Geng
- Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), School of Food and Biological Engineering, Chengdu University, Chengdu, China
| | - Xiao-Qin He
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
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Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers. Am J Gastroenterol 2021; 116:106-115. [PMID: 32868629 DOI: 10.14309/ajg.0000000000000833] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 06/17/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. METHODS We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. RESULTS The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. DISCUSSION If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.
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Jain P, Shasthry SM, Choudhury AK, Maiwall R, Kumar G, Bharadwaj A, Arora V, Vijayaraghavan R, Jindal A, Sharma MK, Bhatia V, Sarin SK. Alcohol associated liver cirrhotics have higher mortality after index hospitalization: Long-term data of 5,138 patients. Clin Mol Hepatol 2021; 27:175-185. [PMID: 33317256 PMCID: PMC7820216 DOI: 10.3350/cmh.2020.0068] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 07/01/2020] [Accepted: 09/29/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC. METHODS Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included. RESULTS Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2-10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P<0.001) male (97.7% vs. 67.7%), younger (40-50 group, 36.2% vs. 20.2%; P<0.001) with higher liver related complications at baseline, (P<0.001 for each), sepsis: 20.3% vs. 14.9%; ascites: 82.2% vs. 65.9%; spontaneous bacterial peritonitis: 21.8% vs. 15.7%; hepatic encephalopathy: 41.0% vs. 25.0%; acute variceal bleeding: 32.0% vs. 23.7%; and acute kidney injury 30.5% vs. 19.6%. ALC patients had higher Child-Pugh (10.6±2.0 vs. 9.0±2.3), model for end-stage liver-disease scores (21.49±8.47 vs. 16.85±7.79), and higher mortality (42.3% vs. 27.3%, P<0.001) compared to non-ALC. CONCLUSION One-third of cirrhosis patients die in index hospitalization. 60% of the survivors require at least one rehospitalization within a year. ALC patients present with higher morbidity and mortality and at a younger age.
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Affiliation(s)
- Priyanka Jain
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | | | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankit Bharadwaj
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikram Bhatia
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Fuster D, García-Calvo X, Bolao F, Zuluaga P, Rocamora G, Hernández-Rubio A, Sanvisens A, Tor J, Muga R. Cannabis use is associated with monocyte activation (sCD163) in patients admitted for alcohol use disorder treatment. Drug Alcohol Depend 2020; 216:108231. [PMID: 32818911 DOI: 10.1016/j.drugalcdep.2020.108231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 07/20/2020] [Accepted: 08/06/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The effect of concomitant cocaine and cannabis use on monocyte activation and inflammation in patients with alcohol use disorder (AUD) is unknown. METHODS To analyze the impact of cocaine and cannabis use on levels of markers of monocyte activation (sCD163 and sCD14) and systemic inflammation (interleukin-6 [IL-6]) in AUD patients admitted for hospital treatment between 2013 and 2018. Clinical and laboratory parameters were obtained upon admission. IL-6, sCD163, and sCD14 were measured in frozen plasma samples. We performed logistic regression to detect associations between cocaine and cannabis use and markers of monocyte activation and inflammation in the highest quartile. RESULTS A total of 289 patients (77.5 % male) were included (median age = 50 years). The median alcohol intake upon admission was 142 g/day. The median duration of AUD was 20 years. Of the 289 patients with AUD, 76 % were active smokers, 23.1 % and 22.1 % concomitantly used cocaine and cannabis, respectively The median levels of IL-6, sCD163, and sCD14 were 4.37 pg/mL, 759 ng/mL, and 1.68 × 106 pg/mL, respectively. We did not detect associations between cocaine use and inflammation or monocyte activation. Cannabis use was associated with a higher odds of having sCD163 levels in the highest quartile (adjusted odds ratio = 2.34, 95 % confidence interval = 1.07-5.15, p = 0.03). Cannabis use was not associated with inflammation. CONCLUSION In this series of AUD patients the concomitant use of cannabis use was associated with sCD163 levels that were in the highest quartile, consistent with monocyte activation.
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Affiliation(s)
- Daniel Fuster
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain.
| | - Xavier García-Calvo
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain
| | - Ferran Bolao
- Department of Internal Medicine, Hospital Universitari Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08907, Spain
| | - Paola Zuluaga
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain
| | - Gemma Rocamora
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain
| | - Anna Hernández-Rubio
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain
| | - Arantza Sanvisens
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain
| | - Jordi Tor
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain
| | - Robert Muga
- Department of Internal Medicine, Addiction Unit Hospital Universitari Germans Trias i Pujol, Badalona, 08916, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Badalona, 08916, Spain
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Benefits of cannabis use for metabolic disorders and survival in people living with HIV with or without hepatitis C co-infection. AIDS 2020; 34:953-954. [PMID: 32271254 DOI: 10.1097/qad.0000000000002480] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Rivera P, Vargas A, Pastor A, Boronat A, López-Gambero AJ, Sánchez-Marín L, Medina-Vera D, Serrano A, Pavón FJ, de la Torre R, Agirregoitia E, Lucena MI, Rodríguez de Fonseca F, Decara J, Suárez J. Differential hepatoprotective role of the cannabinoid CB 1 and CB 2 receptors in paracetamol-induced liver injury. Br J Pharmacol 2020; 177:3309-3326. [PMID: 32167157 DOI: 10.1111/bph.15051] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 02/19/2020] [Accepted: 03/02/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND PURPOSE Protective mechanisms of the endogenous cannabinoid system against drug-induced liver injury (DILI) are actively being investigated regarding the differential regulatory role of the cannabinoid CB1 and CB2 receptors in liver fibrogenesis and inflammation. EXPERIMENTAL APPROACH The 2-arachidonoylglycerol (2-AG)-related signalling receptors and enzymatic machinery, and inflammatory/fibrogenic factors were investigated in the liver of a mouse model of hepatotoxicity induced by acute and repeated overdoses (750 mg·kg-1 ·day-1 ) of paracetamol (acetaminophen), previously treated with selective CB1 (ACEA) and CB2 (JWH015) agonists (10 mg·kg-1 ), or lacking CB1 and CB2 receptors. KEY RESULTS Acute paracetamol increased the expression of CB2 , ABHD6 and COX-2, while repeated paracetamol increased that of CB1 and COX-2 and decreased that of DAGLβ. Both acute paracetamol and repeated paracetamol decreased the liver content of acylglycerols (2-AG, 2-LG and 2-OG). Human liver samples from a patient suffering APAP hepatotoxicity confirmed CB1 and CB2 increments. Acute paracetamol-exposed CB2 KO mice had higher expression of the fibrogenic αSMA and the cytokine IL-6 and lower apoptotic cleaved caspase 3. CB1 deficiency enhanced the repeated APAP-induced increases in αSMA and cleaved caspase 3 and blocked those of CYP2E1, TNF-α, the chemokine CCL2 and the circulating γ-glutamyltransferase (γGT). Although JWH015 reduced the expression of αSMA and TNF-α in acute paracetamol, ACEA increased the expression of cleaved caspase 3 and CCL2 in repeated paracetamol. CONCLUSION AND IMPLICATIONS The differential role of CB1 versus CB2 receptors on inflammatory/fibrogenic factors related to paracetamol-induced hepatotoxicity should be considered for designing alternative therapies against DILI.
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Affiliation(s)
- Patricia Rivera
- Department of Endocrinology, Fundación Investigación Biomédica del Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Biomédica la Princesa, Madrid, Spain.,UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Antonio Vargas
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Antoni Pastor
- Farmacología Integrada y Neurociencia de Sistemas, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain
| | - Anna Boronat
- Farmacología Integrada y Neurociencia de Sistemas, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain
| | - Antonio Jesús López-Gambero
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Laura Sánchez-Marín
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Dina Medina-Vera
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Antonia Serrano
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Francisco Javier Pavón
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.,UGC Corazón, Hospital Universitario Virgen de la Victoria, IBIMA, Universidad de Málaga, Málaga, Spain
| | - Rafael de la Torre
- Farmacología Integrada y Neurociencia de Sistemas, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain
| | - Ekaitz Agirregoitia
- Department of Physiology, Faculty of Medicine and Nursing, UPV/EHU, Leioa, Spain
| | - María Isabel Lucena
- Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, IBIMA, Universidad de Málaga, Málaga, Spain
| | - Fernando Rodríguez de Fonseca
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Juan Decara
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Juan Suárez
- UGC Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
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Hua JT, Afshar M, Clark BJ, Kovacs EJ, Burnham EL. The relationship of cannabis decriminalization in Colorado and cannabis use in individuals with alcohol use disorders. J Cannabis Res 2020; 2:13. [PMID: 33526125 PMCID: PMC7819320 DOI: 10.1186/s42238-020-00018-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 02/18/2020] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE Over the past decade, cannabis use has become increasingly popular in states that include Colorado. During this time, alcohol use disorders (AUDs) and alcohol-related medical conditions have also been consistently recognized as public health problems with increasing prevalence in the state. Despite the widespread use of cannabis in Colorado, the epidemiology of cannabis use among those with AUDs has been poorly described. Therefore, we sought to examine cannabis use among individuals with likely AUDs and individuals with low-risk alcohol use during a time of major Colorado legislative changes before and after legalization of recreational cannabis in 2012. METHODS This study was a secondary data analysis conducted with information from 303 participants (80% male) in the Denver, CO metropolitan enrolled between August 2007 and April 2016 for studies related to alcohol and lung health. Of these participants, 188 (62%) were completing inpatient alcohol detoxification with likely AUDs. All participants completed the Alcohol Use Disorder Identification Test (AUDIT) to establish their likelihood of an AUD, and all had information on current cannabis use assessed by questionnaire and urine toxicology testing. RESULTS Individuals with likely AUDs more commonly used cannabis compared to control participants (42% vs 27%, p = 0.007). In multiple logistic regression analyses, participant type (likely AUD versus control), tobacco smoking, and age were significantly associated with cannabis smoking; however, the year of participant enrollment was not. Adjusted odds for cannabis use among participants with likely AUDs were 2.97 (1.51-5.82), p = 0.002, while odds for cannabis use among tobacco smokers were 3.67 (1.94-6.93), p < 0.0001. Among control participants, tobacco smoking increased odds of cannabis use seven-fold. CONCLUSIONS Our findings highlight the exceptionally high odds of cannabis use among individuals with likely AUDs undergoing alcohol detoxification at a Colorado treatment facility before and after legalization of recreational cannabis. Targeted investigations into the medical and psychiatric consequences of combined alcohol and cannabis use are urgently needed to define its health impact in these vulnerable individuals.
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Affiliation(s)
- Jeremy T Hua
- Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Majid Afshar
- Department of Medicine, Division of Pulmonary and Critical Care, Loyola University Chicago Health Sciences Campus, Chicago, IL, USA
| | - Brendan J Clark
- Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, 12700 E. 19th St. C272, Aurora, CO, 80045, USA
| | - Elizabeth J Kovacs
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Ellen L Burnham
- Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, 12700 E. 19th St. C272, Aurora, CO, 80045, USA.
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Cannabis use and risk of Clostridioides difficile infection: Analysis of 59,824 hospitalizations. Anaerobe 2020; 61:102095. [DOI: 10.1016/j.anaerobe.2019.102095] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 08/24/2019] [Accepted: 09/02/2019] [Indexed: 12/17/2022]
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Karoly HC, Mueller RL, Bidwell LC, Hutchison KE. Cannabinoids and the Microbiota-Gut-Brain Axis: Emerging Effects of Cannabidiol and Potential Applications to Alcohol Use Disorders. Alcohol Clin Exp Res 2019; 44:340-353. [PMID: 31803950 DOI: 10.1111/acer.14256] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Abstract
The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the nonpsychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota-gut-brain axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control. Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation. Thus, cannabinoids may exert AUD harm-reduction effects, at least in part, through their beneficial actions across the MGBA. This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions.
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Affiliation(s)
- Hollis C Karoly
- Institute of Cognitive Science, University of Colorado Boulder, Boulder, Colorado
| | - Raeghan L Mueller
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado
| | - L Cinnamon Bidwell
- Institute of Cognitive Science, University of Colorado Boulder, Boulder, Colorado.,Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado
| | - Kent E Hutchison
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado
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Vázquez-Bourgon J, Ortiz-García de la Foz V, Suarez-Pereira I, Iruzubieta P, Arias-Loste MT, Setién-Suero E, Ayesa-Arriola R, Gómez-Revuelta M, Crespo J, Crespo Facorro B. Cannabis consumption and non-alcoholic fatty liver disease. A three years longitudinal study in first episode non-affective psychosis patients. Prog Neuropsychopharmacol Biol Psychiatry 2019; 95:109677. [PMID: 31228640 DOI: 10.1016/j.pnpbp.2019.109677] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 05/28/2019] [Accepted: 06/17/2019] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Increased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis. MATERIAL AND METHODS A total of 390 patients were evaluated at baseline and after 3 years of initiating the antipsychotic treatment. Anthropometric measurements and liver, lipid, and glycemic parameters were obtained at both time points. All but 6.7% of patients were drug-naïve at entry, and they self-reported their cannabis use at both time points. Liver steatosis and fibrosis were evaluated through validated clinical scores (Fatty Liver Index [FLI], Fibrosis-4 [FIB-4], and NAFLD). RESULTS At 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F = 13.874; p < .001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X2 = 7.97, p = .019). Longitudinally, patients maintaining cannabis consumption after 3 years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p = .022) and never-users (p = .016). No differences were seen in fibrosis scores associated with cannabis. CONCLUSIONS Cannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain.
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Affiliation(s)
- Javier Vázquez-Bourgon
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain.
| | - Víctor Ortiz-García de la Foz
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.
| | - Irene Suarez-Pereira
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Neuropsychopharmacology & Psychobiology Research Group, University of Cádiz, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Edificio "Andrés Segovia", Cádiz, Spain.
| | - Paula Iruzubieta
- Gastroenterology and Hepatology Unit, University Hospital de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain.
| | - María Teresa Arias-Loste
- Gastroenterology and Hepatology Unit, University Hospital de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain.
| | - Esther Setién-Suero
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain
| | - Rosa Ayesa-Arriola
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain.
| | - Marcos Gómez-Revuelta
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain
| | - Javier Crespo
- Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; Gastroenterology and Hepatology Unit, University Hospital de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain.
| | - Benedicto Crespo Facorro
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain.
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Quraishi R, Varshney M, Singh A, Singh D, Kumar M, Rao R, Jain R, Ambekar A. Use of Filter Paper to Measure Alcohol Biomarkers among Opioid-Dependent Patients on Agonist Maintenance Treatment: A Community-Based Study. Indian J Psychol Med 2019; 41:529-534. [PMID: 31772439 PMCID: PMC6875832 DOI: 10.4103/ijpsym.ijpsym_304_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 09/28/2019] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Harmful Alcohol use is frequent among opioid dependents patients undergoing agonist maintenance treatment. The objective assessment of harmful alcohol use can be done using laboratory measures of serum biomarkers. For community-based patients, there is often a requirement of an alternative method due to lack of onsite laboratory services. The aim of the study was to examine filter paper as a matrix to measure serum biomarkers of harmful alcohol use. METHODS The initial phase involved standardization of the filter-paper-based assay. Conditions were optimised for extraction and estimation of alcohol biomarkers (Aspartate Aminotransferase; AST, Alanine Aminotransferase; ALT, Gamma Glutamyl transferase; GGT and Carbohydrate Deficient Transferrin; CDT) from the filter paper. For clinical validation, serum samples were collected from community clinics. Biomarker levels obtained from both the methods were correlated using linear regression analysis. Limits of agreement between the two methods was estimated using the Intraclass Correlation Coefficient (ICC). RESULTS The extraction of enzymes (AST, ALT and GGT) from filter paper was carried out using the substrate buffer available with the reagent kit (Randox, UK). CDT was readily extracted from filter paper using deionised water. Serum biomarker levels measured from samples collected from community clinics correlated well with filter paper extracted levels (ICC 0.97-0.99). More than 90% of alcohol biomarker levels were recovered from the filter paper matrix using this method. CONCLUSION Filter paper has the potential to be used as a matrix to objectively measure alcohol biomarkers among opioid-dependent patients from community settings lacking onsite laboratory facilities.
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Affiliation(s)
- Rizwana Quraishi
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Mohit Varshney
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Amit Singh
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Dharamveer Singh
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh Kumar
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Ravindra Rao
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Raka Jain
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Atul Ambekar
- National Drug-Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
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Abstract
OBJECTIVES Chronic pancreatitis (CP) is associated with high rates of recurrent hospitalizations, which predisposes to Clostridium difficile infection (CDI). We investigate the burden of CDI in CP. METHODS We identified records of patients with CP from the Nationwide Inpatient Sample (NIS) 2012-2014 and estimated the impact of CDI on their outcomes. We calculated the adjusted odds ratio (AOR) of CP on having CDI (NIS 2014). From NIS 2007-2014, we plotted the trends of CDI and its interaction with CP. RESULTS From 2012 to 2014, 886 (2.72%) of the 32,614 CP patients had concomitant CDI, which was associated with poorer outcomes: acute kidney injury (AOR, 2.57 [95% confidence interval {CI}, 2.11-3.13]), length of stay (13.3 vs 7.4 days), and charges (US $127,496 vs US $72,767), but not mortality (AOR, 0.93 [95% CI, 0.28-3.05]). In 2014, CP was associated with an increased risk of CDI (crude odds ratio, 2.10 [95% CI, 1.95-2.26]), which persisted after multivariate adjustment (AOR, 2.03 [95% CI, 1.87-2.19]). From 2007 to 2014, the annual prevalence of CDI was 106.4 cases per 10,000 hospitalizations, increasing from 2007 (95.5/10,000) to 2014 (118.4/10,000), with a 3.7 times higher annual rate of increase among CP versus no-CP patients (13.4/10,000 vs 3.7/10,000 population/year). CONCLUSIONS Chronic pancreatitis patients have high burden of CDI and may benefit from CDI prophylaxis.
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Di Marzo V, Silvestri C. Lifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome. Nutrients 2019; 11:nu11081956. [PMID: 31434293 PMCID: PMC6722643 DOI: 10.3390/nu11081956] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 08/07/2019] [Accepted: 08/09/2019] [Indexed: 12/14/2022] Open
Abstract
Lifestyle is a well-known environmental factor that plays a major role in facilitating the development of metabolic syndrome or eventually exacerbating its consequences. Various lifestyle factors, especially changes in dietary habits, extreme temperatures, unusual light-dark cycles, substance abuse, and other stressful factors, are also established modifiers of the endocannabinoid system and its extended version, the endocannabinoidome. The endocannabinoidome is a complex lipid signaling system composed of a plethora (>100) of fatty acid-derived mediators and their receptors and anabolic and catabolic enzymes (>50 proteins) which are deeply involved in the control of energy metabolism and its pathological deviations. A strong link between the endocannabinoidome and another major player in metabolism and dysmetabolism, the gut microbiome, is also emerging. Here, we review several examples of how lifestyle modifications (westernized diets, lack or presence of certain nutritional factors, physical exercise, and the use of cannabis) can modulate the propensity to develop metabolic syndrome by modifying the crosstalk between the endocannabinoidome and the gut microbiome and, hence, how lifestyle interventions can provide new therapies against cardiometabolic risk by ensuring correct functioning of both these systems.
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Affiliation(s)
- Vincenzo Di Marzo
- École de nutrition, Université Laval, Québec, QC G1V 0A6, Canada
- Institut sur la nutrition et les aliments fonctionnels, Université Laval, Québec, QC G1V 0A6, Canada
- Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Université Laval, Québec, QC G1V 0A6, Canada
- Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC G1V 4G5, Canada
- Department de médecine, Université Laval, Québec, QC G1V 0A6, Canada
- Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy
| | - Cristoforo Silvestri
- Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Université Laval, Québec, QC G1V 0A6, Canada.
- Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC G1V 4G5, Canada.
- Department de médecine, Université Laval, Québec, QC G1V 0A6, Canada.
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Adejumo AC, Adejumo KL, Adegbala OM, Enwerem N, Ofosu A, Akanbi O, Fijabi DO, Ogundipe OA, Pani L, Adeboye A. Inferior Outcomes of Patients With Acute Myocardial Infarction and Comorbid Protein‐Energy Malnutrition. JPEN J Parenter Enteral Nutr 2019; 44:454-462. [DOI: 10.1002/jpen.1680] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 06/28/2019] [Indexed: 12/21/2022]
Affiliation(s)
- Adeyinka Charles Adejumo
- Department of MedicineNorth Shore Medical Center Salem Massachusetts USA
- Department of MedicineTufts University Medical School Boston Massachusetts USA
- School of Public HealthUniversity of Massachusetts Lowell Lowell Massachusetts USA
| | | | | | - Ngozi Enwerem
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego California USA
| | - Andrew Ofosu
- Department of Gastroenterology and HepatologyBrooklyn Hospital Brooklyn New York USA
| | - Olalekan Akanbi
- Division of Hospital MedicineUniversity of Kentucky College of Medicine Lexington Kentucky USA
| | | | | | - Lydie Pani
- Department of MedicineNorth Shore Medical Center Salem Massachusetts USA
- Department of MedicineTufts University Medical School Boston Massachusetts USA
| | - Adedayo Adeboye
- WJB Dorn VAMC Heart and Vascular Institute/USC School of Medicine Columbia South Carolina USA
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27
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Predictors, burden and impact of cardiac arrhythmias among patients hospitalized with end-stage liver disease. Heart Lung 2019; 49:73-79. [PMID: 31320178 DOI: 10.1016/j.hrtlng.2019.07.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 06/27/2019] [Accepted: 07/03/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Cirrhotic cardiomyopathy, hyperammonemia, and hepatorenal syndrome predispose to cardiac arrhythmias in End-stage liver disease (ESLD). OBJECTIVES Among ESLD hospitalizations, we evaluate the distribution and predictors of arrhythmias and their impact on hospitalization outcomes. METHODS We selected ESLD records from the Nationwide Inpatient Sample (2007-2014), identified concomitant arrhythmias (tachyarrhythmias and bradyarrhythmias), and their demographic and comorbid characteristics, and estimated the effect of arrhythmia on outcomes (SAS 9.4). RESULTS Of 57,119 ESLD hospitalizations, 6,615 had arrhythmias with higher odds with increasing age, males, jaundice, hepatorenal syndrome, alcohol use, and cardiopulmonary disorders. The most common arrhythmias were atrial fibrillation, cardiac arrest/asystole, and ventricular tachycardia. After propensity-matching (arrhythmia: no-arrhythmia, 6,609:6,609), arrhythmias were associated with 200% higher mortality, 1.7-days longer stay, $32,880 higher cost, and higher rates of shock, respiratory and kidney failures. CONCLUSIONS Due to worse outcomes with arrhythmias, there is a need for better screening and follow-up of ESLD patients for dysrhythmias.
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28
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Higher odds of irritable bowel syndrome among hospitalized patients using cannabis: a propensity-matched analysis. Eur J Gastroenterol Hepatol 2019; 31:756-765. [PMID: 30807448 DOI: 10.1097/meg.0000000000001382] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The endogenous cannabinoid system modulates many brain-gut and gut-brain physiologic pathways, which are postulated to be dysfunctional in irritable bowel syndrome (IBS). Herein, we examine the relationship between cannabis use disorder (CUD) and having IBS. PATIENTS AND METHODS After selecting patients aged 18 years and above from the 2014 Nationwide Inpatient Survey, we used the International Classification of Diseases, 9th ed. codes to identify individuals with CUD, IBS, and the established risk factors for IBS. We then estimated the crude and adjusted odds ratios of having a diagnosis of IBS with CUD and assessed for the interactions of CUD with other risk factors (SAS 9.4). We confirmed our findings in two ways: conducting a similar analysis on a previous Nationwide Inpatient Survey data (2012); and using a greedy algorithm to design a propensity-scored case-control (1 : 10) study, approximating a pseudorandomized clinical trial. RESULTS Out of 4 709 043 patients evaluated, 0.03% had a primary admission for IBS and 1.32% had CUD. CUD was associated with increased odds of IBS [adjusted odds ratio: 2.03; 95% confidence interval (CI): 1.53-2.71]. CUD was related to higher odds for IBS among males compared with females (3.48; 1.98-6.12 vs. 1.48; 0.88-2.50), and Hispanics and Caucasians compared with Blacks (5.28; 1.77-15.76, 1.80; 1.02-3.18 vs. 1.80; 0.65-5.03). On propensity-matching, CUD was associated with 80% increased odds for IBS (1.82; 1.27-2.60). CONCLUSION Our findings suggest that CUD is significantly associated with IBS among the general population. Males, Caucasians, and Hispanics might be more impacted by CUD associated IBS. Additional biomedical studies are required to elucidate this relationship.
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Adejumo AC, Adejumo KL, Adegbala OM, Chinedozi I, Ndansi J, Akanbi O, Onyeakusi NE, Ogundipe OA, Bob-Manuel T, Adeboye A. Protein-Energy Malnutrition and Outcomes of Hospitalizations for Heart Failure in the USA. Am J Cardiol 2019; 123:929-935. [PMID: 30612726 DOI: 10.1016/j.amjcard.2018.12.014] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 12/03/2018] [Accepted: 12/07/2018] [Indexed: 01/01/2023]
Abstract
Chronically elevated cytokines from un-abating low-grade inflammation in heart failure (HF) results in Protein-Energy Malnutrition (PEM). However, the impact of PEM on clinical outcomes of admissions for HF exacerbations has not been evaluated in a national data. From the 2012 to 2014 Nationwide Inpatient Sample (NIS) patient's discharge records for primary HF admissions, we identified patients with concomitant PEM, and their demographic and comorbid factors. We propensity-matched PEM cohorts (32,771) to no-PEM controls (1:1) using a greedy algorithm-based methodology and estimated the effect of different clinical outcomes (SAS 9.4). There were 32,771 (∼163,885) cases of PEM among the 541,679 (∼2,708,395) primary admissions for HF between 2012 and 2014 in the US. PEM cases were older (PEM:76 vs no-PEM:72 years), Whites (70.75% vs 67.30%), and had higher comorbid burden, with Deyo-comorbidity index >3 (31.61% vs 26.30%). However, PEM cases had lower rates of obesity, hyperlipidemia and diabetes. After propensity-matching, PEM was associated with higher mortality (AOR:2.48 [2.31 to 2.66]), cardiogenic shock (3.11[2.79 to 3.46]), cardiac arrest (2.30[1.96 to 2.70]), acute kidney failure (1.49[1.44 to 1.54]), acute respiratory failure (1.57[1.51 to 1.64]), mechanical ventilation (2.72[2.50 to 2.97]). PEM also resulted in higher non-routine discharges (2.24[2.17 to 2.31]), hospital cost ($80,534[78,496 to 82,625] vs $43,226[42,376 to 44,093]) and longer duration of admission (8.6[8.5 to 8.7] vs 5.3[5.2 to 5.3] days). In conclusion, PEM is a prevailing comorbidity among hospitalized HF subjects, and results in devastating health outcomes. Early identification and prevention of PEM in HF subjects during clinic visits and prompt treatment of PEM both in the clinic and during hospitalization are essential to decrease the excess burden of PEM.
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Affiliation(s)
- Adeyinka Charles Adejumo
- Department of Medicine, North Shore Medical Center, Salem, Massachusetts; Department of Medicine, Tufts University Medical School, Boston, Massachusetts; School of Public Health, University of Massachusetts Lowell, Lowell, Massachusetts.
| | | | | | | | - Jordan Ndansi
- Department of Biochemistry, University of Massachusetts Amherst, Amherst, Massachusetts
| | - Olalekan Akanbi
- University of Kentucky College of Medicine, Division of Hospital Medicine, Lexington, Kentucky
| | | | | | | | - Adedayo Adeboye
- Associate Professor of Medicine, WJB Dorn VAMC Heart and Vascular Institute/USC School of Medicine, Columbia, South Carolina
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30
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Adejumo AC, Akanbi O, Adejumo KL, Bukong TN. Reduced Risk of Alcohol-Induced Pancreatitis With Cannabis Use. Alcohol Clin Exp Res 2018; 43:277-286. [DOI: 10.1111/acer.13929] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 11/13/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Adeyinka Charles Adejumo
- Department of Medicine ; North Shore Medical Center; Salem Massachusetts
- Department of Medicine ; University of Massachusetts Medical School; Worcester Massachusetts
- School of Public Health ; University of Massachusetts Lowell; Lowell Massachusetts
| | - Olalekan Akanbi
- Division of Hospital Medicine ; University of Kentucky College of Medicine; Lexington Kentucky
| | | | - Terence Ndonyi Bukong
- Department of Medicine ; University of Massachusetts Medical School; Worcester Massachusetts
- INRS-Institut Armand-Frappier ; Institut National de la Recherche Scientifique; Laval Québec Canada
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31
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Andrews CN, Devlin SM, Le Foll B, Fischer B, Tse F, Storr M, Congly SE. Canadian Association of Gastroenterology Position Statement: Use of Cannabis in Gastroenterological and Hepatic Disorders. J Can Assoc Gastroenterol 2018; 2:37-43. [PMID: 31294362 PMCID: PMC6507278 DOI: 10.1093/jcag/gwy064] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 10/17/2018] [Indexed: 12/19/2022] Open
Affiliation(s)
- Christopher N Andrews
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Correspondence: Christopher N Andrews, MD, MSc, FRCPC, Clinical Professor, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, 6th Floor, TRW Building, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada. E-mail
| | - Shane M Devlin
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Bernard Le Foll
- Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Acute Care Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Departments of Family and Community Medicine, Pharmacology and Toxicology, Psychiatry, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Benedikt Fischer
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Frances Tse
- Department of Gastroenterology and Hepatology, McMaster University, Hamilton, Ontario, Canada
| | - Martin Storr
- Department of Medicine, University of Munich and Center of Endoscopy, Starnberg, Germany
| | - Stephen E Congly
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Wijarnpreecha K, Panjawatanan P, Ungprasert P. Use of cannabis and risk of advanced liver fibrosis in patients with chronic hepatitis C virus infection: A systematic review and meta-analysis. J Evid Based Med 2018; 11:272-277. [PMID: 30398032 DOI: 10.1111/jebm.12317] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Accepted: 10/10/2018] [Indexed: 01/11/2023]
Abstract
OBJECTIVES Chronic hepatitis C virus (HCV) infection is one of the most common chronic liver diseases. Several risk factors for the progression of liver fibrosis among these patients have been identified. Use of cannabis could be another risk factor, but the results from epidemiological studies remain inconclusive. METHODS Comprehensive literature review was conducted using MEDLINE and EMBASE databases through December 2017 to identify studies that compared the risk of advanced liver fibrosis among HCV-infected patients who use and who do not use cannabis. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS A total of three cohort studies with 898 participants met the eligibility criteria and were included in the meta-analysis. The risk of advanced liver fibrosis among HCV-infected patients who use cannabis was numerically higher than those who do not use cannabis, although the result did not achieve statistical significance (pooled odds ratio, 1.77; 95% confidence interval, 0.78-4.02). The statistical heterogeneity was high with an I2 of 75%. CONCLUSIONS This meta-analysis showed that the risk of advanced liver fibrosis among HCV-infected patients who use cannabis was higher than those who do not use cannabis, but the result was not statistically significant. Further studies are required to better characterize the risk.
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Affiliation(s)
- Karn Wijarnpreecha
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, Florida
| | | | - Patompong Ungprasert
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Abstract
The recent legalization of recreational marijuana use in some parts of the world, the discovery of new indications for the clinical application of cannabis, and the acceptance of the use of cannabis in practice has been paralleled by extensive research on the active components of cannabis and the endocannabinoid system within the human body. In this review, we evaluate the available evidence on cannabis and its constituents and the application of this evidence in clinical practice, focusing particularly on the liver and liver diseases. Constituents of cannabis, such as cannabidiol and Δ-tetrahydrocannabinol, have shown anti-inflammatory, antioxidant, and hepatoprotective effects both in in vitro and clinical studies, and appear to have potential in the symptom management and treatment of various liver diseases that were previously considered difficult to manage conservatively. In addition, the manipulation of the inherent endocannabinoid response system has found favor in many clinical fields and has generated considerable research and clinical interest. Moreover, evidence with regard to the adverse effects of marijuana use in liver diseases is weak, which has led to raise a question on the prior rules, with regard to a denial of liver transplantation to marijuana users. All in all, the recent trends in research, clinical experiences, as well as the legislature, has opened up new avenues towards the widespread clinical application of cannabis and its derivatives as well as modifiers of the components of the endocannabinoid system. More research is required to fully exploit these new evidences.
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Reduced Incidence and Better Liver Disease Outcomes among Chronic HCV Infected Patients Who Consume Cannabis. Can J Gastroenterol Hepatol 2018; 2018:9430953. [PMID: 30345261 PMCID: PMC6174743 DOI: 10.1155/2018/9430953] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 08/13/2018] [Accepted: 08/29/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIM The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals. METHODS We analyzed hospital discharge records of adults (age ≥ 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to nonusers on 1:1 ratio (4,728:4,728), using a propensity-based matching system, with a stringent algorithm. We then used conditional regression models with generalized estimating equations to measure the adjusted prevalence rate ratio (aPRR) for having liver cirrhosis (and its complications), carcinoma, mortality, discharge disposition, and the adjusted mean ratio (aMR) of total hospital cost and length of stay (LOS) [SAS 9.4]. RESULTS Our study revealed that cannabis users (CUs) had decreased prevalence of liver cirrhosis (aPRR: 0.81[0.72-0.91]), unfavorable discharge disposition (0.87[0.78-0.96]), and lower total health care cost ($39,642[36,220-43,387] versus $45,566[$42,244-$49,150]), compared to noncannabis users (NCUs). However, there was no difference among CUs and NCUs on the incidence of liver carcinoma (0.79[0.55-1.13]), in-hospital mortality (0.84[0.60-1.17]), and LOS (5.58[5.10-6.09] versus 5.66[5.25-6.01]). Among CUs, dependent cannabis use was associated with lower prevalence of liver cirrhosis, compared to nondependent use (0.62[0.41-0.93]). CONCLUSIONS Our findings suggest that cannabis use is associated with decreased incidence of liver cirrhosis, but no change in mortality nor LOS among HCV patients. These novel observations warrant further molecular mechanistic studies.
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