Therapeutic Effects of Cannabinoids on Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Authors

  • Rajesh Kumar Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Patna, Bihar 801507, India.
  • Shruti Singh Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Patna, Bihar 801507, India.
  • Vikas Maharshi Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Patna, Bihar 801507, India.

DOI:

https://doi.org/10.31584/jhsmr.20241041

Keywords:

cannabinoids, disease activity score, endoscopic score, QOL, ulcerative colitis

Abstract

ObjectiveThis study aimed to perform a meta-analysis to ascertain the efficacy and safety of Cannabis in treating ulcerative colitis (UC).
Material and MethodsA meta-analysis of randomized controlled trials (RCTs) included in three databases (PubMed, Google Scholar and Science Direct) was performed; from inception till 31st July 2023, so as to ascertain the efficacy and safety of Cannabis in UC. Primary outcomes included: disease activity and endoscopic indices, and quality of life (QOL). The risk of bias in the studies was assessed via the RoB2 tool.
ResultsIn total 1,928 records identified; of which four were eligible for inclusion. The risk of bias in the included studies was moderate. The patients were randomized to the cannabinoid group had significantly improved disease activity indices (standardized mean difference (SMD) -1.78; 95% confidence interval (CI) (-2.89 to 0.67); I2=74%) and QOL (SMD -1.70; 95% CI (0.24 to 3.17); I2=75%) than those in the placebo group. However, cannabinoids did not have a significant impact on endoscopic indices (SMD -0.40; 95% CI (-0.92 to 0.11); I2=0%) nor C-reactive protein (CRP) levels (SMD -0.49; 95% CI (-0.87 to 1.85); I2=85%) of UC patients.
ConclusionCannabinoids show potential in improving disease activity and QOL; however, their impact on endoscopic indices and CRP levels remains inconclusive.

References

Baumgart D, Baumgart DC. Crohn’s disease and ulcerative colitis. New York: Springer; 2017.

Ng SC , Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol, EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017;390:2769–78.

Sýkora J, Pomahačová R, Kreslová M, Cvalínová D, Štych P, Schwarz J. Current global trends in the incidence of pediatriconset inflammatory bowel disease. World J Gastroenterol 2018;24:2741-63.

Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet Lond Engl 2012;380:1606–19.

Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol 2014;20:91–9.

Maaser C, Sturm A, Vavricka SR, Kucharzik T, Fiorino G, Annese V, et al. ECCO-ESGAR Guideline for diagnostic assessment in IBD part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis 2019;13:144–64.

Sturm A, Maaser C, Calabrese E, Annese V, Fiorino G, Kucharzik T, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 2: IBD scores and general principles and technical aspects. J Crohns Colitis 2019;13:273–84.

Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021;160:1570–83.

Park S, Abdi T, Gentry M, Laine L. histological disease activity as a predictor of clinical relapse among patients with ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol 2016;111:1692–701.

Zaami S, Di Luca A, Di Luca NM, Vergallo GM. Medical use of cannabis: Italian and European legislation. Eur Rev Med Pharmacol Sci 2018;22:1161–7.

Raad MA, Chams NH, Sharara AI. New and evolving immunotherapy in inflammatory bowel disease. Inflamm Intest Dis 2016;1:85–95.

Vernia F, Valvano M, Longo S, Cesaro N, Viscido A, Latella G. Vitamin D in inflammatory bowel diseases. Mechanisms of action and therapeutic implications. Nutrients 2022;14:269.

Zhao Z, Xu S, Zhang W, Wu D, Yang G. Probiotic Escherichia coli NISSLE 1917 for inflammatory bowel disease applications. Food Funct 2022;13:5914–24.

Burri E, Maillard MH, Schoepfer AM, Seibold F, Assche GV, Rivière P, et al. Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update. Digestion 2020;101(Suppl 1):2–15.

Pithadia AB, Jain S. Treatment of inflammatory bowel disease (IBD). Pharmacol Rep 2011;63:629–42.

Halpin SJ, Ford AC. Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2012;107:1474.

Johnston LD, Miech RA, O’Malley PM, Bachman JG, Schulenberg JE, Patrick ME, et al. Monitoring the future national survey results on drug use, 1975-2017: overview, key findings on adolescent drug use. Ann Arbor: University of Michigan; 2018.

Buckley MC, Kumar A, Swaminath A. Inflammatory bowel disease and cannabis: a practical approach for clinicians. Adv Ther 2021;38:4152-61.

Weiss A, Friedenberg F. Patterns of cannabis use in patients with inflammatory bowel disease: a population-based analysis. Drug Alcohol Depend 2015;156:84–89.

Wynne J, Kozuch P. Medical marijuana for inflammatory bowel disease: The highs and lows. Scand J Gastroenterol 2022;57:197–205.

Capasso R, Borrelli F, Aviello G, Romano B, Scalisi C, Capasso F, et al. Cannabidiol, extracted from cannabis sativa, selectively inhibits inflammatory hypermotility in mice: cannabidiol and intestinal motility. Br J Pharmacol 2008;154:1001–8.

Alhouayek M, Muccioli GG. The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends Mol Med 2012;18:615–25.

Esfandyari T, Camilleri M, Busciglio I, Burton D, Baxter K, Zinsmeister AR. Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study. Am J Physiol Gastrointest Liver Physiol 2007;293:G137–45.

Hong S, Fan J, Kemmerer ES, Evans S, Li Y, Wiley JW. Reciprocal changes in vanilloid (TRPV1) and endocannabinoid (CB1) receptors contribute to visceral hyperalgesia in the water avoidance stressed rat. Gut 2009;58:202–10.

Li L, Xuan Y, Zhu B, Wang X, Tian X, Zhao L, et al. Protective effects of cannabidiol on chemotherapy-induced oral mucositis via the Nrf2/Keap1/ARE signaling pathways. Oxid Med Cell Longev 2022;2022:4619760. doi: 10.1155/2022/4619760.

Klein M, de Quadros De Bortolli J, Guimarães FS, Salum FG, Cherubini K, de Figueiredo MAZ. Effects of cannabidiol, a cannabis sativa constituent, on the oral wound healing process in rats: clinical and histological evaluation: cannabidiol in oral ulcers. Phytother Res 2018;32:2275–81.

Kafil TS, Nguyen TM, Macdonald JK, Chande, N. Cannabis for the treatment of Crohn’s disease. Cochrane Database Syst Rev 2018;11:CD012853.

Langhorst J, Wulfert H, Lauche R, Klose P, Cramer H, Dobos GJ, et al. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases. J Crohns Colitis 2015;9:86-106.

Doeve BH, van de Meeberg MM, van Schaik FDM, Fidder HH. A systematic review with meta analysis of the efficacy of cannabis and cannabinoids for inflammatory bowel disease: what can we learn from randomized and nonrandomized studies? J Clin Gastroenterol 2021;55:798-809. doi: 10.1097/MCG.0000000000001393.

Vinci A, Ingravalle F, Bardhi D, Cesaro N, Frassino S, Licata F, Valvano M. Cannabinoid therapeutic effects in inflammatory bowel diseases: a systematic review and meta-analysis of randomized controlled trials. Biomedicines 2022;10:2439. doi: 10.3390/biomedicines10102439.

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions [monograph on the Internet]. John Wiley & Sons; 2019 [cited 2023 Jan 15]. Available from: http://www.cochranelibrary.com

Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement [homepage on the Internet]. PRISMA; 2009 [cited 2023 Jan 15]. Available from: http://prismastatement.org/prismastatement/Checklist.aspx

Naftali T, Bar-Lev Schleider L, Scklerovsky Benjaminov F, Konikoff FM, Matalon ST, Ringel Y. Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: a randomized controlled trial. PLoS ONE 2021;16:e0246871.

Tartakover Matalon S, Azar S, Meiri D, Hadar R, Nemirovski A, Abu Jabal N, et al. Endocannabinoid levels in ulcerative colitis patients correlate with clinical parameters and are affected by cannabis consumption. Front Endocrinol 2021;12:685289. doi: 10.3389/fendo.2021.685289.

Naftali T, Bar Lev Schlieder L, Sklerovsky Benjaminov F, Lish I, Hirsch J, Konikoff FM. Cannabis induces clinical and endoscopic improvement in moderately active ulcerative colitis (UC). J Crohns Colitis 2018;12(Suppl 1):S306.

Irving PM, Iqbal T, Nwokolo C, Subramanian S, Bloom S, Prasad N. A randomized, double-blind, placebo-controlled, parallel-group, pilot study of cannabidiol-rich botanical extract in the symptomatic treatment of ulcerative colitis. Inflamm Bowel Dis 2018;24:714-23.

Couch DG, Maudslay H, Doleman B, Lund JN, O'Sullivan SE. The use of cannabinoids in colitis: a systematic review and meta-analysis. Inflamm Bowel Dis 2018;24:680–97.

Bacalia KMA, Tveter KM, Palmer H, Douyere J, Martinez S, Sui K, et al. Cannabidiol decreases intestinal inflammation in the ovariectomized murine model of postmenopause. Biomedicines 2022;11:74. doi: 10.3390/biomedicines11010074.

Moniruzzaman M, Rewatkar P, Begun J, Popat A. P037 Enhancing the efficacy of cannabidiol using protein nanoparticles to treat inflammatory bowel disease. J Crohns Colitis 2023;17:i204–5.

Di Marzo V, Piscitelli F. The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics 2015;12:692–98.

Esfandyari T, Camilleri M, Busciglio I, Burton D, Baxter K, Zinsmeister AR. Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study. Am J Physiol Gastrointest Liver Physiol 2007;293:G137-45.

Dalavaye N, Erridge S, Nicholas M, Pillai M, Bapir L, Holvey C, et al. The effect of medical cannabis in inflammatory bowel disease: analysis from the UK Medical Cannabis Registry. Expert Rev Gastroenterol Hepatol 2023;17:85-98. doi: 10.1080/17474124.2022.2161046.

Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol 2018;84;2477–82.

Downloads

Published

2024-09-06

How to Cite

1.
Kumar R, Singh S, Maharshi V. Therapeutic Effects of Cannabinoids on Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Health Sci Med Res [Internet]. 2024 Sep. 6 [cited 2024 Dec. 23];42(5):e20241041. Available from: https://he01.tci-thaijo.org/index.php/jhsmr/article/view/273624

Issue

Section

Original Article