PMID- 31826058
OWN - NLM
STAT- MEDLINE
DCOM- 20200616
LR  - 20200616
IS  - 1842-1121 (Electronic)
IS  - 1841-8724 (Linking)
VI  - 28
IP  - 4
DP  - 2019 Dec 9
TI  - Gastrointestinal Adverse Events of Cannabinoid 1 Receptor Inverse Agonists 
      suggest their Potential Use in Irritable Bowel Syndrome with Constipation: A 
      Systematic Review and Meta-Analysis.
PG  - 473-481
LID - 10.15403/jgld-265 [doi]
AB  - BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is one of the most common 
      functional gastrointestinal (GI) disorders characterized by pain and impaired 
      bowel movements. Currently available drugs show limited efficacy. Cannabinoid 1 
      receptor (CB1) inverse agonists (CB1-RAN) cause diarrhea and may be candidates 
      for the treatment of constipation-predominant IBS (IBS-C). We evaluated the 
      effects of CB1-RAN in clinical trials for their potential use in IBS-C. METHODS: 
      Database search identified all clinical trials published up to May 2018 that 
      reported rimonabant and taranabant treatment for at least one month and detailed 
      the GI adverse events (AEs). Categorical outcomes (subgroups of AEs) were 
      analyzed using the odds ratio (OR). RESULTS: Eighteen trials met the inclusion 
      criteria. Rimonabant 20 mg produced significantly more overall AEs (OR=1.35, CI: 
      1.19-1.52, p<0.0001), psychiatric events (OR=1.79, CI: 1.46-2.21, p<0.001) and GI 
      AEs (OR=2.05, CI: 1.65-2.55, p<0.001) compared to placebo. Taranabant at doses 
      ranging from 0.5 to 8 mg produced significantly more overall AEs (OR=1.36, CI: 
      1.13-1.64, p<0.002), psychiatric AEs (1.82, CI: 1.54-2.16, p<0.001) and GI AEs 
      (OR=1.75, CI: 1.29-2.37, p<0.001) compared to placebo. CONCLUSIONS: The approach 
      to target CB1 in the gut for the treatment of IBS-C or chronic constipation seems 
      a promising therapeutic option. Prospective clinical trials on the possible 
      targeting of CB1 and the endocannabinoid system are warranted.
FAU - Fabisiak, Adam
AU  - Fabisiak A
AD  - Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 
      Lodz, Poland; Department of Digestive Tract Diseases, Faculty of Medicine, 
      Medical University of Lodz, Lodz, Poland. . adam.fabisiak@umed.lodz.pl.
FAU - Wlodarczyk, Marcin
AU  - Wlodarczyk M
AD  - Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 
      Lodz, Poland; Department of General and Colorectal Surgery, Faculty of Military 
      Medicine, Medical University of Lodz, Poland. dr.mwlodarczyk@gmail.com.
FAU - Fabisiak, Natalia
AU  - Fabisiak N
AD  - Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 
      Lodz, Poland; Department of Gastroenterology, Faculty of Military Medicine, 
      Medical University of Lodz, Poland. nat.fabisiak@gmail.com.
FAU - Storr, Martin
AU  - Storr M
AD  - Center of Endoscopy, Starnberg, Germany; Department of Medicine II, Ludwig 
      Maximilians University of Munich, Germany. gidoc@gmx.com.
FAU - Fichna, Jakub
AU  - Fichna J
AD  - Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 
      Lodz, Poland. jakub.fichna@umed.lodz.pl.
LA  - eng
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20191209
PL  - Romania
TA  - J Gastrointestin Liver Dis
JT  - Journal of gastrointestinal and liver diseases : JGLD
JID - 101272825
RN  - 0 (Amides)
RN  - 0 (Cannabinoid Receptor Antagonists)
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Pyridines)
RN  - RML78EN3XE (Rimonabant)
RN  - X9U622S114 
      (N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide)
SB  - IM
MH  - Amides/adverse effects/therapeutic use
MH  - Cannabinoid Receptor Antagonists/adverse effects/*therapeutic use
MH  - Constipation/*drug therapy
MH  - Gastrointestinal Agents/adverse effects/*therapeutic use
MH  - Gastrointestinal Diseases/chemically induced
MH  - Humans
MH  - Irritable Bowel Syndrome/*drug therapy
MH  - Mental Disorders/chemically induced
MH  - Pyridines/adverse effects/therapeutic use
MH  - Rimonabant/adverse effects/therapeutic use
EDAT- 2019/12/12 06:00
MHDA- 2020/06/17 06:00
CRDT- 2019/12/12 06:00
PHST- 2019/07/10 00:00 [received]
PHST- 2019/11/10 00:00 [accepted]
PHST- 2019/12/12 06:00 [entrez]
PHST- 2019/12/12 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
AID - 10.15403/jgld-265 [doi]
PST - epublish
SO  - J Gastrointestin Liver Dis. 2019 Dec 9;28(4):473-481. doi: 10.15403/jgld-265.