Table 1.
The effect of cannabinoids in experimental models of inflammatory intestinal diseases.
| Source of Study | Cannabinoid Receptors | Endocannabinoids | Changes in Endocannabinoid Synthesis | Changes in Endocannabinoid Degradation | Methods of Analysis | Effects | References |
|---|---|---|---|---|---|---|---|
| Human intestinal biopsies of CD | CB1, GPR55, GPR119 decreased; PPARδ, TRPV1 increased | OEA elevated | DAGL-α increased | FAAH, NAAA increased | mRNA levels | Correlates with disease severity | [20] |
| Human intestinal biopsies of UC | CB1, CB2, GPR119, PPARα, PPARγ, GPR18, GPR55 decreased; PPARδ, TRPV1 increased | AEA, OEA, and 2-AG elevated | NAPE-PLD decreased | FAAH decreased | mRNA levels | Correlates with disease severity | [20] |
| Human colonic biopsies of UC. Acute mild/moderate colitis |
Increased CB2 | - | DAGLα increased, NAPE-PLD decreased | FAAH, MAGL increased | Western blot and immunohistochemistry | CB2 signaling reduces colitis-associated inflammation | [89] |
| Human colonic biopsies of UC Quiescent pancolitis | CB1, CB2 decreased | - | DAGLα decreased, NAPE-PLD elevated | FAAH decreased | Western blot and immunohistochemistry | CB2 signaling reduces colitis-associated inflammation | [89] |
| DNBS, TNBS colitis, human UC biopsies | CB1/CB2 increased | AEA elevated | - | FAAH increased | Chromatography/mass spectrometry | Anti-inflammatory action | [133] |
| DNBS-induced colitis in mice | Increased CB1 expression, and CB1 stimulation | Treatment with CB1 agonist HU210 | - | FAAH experimental genetic ablation | mRNA levels | Alleviates intestinal inflammation | [135] |
| DNBS-induced colitis in mice | TRPV1 and GPR55 downregulation | Increased PEA | NAPE-PLD not changed | NAAA, FAAH not changed | Immunohistochemistry, mRNA, liquid chromatography, and mass spectrometry | Decreased intestinal permeability | [157] |
| DNBS experimental colitis | CB2 stimulation | CBG treatment | - | - | mRNA levels | Anti-inflammatory effect | [166] |
| TNBS-induced colitis in mice | CB2 increased | Addition of CB2 agonists JWH133, AM1241 | - | - | mRNA levels | Protects against inflammation | [136] |
| TNBS- and DSS-induced colitis in mice | Increased PPAR-α | AEA increased; PEA treatment | - | Inhibition of NAAA | HPLC-mass spectrometry, mRNA | Reduction of inflammation | [153] |
| Mustard oil and DSS-induced colitis in mice | CB2 increased expression (higher in mustard oil colitis than in DSS-induced colitis) | CB1, CB2 stimulation with arachidonoyl-chloro-ethanolamide and JWH-133 | - | - | Immunohistochemistry (protein levels) | Alleviates intestinal inflammation | [137] |
| DSS and TNBS-induced colitis in. mice | - | - | - | FAAH inhibition | mRNA levels | Protective on colonic mucosa | [138] |
| DSS-induced colitis in mice | CB1 increased expression | Addition of CB receptor agonists WIN 55,212-2 | - | - | Protein levels | Protective effect on colonic mucosa | [139] |
| TNBS-induced colitis, DSS-induced colitis | - | Addition of AEA | - | Inhibition of FAAH | Microarray analysis, miRNA expression, liquid chromatography/mass spectrometry | Decreased macro- and microscopic signs of colitis | [164,165] |
| TNBS-induced colitis in rats | Inhibition of GPR55, activation of PPAR-γ, TRPV1 | THC, CBD | - | Inhibition of FAAH | - | Anti-inflammatory | [167] |
| Croton oil-induced ileitis in mice | CB1 increased expression | No significant change in AEA and 2-AG levels. Addition of CB receptor agonist CP 55,940 and CBN |
- | - | HPLC, protein levels | Reduced intestinal motility | [124] |
| LPS-induced intestinal propulsions | CB2 induction | CB2 induction by JWH-133 | - | - | - | Reduced transit time | [141] |
| LPS-induced colitis and intestinal biopsies from patients with UC | PPAR-γ activation | CBD treatment | - | - | - | Anti-inflammatory, decreased reactive gliosis | [162] |
| Caco-2 CRC cells | OEA acts on TRPV1 and PEA acts on PPAR-α receptor signaling | OEA and PEA treatment | - | Inhibition of FAAH | Liquid chromatography-mass spectrometry | Increased transepithelial electrical resistance and decreased intercellular permeability | [116] |
| Caco-2 CRC cells | CB1 activation | 2-AG treatment | - | Inhibition of FAAH | Liquid chromatography-mass spectrometry | Increased intestinal permeability under inflammation and hypoxia | [163] |
| Human tissue biopsies of IBD patients, HCT-116, HT-29, and Caco-2 CRC cell lines | GPR55 stimulation | High-THCA cannabis extract | - | - | mRNA levels | Anti-inflammatory effect | [34] |
| Human intestinal biopsies from normal mucosa, intestinal adenomas, colorectal carcinomas, CRC cell lines | CB1 and CB2 stimulation | 2-AG, AEA are 2- and 3-fold higher in adenomas and carcinomas | - | Increased FAAH in CRC | Liquid chromatography/mass spectrometry, mRNA levels, western blotting | Anti-cancer effect | [15] |