Review highlights cannabinoids’ therapeutic potential in gastrointestinal dysfunction

Writing in the International Journal of Molecular Sciences​, the tesearchers highlighted the significant role of the compounds in regulating GIT peristalsis (muscle contractions in the digestive tract) and intestinal barrier permeability. Pre-clinical data suggests cannabinoids can inhibit and stimulate gut peristalsis. The authors also underlined the important interaction between endocannabinoids and the TRPV1 system.

Phytocannabinoids like THC and CBD impact gut motility mainly through the CB1 receptor. The study reported how they improved intestinal barrier integrity—not just through CB1 stimulation but also through protein kinase A (PKA), mitogen-associated protein kinase (MAPK) and adenylyl cyclase signaling pathways.

The authors acknowledged cannabinoids’ therapeutic promise as anti-inflammatory agents, offering potential benefits in the treatment of Crohn’s disease, ulcerative colitis and IBD.

“Their role in modulating intestinal motility and relieving pain implicates cannabinoids as potential agents for improving quality of life in gastrointestinal disorders, especially chronic disorders such as IBS,” they wrote.

Potential therapeutic effects ​

The endocannabinoid system (ECS) regulates the levels and activity of most other neurotransmitters in the body, mainly gamma aminobutyric acid (GABA) and glutamate. It affects the digestive system by regulating peristaltic movements and intestinal barrier permeability.

Researchers have extensively studied endocannabinoids for their effects on GI motility. Phytocannabinoids like THC, CBD, CBC and CBN have also attracted interest for their potential therapeutic effects on GI contractility disorders.

The researchers noted that both ex vivo​ and in vivo​ studies have explored their roles in modulating contractile responses​, neurotransmitter release and receptor interactions, particularly through cannabinoid receptors CB1 and CB2.

Endocannabinoids and endocannabinoid-like compounds seem to mainly inhibit GIT contractility (but several studies have shown the opposite).

Most studies show activity around CB1 and TRPV1 receptors for these compounds. Yet some research has shown endocannabinoids influence GIT motility through pathways researchers could not fully classify. A few research papers have linked GIT endocannabinoid dysregulation to pathological states of the intestine, though the relationship is not yet clear.

Overall, phytocannabinoids show a strong ability to inhibit spontaneous and induced GIT contractions. This looks to be mediated through CB1.

Impact on the intestine ​

The endocannabinoid system has an important role in modulating intestinal permeability. In rats, centrally administered oxytocin has shown to decrease LPS-induced intestinal hyperpermeability, partly through CB1 signaling​. Changes in intestinal permeability associated with cellular senescence have been linked to reduced cellular CB1 expression​.

The authors noted that the effect of endocannabinoids on intestinal permeability varies widely depending on the compound used and whether it is applied directly onto or below the Caco-2 monolayer. The impact on permeability is mainly achieved through CB1 and TRPV1 but also PPARα activation. Endocannabinoids also caused changes in the synthesis of certain cellular membrane proteins, which play a part in intestinal barrier integrity.

Phytocannabinoids like THC and CBD can improve intestinal barrier integrity. They also cause changes in synthesis of proteins involved in paracellular transport and the intestinal barrier.

The authors noted the complex interaction between cannabinoids and gastrointestinal physiology, while shining a spotlight on potential therapeutic applications.

They highlighted the fact that cannabinoids like THC and CBD show receptor-specific effects on GIT motility through CB1 receptors, causing muscle contractility inhibition, “which may suggest targets for therapeutic interventions.” Also, the involvement of CB1 and CB2 receptors in regulating intestinal permeability underscores the complex mechanisms mediated by cannabinoids in gastrointestinal health.

Source: Int. J. Mol. Sci.​ 2024​, 25​(12), 6682

doi: 10.3390/ijms25126682​

"Effects of Cannabinoids on Intestinal Motility, Barrier Permeability, and Therapeutic Potential in Gastrointestinal Diseases"

Authors: Crowley, K., Kiraga, Ł., Miszczuk, E., Skiba, S., Banach, J., Latek, U., Mendel, M. and Chłopecka, M.