Cannabinoids for gastrointestinal diseases: potential therapeutic applications

@article{Carlo2003CannabinoidsFG,
  title={Cannabinoids for gastrointestinal diseases: potential therapeutic applications},
  author={Giulia Di Carlo and Angelo A. Izzo},
  journal={Expert Opinion on Investigational Drugs},
  year={2003},
  volume={12},
  pages={39 - 49}
}
  • G. Carlo, A. Izzo
  • Published 1 January 2003
  • Medicine, Biology, Chemistry
  • Expert Opinion on Investigational Drugs
Δ9-Tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB1 and CB2 receptors. CB1 receptors have been detected on enteric nerves, and pharmacological effects of their activation include gastroprotection, reduction of gastric and intestinal motility and reduction of intestinal secretion. The digestive tract also contains endogenous cannabinoids (i.e., the… 
Cannabinoids and gastrointestinal motility: animal and human studies.
TLDR
Modulation of the gut endogenous cannabinoid system may provide a useful therapeutic target for disorders of gastrointestinal motility.
Cannabinoids and the gut: new developments and emerging concepts.
Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation
TLDR
Experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies.
GASTROINTESTINAL ENDOCANNABINOID SYSTEM: MULTIFACETED ROLES IN THE HEALTHY AND INFLAMED INTESTINE
  • S. Smid
  • Biology, Medicine
    Clinical and experimental pharmacology & physiology
  • 2008
1 The endogenous cannabinoid (endocannabinoid) system is emerging as a key modulator of intestinal physiology, influencing motility, secretion, epithelial integrity and immune function in the gut, in
Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation
TLDR
This review of the current knowledge of CB2 receptors in the gastrointestinal tract highlights its role in regulating abnormal motility, modulating intestinal inflammation and limiting visceral sensitivity and pain.
The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract
TLDR
An alternative and promising avenue for therapeutic applications resides in the treatment with CB1 receptor agonists that are unable to cross the blood–brain barrier, or with compounds that inhibit the degradation of endogenous ligands (endocannabinoids) of CB1 receptors, hence prolonging the activity of the endocannabinoid system.
Cannabis and endocannabinoid modulators: Therapeutic promises and challenges
The gastrointestinal pharmacology of cannabinoids: an update.
Recent Advances in Research and Therapeutic Application of Cannabinoids in Cancer Disease
TLDR
The present review shows that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues, and strongly support the idea that cannabinoids may induce benefical effect in cancer treatment.
Endocannabinoids and the gastrointestinal tract: what are the key questions?
  • G. Sanger
  • Medicine, Biology
    British journal of pharmacology
  • 2007
Cannabinoid (CB1) receptor activation acts neuronally, reducing GI motility, diarrhoea, pain, transient lower oesophageal sphincter relaxations (TLESRs) and emesis, and promoting eating. CB2 receptor
...
...

References

SHOWING 1-10 OF 91 REFERENCES
The endocannabinoid nervous system: unique opportunities for therapeutic intervention.
Molecular characterization of a peripheral receptor for cannabinoids
TLDR
The cloning of a receptor for cannabinoids is reported that is not expressed in the brain but rather in macrophages in the marginal zone of spleen, which helps clarify the non-psychoactive effects of cannabinoids.
Psychoactive cannabinoids reduce gastrointestinal propulsion and motility in rodents.
  • J. Shook, T. Burks
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1989
TLDR
Intravenous delta 9-tetrahydrocannabinol (delta 9-THC) slowed the rate of gastric emptying and small intestinal transit in mice and in rats, indicating a selectivity for the more proximal sections of the gut.
Cannabinoids and the gastrointestinal tract
TLDR
Findings that the CB1 selective antagonist/inverse agonist SR141716A produces in vivo and in vitro signs of increased motility of rodent small intestine probably reflect the presence in the enteric nervous system of a population of CB1 receptors that are precoupled to their effector mechanisms.
The neurobiology and evolution of cannabinoid signalling.
  • M. Elphick, M. Egertová
  • Biology
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 2001
TLDR
A model of cannabinoid signalling is presented in which anandamide is synthesized by postsynaptic cells and acts as a retrograde messenger molecule to modulate neurotransmitter release from presynaptic terminals, concluding that the cannabinoid signalling system may be quite restricted in its phylogenetic distribution.
Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret.
TLDR
CB1r mediates the anti-emetic action of cannabinoids in the dorsal vagal complex and is found in the myenteric plexus of the stomach and duodenum and a novel neuroregulatory system involved in the control of emesis.
Endocannabinoids as physiological regulators of colonic propulsion in mice.
TLDR
Endocannabinoids acting on myenteric CB1 receptors tonically inhibit colonic propulsion in mice, and high amounts of 2-arachidonylglycerol and particularly anandamide were found in the colon, together with a high activity of an andamide amidohydrolase.
Endocannabinoid structure-activity relationships for interaction at the cannabinoid receptors.
  • P. Reggio
  • Biology, Chemistry
    Prostaglandins, leukotrienes, and essential fatty acids
  • 2002
TLDR
This review considers cannabinoid receptor SAR developed to date for the endocannabinoids with emphasis upon the conformational implications forendocannabinoid recognition at the cannabinoid receptors.
Cannabinoid CB1‐receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation
TLDR
It is concluded that inflammation of the gut increases the potency of cannabinoid agonists possibly by ‘up‐regulating’ CB1 receptor expression; in addition, endocannabinoids, whose turnover is increased in inflamed gut, might tonically inhibit intestinal motility.
Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology.
TLDR
A more thorough characterization of the roles of endocannabinoids in health and disease will be necessary to define the significance ofendocannabinoid inactivation mechanisms as targets for therapeutic drugs.
...
...