The marijuana plant Cannabis sp. and its derivatives and analogues, known as cannabinoids (CBs), induce many effects throughout the whole body.
Herein we briefly review the gastrointestinal (GI) pharmacology of CBs, with special focus on motor function. Some drugs are available to treat nausea and emesis, and evidences in humans and animal models suggest that other GI motility alterations (gastro-oesophageal reflux, inflammatory bowel conditions or paralytic ileus) might benefit from modifications of the CB tone throughout the gut.
Cannabinoids Reduce Gastrointestinal Motor Function
CB Effects on Altered GI Motility
CB1 receptors are located on nerve fibres and synapses throughout the gut wall, but with the highest density in the myenteric and submucosal plexuses of the enteric nervous system . In contrast, CB2 receptors are less frequent but are overexpressed under inflammatory conditions . Additional receptors upon which the CBs and related lipids might exert different GI effects are transient receptor potential vanilloid 1 (TRPV1), peroxisome proliferator-activated receptor α, GRP55 or GRP119
CBs in the gut mediate gastroprotection and modulate gastric secretion, GI motility, ion transport, visceral sensation and cell proliferation , as well as other effects in the oral cavity, including modifications in salivation . In addition, evidence is emerging that exogenous and endogenous CBs have an important role in GI physiopathology, such as GI inflammation
In agreement with the effects traditionally recognized for the CBs in the GI tract, early reports showed that THC reduced faecal bolus counts in open-field experiments  and decreased intestinal transit
The CB antipropulsive actions are likely the result from a reduction of peristalsis throughout the gut
Nausea, as well as delayed and anticipatory vomiting associated with chemotherapy, is not well controlled with the current anti-emetic medication, and CBs have been proposed as an attractive alternative.
Different CBs (THC and nabilone, its synthetic analogue) and CB extracts (containing both THC and CBD) have proved to be effective anti-emetics in humans [39,40]. Moreover, CBs exert antinauseant effects
As mentioned above, Cannabis has been empirically used for centuries to treat diarrhoeas.
From the existing data (obtained in vivo both in humans and in animal models, as well as from isolated GI preparations), it is clear that CBs profoundly alter GI motor function and that this, mediated via different mechanisms of action, may be therapeutically exploited
Cannabis has been used to treat gastrointestinal (GI) conditions that range from enteric infections and inflammatory conditions to disorders of motility, emesis and abdominal pain
The mechanistic basis of these treatments emerged after the discovery of Delta(9)-tetrahydrocannabinol as the major constituent of Cannabis. Further progress was made when the receptors for Delta(9)-tetrahydrocannabinol were identified as part of an endocannabinoid system, that consists of specific cannabinoid receptors, endogenous ligands and their biosynthetic and degradative enzymes
Anatomical, physiological and pharmacological studies have shown that the endocannabinoid system is widely distributed throughout the gut, with regional variation and organ-specific actions.
It is involved in the regulation of
- food intake,
- nausea and emesis,
- gastric secretion and
- GI motility,
- ion transport,
- visceral sensation,
- intestinal inflammation and
- cell proliferation in the gut.
Cellular targets have been defined that include the enteric nervous system, epithelial and immune cells.
Molecular targets of the endocannabinoid system include, in addition to the cannabinoid receptors,
- transient receptor potential vanilloid 1 receptors,
- peroxisome proliferator-activated receptor alpha receptors and
- the orphan G-protein coupled receptors, GPR55 and GPR119.
Pharmacological agents that act on these targets have been shown in preclinical models to have therapeutic potential.
Here, we discuss cannabinoid receptors and their localization in the gut, the proteins involved in endocannabinoid synthesis and degradation and the presence of endocannabinoids in the gut in health and disease. We focus on the pharmacological actions of cannabinoids in relation to GI disorders, highlighting recent data on genetic mutations in the endocannabinoid system in GI disease.