Considerable evidence demonstrates that manipulation of the
endocannabinoid system regulates
nausea and
vomiting in humans and other animals. The
anti-emetic effect of
cannabinoids has been shown across a wide variety of animals that are capable of
vomiting in response to a toxic challenge. CB(1) agonism suppresses
vomiting, which is reversed by CB(1) antagonism, and CB(1) inverse agonism promotes
vomiting. Recently, evidence from animal experiments suggests that
cannabinoids may be especially useful in treating the more difficult to control symptoms of
nausea and anticipatory
nausea in
chemotherapy patients, which are less well controlled by the currently available conventional
pharmaceutical agents. Although rats and mice are incapable of
vomiting, they display a distinctive conditioned gaping response when re-exposed to cues (flavours or contexts) paired with a nauseating treatment.
Cannabinoid agonists (Δ(9) -THC, HU-210) and the
fatty acid amide hydrolase (FAAH) inhibitor,
URB-597, suppress conditioned gaping reactions (
nausea) in rats as they suppress
vomiting in
emetic species. Inverse agonists, but not neutral antagonists, of the CB(1) receptor promote
nausea, and at subthreshold doses potentiate
nausea produced by other toxins (LiCl). The primary non-psychoactive compound in cannabis,
cannabidiol (CBD), also suppresses
nausea and
vomiting within a limited dose range. The anti-
nausea/
anti-emetic effects of CBD may be mediated by indirect activation of somatodendritic 5-HT(1A) receptors in the dorsal raphe nucleus; activation of these
autoreceptors reduces the release of
5-HT in terminal forebrain regions. Preclinical research indicates that cannabinioids, including CBD, may be effective clinically for treating both
nausea and
vomiting produced by
chemotherapy or other therapeutic treatments.