Parker LA, Rock EM, Limebeer CL.
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