3. Umbruch 4.4..2005 - Online Pot

190 L.A. Parker et al.
[27] indicated that, unlike other cannabinoids tested including ∆ 9 -THC, CBD
(10 and 20 mg/kg, ip) did not reverse retching and vomiting induced by the
endogenous cannabinoid, 2-AG, in the much smaller least shrew. It has also
been reported to be ineffective at inhibiting gastric motility in mice [71].
However, we had previously shown that CBD did prevent the establishment of
lithium-induced conditioned gaping in rats [38], a putative rat model of nausea
(reviewed below). We [31] found that ∆ 9 -THC produced a dose-dependent
suppression of lithium-induced vomiting with higher doses producing greater
suppression than lower doses. CBD, however, produced a biphasic effect with
lower doses (5 and 10 mg/kg, ip), producing suppression and higher doses (20
and 40 mg/kg) producing enhancement of lithium-induced vomiting. The
anti-emetic properties of CBD are of clinical relevance, because CBD does not
produce the psychomimetic effects that are produced by ∆ 9 -THC. The suppression
of lithium-induced vomiting by ∆ 9 -THC, but not by CBD, was
reversed by pretreatment with SR-141716, confirming previous findings that
CBD does not act at the CB 1 receptor [61].
Cannabinoid and serotonin systems interact centrally and both systems are
involved in the control of emesis. There have been no studies with humans that
have systematically evaluated the relative effectiveness of 5-HT 3 receptor
antagonists and cannabinoid agonists to suppress acute and/or delayed nausea
and vomiting produced by chemotherapeutic agents, such as cisplatin. Using
the Suncus model of emesis, Kwiatkowska et al. [32] found that ip-injected
ondansetron and ∆ 9 -THC both dose-dependently suppressed cisplatin-induced
vomiting and retching; however, the minimally effective dose of ondansetron
(0.2 mg/kg, ip) was considerably lower than the minimally effective dose of
∆ 9 -THC (2.5 mg/kg, ip). A combined pretreatment of doses of the two drugs
that were ineffective alone (0.02 mg/kg ondansetron and 1.25 mg/kg ∆ 9 -THC)
completely suppressed cisplatin-induced vomiting and retching. These results
suggest that a combination of lower doses of ondansetron and ∆ 9 -THC may be
an effective alternative treatment for the acute phase of chemotherapy-induced
vomiting that may have fewer side effects than higher doses of either agent
alone. The anti-emetic effects of ondansetron were not affected by pretreatment
with SR-141716, suggesting that ondansetron does not act at the CB 1
receptor. Finally, as we saw with lithium-induced vomiting [31], low doses
(5–10 mg/kg, ip) of the nonpsychoactive cannabinoid, CBD, effectively suppressed
cisplatin-induced vomiting, but high doses of CBD (20–40 mg/kg, ip)
potentiated vomiting.
The anti-emetic effect of low doses of CBD against lithium- and cisplatin-induced
emesis in Suncus is inconsistent with the failure of a dose of
10 mg/kg to suppress emesis produced by 2-AG in the least shrew [27]. The
difference may be related to the mechanism of action of the emetogens, the
difference in body mass of the two species (the least shrew is 10 times smaller
than the Suncus), or the biphasic effects of CBD on toxin-induced emesis.
Our [32] results suggest that both primary cannabinoids found in cannabis, the