3. Umbruch 4.4..2005 - Online Pot

Cannabinoids: effects on vomiting and nausea in animal models 185
reduced by ∆ 9 -THC [34, 35]. Endogenous cannabinoid ligands, such as anandamide,
as well as synthetic cannabinoids, such as WIN-55,212-2, also act on
these receptors [33].
Recent findings indicate that the cannabinoid system interacts with the serotonergic
system in the control of emesis. The dorsal vagal complex not only
contains CB 1 receptors, but is also densely populated with 5-HT 3 receptors [48,
49], potentially a site of anti-emetic effects of 5-HT 3 antagonists. Anandamide
has also been reported to interact with serotonin [50]. Cannabinoid receptors
are co-expressed with serotonin 5-HT 3 receptors in some neurons in the central
nervous system [51] and inhibitory functional interactions have been reported
between cannabinoid CB 1 and 5-HT 3 receptors [52, 53]. Additionally, canabinoids
reduced the ability of 5-HT 3 agonists to produce emesis [28] and this
effect was prevented by pretreatment with the selective cannabinoid CB 1 receptor
antagonist SR-141716. Cannabinoids may act at CB 1 presynaptic receptors
to inhibit release of newly synthesized serotonin [28, 54, 55].
Anti-emetic effects of cannabinoids in human clinical trials
The potential for marijuana to suppress nausea and vomiting produced by
chemotherapy is of considerable therapeutic interest. Indeed, three cannabis-based
medicines are available: dronabinol, nabilone and levonantradol.
Tramer et al. [56] present a thorough systematic review of 30 clinical trial comparisons
of cannabis (oral nabilone, dronabinol (THC) and intramuscular levonantradol)
with a placebo or other anti-emetics (predominantly dopamine antagonists).
Tramer et al. [56] conclude that the cannabinoids were superior to the
conventional dopaminergic antagonists in the treatment of nausea and vomiting.
There has been only one [57] comparison of cannabis with a 5-HT 3 antagonist
using the short-acting emetic agent syrup of ipecac. Human participants
compared the effectiveness of a single dose of ondansetron (8 mg) with one of
two doses of smoked marijuana (8.4 and 16.9 mg ∆ 9 -THC) in attenuating nausea
and vomiting produced by syrup of ipecac. Unlike cisplatin, ipecac produces
short-lasting nausea and vomiting with a fast onset. They report that
within the limited dose range tested, ondansetron was considerably more
effective than smoked marijuana in attenuating vomiting and nausea and nausea
produced by the ipecac. There have been no clinical trials comparing the
relative efficacy of marijuana and 5-HT 3 antagonists in suppressing long-lasting
nausea and vomiting produced by chemotherapy treatment.
Cannabinoids produce psychotropic side effects, which partially accounts
for their lack of popularity in clinical use [58]. Patients who have not had any
experience with cannabis often find the psychotropic effects unpleasant and
disturbing. Most importantly, the development of 5-HT 3 antagonist anti-emetic
drugs, with few side effects, has limited clinical use of cannabis-based medicines.
The 5-HT 3 antagonist anti-emetic agents are highly effective at preventing
chemotherapy-induced vomiting, but are much less effective at inhibit-