3. Umbruch 4.4..2005 - Online Pot

Cannabinoids and anxiety 143
CB 1 receptor-knockout studies
Martin et al. [12] tested CB 1-knockout mice and wild-type mice in the
light/dark box test. They found that knockout mice spent more time in the dark
section of the box and less time in the light part of the box compared with the
wild-type mice, indicating that the knockout mice were more anxious, thus
providing strong support that the CB 1 receptor system is involved in the control
of emotional behaviors such as fear and anxiety.
Rodgers et al. [13] extended the findings of Martin et al. [12]. They tested
CB 1-knockout mice and wild-types in the elevated-plus maze under two conditions,
low light and high light, the latter having been shown to induce greater
anxiety. They found that there were no differences or indications of anxiogenic
activity in the low-light condition between knockout and wild-type mice.
However, in the high-light condition knockout mice spent significantly more
time the in the closed arms of the maze and less time in the open arms of the
maze, as compared with the wild-type mice. These data provide more convincing
evidence that the CB 1 receptor system is involved in the control of
anxiety.
Anandamide hydrolysis and anxiety
Kathuria et al. [14] hypothesized that that anxiolytic effects of cannabinoids
might be enhanced by endogenous cannabinoids by preventing their inactivation.
Accordingly, this group synthesized several fatty acid amide hydrolase
(FAAH) inhibitors. Two of these (named URB532 and URB597) selectively
inhibited breakdown of anandamide in vitro while an inactive analog did not.
These inhibitors were also tested in the elevated-plus maze. Both increased the
time spent in the open arms of the maze, in a dose-dependent manner. These
effects were blocked by several doses of SR-141716. The researchers also used
the ultrasonic emission test. In this test rat pups are separated from their mother,
which causes them to emit ultrasonic distress cries. Normally the mother
uses these signals to locate and retrieve the pups. Anxiolytic drugs selectively
reduce these cries dose-dependently. In this test both FAAH inhibitors reduced
vocalizations in the pups which was reversed by co-administration of
SR-141716. The authors conclude that raising anandamide levels seems to be
important in the regulation of anxiety and suggest a potential new class of
compounds which might be useful in the treatment of anxiety.
Discussion of animal studies
It seems that there is a paradox in the data discussed above. Regarding CB 1
antagonists, it seems that the preponderance of the data suggest that these compounds
are anxiolytic. Agonists on the other hand seem to have biphasic