annabinoid receptors are activated by cannabinoids, generated naturally inside the body (
endocannabinoids) or introduced into the body as
cannabis or a related
synthetic compound. After the receptor is engaged, multiple
intracellular signal transduction pathways are activated. At first, it was thought that cannabinoid receptors mainly inhibited the
enzyme adenylate cyclase (and thereby the production of the
second messenger molecule
cyclic AMP), and positively influenced
inwardly rectifying potassium channels (=Kir or IRK)
[8]. However, a much more complex picture has appeared in different cell types, implicating other
potassium ion channels,
calcium channels,
protein kinase A and
C,
Raf-1,
ERK,
JNK,
p38,
c-fos,
c-jun and many more
[4].
Cannabis sativa preparations have been known as therapeutic agents against various
diseases for millennia
[9]. The native active constituent, Delta 9-
tetrahydrocannabinol (delta-9-THC) was found to be the principal mediator of the effects of cannabis
[10] Δ9-THC is prescribed today under the generic name
Dronabinol, to treat
vomiting and for enhancement of
appetite, mainly in
AIDS patients.
Separation between the therapeutically undesirable psychotropic effects, and the clinically desirable ones however, has not been reported with
agonists that bind to cannabinoid receptors. THC, as well as the two major
endogenous compounds identified so far that bind to the cannabinoid receptors —
anandamide and
2-arachidonylglycerol (2-AG)— produce most of their effects by binding to both the CB1 and CB2 cannabinoid receptors. While the effects mediated by CB1, mostly in the CNS, have been thoroughly investigated, those mediated by CB2 are not equally well defined.
CB1
CB1 receptors are thought to be the most widely
expressed G-protein coupled receptors in the brain. Varying levels of expression can be detected in the
olfactory bulb,
cortical regions (
neocortex,
pyriform cortex,
hippocampus, and
amygdala), several parts of
basal ganglia,
thalamic and
hypothalamic nuclei and other subcortical regions (
e.g. the
septal region),
cerebellar cortex, and
brainstem nuclei (
e.g. the
periaqueductal gray)
[4].
CB1 is expressed on several cell types of the
pituitary gland, in the
thyroid gland, and most likely in the
adrenal gland[4].
CB1 is also expressed in several cells relating to metabolism, such as
fat cells,
muscle cells,
liver cells (and also in the
endothelial cells,
Kupffer cells and
stellate cells of the
liver), and in the
digestive tract[4]. It is also expressed in the
lungs and the
kidney. In the liver, activation of the CB1 receptor is known to increase de novo
lipogenesis[5]. Activation of presynaptic CB1 receptors is also known to inhibit sympathetic innervation of blood vessels and contributes to the suppression of the neurogenic vasopressor response in
septic shock[6].
CB1 is present on
Leydig cells and human
sperms. In
females, it is present in the
ovaries,
oviducts myometrium,
decidua and
placenta. It is probably important also for the
embryo[4].
So they are all over...
-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol