Authors:
Murillo-Rodríguez E, Millán-Aldaco D, Palomero-Rivero M, Mechoulam R, Drucker-Colín R.
Abstract:
Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Delta(9)-THC modulates sleep, but no clear evidence on the role of CBD is available. In order to determine the effects of CBD on sleep,
it was administered intracerebroventricular (icv) in a dose of 10
microg/5 microl at the beginning of either the lights-on or the
lights-off period. We found that CBD administered during the lights-on
period increased wakefulness (W) and decreased rapid eye movement sleep (REMS). No changes on sleep
were observed during the dark phase. Icv injections of CBD (10
microg/5microl) induced an enhancement of c-Fos expression in
waking-related brain areas such as hypothalamus and dorsal raphe nucleus
(DRD). Microdialysis in unanesthetized rats was carried out to
characterize the effects of icv administration of CBD (10 microg/5
microl) on extracellular levels of dopamine (DA) within the nucleus
accumbens. CBD induced an increase in DA release. Finally, in order to
test if the waking properties of CBD could be blocked by the sleep-inducing
endocannabinoid anandamide (ANA), animals received ANA (10 microg/2.5
microl, icv) followed 15 min later by CBD (10 microg/2.5 microl).
Results showed that the waking properties of CBD were not blocked by
ANA. In conclusion, we found that CBD modulates waking via activation of
neurons in the hypothalamus and DRD. Both regions are apparently
involved in the generation of alertness. Also, CBD increases DA levels
as measured by microdialysis and HPLC procedures. Since CBD induces
alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.