Abstract Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Δ9-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 μg/5 μl 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 μg/5 μl) induced an enhancement of c-Fos expression in waking-related brain areas such as hypothalamus...