Cannabinoids and hamster circadian activity rhythms

Circadian activity rhythms in hamsters are entrained to the daily light:dark cycle by photic information arriving from the retina to the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals. The effects of light on adjusting the timing of the circadian pacemaker is modified, both positively and negatively, by a variety of transmitter systems, but the effects of endocannabinoids have not been reported. Therefore, in this study we evaluated cannabinoids specific for the cannabinoid type 1 receptor (CB1) for their ability to modulate light-induced phase advances in hamster circadian activity rhythms. All compounds were administered intraperitoneally. The CB1 agonist CP55940 potently inhibited light-induced phase shifts with near 90% inhibition achieved with a dose of 0.125 mg/kg. The inhibitory effect of CP55940 was partially reversed by the CB1 antagonist LY320135 and completely reversed with 1 mg/kg of the CB1 antagonist AM 251. Neither LY320135 nor AM 251 had any effect on light-induced phase shifts when administered alone. Further evidence for CB1 involvement in hamster circadian rhythms was provided by immunohistochemical detection of CB1 receptors in four separate nuclei comprising the principal components of the hamster circadian system: the suprachiasmatic nucleus, intergeniculate leaflet of the thalamus, and dorsal and median raphe nuclei. Altogether these data indicate that the endocannabinoid system has the capability to modulate circadian rhythms in the hamster and cannabis use should be evaluated for adverse effects on circadian rhythms in humans.