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Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats.

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.

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  • Authors+Show Affiliations

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    Depto de Neurociencias, Instituto de Fisiología Celular, Ciudad Universitaria, Circuito Interior, Universidad Nacional Autónoma de México, México DF, CP 04510, Mexico. emurillo@ifc.unam.mx

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    Source

    FEBS letters 580:18 2006 Aug 07 pg 4337-45

    MeSH

    Animals
    Arachidonic Acids
    Cannabidiol
    Dopamine
    Endocannabinoids
    Hypothalamus
    Injections, Intraventricular
    Male
    Polyunsaturated Alkamides
    Proto-Oncogene Proteins c-fos
    Raphe Nuclei
    Rats
    Rats, Wistar
    Sleep
    Wakefulness

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16844117

    Citation

    Murillo-Rodríguez, Eric, et al. "Cannabidiol, a Constituent of Cannabis Sativa, Modulates Sleep in Rats." FEBS Letters, vol. 580, no. 18, 2006, pp. 4337-45.
    Murillo-Rodríguez E, Millán-Aldaco D, Palomero-Rivero M, et al. Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats. FEBS Lett. 2006;580(18):4337-45.
    Murillo-Rodríguez, E., Millán-Aldaco, D., Palomero-Rivero, M., Mechoulam, R., & Drucker-Colín, R. (2006). Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats. FEBS Letters, 580(18), pp. 4337-45.
    Murillo-Rodríguez E, et al. Cannabidiol, a Constituent of Cannabis Sativa, Modulates Sleep in Rats. FEBS Lett. 2006 Aug 7;580(18):4337-45. PubMed PMID: 16844117.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats. AU - Murillo-Rodríguez,Eric, AU - Millán-Aldaco,Diana, AU - Palomero-Rivero,Marcela, AU - Mechoulam,Raphael, AU - Drucker-Colín,René, Y1 - 2006/07/10/ PY - 2006/03/02/received PY - 2006/04/10/revised PY - 2006/04/17/accepted PY - 2006/7/18/pubmed PY - 2006/9/20/medline PY - 2006/7/18/entrez SP - 4337 EP - 45 JF - FEBS letters JO - FEBS Lett. VL - 580 IS - 18 N2 - 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. SN - 0014-5793 UR - https://www.unboundmedicine.com/medline/citation/16844117/Cannabidiol_a_constituent_of_Cannabis_sativa_modulates_sleep_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-5793(06)00815-5 DB - PRIME DP - Unbound Medicine ER -