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Neurochem Res. 2018 Aug;43(8):1511-1518. doi: 10.1007/s11064-018-2565-0. Epub 2018 Jun 6.

Systemic Injections of Cannabidiol Enhance Acetylcholine Levels from Basal Forebrain in Rats.

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Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Carretera Mérida-Progreso Km. 15.5, A.P. 96 Cordemex, C.P. 97310, Mérida, Yucatán, Mexico.
Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico.
Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico.
Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico.
Health School, Polytechnic Institute of Porto, Porto, Portugal.
Coordinación de Psicología Organizacional, División de Estudios Profesionales, Facultad de Psicología, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Universidade Catolica Dom Bosco, Campo Grande, Mato Grosso Do Sul, Brazil.
Laboratory of Panic and Respiration, Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Salgado de Oliveira University, Rio de Janeiro, Brazil.
Physical Activity Neuroscience Laboratory, Physical Activity Sciences Postgraduate Program-Salgado de Oliveira University (UNIVERSO), Rio de Janeiro, Brazil.
Faculty of Human Sciences, Medical School Hamburg, Hamburg, Germany.
Physical Activity, Physical Education, Health and Sport Research Centre (PAPESH), Sports Science Department, School of Science and Engineering, Reykjavik University, Reykjavík, Iceland.
Lithuanian Sports University, Kaunas, Lithuania.


Cannabis sativa is a plant that contains more than 500 components, of which the most studied are Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Several studies have indicated that CBD displays neurobiological effects, including wake promotion. Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines (dopamine, serotonin, epinephrine, and norepinephrine). However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine (ACh). Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means. Moreover, the time course effects on the contents of ACh were present 5 h post-injection of CBD. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD-treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.


Cannabis; Dopamine; Monoamines; Sleep; Wakefulness

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