Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments.

Justine Renard, Christopher Norris, Walter Rushlow, Steven R Laviolette

Journal: Neuroscience and biobehavioral reviews 2017;75():157-165

PMID: 28185872

Full Text on Elsevier Science View on PubMed

Abstract

Growing clinical and pre-clinical evidence points to a critical role for cannabidiol (CBD), the largest phytochemical component of cannabis, as a potential pharmacotherapy for various neuropsychiatric disorders. In contrast to delta-9-tetrahydrocannabinol (THC), which is associated with acute and neurodevelopmental pro-psychotic side-effects, CBD possesses no known psychoactive or dependence-producing properties. However, evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising anti-psychotic properties. Despite the psychotropic differences between CBD and THC, little is known regarding their molecular and neuronal effects on the mesolimbic DA system, nor how these differential effects may relate to their potential pro vs. anti-psychotic properties. This review summarizes clinical and pre-clinical evidence demonstrating CBD's modulatory effects on DA activity states within the mesolimbic pathway, functional interactions with the serotonin 5-HT receptor system, and their downstream molecular signaling effects. Together with clinical evidence showing that CBD may normalize affective and cognitive deficits associated with schizophrenia, CBD may represent a promising treatment for schizophrenia, acting through novel molecular and neuronal mesolimbic substrates.

Address: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada; Dept. of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada.; Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada; Dept. of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada; Dept. of Psychiatry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada.; Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada; Dept. of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada; Dept. of Psychiatry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada; Dept. of Psychology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6C 5A1, Canada. Electronic address: [email protected].

DOI: 10.1016/j.neubiorev.2017.02.006

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MeSH Terms: Cannabidiol, Dopamine, Dronabinol, Humans, Schizophrenia