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Potential Protective Effects of Cannabidiol on Neuroanatomical Alterations in Cannabis Users and Psychosis: A Critical Review

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Cannabis use and the development of schizophrenic psychoses share a variety of similarities. Both start during late adolescence; go along with neuropsychological deficits, reduced activity, motivation deficits, and hallucinations suggesting impairment of similar brain structures. In cannabis heavy users diminished regional gray and white matter volume was reported. Similar alterations were observed in the large literature addressing structural abnormalities in schizophrenia. Furthermore, in cannabis using schizophrenic patients, these brain alterations were especially pronounced. Close relatives of schizophrenic patients showed greater cannabis-associated brain tissue loss than non-relatives indicating a genetically mediated particular sensitivity to brain tissue loss.

Possible mechanisms for the induction of structural brain alterations are here discussed including impairments of neurogenesis, disturbance of endocannabinoids and diminished neuroplasticity. Especially direct THC effects (or via endocannabinoids) may mediate diminished glutamatergic neurotransmission usually driving neuroplasticity. Correspondingly, alterations of the kynurenic acid blocking NMDA receptors may contribute to brain structure alterations. However, different cannabis compounds may exert opposite effects on the neuroanatomical changes underlying psychosis. In particular, cannabidiol (CBD) was shown to prevent THC associated hippocampal volume loss in a small pilot study. This finding is further supported by several animal experiments supporting neuroprotective properties of CBD mainly via anti-oxidative effects, CB2 receptors or adenosine receptors. We will discuss here the mechanisms by which CBD may reduce brain volume loss, including antagonism of THC, interactions with endocannabinoids, and mechanisms that specifically underlie antipsychotic properties of CBD.
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Keywords: Cannabis; adolescence; cannabidiol; endocannabinoid system; hallucinations; motivation deficits; neuropsychological deficits; reduced activity; schizophrenia; structural brain alterations

Document Type: Research Article

Publication date: November 1, 2012

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  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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