An insight into the acute effects of cannabidiol on human brain function and their relationship with the brain expression of its molecular targets: a neuroimaging meta-regression analysis

Abstract

Abstract Background Cannabidiol (CBD) is a non-intoxicating substance present in the extract of Cannabis sativa popularised by its therapeutic potential. A limited number of neuroimaging studies have investigated CBD effects on brain function primarily in healthy individuals, people with early/ clinical high risk of psychosis, and social anxiety disorder. As a result of heterogeneity in the population examined, imaging modality and neurocognitive paradigm, the acute brain effects of CBD and the molecular mechanisms that may underlie its effects remain unclear. Methods We meta-analysed neuroimaging studies that examined the acute effects of CBD, relative to placebo, on human brain function using SPECT and fMRI while performing diverse cognitive tasks. Subsequently, we examined the relationship between the spatially distributed pooled effects of CBD on brain signal and the distribution of candidate mechanistic targets for the effects of CBD including fatty acid amide hydrolase (FAAH), dopamine D2, serotonin and cannabinoid-type-1 receptors as indexed by their gene expression data. Results CBD modulated the function of several brain regions, including the medial frontoparietal, midcingulo-insular, pericentral, lateral frontoparietal, and dorsal frontoparietal networks as well as the striatum and cerebellum. There was a significant inverse relationship between the magnitude of pooled CBD effect on brain activation and expression of FAAH but not the other targets. Discussion These preliminary findings suggest that the effect of CBD in the human brain may be linked to local FAAH availability and suggests that there is a strong case for directly examining whether the effects of CBD on FAAH underlie its effects on brain function and behaviour.