Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

Brain imaging techniques allow the in vivo evaluation of the human brain, leading to a better understanding of its anatomical, functional and metabolic substrate. The aim of this current report is to present a systematic and critical review of neuroimaging findings in Social Anxiety Disorder (SAD). A literature review was performed in the PubMed Medline, Scielo and Web of Science databases using the following keywords: 'MRI', 'functional', 'tomography', 'PET', 'SPECT', 'spectroscopy', 'relaxometry', 'tractography' and 'voxel' crossed one by one with the terms 'social anxiety' and 'social phobic', with no limit of time. We selected 196 articles and 48 of them were included in our review. Most of the included studies have explored the neural response to facial expressions of emotion, symptoms provocation paradigms, and disorder-related abnormalities in dopamine or serotonin neurotransmission. The most coherent finding among the brain imaging techniques reflects increased activity in limbic and paralimbic regions in SAD. The predominance of evidence implicating the amygdala strengthens the notion that it plays a crucial role in the pathophysiology of SAD. The observation of alterations in pre-frontal regions and the reduced activity observed in striatal and parietal areas show that much remains to be investigated within the complexity of SAD. Interesting, follow-up designed studies observed a decrease in perfusion in these same areas after either by pharmacological or psychological treatment. The medial prefrontal cortex provided additional support for a corticolimbic model of SAD pathophysiology, being a promising area to investigation. Furthermore, the dopaminergic and GABAergic hypotheses seem directed related to its physiopathology. The present review indicates that neuroimaging has contributed to a better understanding of the neurobiology of SAD. Although there were several methodological differences among the studies, the global results have often been consistent, reinforcing the evidence of a specific cerebral circuit involved in SAD, formed by limbic and cortical areas.

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