Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

Abstract
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-naı¨ve 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.
Introduction
Generalized Social Anxiety Disorder (SAD) is one of the most common and impairing anxiety conditions. However, the pharmacological treatment of SAD remains problematic since it is poorly controlled by the currently available drugs, with only about 30% of the subjects achieving true recovery or remission (Blanco et al., 2002). Therefore, there is a clear need to develop and explore novel therapeutic agents for the management of SAD.  Although it is well recognized that cannabis use can cause adverse effects, including anxiety, there is consistent evidence that many individuals use the drug to obtain relief from anxiety symptoms (Crippa et al., 2009).
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