Authors:

Crippa JA, Zuardi AW, Garrido GE, Wichert-Ana L, Guarnieri R, Ferrari L, Azevedo-Marques PM, Hallak JE, McGuire PK, Filho Busatto G.

Abstract:

Animal and human studies have suggested that cannabidiol (CBD) may

possess anxiolytic properties, but how these effects are mediated
centrally is unknown. The aim of the present study was to investigate
this using functional neuroimaging. Regional cerebral blood flow (rCBF)
was measured at rest using (99m)Tc-ECD SPECT in 10 healthy male
volunteers, randomly divided into two groups of five subjects. Each
subject was studied on two occasions, 1 week apart. In the first
session, subjects were given an oral dose of CBD (400 mg) or placebo, in
a double-blind procedure. SPECT images were acquired 90 min after drug
ingestion. The Visual Analogue Mood Scale was applied to assess
subjective states. 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 (SPM). CBD significantly
decreased subjective anxiety and increased mental sedation, while
placebo did not induce significant changes. Assessment of brain regions
where anxiolytic effects of CBD were predicted a priori revealed two
voxel clusters of significantly decreased ECD uptake in the CBD relative
to the placebo condition (p<0.001, uncorrected for multiple
comparisons). These included a medial temporal cluster encompassing the
left amygdala-hippocampal complex, extending into the hypothalamus, and a
second cluster in the left posterior cingulate gyrus. There was also a
cluster of greater activity with CBD than placebo in the left
parahippocampal gyrus (p<0.001). These results suggest that CBD has
anxiolytic properties, and that these effects are mediated by an action
on limbic and paralimbic brain areas.