Effects of cannabidiol (CBD) on regional cerebral blood flow.
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.
Department of Neuropsychiatry and Medical Psychology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
José Alexandre de Souza
JA
Crippa
Antonio Waldo
AW
Zuardi
Griselda E J
GE
Garrido
Lauro
L
Wichert-Ana
Ricardo
R
Guarnieri
Lucas
L
Ferrari
Paulo M
PM
Azevedo-Marques
Jaime Eduardo Cecílio
JE
Hallak
Philip K
PK
McGuire
Geraldo
G
Filho Busatto
D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001931:Brain Mapping; D002185:Cannabidiol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009483:Neuropsychological Tests; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010147:Pain Measurement; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000187:drug effects*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
D014151:Anti-Anxiety Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D002185:Cannabidiol; C059659:technetium Tc 99m bicisate; D003545:Cysteine