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.
Subject(s)
Anti-Anxiety Agents/pharmacology , Cannabidiol/pharmacology , Cerebral Cortex/drug effects , Cysteine/analogs & derivatives , Regional Blood Flow/drug effects , Adult , Anxiety/drug therapy , Anxiety/physiopathology , Brain Mapping , Cerebral Cortex/anatomy & histology , Cerebral Cortex/blood supply , Cerebral Cortex/metabolism , Cerebrovascular Circulation/drug effects , Cysteine/pharmacokinetics , Double-Blind Method , Functional Laterality , Humans , Image Processing, Computer-Assisted , Male , Neuropsychological Tests , Organotechnetium Compounds/pharmacokinetics , Pain Measurement , Radiopharmaceuticals/pharmacokinetics , Time Factors , Tomography, Emission-Computed, Single-PhotonABSTRACT
Several MRI studies have reported reductions in temporal lobe volumes in Alzheimer's disease (AD). Measures have been usually obtained with regions-of-interest (ROI) drawn manually on selected medial and lateral portions of the temporal lobes, with variable choices of anatomical borders across different studies. We used the fully automated voxel-based morphometry (VBM) approach to investigate gray matter abnormalities over the entire extension of the temporal lobe in 14 AD patients (MMSE 14-25) and 14 healthy controls. Foci of significantly reduced gray matter volume in AD patients were detected in both medial and lateral temporal regions, most significantly in the right and left posterior parahippocampal gyri and the left posterior inferior temporal gyrus/fusiform gyrus (P<0.05, corrected for multiple comparisons). At a more flexible statistical threshold (P<0.001, uncorrected for multiple comparisons), circumscribed foci of significant gray matter reduction were also detected in the right amygdala/enthorinal cortex, the anterior and posterior borders of the superior temporal gyrus bilaterally, and the anterior portion of the left middle temporal gyrus. These VBM results confirm previous findings of temporal lobe atrophic changes in AD, and suggest that these abnormalities may be confined to specific sites within that lobe, rather than showing a widespread distribution.
Subject(s)
Alzheimer Disease/pathology , Magnetic Resonance Imaging , Temporal Lobe/pathology , Aged , Aging/pathology , Atrophy , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Delusions and/or hallucinations are not an uncommon feature in severe major depressive episodes. Functional imaging studies of depression have been widely reported in the literature, but few of these have attempted to investigate the neurophysiological correlates of psychotic symptoms. METHODS: We measured resting regional cerebral blood flow (rCBF) with the (99m)Tc-ECD SPECT technique in patients with major depressive disorder with (n=9) and without (n=12) psychotic features, as well as in a group of healthy volunteers (n=12). Between-group rCBF comparisons were performed using the voxel-based statistical parametric mapping method. RESULTS: Major depressed patients with psychotic features showed decreased rCBF in the left subgenual anterior cingulate cortex relative to both non-psychotic patients and healthy controls (P<0.001 one-tailed, uncorrected for multiple comparisons). Relative to the non-psychotic group, depressed patients with psychotic symptoms also had a focus of decreased rCBF in the right inferior frontal cortex, with the voxel of maximal significance in the insula (P<0.031, corrected for multiple comparisons). A similar pattern of significant between-group rCBF differences between psychotic and non-psychotic patients emerged after covarying the analysis for the confounding influence of overall illness severity. CONCLUSIONS: These results provide preliminary evidence that psychotic symptoms in major depression may be associated with abnormalities in ventral paralimbic regions previously implicated in mood regulation and depression.
