Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

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 (po0.001, 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 (po0.001). These results suggest that CBD has anxiolytic properties, and that these effects are mediated by an action on limbic and paralimbic brain areas.

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“…Not surprisingly, and as witnessed in the aforementioned preclinical data, CBD has been shown to reduce anxiety in patients with social phobia and generalized social anxiety disorders [62][63][64]. CBD decreases autonomic arousal and subjective anxiety [65]; these anxiolytic effects were found to be linked to the modulation of limbic and paralimbic structures [57,62]. It remains to be determined if these properties translate in the attenuation of symptoms for other anxiety disorders than social phobia (e.g., post-traumatic stress disorder, panic disorder) [66].…”

“…CBD also possesses antipsychotic properties [2,[57][58][59][60][61]. Not surprisingly, and as witnessed in the aforementioned preclinical data, CBD has been shown to reduce anxiety in patients with social phobia and generalized social anxiety disorders [62][63][64].…”

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“…In a SPECT study of resting cerebral blood flow (rCBF) in normal subjects, CBD reduced rCBF in left medial temporal areas, including the amygdala and hippocampus, as well as the hypothalamus and left posterior cingulate gyrus, but increased rCBF in the left parahippocampal gyrus. These rCBF changes were not correlated with anxiolytic effects [102]. In a SPECT study, by the same authors, in patients with SAD, CBD reduced rCBF in overlapping, but distinct, limbic and paralimbic areas; again, with no correlations to anxiolytic effects [104].…”

“…CBD reduced anxiety associated with a simulated public speaking test in healthy subjects, and in subjects with SAD, showing a comparable efficacy to ipsapirone (a 5-HT 1A R agonist) or diazepam [98,105]. CBD also reduced the presumed anticipatory anxiety associated with undergoing a single-photon emission computed tomography (SPECT) imaging procedure, in both healthy and SAD subjects [102,104]. Finally, CBD enhanced extinction of fear memories in healthy volunteers: specifically, inhaled CBD administered prior to or after extinction training in a contextual fear conditioning paradigm led to a trend-level enhancement in the reduction of skin conductance response during reinstatement, and a significant reduction in expectancy (of shock) ratings during reinstatement [106].…”

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“…, anxiolytic effect; , anxiogenic effect; CFC, contextual fear conditioning; EPM, elevated plus maze; ETM, elevated T maze; GAD, generalized anxiety patients; OF, open field; VCT, Vogel conflict test; i.p., intraperitoneal injection; i.c.v., intracerebroventricular injection; DPAG, dorsal periaqueductal grey; BNST, bed nucleus of the stria terminalis; PL, prelimbic cortex; IL, infralimbic cortex; CeA, central amygdala. [24] neuroimaging study healthy volunteers 400 mg [25] fearful facial stimuli healthy volunteers 600 mg [26] fearful facial stimuli healthy volunteers 600 mg [27] anxiety symptoms (visual analogue mood scale) GAD 400 mg [28] simulated public speaking social phobics 400 mg [29] been associated with PTSD pathophysiology [30]. Intracerebroventricular administration of CBD facilitates extinction in a contextual aversive conditioning model [15].…”