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-naïve 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.

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

“…An investigation with a larger number of participants is currently being conducted, but it is clear more studies are necessary to confirm these preliminary findings, as well as to evaluate different treatment schedules in order to fully evaluate the spectrum of CBD's effects. Nevertheless, the current human data are consistent with results from the rat models, suggesting that CBD attenuates cue-induced and general craving in opioid-dependent individuals and that the effects are protracted even after the acute exposure to the cannabinoid [62][63][64]. Overall, the pilot human and preclinical animal laboratory studies provide a foundation for continued exploration of CBD in treating opioid dependence.…”

“…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]. 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].…”

Cannabidiol as a Potential Treatment for Anxiety Disorders

“…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].…”