Ignorance is not all bliss: Investigating the added benefit of cannabidiol in anxiety disorder treatment

Approximately 30-50% of patients do not benefit from current treatments for anxiety disorders. The development of novel treatment strategies besides existing treatments is therefore highly needed. Cannabidiol (CBD), a cannabis constituent with an advantageous safety profile, is frequently used by patients for treating anxiety symptoms, but its effectiveness in this regard has not often been studied. We synthesized past research into CBD and anxiety to 1) provide an indication of clinical efficacy and 2) elucidate what constitutes a dose that is anxiety-reducing. We found generally positive evidence in the literature for anxiety reducing effects of CBD and related compounds, however, the quality of the evidence was low. The results of our analyses precluded a straightforward dosing recommendation in humans. We investigated whether augmentation of exposure therapy with CBD could benefit treatment refractory patients with social anxiety disorder and patients with panic disorder with agoraphobia. As an adjunct to exposure therapy, CBD compared to placebo did not lead to faster, stronger and/or more enduring improvement on clinical outcomes. A fear conditioning task was administered as part of this clinical trial. Our results indicated decreased threat expectation under increasing levels of threat imminence at retention in the group randomized to receive CBD. Lastly, we examined whether we could predict response to exposure therapy with a fear conditioning task before therapy commencement, by looking into individual differences in fear extinction and safety learning. Our findings were inconclusive, which may be due to the relatively small sample size. In this thesis we demonstrated that CBD, when applied before each exposure therapy session, is not effective, and that there is a lack of clarity about what constitutes the ‘right’ dose of CBD for treating anxiety symptoms. Our work narrowed down potential clinical applications of CBD, which should be scrutinized in future research.