CBD-study (WC 2015-026)

Background

Starting date: 01/02/2016

Phobic disorders (e.g., social anxiety, panic disorder with agoraphobia) have an estimated lifetime prevalence of 19% (de Graaf et al. 2012), and are among the most prevalent disorders according to the WHO (2003). The estimated annual health care costs in the USA due to anxiety disorders are $42 billion, and these disorders are burdensome in terms of loss of quality of life and loss of work productivity. Standard treatments (exposure with response prevention therapy (ERP), either alone or in combination with serotonin reuptake inhibitors) are relatively successful, with improvement in up to 60% of patients, but only 30% to 50% phobic patients achieve full remission (Gloster et al. 2013). Therefore, there is still substantial room for improvement, especially in treatment resistant patients. Preclinical research has yielded solid evidence that the cannabinoid system is involved in the extinction of fear, presumed to underlie the beneficial effects of exposure therapy with response prevention in anxiety disorders (Hofmann 2008). A recent study from our experimental psychology group (Heitland et al. 2012) uncovered a genetic variant in the cannabinoid system that is associated with little to no spontaneous extinction of fear in a large group of normal individuals. Together, these findings suggest that: 1) the endocannabinoid system may form a novel target for the facilitation of extinction of pathological anxiety in general; 2) Those individuals who have a high risk genetic profile within the endocannabinoid system, with the consequence of reduced efficacy of fear extinction mechanisms, may be particularly enhanced by administration of cannabidiol preceding exposure therapy. Cannabidiol functions through inhibition of the FAAH enzyme that degrades endogenously released cannabinoid neurotransmitters (Leweke et al. 2012), thereby enhancing endogenous endocannabinoid signalling. As opposed to tetra hydrocannabinol (THC), the psychoactive compound in cannabis that produces "high" feelings, cannabidiol does not produce any of these effects, nor other significant side effects (see Chapter 6 and the Investigator’s Brochure, IB), which makes it relatively safe to use.