CBD was shown to have anxiolytic effects in animal models (Twardowschy et al. 2013, Do Monte et al. 2013, Campos et al. 2012, Stern et al. 2012, Elbatsh et al. 2012) and humans (Zuardi et al. 1993, Das et al. 2013, Bergamaschi et al. 2011, Crippa et al. 2010).
In a clinical study, subjects were asked to perform a speech in front of a video camera (Zuardi et al. 1993). The procedure increases subjective anxiety and its physiological concomitants and is sensible to anxiolytic and anxiogenic compounds. CBD (300 mg, P.O.) was compared, under a double-blind design, to ipsapirone (5-HT1A partial agonist, 5 mg), diazepam (anxiolytic benzodiazepine, 10 mg) or placebo. The results showed that both CBD and the two other anxiolytic compounds attenuated anxiety induced by the test. At this dosage, CBD did not induce any significant sedative effects. The results, therefore, support the claim of anxiolytic properties of CBD.
In an experiment with 48 healthy participants who underwent a fear-conditioning test CBD enhanced consolidation of subsequent extinction learning and thus may be helpful in anxiety disorders (Das et al. 2013). Participants received 32 mg of CBD either following before or after extinction in a double-blind, placebo-controlled design. Successful conditioning and extinction were found in in the treatment groups. CBD, given post-extinction, enhanced consolidation of extinction learning. No acute effects of CBD were found on extinction.
Scientists at the University of Sao Paulo, Brazil, investigated the effects of CBD on patients with generalized social anxiety disorder in a simulation public speaking test (Bergamaschi et al. 2011). Three groups were compared, 12 healthy controls without any medication, 12 patients with anxiety disorder, who received a single dose of CBD (600 mg) and a group of 12 patients, who received a placebo in a double-blind design. Pre-treatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in the speech performance of patients with social anxiety disorder, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group. No significant differences were observed between patients, who had received CBD, and healthy controls in anxiety cores or in the cognitive impairment, discomfort, and alert factors. This study confirmed previous research of the same group involving 10 patients with social anxiety disorder (Crippa et al. 2010).
Research with mice shows that the serotonin 5-HT1A receptor is involved in the anxiolytic effects of CBD (Twardowschy et al. 2013). Blocking of this receptor reduced the anti-panic effects of this natural cannabinoid. Repeated microinjections of CBD into the infralimbic cortex of mice facilitated fear extinction (Do Monte et al. 2013). This effect was mediated by the CB1 receptor. In a study with rats, which were exposed to cats, CBD reduced fear reactions one hour after the exposure to the predator (Campos et al. 2012). This effect was also mediated at least in part by the 5-HT1A receptor. Authors concluded: “Our results suggest that CBD has the beneficial potential for PTSD [posttraumatic stress disorder] treatment and that 5-HT1A receptors could be a therapeutic target in this disorder.” However, animal research at the University of Nottingham, UK, showed that chronic administration of cannabidiol increased anxiety in rats (Elbatsh et al. 2012). Rats were treated for 14 days with CBD. Researchers concluded that „chronic administration of CBD produced an anxiogenic-like effect in clear opposition to the acute anxiolytic profile previously reported.“