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. 2019 Feb 13;19(1):69.
doi: 10.1186/s12888-019-2022-x.

Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: study protocol of a randomized controlled trial

Febe E van der Flier  1   2   3   4 , Caroline M B Kwee  2 , Danielle C Cath  2   5   6 , Neeltje M Batelaan  3 , Lucianne Groenink  7 , Puck Duits  2 , Date C van der Veen  4 , Anton J L M van Balkom  3 , Johanna M P Baas  8
Affiliations

Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: study protocol of a randomized controlled trial

Febe E van der Flier et al. BMC Psychiatry. .

Abstract

Background: Phobic anxiety disorders are among the most prevalent psychiatric disorders and are burdensome in terms of loss of quality of life and work productivity. Evidence-based treatments are relatively successful in the majority of patients, especially exposure therapy. However, a substantial subset of patients fails to achieve or stay in remission. Preclinical and genetic research have yielded evidence that the cannabinoid system is involved in the extinction of fear, presumed to underlie the beneficial effects of exposure therapy in phobic disorders. A cannabinoid constituent that may enhance endocannabinoid signaling is cannabidiol (CBD), a non-psychoactive component of cannabis. Hence, the addition of CBD to exposure therapy is expected to strengthen effects of treatment. To determine the added benefit of CBD on exposure therapy, we conduct a randomized controlled trial, in which patients in whom previous treatment as usual has not yielded sufficient response receive either CBD or placebo preceding 8 exposure sessions in a double-blind fashion. A subsidiary aim is to explore which (combination of) clinical, behavioral and genetic profiles of patients are related to treatment response.

Methods/design: This is an 8-week multicenter, randomized, double-blind, placebo-controlled trial. Seventy-two patients with social phobia or panic disorder with agoraphobia with incomplete response to earlier treatment will be included from outpatient clinics in the Netherlands. Patients are randomized to augmentation of exposure therapy with 300 mg CBD or placebo. The study medication is administered orally, 2 h preceding each of the eight 90 min exposure sessions. Measurements will take place at baseline, first administration of medication, every session, mid-treatment, last administration of medication, post-treatment and at 3 and 6 months' follow-up. The primary outcome measure is the score on the Fear Questionnaire (FQ). In addition, determinants of the expected treatment enhancing effect of CBD will be explored.

Discussion: This is the first trial to investigate whether the addition of CBD to exposure therapy is effective in reducing phobic symptoms in treatment refractory patients with social phobia or panic disorder with agoraphobia.

Trial registration: Netherlands Trial Register NTR5100 . Registered 13 March 2015. Protocol version: issue date 17 Jan 2018, protocol amendment number 7.

Keywords: Anxiety disorders; Cannabidiol; Cannabinoid system; Exposure therapy; Panic disorder with agoraphobia; Randomized controlled trial; Social phobia; Treatment resistance.

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Conflict of interest statement

Ethics approval and consent to participate

The study has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht (reference number: NL50898.041.15). Written informed consent will be obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of the study design. Data is collected both during T0-T6 measurements and therapy sessions, see Table 1 for a complete overview
See this image and copyright information in PMC

References

    1. Kessler RC, Angermeyer M, Anthony JC, DE Graaf R, Demyttenaere K, Gasquet I, et al. Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization’s world mental health survey initiative. World Psychiatry. 2005;6(3):168–176. - PMC - PubMed
    1. Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, et al. Prevalence of mental disorders in Europe: results from the European study of the epidemiology of mental disorders (ESEMeD) project. Acta Psychiatr Scand Suppl. 2004;109(s420):21–27. - PubMed
    1. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, et al. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(10):718–779. - PubMed
    1. Souětre E, Lozet H, Cimarosti I, Martin P, Chignon JM, Adés J, et al. Cost of anxiety disorders: impact of comorbidity. J Psychosom Res. 1994;38:151–160. - PubMed
    1. Klein Hofmeijer-Sevink M, Batelaan NM, Van Megen HJGM, Penninx BW, Cath DC, Van Den Hout MA, et al. Clinical relevance of comorbidity in anxiety disorders: a report from the Netherlands study of depression and anxiety (NESDA) J Affect Disord. 2012;137(1):106–112. - PubMed

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