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Modulation of the Endocannabinoid and Oxytocinergic Systems as a Potential Treatment Approach for Social Anxiety Disorder

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Abstract

Social anxiety disorder (SAD), or social phobia, is one of the most common types of anxiety disorder, with a lifetime prevalence that can reach 15%. Pharmacological treatments for SAD have moderate efficacy and are associated with significant adverse reactions. Therefore, recent studies have focused on searching for new treatments for this disorder. Preclinical studies and preliminary evidence in humans suggest that the phytocannabinoid cannabidiol and the neuropeptide oxytocin have anxiolytic effects. In the present text, we review this evidence and its implications for pharmacological treatment. We conclude that although current available studies show promising results regarding both the safety and efficacy of cannabidiol and oxytocin for the treatment of SAD, most studies were performed using single or few doses of these compounds, with small sample sizes. Therefore, future studies should explore the anxiolytic potential of these compounds using long-term, placebo-controlled designs with larger samples to elucidate the possible use of these compounds in the treatment of SAD.

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Authors and Affiliations

  1. Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, Ribeirão Preto, São Paulo, 3900, Brazil

    Rafael Guimarães Dos Santos, Flávia de Lima Osório, Rocio Martin-Santos, Antonio Waldo Zuardi, Jaime Eduardo Cecilio Hallak & José Alexandre S. Crippa

  2. National Institute for Translational Medicine (INCT-TM), CNPq, Ribeirão Preto, Brazil

    Rafael Guimarães Dos Santos, Flávia de Lima Osório, Rocio Martin-Santos, Antonio Waldo Zuardi, Jaime Eduardo Cecilio Hallak & José Alexandre S. Crippa

  3. Department of Psychiatry and Psychology, Hospital Clinic, University of Barcelona, Institute d’Investigació Mèdiques August Pi i Sunyer (IDIBAPS), CIBER en Salud Mental (CIBERSAM), Barcelona, Spain

    Rocio Martin-Santos

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  1. Rafael Guimarães Dos Santos
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  2. Flávia de Lima Osório
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  5. Jaime Eduardo Cecilio Hallak
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  6. José Alexandre S. Crippa
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Correspondence to José Alexandre S. Crippa.

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Funding

RGS is a Fellow of the Brazilian National Post-Doctorate Program (PNPD/CAPES). FdLO has received support from the São Paulo Research Foundation (FAPESP). RMS has received support from the Generalitat de Catalunya (Spain) (SGR2017/1798). JASC and JECH received a CNPq (Brazil) Productivity Fellowship Award. None of the authors received any specific funding for writing this article.

Conflict of interest

JASC and JECH have received travel support from and were medical advisors of SCBD Centre. JASC has received a grant from the University Global Partnership Network (UGPN)—“Global priorities in cannabinoid research excellence.” JASC is a member of the international advisory board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), funded by the National Health and Medical Research Council through the Centre of Research Excellence. JASC and JECH are co-inventors (Mechoulam R, Crippa JA, Guimaraes FS, Zuardi A, Hallak JE, and Breuer A) of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023” Def. US no. Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927). Universidade de São Paulo has licensed the patent to Phytecs Pharm (USP Resolution no. 15.1.130002.1.1). The University of São Paulo (USP) has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” RGS, FdLO, RMS and AWZ report no conflicts of interest.

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Dos Santos, R.G., de Lima Osório, F., Martin-Santos, R. et al. Modulation of the Endocannabinoid and Oxytocinergic Systems as a Potential Treatment Approach for Social Anxiety Disorder. CNS Drugs 33, 1031–1038 (2019). https://doi.org/10.1007/s40263-019-00669-5

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