Social Safety Learning in the Brain Oxytocin System

NCT05968651 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00013670
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are conducting this research study to examine whether oxytocin enhances social safety learning (learning safety through the experience of another individual) in people with social anxiety disorder (SAD) compared to healthy volunteers. Oxytocin is a hormone that can also act as a chemical messenger in the brain. Oxytocin plays a role in a number of functions, including responding to fear and social interactions. In this study, the investigators would like to compare the effects of oxytocin and placebo nasal sprays in adults with SAD and healthy adults. This research study will compare an oxytocin nasal spray to a placebo nasal spray. About 120 people will take part in this research study, all at the University of Washington (UW).

Conditions

Social Phobia

Keywords

Social Phobia; Social Anxiety Disorder; Social Safety Learning; Intranasal Oxytocin

Outcome Measures

Primary Outcomes (36)

• Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the insula during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the insula during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Amygdala During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Skin Conductance Responses (SCR) to CS- During Extinction

  mean skin conductance responses (SCR) for CS- stimuli during Extinction

  immediately (45 minutes) after receiving drug

• Skin Conductance Responses (SCR) to CS+S During Extinction

  mean skin conductance responses (SCR) for CS+S stimuli during Extinction

  immediately (45 minutes) after receiving drug

• Skin Conductance Responses (SCR) to CS+R During Extinction

  mean skin conductance responses (SCR) for CS+R stimuli during Extinction

  immediately (45 minutes) after receiving drug

• Skin Conductance Responses (SCR) to CS- During Reinstatement

  mean skin conductance responses (SCR) for CS- stimuli during Reinstatement

  immediately (45 minutes) after receiving drug

• Skin Conductance Responses (SCR) to CS+S During Reinstatement

  mean skin conductance responses (SCR) for CS+S stimuli during Reinstatement

  immediately (45 minutes) after receiving drug

• Skin Conductance Responses (SCR) to CS+R During Reinstatement

  mean skin conductance responses (SCR) for CS+R stimuli during Reinstatement

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Insula During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the insula during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Insula During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the insula during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Insula During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the insula during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Insula During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the insula during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.

  immediately (45 minutes) after receiving drug

• Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

  Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.

  immediately (45 minutes) after receiving drug

Study Arms (2)

Clinical

EXPERIMENTAL

This group consists of individuals with at least moderate symptoms of social anxiety disorder. This group will receive either an oxytocin or placebo administration (blind randomization).

Drug: Oxytocin nasal spray or placebo

Controls

PLACEBO COMPARATOR

This group consists of a healthy sample of individuals (no lifetime diagnoses of mania or psychotic disorders). This group will receive either an oxytocin or placebo administration (blind randomization).

Drug: Oxytocin nasal spray or placebo

Interventions

Oxytocin nasal spray or placebo DRUG

Single acute administration of 24 international units (IU) oxytocin or matching placebo

Clinical; Controls

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For Clinical Sample
• Men and women age 18-45
• Women must be having regular menstrual cycles and not be taking oral contraception
• Primary diagnosis of social anxiety disorder
• For Healthy Sample
• Men and women age 18-45
• Women must be having regular menstrual cycles and not be taking oral contraception
• No current or lifetime history of psychiatric, neurological, or medical disorders

You may not qualify if:

• For All Groups
• Pregnancy or breastfeeding
• Positive urine drug screening test result
• History of nasal pathology
• Current use of any psychotropic medication or steroids
• Active substance use disorder within the past 6 months
• History of serious medical illnesses or untreated endocrine diseases
• History of head injury, neurological disorder, or neurosurgical procedure
• Positive magnetic resonance (MR) screen
• For Clinical Sample
• Lifetime diagnoses of mania or psychotic disorder based on the Diagnostic and Statistical Manual (DSM- 5th ed)
• Acute suicidal ideation
• For Healthy Sample
• Lifetime DSM-5 diagnosis of any medical, neurological, or psychiatric illness

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Phobia, Social

Condition Hierarchy (Ancestors)

Phobic Disorders; Anxiety Disorders; Mental Disorders

Results Point of Contact

• Title: Angela Fang
• Organization: University of Washington

angfang@uw.edu

206-616-5783

Study Officials

• Angela Fang, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Psychology

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: August 1, 2023
• Study Start: June 26, 2023
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: June 11, 2026
• Results First Posted: June 11, 2026

Record last verified: 2026-03

Locations

US (1)