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Fear, whether it occurs in humans suffering from an anxiety disorder or in experimental models with rodents, is reduced by exposing the frightened organism to the fearful stimulus in the absence of any negative consequences (i.e., extinction, or exposure therapy). However, fear often renews when the feared stimulus is encountered in a context different from the exposure context. In rats, the investigators found that interfering with the animal's ability to process contexts during extinction by administering an anticholinergic drug prevented fear renewal. This proposal will determine if the beneficial effect of this drug translates to exposure therapy in socially anxious humans. To this end, 100 individuals with Social Phobia who fear public speaking will undergo repeated sessions of exposure to public speaking, within a virtual reality context. Participants will be randomized to either drug placebo, .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy. One month after completion of exposure therapy, context renewal will be tested by comparing physiological and subjective responses to public speaking in the same virtual context as used during exposure therapy versus a context different than the one used during exposure therapy. The goal is to identify the dose of Scopolamine associated with the greatest reduction in context renewal. In addition, a secondary analysis will attempt to identify those individuals who benefit most from Scopolamine-augmentation of exposure therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Scopolamine .4mg | Experimental | Participants will be randomized to either .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy |
|
| Intranasal placebo | Placebo Comparator | Participants will be randomized to a placebo, administered via nasal drops, prior to each session of exposure therapy |
|
| Scopolamine .5mg | Experimental | Participants will be randomized to either .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy |
|
| Scopolamine .6mg | Experimental | Participants will be randomized to either .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Scopolamine | Drug | Participants will be randomized to either, .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Eye blink startle reflex | change from final exposure session to follow-up (8 weeks following baseline) | |
| Skin conductance responses and heart rate | change from final exposure session to follow-up (8 weeks following baseline) | |
| Subjective Units of Distress | change from final exposure session to follow-up (8 weeks following baseline) |
| Measure | Description | Time Frame |
|---|---|---|
| Self Statements During Public Speaking Scale | change from baseline to follow-up (8 weeks following baseline) | |
| Personal Report of Confidence as a Speaker Scale | change from baseline to follow-up (8 weeks following baseline) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michelle G. Craske, Ph.D. | Department of Psychology, UCLA | Principal Investigator |
| Michael Fanselow, Ph.D. | Department of Psychology, UCLA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Los Angeles | Los Angeles | California | 90095 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31174846 | Derived | Craske MG, Fanselow M, Treanor M, Bystritksy A. Cholinergic Modulation of Exposure Disrupts Hippocampal Processes and Augments Extinction: Proof-of-Concept Study With Social Anxiety Disorder. Biol Psychiatry. 2019 Nov 1;86(9):703-711. doi: 10.1016/j.biopsych.2019.04.012. Epub 2019 Apr 19. |
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| ID | Term |
|---|---|
| D000072861 | Phobia, Social |
| ID | Term |
|---|---|
| D010698 | Phobic Disorders |
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D012601 | Scopolamine |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
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| intranasal placebo | Drug | Participants will be randomized to a drug placebo, administered via nasal drops, prior to each session of exposure therapy |
|
| Subjective units of distress during in vivo speech | change from baseline to follow-up (8 weeks following baseline) |
| D009930 |
| Organic Chemicals |
| D001533 | Belladonna Alkaloids |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |