Behavioral and Pharmacological Reconsolidation Interference in Misophonia

• Propranolol Hydrochloride tablet (Drug): Single dose of 40 mg propranolol tablet
• Reminder (Behavioral): Reactivation of misophonia trigger memory
• Counterconditioning (Behavioral): Counterconditioning will consist of presentation of misophonia cues paired with monetary rewards.
• Placebo (Drug): Matching placebo tablet

Primary outcomes

• Change in average Galvanic skin response based on deflections of a wave [Baseline and after 6 hours]: Using galvanic skin response based on deflections of a wave, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. A greater deflection indicates greater sympathetic nervous system arousal.
• Change in average heart rate [Baseline and after 6 hours]: Using heart rate measurement, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. Reduced heart rate will indicate manipulation efficacy
• Change in Approach-Avoidance test [Baseline and after 6 hours]: Using an approach-avoidance test, the difference between the monetary amounts earned before and after the pharmacological or behavioral manipulation will be measured. The minimum monetary amount earned is $0 and the maximum monetary amount earned is $23. A higher monetary amount earned indicates greater approach towards an avoidant cue. The difference in monetary amounts across conditions will be compared.

Secondary outcomes

• Change in Approach-Avoidance test [about 1 week later]: Using an approach-avoidance test, the difference between the monetary amounts earned before and after the pharmacological or behavioral manipulation will be measured. The minimum monetary amount earned is $0 and the maximum monetary amount earned is $23. A higher monetary amount earned indicates greater approach towards an avoidant cue. The difference in monetary amounts across conditions will be compared.
• Change in Approach-Avoidance test [Baseline and 1 month later]: Using an approach-avoidance test, the difference between the monetary amounts earned before and after the pharmacological or behavioral manipulation will be measured. The minimum monetary amount earned is $0 and the maximum monetary amount earned is $23. A higher monetary amount earned indicates greater approach towards an avoidant cue. The difference in monetary amounts across conditions will be compared.
• Change in decision making task [Baseline and after 6 hours]: Using a decision making task based on choice behavior (choosing the correct machine more often), the study team will fit computational models to understand reactivity to misophonia-related cues across conditions. The study team will measure a difference in the task responses after the pharmacological or behavioral manipulation. Measures will include learning rate, and a link between prediction error and self-reported mood. The scores across conditions will be compared.
• Change in decision making task [Baseline and about 1 week]: Using a decision making task based on choice behavior (choosing the correct machine more often), the study team will fit computational models to understand reactivity to misophonia-related cues across conditions. The study team will measure a difference in the task responses after the pharmacological or behavioral manipulation. Measures will include learning rate, and a link between prediction error and self-reported mood. The scores across conditions will be compared.
• Change in decision making task [Baseline and 1 month later]: Using a decision making task based on choice behavior (choosing the correct machine more often), the study team will fit computational models to understand reactivity to misophonia-related cues across conditions. The study team will measure a difference in the task responses after the pharmacological or behavioral manipulation. Measures will include learning rate, and a link between prediction error and self-reported mood. The scores across conditions will be compared.
• Change in Average Galvanic skin response based on deflections of a wave [about 1 week later]: Using galvanic skin response based on deflections of a wave, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. A greater deflection indicates greater sympathetic nervous system arousal.
• Change in Average Galvanic skin response based on deflections of a wave [about 1 month later]: Using galvanic skin response based on deflections of a wave, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. A greater deflection indicates greater sympathetic nervous system arousal.
• Change in average heart rate [about 1 week later]: Using heart rate measurement, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. Reduced heart rate will indicate manipulation efficacy
• Change in average heart rate [about 1 month later]: Using heart rate measurement, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. Reduced heart rate will indicate manipulation efficacy

Sex: All, ages: 18 Years to 55 Years

Inclusion Criteria:

* Hypersensitive to presence of a specific sound, which may be accompanied by irritation, anger/outbursts, or fear.
* Must be between the ages of 18 - 55.
* Must be fluent in English since the study's instructions, surveys, and tasks will be in English

Exclusion Criteria:

* Disability or medical condition that prohibits completion of study. Participants must be able to complete all study procedures to ensure optimal conditions for data analysis.
* CNS disease, such as history of brain abnormalities (e.g., neoplasms, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), or other neurological disease, history of head trauma (defined as loss of consciousness>3 min), or history of seizures without a resolved etiology. CNS disease and drugs that act in the peripheral or central nervous system are likely to have effects on patterns of neural activity. We wish to minimize confounding variables.
* Recently used drugs of abuse.
* Pregnancy. The risks associated with neither propranolol exposure during gestation have been studied extensively. We wish to safeguard the health of potential participants and their children.
* Lactation. Propranolol is excreted in human breast-milk, and its impact on infant development has not been studied. We wish to safeguard the health of potential participants and their children.
* Regular use of medication metabolized in the CYP2D6, 1A2, or 2C19 pathways. Drugs that are metabolized in the same pathway as propranolol may increase its efficacy or toxicity. We wish to safeguard the health of participants.
* Blood pressure over 150/100 or under 100/60 (applicable for either systolic or diastolic measures) and any hypertension requiring medication. Propranolol is known to pose additional risk to individuals with a number of medical conditions. We wish to safeguard the health of our participants.
* Pulse over 100 or under 55.
* History of cardiovascular illness such as cardiac arrhythmia, coronary heart disease or any cardiac dysfunction that requires medication.
* Active respiratory illness including bronchospastic pulmonary disease and chronic obstructive pulmonary disease
* Diabetes mellitus.
* Other medical conditions that make it unsafe to take propranolol (e. g. allergy to propranolol).

• Daniela Schiller, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
• James Murrough, MD, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
• Laili Soleimani, MD, Msc, Principal investigator, Icahn School of Medicine at Mount Sinai