Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder

In Phase II, participants will provide a weekly urine sample to determine if opioids have been used in the past week (in conjunction with a self-report). A urine drug screen cup will be used to detect presence of: Amphetamines, Buprenorphine, Benzodiazepines, Cocaine, Ethyl Glucuronide, Fentanyl, Synthetic Marijuana, Ecstasy, Methamphetamines, Methadone, Opiates / Morphine, Oxycodone, Cannabinoid (Marijuana), and Tramadol. The urine drug screen cup also contains a temperature strip to confirm appropriate temperature of the sample and an adulteration panel for determination of sample tampering.

In Phase II, participants will be asked weekly to self-report any use of opioids to determine if opioids have been used in the past week (in conjunction with a UDS sample).

The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.

The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.

The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.

The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.

The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.

The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.

The 3-item Opioid Craving Scale was adapted from the 3-item Cocaine Craving Scale for use with opioids. The original 5-item version was found to be valid and unidimensional among cocaine-dependent individuals. Participants are asked to answer the following three questions with responses ranging from 0-10, where 0 = Not at all and 10 = Extremely. Total possible score ranges from 0 to 30 with greater scores indicating higher opioid craving.

• How much do you currently crave opiates?
• In the past week, please rate how strong your desire to use opiates has been when something in the environment has reminded you of opiates?
• Please imagine yourself in the environment in which you previously used opiates. If you were in this environment today and if it were the time of day that you typically used opiates, what is the likelihood that you would use opiates today?

The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.

The PHQ-9 is a validated tool in mental health and considered a powerful tool to assist clinicians with diagnosing depression and monitoring treatment response. The relationship between opioid use and depression is bidirectional. The PHQ-9 is a nine-item depression scale and is based directly on the nine diagnostic criteria for major depressive disorder in the DSM-IV. Each of the nine items is rated on a 0 (not at all) to 3 (nearly every day) scale. A total score is calculated by summing the nine items. Scores range from 0 to 27 and higher scores indicate a higher degree of depression.

The PHQ-9 is a validated tool in mental health and considered a powerful tool to assist clinicians with diagnosing depression and monitoring treatment response. The relationship between opioid use and depression is bidirectional. The PHQ-9 is a nine-item depression scale and is based directly on the nine diagnostic criteria for major depressive disorder in the DSM-IV. Each of the nine items is rated on a 0 (not at all) to 3 (nearly every day) scale. A total score is calculated by summing the nine items. Scores range from 0 to 27 and higher scores indicate a higher degree of depression.

Symptoms of post-traumatic stress disorder (PTSD) and opiate dependency may overlap, to which, opioid withdrawal symptoms may emulate PTSD hyperactive startle response. This is indicative a common physiological mechanism. The PCL-5 scale is the gold standard in PTSD assessment. It consisted of a 20-item self-report measurement that is capable of measuring symptom change during and after treatment. Additionally, the scale can provide a provisional PTSD diagnosis. Each of the 20 items is rated on a 0 (not at all) to 4 (extremely) scale. A total symptom severity score is calculated by summing the 20 items. Scores range from 0 and 80 and higher scores indicating a higher degree of PTSD symptomology. Evidence suggests that a10 to 20-point reduction in score represents a clinically significant change in PTSD symptoms.

Symptoms of post-traumatic stress disorder (PTSD) and opiate dependency may overlap, to which, opioid withdrawal symptoms may emulate PTSD hyperactive startle response. This is indicative a common physiological mechanism. The PCL-5 scale is the gold standard in PTSD assessment. It consisted of a 20-item self-report measurement that is capable of measuring symptom change during and after treatment. Additionally, the scale can provide a provisional PTSD diagnosis. Each of the 20 items is rated on a 0 (not at all) to 4 (extremely) scale. A total symptom severity score is calculated by summing the 20 items. Scores range from 0 and 80 and higher scores indicating a higher degree of PTSD symptomology. Evidence suggests that a10 to 20-point reduction in score represents a clinically significant change in PTSD symptoms.

The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research. The questionnaire consists of 7 questions in which participants are asked to rate each item on a 0 (not at all) to 3 (nearly every day). GAD-7 total score for the seven items ranges from 0 to 21 where 0-4 represents minimal anxiety, 5-9 represents mild anxiety, 10-14 represents moderate anxiety and 15-21 represent severe anxiety.

The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research. The questionnaire consists of 7 questions in which participants are asked to rate each item on a 0 (not at all) to 3 (nearly every day). GAD-7 total score for the seven items ranges from 0 to 21 where 0-4 represents minimal anxiety, 5-9 represents mild anxiety, 10-14 represents moderate anxiety and 15-21 represent severe anxiety.

The WHOQOL-BREF is a shorter version of the original assessment tool and is commonly used in clinical trials with participants undergoing substance use disorder intervention. The WHOQOL-BREF is comprised of 26-items and assesses the participant's quality of life across specific domains: physical health, psychological health, social relationships, and environment. In addition, there are 2 items that measure overall quality of life and general health. Participants rate how much they have experienced each item in the preceding 2 weeks on a 5-point Likert scale ranging from 1 (not at all) to 5 (completely). Domain scores are scaled in a positive direction with higher scores denoting higher quality of life. The mean score of items within each domain is used to calculate the domain score. Raw domain scores will be converted to a 0 to 100 scale.

The WHOQOL-BREF is a shorter version of the original assessment tool and is commonly used in clinical trials with participants undergoing substance use disorder intervention. The WHOQOL-BREF is comprised of 26-items and assesses the participant's quality of life across specific domains: physical health, psychological health, social relationships, and environment. In addition, there are 2 items that measure overall quality of life and general health. Participants rate how much they have experienced each item in the preceding 2 weeks on a 5-point Likert scale ranging from 1 (not at all) to 5 (completely). Domain scores are scaled in a positive direction with higher scores denoting higher quality of life. The mean score of items within each domain is used to calculate the domain score. Raw domain scores will be converted to a 0 to 100 scale.

The BARC-10 is a short,10-item measure that examines recovery capital globally. Items were selected from the ARC for the BARC-10 using item response theory. The BARC-10 measures a unidimensional (i.e., global) construct of recovery capital across all the original 10 domains of the ARC. On average, it takes 2-5 minutes to complete. Scores range from 6-60. Individuals who have a recovery capital score of 47 or higher are likely to reach or sustain a year or longer of recovery from substance use disorder.

The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.

In Phase II, participants will provide a weekly urine sample to determine if opioids have been used in the past week (in conjunction with a self-report). A urine drug screen cup will be used to detect presence of: Amphetamines, Buprenorphine, Benzodiazepines, Cocaine, Ethyl Glucuronide, Fentanyl, Synthetic Marijuana, Ecstasy, Methamphetamines, Methadone, Opiates / Morphine, Oxycodone, Cannabinoid (Marijuana), and Tramadol. The urine drug screen cup also contains a temperature strip to confirm appropriate temperature of the sample and an adulteration panel for determination of sample tampering.

In addition to the 14-Panel Urine Drug Screen cup, a xylazine test strip will be used to detect the presence of xylazine in the urine.