Opioid Use Disorder
Conditions
Brief summary
Although stress has long been linked to substance use, craving and relapse, there are no available medications that target stress-induced substance use disorder (SUD). In particular, with the rise in opioid use, there is still a crucial need for developing effective pharmacological treatments that target and integrate the complexity of this disease. The long term goal of this project is to identify the key neuroendocrine pathways that are responsible for stress-induced craving in individuals with opioid use disorder (OUD) in order to better understand how they can be effectively treated.
Detailed description
The goal of this research is to evaluate whether oxytocin, a hormone with anti-stress properties, dampens the effects of stress and opioid-associated cues on opioid craving and thus may be an effective adjunctive treatment for OUD. The central hypothesis of this research is that oxytocin will reduce stress-induced opioid craving in patients with OUD treated with buprenorphine/naloxone as opioid replacement therapy (ORT). This hypothesis is based on the model of addiction (Koob, Neuron 2008) in which chronic substance use and stress lead to neurobehavioral counter-adaptations that dysregulate biobehavioral response. In this double-blind, cross-over, placebo controlled, randomized trial, individuals with OUD (N=20 who are currently receiving treatment with buprenorphine/naloxone or methadone will be randomized to intranasal oxytocin (40 international units, IU) and oxytocin-matched placebo, administered twice/day for 7 days with a minimum of two days between the opposite condition (oxytocin or placebo). On days 5 and 7, and on days 14 and 16, participants will complete two counter-balanced sessions in which they receive yohimbine (32.4 mg) or yohimbine-matched placebo.
Interventions
DRUGintranasal oxytocin, 40 IU, twice a day for 7 days
Adjunct therapy
Sponsors
National Institute of General Medical Sciences (NIGMS)
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female (50%), 18 to 70 (inclusive) years of age; * Currently meets DSM-5 criteria for OUD; * Currently on a stable dose of buprenorphine/naloxone or methadone for at least 3 months; * In good health as confirmed by medical history, physical examination and blood work (Liver function within 5x the Upper normal limits (AST/ALT) and renal function within 2x the Lower Normal Limit (bilirubin, creatine clearance). * Willing to take medication and adhere to the study procedures;- Understand informed consent and questionnaires in English at an 8th grade level; * Clinical Opiate Withdrawal Scale (COWS) = 0 at study screening and prior laboratory sessions.
Exclusion criteria
* Women who are breastfeeding, test positive for pregnancy or are unwilling to use medically-approved birth control; * Suicide attempts in the last three months; * Current substance disorder other than marijuana, nicotine and caffeine as assessed by self-report and urine toxicology screen at baseline; * Current use of medications that may interact with study medications; * History of hypersensitivity to study medications; * Clinically significant electrolyte abnormalities, current rhinitis or use of vasoconstricting medications or prostaglandins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Craving | Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16. | The primary outcome will test the effect of oxytocin, compared to placebo, on opioid craving during two laboratory stress induction, paired to a cue reactivity paradigm. The dependent measure for the primary aim is the Desire for Drug Questionnaire (DDQ). The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the DDQ will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo. Minimum score=0 no craving at all, maximum score= 91 severe craving (13 questions on a 7-step Likert-scale) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16. | Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: opiate withdrawal syndrome by Clinical Opiate Withdrawal Scale (COWS) pre and post the laboratory procedures. The COWS is an 11-item scale designed to be administered by a clinician. Minimum=0 (no withdrawal); Maximum=36 (sever withdrawal). The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. High score worse outcome. At each visit the COWS will be administered 2 times: before starting any procedure, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo. |
| Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16. | Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor anxiety (HAMA) during lab sessions. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of Minimum=0 (not present), Maximum=56 (sever), where \<17 mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. High score worse outcome. At each visit the HAMA will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo. |
| Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16. | Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor systolic blood pressure (SBP) during lab sessions. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the SBP will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo. |
| Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16. | Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor Heart rate (HR) during lab sessions. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the HR will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16. | Cortisol (biomarker for stress level) will be measured at the same 3 time points as other measures. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the cortisol will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Outcome measures are grouped into a single arm: all study participants. This is because the crossover design led participants to receive both oxytocin and the matched placebo during the study. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 2nd Allocation (Cross Over) | Completed the study prior to initiation cross-over design | 2 | 2 |
| 2nd Allocation (Cross Over) | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 49.6 years STANDARD_DEVIATION 11.65 |
| Clinical Opiate Withdrawal Scale (COWS) | .9 score on an 11-item scale STANDARD_DEVIATION 1.4 |
| Race/Ethnicity, Customized Race Black or multiracial | 4 Participants |
| Race/Ethnicity, Customized Race Caucasian | 16 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 8 / 16 | 8 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Opioid Craving
The primary outcome will test the effect of oxytocin, compared to placebo, on opioid craving during two laboratory stress induction, paired to a cue reactivity paradigm. The dependent measure for the primary aim is the Desire for Drug Questionnaire (DDQ). The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the DDQ will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo. Minimum score=0 no craving at all, maximum score= 91 severe craving (13 questions on a 7-step Likert-scale)
Time frame: Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Opioid Craving | baseline (yohimbine condition) | 21.6 score on a scale | Standard Deviation 7.55 |
| Oxytocin | Opioid Craving | after stress (yohimbine condition) | 23.3 score on a scale | Standard Deviation 7.66 |
| Oxytocin | Opioid Craving | cue exposure (yohimbine condition) | 22.9 score on a scale | Standard Deviation 8.09 |
| Oxytocin | Opioid Craving | baseline (yohimbine-placebo condition) | 22.7 score on a scale | Standard Deviation 7.85 |
| Oxytocin | Opioid Craving | after stress (yohimbine-placebo condition) | 23.1 score on a scale | Standard Deviation 6.95 |
| Oxytocin | Opioid Craving | cue exposure (yohimbine-placebo condition) | 22.6 score on a scale | Standard Deviation 6.74 |
| Matching Placebo | Opioid Craving | after stress (yohimbine-placebo condition) | 21.7 score on a scale | Standard Deviation 7.18 |
| Matching Placebo | Opioid Craving | baseline (yohimbine condition) | 22.4 score on a scale | Standard Deviation 6.26 |
| Matching Placebo | Opioid Craving | baseline (yohimbine-placebo condition) | 19.5 score on a scale | Standard Deviation 6.16 |
| Matching Placebo | Opioid Craving | after stress (yohimbine condition) | 23.4 score on a scale | Standard Deviation 7.53 |
| Matching Placebo | Opioid Craving | cue exposure (yohimbine-placebo condition) | 20.9 score on a scale | Standard Deviation 7.88 |
| Matching Placebo | Opioid Craving | cue exposure (yohimbine condition) | 23.0 score on a scale | Standard Deviation 7.92 |
Secondary
Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety
Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor anxiety (HAMA) during lab sessions. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of Minimum=0 (not present), Maximum=56 (sever), where \<17 mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. High score worse outcome. At each visit the HAMA will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo.
Time frame: Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | Baseline (Yohimbine condition) | 1.8 score on a scale | Standard Deviation 2.1 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after stress (Yohimbine condition) | 2.0 score on a scale | Standard Deviation 2.98 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after cue exposure (Yohimbine condition) | 1.9 score on a scale | Standard Deviation 1.85 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | Baseline (Yohimbine-placebo condition) | 1.3 score on a scale | Standard Deviation 1.69 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after stress (Yohimbine-placebo condition) | 0.9 score on a scale | Standard Deviation 1.3 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after cue exposure (Yohimbine-placebo condition) | 0.9 score on a scale | Standard Deviation 1.7 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after stress (Yohimbine-placebo condition) | 1.2 score on a scale | Standard Deviation 1.5 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | Baseline (Yohimbine condition) | 2.5 score on a scale | Standard Deviation 2.39 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | Baseline (Yohimbine-placebo condition) | 2.2 score on a scale | Standard Deviation 2.35 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after stress (Yohimbine condition) | 2.7 score on a scale | Standard Deviation 3.65 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after cue exposure (Yohimbine-placebo condition) | 1.0 score on a scale | Standard Deviation 2.14 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Anxiety | after cue exposure (Yohimbine condition) | 2.7 score on a scale | Standard Deviation 2.53 |
Secondary
Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR)
Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor Heart rate (HR) during lab sessions. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the HR will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo.
Time frame: Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | baseline (yohimbine condition) | 83.0 beat/min | Standard Deviation 16.7 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after stress (yohimbine condition) | 75.5 beat/min | Standard Deviation 14.6 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after cue exposure (yohimbine condition) | 74.6 beat/min | Standard Deviation 18.2 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | baseline (yohimbine-placebo condition) | 77.9 beat/min | Standard Deviation 16.1 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after stress (yohimbine-placebo condition) | 69.4 beat/min | Standard Deviation 14.7 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after cue exposure (yohimbine-placebo condition) | 66.3 beat/min | Standard Deviation 12.4 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after stress (yohimbine-placebo condition) | 81.0 beat/min | Standard Deviation 12.9 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | baseline (yohimbine condition) | 80.0 beat/min | Standard Deviation 13.9 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | baseline (yohimbine-placebo condition) | 80.0 beat/min | Standard Deviation 13.1 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after stress (yohimbine condition) | 83.1 beat/min | Standard Deviation 11.2 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after cue exposure (yohimbine-placebo condition) | 82.0 beat/min | Standard Deviation 17.9 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Heart Rate (HR) | after cue exposure (yohimbine condition) | 77.5 beat/min | Standard Deviation 13.1 |
Secondary
Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome
Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: opiate withdrawal syndrome by Clinical Opiate Withdrawal Scale (COWS) pre and post the laboratory procedures. The COWS is an 11-item scale designed to be administered by a clinician. Minimum=0 (no withdrawal); Maximum=36 (sever withdrawal). The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. High score worse outcome. At each visit the COWS will be administered 2 times: before starting any procedure, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo.
Time frame: Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Baseline (Yohimbine Condition) | 1.2 score on a scale | Standard Deviation 1.17 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Post (Yohimbine Condition) | 1.8 score on a scale | Standard Deviation 2.23 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Baseline (Yohimbine-placebo Condition) | 1.0 score on a scale | Standard Deviation 1.45 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Post (Yohimbine-placebo Condition) | 0.7 score on a scale | Standard Deviation 0.84 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Post (Yohimbine-placebo Condition) | 0.6 score on a scale | Standard Deviation 1.1 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Baseline (Yohimbine Condition) | 0.8 score on a scale | Standard Deviation 0.75 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Baseline (Yohimbine-placebo Condition) | 1.3 score on a scale | Standard Deviation 1.38 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome | Post (Yohimbine Condition) | 3.0 score on a scale | Standard Deviation 3.3 |
Secondary
Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP)
Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor systolic blood pressure (SBP) during lab sessions. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the SBP will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo.
Time frame: Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | baseline (yohimbine condition) | 127.9 mmHg | Standard Deviation 19.97 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after stress (yohimbine condition) | 134.2 mmHg | Standard Deviation 21.9 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after cue exposure (yohimbine condition) | 133.4 mmHg | Standard Deviation 28.8 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | baseline (yohimbine-placebo condition) | 129.2 mmHg | Standard Deviation 16.3 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after stress (yohimbine-placebo condition) | 120.8 mmHg | Standard Deviation 10.9 |
| Oxytocin | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after cue exposure (yohimbine-placebo condition) | 123.9 mmHg | Standard Deviation 16.5 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after stress (yohimbine-placebo condition) | 121.3 mmHg | Standard Deviation 16.6 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | baseline (yohimbine condition) | 124.2 mmHg | Standard Deviation 19.8 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | baseline (yohimbine-placebo condition) | 126.9 mmHg | Standard Deviation 20.5 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after stress (yohimbine condition) | 137.2 mmHg | Standard Deviation 18.3 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after cue exposure (yohimbine-placebo condition) | 123.0 mmHg | Standard Deviation 13.4 |
| Matching Placebo | Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Systolic Blood Pressure (SBP) | after cue exposure (yohimbine condition) | 147.2 mmHg | Standard Deviation 25.4 |
Other Pre-specified
Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol
Cortisol (biomarker for stress level) will be measured at the same 3 time points as other measures. The stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the cortisol will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo.
Time frame: Before starting any procedure, after the yohimbine challenge, and after the cue-reactivity at each laboratory session, which occurred between days 5-7 and days 14-16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | baseline (yohimbine condition) | 0.33 ug/dL | Standard Deviation 0.15 |
| Oxytocin | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after stress (yohimbine condition) | 0.29 ug/dL | Standard Deviation 0.11 |
| Oxytocin | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after cue exposure (yohimbine condition) | 0.32 ug/dL | Standard Deviation 0.25 |
| Oxytocin | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | baseline (yohimbine-placebo condition) | 0.28 ug/dL | Standard Deviation 0.21 |
| Oxytocin | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after stress (yohimbine-placebo condition) | 0.23 ug/dL | Standard Deviation 0.13 |
| Oxytocin | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after cue exposure (yohimbine-placebo condition) | 0.20 ug/dL | Standard Deviation 0.11 |
| Matching Placebo | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after stress (yohimbine-placebo condition) | 0.24 ug/dL | Standard Deviation 0.21 |
| Matching Placebo | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | baseline (yohimbine condition) | 0.24 ug/dL | Standard Deviation 0.14 |
| Matching Placebo | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | baseline (yohimbine-placebo condition) | 0.31 ug/dL | Standard Deviation 0.31 |
| Matching Placebo | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after stress (yohimbine condition) | 0.27 ug/dL | Standard Deviation 0.16 |
| Matching Placebo | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after cue exposure (yohimbine-placebo condition) | 0.17 ug/dL | Standard Deviation 0.13 |
| Matching Placebo | Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol | after cue exposure (yohimbine condition) | 0.80 ug/dL | Standard Deviation 0.7 |