Oxytocin, Stress, Craving, Opioid Use Disorder
- Conditions
- Opioid Use Disorder
- Interventions
- Drug: intranasal oxytocin, 40 IU, twice a day for 7 days
- Registration Number
- NCT04051619
- Lead Sponsor
- Brown University
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description matching placebo intranasal oxytocin, 40 IU, twice a day for 7 days The oxytocin-matched placebo will be formulated at 5mg/0.1mL (5mg/spray) and dispensed as 10-mL nasal spray, twice a day (2 sprays per nostril) for 7 days (total daily dose: 40 international units, IU). oxytocin intranasal oxytocin, 40 IU, twice a day for 7 days The oxytocin will be formulated at 5mg/0.1mL (5mg/spray) and dispensed as 10-mL nasal spray, twice a day (2 sprays per nostril) for 7 days (total daily dose: 40 international units, IU).
- Primary Outcome Measures
Name Time Method Opioid Craving one day 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 during the stress induction produced by yohimbine or matching-placebo.
- Secondary Outcome Measures
Name Time Method Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: stress one day Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor stress (perceived stress scale , PSS) during lab sessions.
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: opiate withdrawal syndrome one day 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.
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: anxiety one day 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.
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: heart rate (HR) one day 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.
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: systolic/diastolic blood pressure (BP) one day Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor systolic/diastolic blood pressure (SBP/DBP) during lab sessions.
Trial Locations
- Locations (1)
Brown University
🇺🇸Providence, Rhode Island, United States