Oxytocin, Stress, Craving, Opioid Use Disorder (OSCO)

Brown University

Status and phase: Completed; Phase 1

Conditions: Opioid Use Disorder

Treatments: Drug: intranasal oxytocin, 40 IU, twice a day for 7 days

Study type: Interventional

Funder types: Other

Identifiers

NCT04051619

1904002426

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups, including a placebo group

oxytocin

Experimental group

Description:

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).

Treatment:

Drug: intranasal oxytocin, 40 IU, twice a day for 7 days

matching placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: intranasal oxytocin, 40 IU, twice a day for 7 days