Oxytocin, Stress, Craving, Opioid Use Disorder

NCT ID: NCT04051619

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-06
• Study Completion Date: 2023-12-23

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.

Conditions

Opioid Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oxytocin first, then placebo

Oxytocin was administered as 40 IU/0.12 mL nasal spray in each nostril once in the morning and once in the afternoon for 7 days. After a 2 day washout period, Placebo was administered as nasal spray in each nostril once in the morning and once in the afternoon for 7 days.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Adjunct therapy

Matching placebo, then oxytocin

Placebo was administered as nasal spray in each nostril once in the morning and once in the afternoon for 7 days. After a 2 day washout period, oxytocin was administered as 40 IU/0.12 mL nasal spray in each nostril once in the morning and once in the afternoon for 7 days.

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: DRUG

Adjunct therapy

Interventions

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

Adjunct therapy

Intervention Type: DRUG

Other Intervention Names

Pitocin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

Brown University

OTHER

Sponsor Role: lead

Responsible Party

Carolina L Haass-Koffler

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brown University

Providence, Rhode Island, United States

Countries

United States

References

Gully BJ, Brown ZE, Hornbacher R, Brown JC, Back SE, McCance-Katz EF, Swift RM, Haass-Koffler CL. Oxytocin Reduces Noradrenergic-Induced Opioid-Like Withdrawal Symptoms in Individuals on Opioid Agonist Therapy. Biol Psychiatry Glob Open Sci. 2024 Sep 18;5(1):100395. doi: 10.1016/j.bpsgos.2024.100395. eCollection 2025 Jan.

Reference Type: RESULT

PMID: 39534517 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

P20GM130414

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1904002426

Identifier Type: -

Identifier Source: org_study_id