Oxytocin, Stress, Craving, Opioid Use Disorder

NCT04051619 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 1904002426P20GM130414
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

Secondary Outcomes (4)

• 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.

• 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.

• 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.

• 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.

Other Outcomes (1)

• 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.

Study Arms (2)

Oxytocin first, then placebo

EXPERIMENTAL

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.

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

Matching placebo, then oxytocin

PLACEBO COMPARATOR

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.

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

Interventions

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

Adjunct therapy

Also known as: Pitocin

Matching placebo, then oxytocin; Oxytocin first, then placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brown University: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Brown University

Providence, Rhode Island, 02291, United States

Location

Related Publications (1)

• 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.

  PMID: 39534517 RESULT

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Attempting to probe and measure opioid craving in this setting. This study utilized a guided opioid visualization technique, the presence of drug paraphernalia, and an opioid-related video cue. These cues were broad, and different aspects of them may have proved significant to participants at different times. While this is a laboratory procedure limitation, it may also further support the use of OAT for craving management. The study's small sample size and balance between males/females.

Results Point of Contact

• Title: Carolina Haass-Koffler, PharmD, PhD (PI)
• Organization: Brown University

carolina_haass-koffler@brown.edu

4155191385

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: August 9, 2019
• Study Start: January 6, 2020
• Primary Completion: December 22, 2023
• Study Completion: December 23, 2023
• Last Updated: May 25, 2025
• Results First Posted: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)