Trial · Interventional

CompletedPhase 1Results postedRegistry data

Oxytocin, Stress, Craving, Opioid Use Disorder

Short name OSCO

NCTNCT04051619Other id1904002426Other idP20GM130414

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 1
Enrollment: 20 participants (actual)
Sponsor: Brown University · Other
Design: Randomized · Quadruple masking
Countries: 1 country
United States
Start: 6 Jan 2020
Primary completion: 22 Dec 2023
Completion: 23 Dec 2023
First posted: 9 Aug 2019
Last update posted: 25 May 2025
Conditions: Opioid Use Disorder

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

20202021202220232024

Ph 1
OSCO
NCT04051619
6 Jan 2020 to 23 Dec 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

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

Arms2

Experimental
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.
Placebo comparator
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.

Primary outcomes1

Outcomes the sponsor listed as primary.

Opioid Craving
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.
Registry description
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 outcomes(4)

Safety and Tolerability of Oxytocin and Yohimbine in OUD Individuals Receiving Opioid Agonist Therapy: Opiate Withdrawal Syndrome
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.
Registry description
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
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.
Registry description
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)
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.
Registry description
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)
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.
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 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.

Opioid Craving

Group	Value (score on a scale)	Spread
Oxytocin	21.6	7.55
Matching Placebo	22.4	6.26

Secondary and other outcome results(5)

Secondary outcomeMean· 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: Opiate Withdrawal Syndrome

Group	Value (score on a scale)	Spread
Oxytocin	1.2	1.17
Matching Placebo	0.8	.75

Secondary outcomeMean· 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

Group	Value (score on a scale)	Spread
Oxytocin	1.8	2.10
Matching Placebo	2.5	2.39

Secondary outcomeMean· 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)

Group	Value (mmHg)	Spread
Oxytocin	127.9	19.97
Matching Placebo	124.2	19.80

Secondary outcomeMean· 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)

Group	Value (beat/min)	Spread
Oxytocin	83.0	16.7
Matching Placebo	80.0	13.9

Other pre specified outcomeMean· 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.

Stress-related Response in OUD Individuals Receiving Opioid Agonist Therapy: Salivary Cortisol

Group	Value (ug/dL)	Spread
Oxytocin	0.33	0.15
Matching Placebo	0.24	0.14

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
OxytocinOxytocin 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: Adjunct therapy	0 / 16	0 / 16	8 / 16
Matching PlaceboPlacebo was administered as nasal spray in each nostril once in the morning and once in the afternoon for 7 days: Adjunct therapy	0 / 17	0 / 17	8 / 17

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

More studies

1 study on this page

PubMed tag: none · 2025

Oxytocin Reduces Noradrenergic-Induced Opioid-Like Withdrawal Symptoms in Individuals on Opioid Agonist Therapy.

Gully et al. 2025Biological psychiatry global open sciencecited by 4

PMID 39534517PMC11555595DOI 10.1016/j.bpsgos.2024.100395PUB-39534517

Free to read · publisher termsCC BY-NC-ND

Read at source

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 70 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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.

PepBank is a research reference. Talk to a doctor before you use any peptide.