Opioid Use DisorderPhase 1OSCONCT04051619
Oxytocin, Stress, Craving, Opioid Use Disorder
A Phase 1 study testing intranasal oxytocin, 40 IU, twice a day for 7 days in people with Opioid Use Disorder, run by Brown University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- intranasal oxytocin, 40 IU, twice a day for 7 days
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jan 2020to 23 Dec 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Oxytocin to Reduce Stress-induced Craving in Individuals With Opioid Use Disorder
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.
Read the 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
- Being tested
- intranasal oxytocin, 40 IU, twice a day for 7 days
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intranasal oxytocin, 40 IU, twice a day for 7 daysDrug
Also called Pitocin
Adjunct therapy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: intranasal oxytocin, 40 IU, twice a day for 7 days |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2019
- Study start6 Jan 2020
- Primary completion22 Dec 2023
- Study completion23 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Carolina L Haass-Koffler, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04051619
- Sponsor's protocol ID
- 1904002426
- Other IDs
- P20GM130414
- Acronym
- OSCO
- Status last verified
- May 2025
- First submitted
- 6 Aug 2019
- Last updated
- 25 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 39534517
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxytocin to Reduce Stress-induced Craving in Individuals With Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT04051619
- Acronym / sponsor ID
- OSCO / 1904002426
- Conditions
- Opioid Use Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 6 Jan 2020 (actual)
- Primary completion
- 22 Dec 2023 (actual)
- Study completion
- 23 Dec 2023 (actual)
- First posted
- 9 Aug 2019 (actual)
- Results
- Posted 25 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oxytocin first, then placebo | Experimental | Drug: intranasal oxytocin, 40 IU, twice a day for 7 daysOxytocin 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. |
| Matching placebo, then oxytocin | Placebo comparator | Drug: intranasal oxytocin, 40 IU, twice a day for 7 daysPlacebo 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intranasal oxytocin, 40 IU, twice a day for 7 daysAlso: PitocinAdjunct therapy | Drug | Matching placebo, then oxytocin, Oxytocin first, then placebo |
Primary outcome
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.
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)
4 secondary outcomes
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 39534517Gully 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing intranasal oxytocin, 40 IU, twice a day for 7 days in people with Opioid Use Disorder, run by Brown University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04051619, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.