Oxytocin + COPE Therapy for Alcoholism and PTSD

(COPE+OT Trial)

Overseen By Sudie Back, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical University of South Carolina

Must be taking: Psychotropic medications

Must not be taking: Psychotropic medications

Disqualifiers: Psychotic, Bipolar, Suicidal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether oxytocin, a hormone that affects social bonding, can reduce symptoms of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) in Veterans. Participants will receive either oxytocin or a placebo spray before weekly therapy sessions designed to treat both PTSD and substance use. The researchers aim to determine if oxytocin eases symptoms more effectively than the placebo. Veterans who struggle with both AUD and PTSD and are not currently undergoing behavioral treatment for these conditions might be a good fit for this trial. As a Phase 2 trial, this research measures how well oxytocin works in an initial, smaller group, offering Veterans a chance to contribute to important findings.

Will I have to stop taking my current medications?

If you are taking psychotropic medications, you need to be on a stable dose for at least 4 weeks before starting the study. If your medications were started in the past 4 weeks, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that intranasal oxytocin is generally safe for people. One study found a single 40-IU dose of intranasal oxytocin to be safe and well-tolerated, with participants not experiencing significant side effects. Another study found that repeated doses of oxytocin helped reduce PTSD symptoms without causing major problems.

Studies have shown that COPE therapy, a treatment for PTSD and substance use disorders, effectively reduces PTSD symptoms without increasing substance use. This indicates that COPE therapy is well-tolerated and does not cause harmful effects.

Overall, previous research has demonstrated the safety of both intranasal oxytocin and COPE therapy. This suggests they might be safe for individuals considering participation in this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using oxytocin with COPE therapy for treating alcoholism and PTSD because it targets the emotional and social aspects of these conditions in a new way. Oxytocin, often called the "love hormone," is administered as a nasal spray, which may enhance trust and emotional bonding, potentially improving therapy outcomes. Unlike traditional treatments like medication or exposure therapy alone, this combination aims to address both the physiological and psychological triggers of addiction and trauma. This dual approach could offer a more comprehensive solution, making therapy sessions more effective and potentially speeding up recovery.

What evidence suggests that this trial's treatments could be effective for alcoholism and PTSD?

Research has shown that oxytocin might help with symptoms of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). In this trial, participants in the Oxytocin Treatment Group will receive intranasal oxytocin alongside COPE Therapy. Studies suggest that oxytocin can enhance the effects of therapy, making it a promising treatment for both conditions simultaneously. Oxytocin appears to influence brain areas that manage emotions and rewards, crucial for both PTSD and AUD. Some evidence indicates that oxytocin can reduce anxiety and cravings, common in these disorders. While more research is needed, the results so far are encouraging for those dealing with AUD and PTSD. ^{6 7 8 9 10}

Who Is on the Research Team?

Sudie Back, PhD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for U.S. military Veterans aged 18-70 with moderate to severe alcohol use disorder (AUD) and PTSD, who are stable on any psychotropic meds for at least 4 weeks. It's not for those with bipolar disorders, current suicidal thoughts, acute alcohol withdrawal, pregnant or breastfeeding women, or anyone currently in AUD or PTSD therapy.

Inclusion Criteria

Able to provide written informed consent

I have been on a stable dose of my mental health medication for at least 4 weeks.

Meet DSM-5 diagnostic criteria for current moderate to severe alcohol use disorder

Exclusion Criteria

For MRI scan component: history of seizures or severe head injury, implanted metal devices or other metal (e.g., shrapnel). These participants will be eligible to enroll in the clinical trial but will not be eligible to participate in the neuroimaging component of the study

I have a history of or currently have severe mental health issues.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 12 weekly sessions of COPE Therapy with either Oxytocin or placebo

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure
• Intranasal Oxytocin
• Placebo

Trial Overview The study tests if oxytocin can help reduce symptoms of AUD and PTSD better than a placebo in Veterans undergoing COPE therapy. Participants will also undergo brain scans before and after treatment to see how the therapy works.

How Is the Trial Designed?

Group I: Oxytocin Treatment Group Experimental Treatment 2 Interventions

Participants will receive 12 weekly sessions of Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE Therapy), plus intranasal Oxytocin. 40-IU dose of Oxytocin self-administered 30 minutes prior to the start of each weekly COPE session.

Group II: Placebo Group Active Control 2 Interventions

Participants will receive 12 weekly sessions of Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE Therapy), plus placebo (intranasal saline spray). Intranasal dose of saline spray self-administered 30 minutes prior to the start of each weekly COPE session.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

In a study involving 67 male U.S. military veterans with PTSD and alcohol use disorder, intranasal oxytocin (40 IU) was found to marginally reduce cortisol reactivity to stress, particularly in those with higher baseline cortisol levels.

However, oxytocin did not significantly decrease alcohol craving, indicating that while it may help with stress response, it may not address all symptoms associated with the dual diagnosis of PTSD and alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of oxytocin on stress reactivity and craving in veterans with co-occurring PTSD and alcohol use disorder. Flanagan, JC., Allan, NP., Calhoun, CD., et al.[2020]

Intranasal oxytocin is a promising, low-cost treatment option for posttraumatic stress disorder (PTSD) with a strong safety profile, especially when combined with established psychotherapy methods.

Current research suggests that while oxytocin may enhance treatment outcomes for PTSD and related substance use disorders, further studies are needed to understand its mechanisms of action and optimize delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmenting Treatment for Posttraumatic Stress Disorder and Co-Occurring Conditions with Oxytocin. Flanagan, JC., Mitchell, JM.[2022]

In a study of 73 veterans with both PTSD and alcohol use disorder, intranasal oxytocin was found to significantly reduce post-stress task anger in individuals with low alcohol craving, suggesting its potential therapeutic value.

However, the effectiveness of oxytocin in reducing anger was less pronounced in those with high alcohol craving, indicating that individual differences in craving levels should be considered when evaluating oxytocin as a treatment for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Craving Moderates the Effects of Intranasal Oxytocin on Anger in Response to Social Stress Among Veterans With Co-Occurring Posttraumatic Stress Disorder and Alcohol Use Disorder. Melkonian, AJ., Flanagan, JC., Calhoun, CD., et al.[2022]

In a study involving 47 male patients with both alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD), intranasal oxytocin did not reduce self-reported alcohol craving or heart rate responses to alcohol cues compared to a placebo.

These results suggest that oxytocin may not be effective in managing cue-induced cravings in individuals with comorbid AUD-PTSD, highlighting the need for further research to explore its potential mechanisms and effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Oxytocin Administration on Cue-Induced Craving in Co-occurring Alcohol Use Disorder and PTSD: A Within-Participant Randomized Clinical Trial. Stauffer, CS., Meinzer, NK., Morrison, T., et al.[2022]

A mouse model of PTSD demonstrated that chronic stress exposure leads to a long-lasting increase in vulnerability to alcohol relapse, indicating a significant link between PTSD and alcohol use disorder.

Administration of oxytocin effectively blocked the stress-induced alcohol relapse in mice, suggesting its potential as a therapeutic option for individuals with PTSD and alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin Reduces Sensitized Stress-Induced Alcohol Relapse in a Model of Posttraumatic Stress Disorder and Alcohol Use Disorder Comorbidity. Becker, HC., Lopez, MF., King, CE., et al.[2023]

The study investigates the effects of intranasal oxytocin combined with psychotherapy (COPE) in treating veterans with co-occurring alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD), involving 180 participants over a 12-week period.

Oxytocin is believed to enhance treatment by targeting neurobiological issues common to both AUD and PTSD, potentially improving treatment outcomes and understanding the underlying brain mechanisms through fMRI assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COPE and oxytocin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in U.S. military veterans. Back, SE., Flanagan, JC., Killeen, T., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9998357/

COPE and Oxytocin for the Treatment of Co-Occurring PTSD ... Accumulating evidence suggests that the neuropeptide oxytocin (OT) is a promising pharmacotherapy to augment psychotherapy for AUD/PTSD. OT targets ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8938422/

Intranasal oxytocin administration impacts the acquisition and ... Administration of oxytocin directly after exposure to stress induced a short-term increase in traumatic memories while chronic administration of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S030645302030024X

Intranasal oxytocin as a potential therapeutic strategy in ... IN-OT modulates activity in cognitive, emotion and reward brain areas in PTSD. · Clinical evidences of efficacy for single IN-OT administrations are limited.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714423000071

COPE and oxytocin for the treatment of co-occurring PTSD ... Accumulating evidence suggests that the neuropeptide oxytocin (OT) is a promising pharmacotherapy to augment psychotherapy for AUD/PTSD. OT targets ...

5. nature.com nature.com/articles/s41398-025-03522-0

Altered association of plasmatic oxytocin with affective ... In humans, intranasal oxytocin was similarly found to decrease stress-induced anxiety and craving of cannabis in a randomized controlled trial [ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6223130/

Concurrent Treatment of PTSD and Substance Use ... Concurrent Treatment of PTSD and SUDs using Prolonged Exposure has been shown to reduce PTSD symptom severity without increasing substance use in an Australian ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6488423/

Concurrent Treatment of Substance Use Disorders and ... This study is the first to report on the use of an integrated, exposure-based treatment for co-occurring SUD and PTSD in a veteran sample.

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2836411

Concurrent Treatment of PTSD and Alcohol Use Disorder ... Conclusions and Relevance In this trial of integrated treatment vs relapse prevention, integrated treatment led to a greater reduction in PTSD ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306460318309882

A randomized clinical trial in military veterans Prolonged Exposure (PE) is an effective, evidence-based treatment for PTSD, but there is limited data on its use among individuals with current alcohol or drug ...

10. ptsd.va.gov ptsd.va.gov/professional/treat/cooccurring/tx_sud_va.asp

Treatment of Co-Occurring PTSD and Substance Use ... This PTSD 101 online course describes the correlates of co-occurring PTSD and SUD, treatment research and VA/DoD Clinical Practice Guideline recommendations.