Oxytocin Nasal Spray for PTSD

(CBCT-OT RCT Trial)

Overseen By Leslie A. Morland, PsyD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Disqualifiers: Substance dependence, Psychotic disorder, Borderline personality, others

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

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help veterans with posttraumatic stress disorder (PTSD) using a nasal spray containing oxytocin, a hormone that may enhance social behavior and trauma recovery. The researchers aim to determine if adding oxytocin to therapy involving both the veteran and their partner can improve PTSD symptoms and relationship satisfaction more effectively than therapy alone. Veterans diagnosed with PTSD for at least three months and in stable intimate relationships might be interested in participating. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking PTSD therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you have been on a stable psychoactive medication regimen for at least 2 months, so you do not need to stop your current medications if they are stable.

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

Research has shown that oxytocin nasal spray is generally safe for people. A review of 38 studies over 20 years found that most participants did not experience serious side effects. Common mild side effects included headaches, a stuffy nose, and temporary mood changes.

In some studies, participants who used the oxytocin nasal spray felt more trusting and empathetic, which are positive effects. Researchers are also studying oxytocin for its potential to aid in trauma recovery, including PTSD.

Overall, while oxytocin nasal spray appears safe for most people, monitoring for any side effects and informing a doctor if any occur is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Researchers are excited about intranasal oxytocin for PTSD because it offers a novel way to target the condition. Most current treatments, like SSRIs and cognitive therapies, focus on altering brain chemistry or behavior over time. However, oxytocin, a naturally occurring hormone, may enhance social bonding and emotional regulation, potentially providing more immediate relief. The nasal spray delivery method also ensures rapid absorption, which could lead to quicker therapeutic effects compared to traditional oral medications. This unique approach might offer a complementary option to existing therapies, providing new hope for those with PTSD.

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

Research has shown that using a nasal spray with oxytocin can enhance PTSD treatment. One study found that oxytocin lowered stress hormone levels in people with PTSD, potentially improving their response to therapy. Oxytocin also boosts brain activity related to feeling rewarded in social situations, which could enhance therapy sessions focused on relationship-building. In this trial, some participants will receive Brief Cognitive-Behavioral Conjoint Therapy combined with intranasal oxytocin to improve communication, empathy, and trust between partners. Early results suggest that when combined with therapy, oxytocin may alleviate PTSD symptoms and increase relationship satisfaction. ^{3 4 6 7 8}

Who Is on the Research Team?

Leslie A. Morland, PsyD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Lauren M. Sippel, PhD

Principal Investigator

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Are You a Good Fit for This Trial?

This trial is for veterans with PTSD who are in a relationship. It's designed to help improve both their PTSD symptoms and relationship quality. Participants must be willing to undergo couples therapy and use either an oxytocin or saline nasal spray.

Inclusion Criteria

I have been on the same mental health medication for at least 2 months.

I am a veteran over 18 with PTSD diagnosed at least 3 months after my trauma.

I am over 18 and willing to join the study but I don't have PTSD.

Exclusion Criteria

Imminent suicidality or homicidality in either member of the couple

Positive screen (7+) for borderline personality disorder (BPD) in either member of the couple as assessed by the MacLean Screening Instrument for BPD

Uncontrolled hypotension (systolic blood pressure <100 mm Hg) or hypertension (BP >160/100 mm Hg) as assessed by self-report and verified with VA chart review (in absence of chart documentation in past month, participant will be sent digital BP device and cuff to verify BP stability during video monitoring)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly, with either intranasal oxytocin or placebo administered prior to each session

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at mid-treatment, post-treatment, 3-month, and 6-month intervals

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Intranasal Oxytocin

Trial Overview The study tests if adding oxytocin nasal spray to brief couples therapy (bCBCT) is more effective than just the therapy with a saline placebo. The goal is to see if this combination can better treat PTSD and enhance relationship satisfaction among veterans.

How Is the Trial Designed?

Group I: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Oxytocin Experimental Treatment 2 Interventions

Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly. Prior to each session, the veteran participant will self-administer intranasal oxytocin.

Group II: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Placebo Placebo Group 2 Interventions

Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly. Prior to each session, the veteran participant will self-administer intranasal placebo solution.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Oxytocin (OXT) can be effectively delivered to the brain through nasal administration, achieving higher brain concentrations compared to intravenous delivery, despite lower plasma levels.

The study found that the nasal bioavailability of OXT is approximately 2%, and its therapeutic effects, such as stress relief, were observed only after intranasal application, highlighting the potential of this route for treating conditions like autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application. Tanaka, A., Furubayashi, T., Arai, M., et al.[2019]

A pilot study involving 10 U.S. veterans with PTSD and their partners showed that combining brief Cognitive-Behavioral Conjoint Therapy (bCBCT) with intranasal oxytocin led to significant improvements in relationship satisfaction and PTSD symptoms, with no serious adverse events reported.

Veterans experienced a large reduction in PTSD severity (effect size of 1.87), while both partners reported moderate to large improvements in relationship satisfaction, indicating that this approach is feasible and may enhance the effectiveness of traditional therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot test of intranasal oxytocin as an enhancer of brief couples therapy for posttraumatic stress disorder. Sippel, LM., Khalifian, CE., Knopp, KC., et al.[2023]

Intranasal administration of oxytocin (OT) effectively increases its concentration in the cerebrospinal fluid (CSF) and plasma, suggesting it can reach central nervous system targets.

Both delivery methods (intranasal spray and nebulizer) were effective in elevating CSF OT levels, with the nasal spray showing greater increases in plasma OT concentration compared to the nebulizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CSF and blood oxytocin concentration changes following intranasal delivery in macaque. Dal Monte, O., Noble, PL., Turchi, J., et al.[2021]

A multicenter randomized controlled trial involving 107 trauma-exposed patients showed that repeated intranasal oxytocin administration significantly reduced the development of PTSD symptoms up to six months after trauma, particularly in those with high acute PTSD symptoms.

Functional MRI studies indicated that a single dose of oxytocin increased amygdala reactivity to fearful stimuli, suggesting that while oxytocin may initially heighten fear responses, its repeated use can help mitigate long-term PTSD risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals. Frijling, JL.[2020]

In a study of 13 participants with PTSD, baseline levels of peripheral oxytocin did not correlate with the severity of PTSD symptoms, suggesting that oxytocin levels may not be a reliable biomarker for PTSD severity.

The study found that changes in peripheral oxytocin levels after treatment did not differ between those receiving intranasal oxytocin and those receiving a placebo, indicating that oxytocin administration may not directly influence PTSD symptom improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Preliminary Examination of Endogenous Peripheral Oxytocin in a Pilot Randomized Clinical Trial of Oxytocin-Enhanced Psychotherapy for Posttraumatic Stress Disorder. Sippel, LM., King, CE., Wahlquist, AE., et al.[2022]

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]

This Phase II study aims to evaluate the effectiveness of intranasal oxytocin combined with Prolonged Exposure (PE) therapy in reducing PTSD symptoms among U.S. military veterans, using a randomized, double-blind, placebo-controlled design.

The study will assess not only the reduction in PTSD symptom severity but also the rate of improvement and retention in therapy, providing insights into how oxytocin may enhance the effectiveness of existing PTSD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. Flanagan, JC., Mitchell, JM., Baker, NL., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6874414/

Augmenting Treatment for Posttraumatic Stress Disorder ... Oxytocin holds promise for facilitating more effective PTSD treatment, particularly when used in combination with evidence-supported psychotherapy interventions ...

2. nature.com nature.com/articles/s41386-021-01247-4

Intranasal oxytocin administration impacts the acquisition ... Oxytocin dampened cortisol reactivity to a laboratory stress task in patients with PTSD and comorbid alcohol use disorder who have high baseline ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5390752/

Intranasal oxytocin increases neural responses to social ... Oxytocin administration significantly increased the otherwise hypoactive left AI responses to social reward feedback observed in PTSD patients to a level ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06194851

Examining Intranasal Oxytocin Augmentation of Brief ... The primary aim of this study is to investigate the effects of Brief Cognitive Behavioral Conjoint Therapy (bCBCT) paired with intranasal oxytocin (OT) versus ...

5. istss.org istss.org/biological-perspectives-can-a-few-sprays-of-oxytocin-improve-treatment-for-posttraumatic-stress-disorder-lauren-m-sippel-phd/

Can a Few Sprays of Oxytocin Improve Treatment ... Intranasal oxytocin may be a safe and effective pharmacological mechanism for improving effectiveness of trauma-focused psychotherapies—but caution is ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306453011000862

A review of safety, side-effects and subjective reactions to ... This paper reviewed side effects and safety data on the use of intranasal oxytocin in 38 controlled trials conducted over the last 20 years.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11751854/

Effect of oxytocin nasal spray pretreatment on postoperative ... This study aims to investigate the effect of pretreatment with oxytocin nasal spray on postoperative ASD in patients with accidental trauma and fracture.

8. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(16)33067-0/fulltext

Intranasal Oxytocin to Prevent Posttraumatic Stress ... Intranasal oxytocin administration early after trauma may prevent PTSD, because oxytocin administration was previously found to beneficially impact PTSD ...