Propranolol + Memory Reactivation for PTSD

Overseen By James Cappellucci

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must be taking: Propranolol

Must not be taking: Antihypertensives, Antiarrhythmics, Benzodiazepines

Disqualifiers: Low blood pressure, Heart conditions, Asthma, Pregnancy, 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: 10

Duration: 6 weeks

80 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 people with post-traumatic stress disorder (PTSD) using propranolol, a beta-blocker that might weaken traumatic memories. The study will test whether adding unexpected elements, such as singing, to memory sessions can further reduce stress responses. Participants will be divided into two groups: one with standard memory reactivation and the other with added surprises. Ideal candidates are those who have experienced a traumatic event and have PTSD symptoms affecting their daily lives. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

If you are taking medications like anti-hypertensives, antiarrhythmics, or benzodiazepines, you may need to stop them due to potential interactions with propranolol. If you are on stable doses of other medications, you should not change them during the study unless it's urgent.

What is the safety track record for these treatments?

Research has shown that taking propranolol while recalling a traumatic memory can help reduce PTSD symptoms. Studies have found that this treatment can lower stress signals in the body, such as heart rate and sweating. Most participants in these studies tolerated propranolol well.

Propranolol is a common medication for heart problems and has FDA approval for other uses, indicating it has been tested for safety in humans for these conditions. Some earlier studies suggested it might not always help with PTSD symptoms, but others showed it can be beneficial. This suggests it might work better for some people than others.

For those considering joining a trial, propranolol has been safely used by many people. However, staying informed and discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores a novel approach to managing PTSD by combining memory reactivation techniques with the beta-blocker propranolol. Unlike traditional treatments like psychotherapy and SSRIs that typically focus on managing symptoms, this method aims to weaken the emotional impact of traumatic memories directly. The "mismatch reactivation condition" introduces subtle changes during memory recall sessions, potentially disrupting the way traumatic memories are stored in the brain. This innovative approach could lead to faster and longer-lasting relief from PTSD symptoms compared to existing options.

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

Research has shown that taking propranolol, a medication, before thinking about traumatic memories can help reduce PTSD symptoms. In this trial, participants in the mismatch reactivation condition will take propranolol before recalling their trauma narratives. Studies have found that this can lead to fewer symptoms and a lower heart rate. Meanwhile, techniques involving revisiting memories to change their impact, as used in the standard reactivation condition, can lessen PTSD symptoms, depression, and feelings of disconnection from reality. These findings suggest that using propranolol with memory reactivation could be a promising way to ease PTSD symptoms. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 who have experienced a traumatic event and show significant stress symptoms, with a PCL-5 score over 33. They must react strongly during baseline imagery testing to qualify. Exclusions include certain medical conditions like heart failure or asthma, low blood pressure or heart rate, drug abuse, pregnancy, other psychiatric disorders, current psychotherapy (except supportive), inability to understand English or give informed consent.

Inclusion Criteria

I am between 18-65, experienced a traumatic event, and have a high stress score.

We are looking for participants who have experienced a traumatic event, which may include those with PTSD.

During a specific test, participants need to meet certain mental and physical criteria to be randomly selected for the study.

Exclusion Criteria

Current participation in any psychotherapy other than supportive. Participants will be asked not to initiate new psychotherapy during the proposed two-month study period (excluding the one-month follow-up) except in clinically urgent circumstances. If this becomes necessary, a decision will be made on a case-by-case basis about retaining the participant or terminating participation

I haven't started or changed any mental health medication in the last two months.

Presence of a contraindicating psychiatric condition, e.g., psychotic, bipolar, melancholic, or active substance use disorder; or suicidality (see below)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Baseline assessment to measure psychophysiological responsivity to script-driven mental imagery

1 day

1 visit (in-person)

Treatment

Participants undergo six weekly sessions of traumatic memory reactivation with propranolol administration

6 weeks

6 visits (in-person)

Post-Treatment Assessment

Post-treatment psychophysiological testing to assess the effect of the intervention

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Memory Reactivation Procedures
• Propranolol

Trial Overview

The study tests if adding an unexpected element ('mismatch') when recalling traumatic memories with propranolol can better reduce physiological stress responses than standard memory reactivation alone. Participants will be randomly assigned to either the mismatch/propranolol group or the standard/propranolol group and undergo six weekly sessions of memory reactivation.

How Is the Trial Designed?

Group I: Mismatch reactivation condition Experimental Treatment 2 Interventions

The participant will recite their trauma narrative to the psychologist for 10-20 minutes. However, during each recitation, a "mismatch" condition, different for each session, will be added to the reactivation procedure by having the participant do the following (in order of sessions.

Group II: Standard reactivation condition Active Control 2 Interventions

The intervention will be the same for each of the six intervention sessions. The participant will recite to the psychologist the narrative they previously composed for 10-20 min. The psychologist will congratulate the participant for having succeeded in this task and advise them they are finished for the day.

Memory Reactivation Procedures is already approved in United States, European Union, India for the following indications:

Approved in United States as Inderal for:

• Angina
• Hypertension
• Atrial fibrillation
• Migraine prevention
• Tremors

Approved in European Union as Inderal for:

• Angina
• Hypertension
• Atrial fibrillation
• Migraine prevention
• Tremors

Approved in India as Ciplar for:

• Angina
• Hypertension
• Atrial fibrillation
• Migraine prevention
• Tremors

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

In a study involving 19 subjects with chronic post-traumatic stress disorder (PTSD), propranolol administered after recalling traumatic memories significantly reduced physiological responses during later mental imagery of those events.

This suggests that propranolol can effectively dampen the body's stress reactions to traumatic memories, similar to its effects when given shortly after a traumatic event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. Brunet, A., Orr, SP., Tremblay, J., et al.[2022]

In a 6-week open-label trial with 33 patients suffering from longstanding PTSD, the combination of propranolol and trauma recall sessions significantly improved quality of life and reduced depressive symptoms and negative emotions.

The study suggests that memory reconsolidation may be effectively blocked by propranolol, leading to better treatment outcomes, although further validation through randomized-controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trauma reactivation under the influence of propranolol: an examination of clinical predictors. Poundja, J., Sanche, S., Tremblay, J., et al.[2021]

In a 6-week clinical trial involving 60 adults with long-standing PTSD, propranolol significantly reduced PTSD symptoms compared to a placebo, with a notable effect size of 1.76 for the Clinician-Administered PTSD Scale (CAPS).

The study suggests that administering propranolol before trauma memory reactivation sessions is an effective treatment strategy for PTSD, indicating its potential as a novel therapeutic approach based on reconsolidation theory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial. Brunet, A., Saumier, D., Liu, A., et al.[2019]

Propranolol, a non-selective β-adrenergic antagonist, has been shown to effectively reduce exaggerated fear responses by decreasing memory trace reactivation in specific brain regions, particularly the dorsal dentate gyrus, in both humans and animal models.

The study found that propranolol also significantly reduced activity in the hilus of the dentate gyrus, particularly affecting parvalbumin-expressing cells, suggesting that it may alter the balance of excitatory and inhibitory signals involved in fear memory processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol Administration Modulates Neural Activity in the Hippocampal Hilus During Fear Retrieval. Leal Santos, S., Chen, BK., Pereira, GR., et al.[2022]

Propranolol, a beta adrenergic receptor antagonist, has been shown to block the reconsolidation of memories, which could potentially be used to treat intrusive memories in PTSD after they are retrieved.

The study indicates that the effects of propranolol on memory reconsolidation are mediated through the amygdala, a brain region involved in emotional processing and altered in PTSD, suggesting a targeted approach for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Debiec, J., Ledoux, JE.[2019]

In a study of 66 adults with longstanding PTSD, both propranolol and placebo led to significant reductions in PTSD and depression symptoms during treatment, but there was no significant difference between the two groups.

However, for patients with severe PTSD symptoms, those treated with propranolol showed continued improvement in symptoms three months after treatment, while those on placebo experienced a worsening, suggesting that propranolol may have long-term benefits for certain individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traumatic memory reactivation with or without propranolol for PTSD and comorbid MD symptoms: a randomised clinical trial. Roullet, P., Vaiva, G., Véry, E., et al.[2021]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960982224009229

Targeted memory reactivation to augment treatment in post ...

Targeted memory reactivation (TMR) enhances memory consolidation by presenting reminder cues (eg, sounds associated with a memory) during sleep.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9718563/

Efficacy of traumatic memory reactivation with or without ...

In our study, traumatic memory reactivation led to a global decrease of PTSD, depressive, and dissociative symptoms in patients with PTSD ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01239173

Emotional Memory Reactivation in Posttraumatic Stress ...

Evidence mainly comes from studies investigating the effect of emotion on encoding processes (Mc GAUGH, 2000). In that view, propranolol has been used somewhat ...

4.

nature.com

nature.com/articles/s41398-021-01570-w

Consolidation/reconsolidation therapies for the prevention ...

We found a large effect of reconsolidation interventions in the treatment of PTSD (11 studies, n = 372, SMD: −1.42 (−2.25 to −0.58), and a ...

5.

brainstimjrnl.com

brainstimjrnl.com/article/S1935-861X(21)00066-8/fulltext

Electroconvulsive therapy with a memory reactivation ...

ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT with non-traumatic memory ...

6.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK562942/

Propranolol for Post-Traumatic Stress Disorder - NCBI - NIH

Propranolol administered prior to trauma memory reactivation decreased the severity of PTSD symptoms, reduced physiological responses (eg, heart rate, skin ...

7.

frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1545493/full

Systematic review and meta-analysis of propranolol in the ...

This systematic review and meta-analysis provide preliminary evidence supporting the possible role of propranolol in alleviating PTSD symptoms.

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01555554

Perioperative Propranolol in Patients With Post Traumatic ...

The investigators hypothesize that patients with PTSD randomized to the propranolol group will demonstrate a reduced incidence of perioperative and ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0022395622001741

Effects of propranolol on the modification of trauma ...

Overall, results indicate that propranolol did not show a beneficial effect on PTSD symptoms (standardized mean difference: 1.29; 95% CI = −2.16 - 0.17).

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6493400/

Effect of Acute Posttrauma Propranolol on PTSD Outcome ...

This preliminary investigation suggested that propranolol administered shortly after an acute traumatic event may have preventive potential for PTSD. In a ...