A quick and easy cure for trauma and dissociation sounds seductive to all vested parties. A simple drug and/or brief standardised protocol could slash government expenditure on mental health care, while exempting patients from the emotional pain of revisiting unprocessed trauma events. Reconsolidation Therapy is one such proposed treatment being explored. This article will examine the limitations of memory reconsolidation therapy.

Post-traumatic stress disorder

PTSD is a stress-related disorder caused by exposure to one or more incidents that the individual considers life-threatening (Phoenix Australia, 2021). Common symptoms include flashbacks, intrusive memories, memory avoidance, dissociative amnesia, hypervigilance, exaggerated startle response, and dissociation. Approximately 11% of Australians will experience PTSD (ABS, 2022). Lifetime prevalence rates are double for women (14%) compared to males (8%). About 80% of PTSD cases show comorbidity with other mental illness disorders (Qassem et al., 2021). Untreated, chronic PTSD leads to increased physical illness, brain damage, and premature death (Nijdam et al., 2023). PTSD is associated with attention, memory, and decision-making problems, resulting in impaired functioning across social, occupational, and daily living activities (Miller et al., 2024). Therefore, PTSD detrimentally impacts our economy via loss of financial participation and increased health care costs.

PTSD can present in over 600,000 different ways (Armour et al., 2017). The heterogeneous nature of PTSD causes clients with this disorder to exhibit a wide range of aetiology, symptomology, comorbidity, and chronicity. Multiple variables interact to adversely impact treatment response. Intervention is further complicated by inconsistency between diagnostic systems. The ICD-11 (WHO, 2019) acknowledges Complex-PTSD (C-PTSD). Up to 80% of veterans with PTSD also have C-PTSD (Sturt et al., 2023). C-PTSD stems from multiple (often developmental) trauma events. It typically features emotional dysregulation, dissociation, and attachment dysfunction. Recovery, therefore, requires long-term intervention and a strong client-therapist relationship (Karatzias et al., 2022).

The DSM-5 (APA, 2013) recognises a Dissociative-PTSD subtype (D-PTSD) but not C-PTSD. About 38% of people with PTSD meet D-PTSD criteria (White et al., 2022). Dissociation is associated with treatment resistance (Kratzer et al., 2021). Dell (2018) considers dissociation a form of autohypnosis that PTSD sufferers induce to psychologically distance themselves from emotional or physical pain. Kluft (2023) agrees that dissociation is a trance state.

Therefore, treating C-PTSD or D-PTSD is vastly different to addressing simple PTSD caused by one adult-onset trauma incident. There exists no generic PTSD treatment incorporating every PTSD presentation. Public healthcare systems lack the resources to provide trauma-informed treatment to complex PTSD cases (Murray, 2017; Winkler et al., 2023). It is therefore imperative to consider new, possibly multimodal, treatment approaches. There is a need for accessible and effective PTSD treatments. Accessible means affordable, brief, engaging, and practical (that is, a standardised protocol).

Mechanism of trauma

The prevailing hypothesis is that PTSD is a memory disorder. PTSD is thought to stem from abnormal memory encoding during a trauma event. This implicates the amygdala–hippocampus–prefrontal cortex (PFC) circuit (Ressler et al., 2022). The fear conditioning model suggests PTSD symptoms stem from concurrent amygdala hyperactivity and hippocampal-PFC suppression (Karl et al., 2006). Fear conditioning occurs when a neutral stimulus becomes a conditioned stimulus (CS) after being paired with a threatening stimulus (Battaglia et al., 2023).

Memory reconsolidation

PTSD is associated with deficits in memory storage (Chalkia et al., 2019). Memory formation is said to involve encoding (learning), consolidation (moving from short to long-term storage), and reconsolidation (updating) (Astill Wright et al., 2021; Ortega-de San Luis & Ryan, 2022).

Brain states are indicated by different oscillations, and these states are essential for learning and memory consolidation (Ritter et al., 2015). Encoded memories (engrams) are linked to predominantly theta and gamma brain oscillations, which support synaptic plasticity, memory reactivation, and event sequencing (Hanslmayr et al., 2012; Ritter et al.).

An engram is reactivated and temporarily destabilised when the conditioned stimulus is presented (Pitman, 2015). This brings the memory into conscious consideration, where it can be changed. During a 6-hour reconsolidation window, memory is thought to be modified by disrupting the link between the unconditioned stimulus and the conditioned fear response. This reduces the associated emotion while preserving contextual memory of the trauma incident.

Critically, the updating process in memory reconsolidation is said to require new protein synthesis (Nader et al., 2000).

Conditions needed for reconsolidation to occur in a therapeutic setting are said to include sufficient memory reactivation, prediction error, and emotional regulation (Taylor-Shore, 2023). Emotion enhances memory recall (Mueller & Cahill, 2010). The trauma memory must be felt emotionally and bodily, triggering the brain to predict a feared outcome. Prediction error (PE) is the mismatch between what is expected and what happens (Sevenster et al., 2014). Too little PE strengthens the old memory; too much creates a new one; and an optimal level of PE may destabilise and update the original engram (Bein et al., 2020; Sinclair & Barense, 2018). The person must be sufficiently emotionally regulated to notice the PE (Taylor-Shore).

Reconsolidation and extinction are considered mutually exclusive (Sevenster et al., 2014). In extinction, a conditioned fear response decreases when reinforcement is removed (Battaglia et al., 2023). The timing and context of the conditioned stimulus (CS) are said to determine whether reconsolidation or extinction occurs (Ferrara et al., 2023). Minor changes to the reconsolidation method or environment can influence the outcome. Reconsolidation requires brief exposure to the CS, whereas extinction requires prolonged CS exposure (Mueller & Cahill, 2010). Reconsolidation or extinction begins once CS exposure ends, in the absence of the expected unconditioned stimulus (Pedreira et al., 2004). Reconsolidation also depends on how the memory was encoded, especially which senses were originally engaged during CS exposure (Agustina-Lopez et al., 2016). Activating the same sensory systems during retrieval to the same extent as happened during encoding increases the likelihood of reactivating the target engram.

Propranolol

Propranolol is a β-adrenergic blocker. The drug’s ability to disrupt memory reconsolidation by blocking new protein synthesis has been widely researched (Beckers et al., 2017). Propranolol inhibits the stress-related hormones adrenaline and noradrenaline (NA), which feature in memory processing (Battaglia et al., 2023). The β1 receptors predominantly exist within the heart, whereas β2 receptors are in the lungs and blood. Propranolol decreases heart rate and blood pressure, which helps reduce stress reactions and maintain emotional regulation (MacCormack et al., 2021). This same mechanism causes bronchoconstriction and makes propranolol contraindicated for asthmatics. PTSD and asthma share a bidirectional relationship (Allgire et al., 2021); therefore, propranolol cannot be universally administered to PTSD subjects.

Kroes et al. (2016) administered propranolol before exposure therapy and concluded that this drug impacts both (1) the dmPFC to prevent retrieval of fear memory and (2) the hippocampus to increase contextual safety learning. While noradrenaline (NA) is known to modulate fear learning and disrupt long-term extinction, its effect on fear consolidation and extinction in humans remains unclear and controversial (Battaglia et al., 2023). Debate exists over propranolol’s mechanism, which may increase NA release. While β-adrenergic receptors seem to support fear extinction, it is unclear whether increased NA helps people learn safety signals or merely remember them.

Criticisms of the memory reconsolidation paradigm

Gisquet-Verrier and Riccio show that so-called reconsolidation effects can occur without protein synthesis, challenging the standard view that new protein formation is required. They argue that earlier animal studies of retrograde amnesia, where drugs were given after learning, missed a key factor – internal state. When they repeated these experiments but reintroduced the same drug state, the apparent amnesia was reversed. This suggests the effect is better explained by state-dependent memory rather than by memory erasure. 

According to this framework:

• Memory is encoded together with the subject’s internal state (e.g., drug-induced calm).
• Recall is strongest when that same state is reinstated.
• If the state differs, the memory may seem inaccessible (amnesia).
• Recreating the original state restores access.

The authors further propose that when a memory is reactivated, it can incorporate the current state, making future retrieval dependent on that condition. Consistent with this, they report that Propranolol can produce clear state-dependent effects.

Reconsolidation effects have been induced without involvement of protein synthesis (Gisquet-Verrier et al., 2015). This contradicts the paradigm that protein synthesis is essential for reconsolidation. Further, the reconsolidation hypothesis was based on animal studies of retrograde amnesia, in which analgesic agents were typically administered after the learning condition. Those studies never examined what might happen if the analgesic were administered beforehand. Gisquet-Verrier and Riccio (2018) repeated and ‘completed’ these original experiments by readministering the treatment condition, which reversed the amnesia.

This finding points to state-dependency as causing the amnesia effects. State-dependent learning, or memory, is when information is better recalled when the subject’s internal state during encoding and retrieval matches. These states are altered by drugs, emotion, hypnosis, and other variables.

Gisquet-Verrier and Riccio conclude that memory retrieval reactivates the memory, allowing the drug-induced state of calm to integrate with it. Later recall then depends on that state. Without it, amnesia occurs, but it can be reversed by re-administering the drug and placing the subject back in the original state. They add (p.28), “…we have recently shown that propranolol may induce clear state-dependency…”

Reconsolidation Therapy

Reconsolidation Therapy (RT) is a novel PTSD treatment based on memory reconsolidation theory (Brunet et al., 2018, 2014, 2008). RT combines propranolol intake with engram reactivation techniques. During six weekly sessions, the subject reads out a written narrative of their trauma incident while under the influence of pre-administered propranolol. The goal is to trigger the engram through script imagery and, using propranolol, disrupt the reconsolidation of the emotional memory to reduce the associated emotional intensity. Results of the therapy approach were measured by comparing pre/post-test physiologic responses and standardised PTSD scale scores.

Key randomised control trials compared RT with placebo (Brunet et al., 2018, 2014, 2008). As a result, RT demonstrated significant PTSD symptom reductions lasting up to 6 months. Medium-to-large effect sizes were observed, primarily for reductions in hyperarousal, intrusions, and emotional distress associated with the conditioned stimulus. In a research context, RT demonstrated equal efficacy as TF-CBT and drugs for treating simple PTSD. These results indicate RT’s potential as a standardised protocol that can be delivered by inexperienced staff in public healthcare settings. RT’s short treatment time improves cost-effectiveness, and its reduced trauma exposure anticipates lower dropout rates.

Limitations

There is limited replication of Brunet’s studies, with mixed results (Lonergan et al., 2013; Raut et al., 2022). This flags potential problems with RT’s theoretical basis, differences in study design, subject characteristics, or test-environment effects.

The exact mechanism by which propranolol induces amnesia remains unclear (Beckers & Kindt, 2017). Therefore, state-dependency and extinction cannot be dismissed as potential explanations. Variations in research design include the employment of eyes-closed mental imagery, plus the use of trauma script audio-recordings featured in the 2008 project. Subsequent (2014, 2018) studies changed to eyes-open, self-read scripts and provided emotional support to subjects by trained therapists. This highlights two potential confounds: mental imagery and research assistant characteristics (including dyadic synchrony).

Mental imagery

Subjects’ level of emotional engagement in the visualisation of the trauma script impacts treatment effects (Jaycox et al., 1998). Based on the theory that maladaptive behaviour is a learned response stemming from antecedent aversive conditioning (Stampfl & Levis, 1967), Levis (1991) combined Pavlovian conditioning with psychotherapy to demonstrate that the most extreme developmental trauma memories can be processed and resolved using mental imagery alone. A suggested mechanism underpinning mental imagery as a treatment modality is its activation of the same brain areas as those engaged during actual movement (Jeannerod, 1995).

Research assistant characteristics

The extent to which the research environment influenced emotional regulation in the later Brunet studies is unclear. Memories are reconsolidated without the amygdala’s emotional effect. A sense of calm contributes to optimal conditions for reconsolidation. Different variables may dampen the amygdala. The drug propranolol does, but so can human connection. In the 2018 (Brunet et al) study, “doctorate-level therapists” interacted with subjects by reading scripts and “commending” subjects’ efforts. This introduced research assistant characteristics (such as empathy, vocal intonation, and microfacial expressions) that may have facilitated emotional bonding between the assistant and the test subject.

Dyadic synchrony is a complex interactional process between two people (e.g., mother-baby or therapist-client). The resulting bond is critical for the development of self-regulation (Mayo & Gordon, 2020). This bond is a consistent predictor of therapeutic change in general, including symptom reduction (Zilcha-Mano et al., 2020). Dyadic synchrony occurs across three physiological levels: (1) synchronisation of autonomic nervous system function, causing synchrony of physiologic responses including heartbeat, breathing, and electrodermal activity; (2) neural oscillations; and (3) release of oxytocin and cortisol (Feldman, 2017).

Oxytocin may enhance empathy, trust, and cooperation (Hohl et al., 2024; Zilcha-Mano et al.). Research (including that by Wagner and Echterhoff, 2018) suggests oxytocin significantly affects memory recall, primarily by enhancing the vividness of social memories and faces, while also modulating emotional memory in context-dependent and attachment-style ways. Oxytocin can strengthen memories of positive social interactions but may also heighten recall of negative and stressful memories, depending on the subject’s emotional state.

Therefore, dyadic synchrony may have led test subjects to bond with their research assistants, thereby enhancing subjects’ affect regulation and cooperation on the research project. As mentioned, subtle environmental changes can significantly influence study outcomes.

Generalisability

That propranolol is contraindicated for asthmatics reduces the treatment’s clinical utility. PTSD subjects with dissociative tendencies were also excluded from Brunet’s studies. The exclusion cut-off was set at Dissociative Experiences Checklist scores >20 (when scores of 20 to 30 indicate PTSD dissociation; Bernstein & Putnam, 1986). This could exclude around 38% of PTSD sufferers (White et al., 2022) because an intervention cannot be given to populations upon whom it was not tested. D-PTSD subjects do not hinder trauma-focused treatment outcomes and so should have been included in research studies (van Minnen et al., 2016; Zoet et al., 2018).

Conclusion

Reconsolidation Therapy as a PTSD treatment has demonstrated several crucial limitations. Its underpinning theory remains contested. Empirical replication of its effects is limited. Its exclusion of dissociative cases, plus its contraindication in asthmatics, restricts generalisability and so clinical applicability. The lack of clarity regarding the mechanism of Reconsolidation Therapy and whether propranolol assists memory updating through state-dependent integration, extinction, or reconsolidation warrants further investigation.