MDMA-Assisted Acceptance and Commitment Therapy for Posttraumatic Stress Disorder: Rationale for a New Approach (MDMA-Assisted Acceptance and Commitment Therapy for Posttraumatic Stress Disorder: Rationale for a New Approach)

Authors: Matthew S. Herbert, Brian H. Blanco, Dimitri Perivoliotis, Jason Luoma, Gisele Fernandes-Osterhold, Andrew Bismark, Josh D. Woolley
Journal: Cognitive and Behavioral Practice
Translated by: Specialist Psychologist Elena Gizem Pozam

https://doi.org/10.1016/j.cbpra.2025.01.001

Keywords: psychological flexibility; process-focused; acceptance; values; self-as-context

Highlights

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  ACT offers a structured yet personalized approach to treating PTSD.

  
  


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  ACT methods may help prepare patients for MDMA administration.

  
  


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  The subjective effects of MDMA support core ACT processes.

  
  


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  ACT may help the therapist guide the MDMA administration session.

  
  


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  ACT may help integrate MDMA experiences to shape adaptive functioning.

  
  

Abstract

3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has the potential to be a highly effective and durable treatment for posttraumatic stress disorder (PTSD). However, the Food and Drug Administration (FDA) rejected MDMA-assisted psychotherapy in its current form, raising concerns about the lack of standardization and empirical grounding of the psychotherapy methods. This highlights the need to consider alternative psychotherapeutic approaches to integrate with MDMA for treating PTSD. We propose that Acceptance and Commitment Therapy (ACT), an evidence-based cognitive behavioral therapy, is particularly well suited to pairing with MDMA administration for PTSD. Specifically: (1) the subjective effects of MDMA directly support core ACT processes; (2) ACT methods may help prepare patients for MDMA administration, potentially enhancing efficacy and tolerability; (3) ACT provides a "process-focused" approach to assist the therapist and support the participant during MDMA administration sessions; and (4) ACT may help optimize the integration of MDMA experiences to shape adaptive functioning and improve quality of life after treatment. We provide examples of how ACT methods can be used for many of these goals. In summary, we believe that ACT provides a highly scalable, structured yet flexible, evidence-based framework that is well suited to integration with MDMA as a new treatment approach for PTSD.

Introduction

Posttraumatic stress disorder (PTSD) is a common, complex, and disabling condition. PTSD develops after an individual experiences or witnesses actual or threatened death, serious injury, or sexual violence. PTSD symptoms fall into four clusters: (1) reexperiencing symptoms (e.g., intrusive memories, nightmares), (2) avoidance symptoms (e.g., attempts to avoid trauma-related thoughts and reminders), (3) negative alterations in cognition and mood (e.g., negative thoughts about oneself or the world, blame, negative affect), and (4) alterations in arousal and reactivity (e.g., hypervigilance, sleep difficulties). The lifetime prevalence of PTSD in US civilian and veteran adults is approximately 8.3% and 9.4%, respectively (Kilpatrick et al., 2013, Wisco et al., 2022). Although current first-line treatments for PTSD, including prolonged exposure and cognitive processing therapy, can be effective, many individuals do not achieve clinically meaningful improvements (Benfer and Litz, 2023, Rutt et al., 2018). Current pharmacological treatments, including SSRIs, are insufficiently effective (Huang et al., 2020). More effective treatments for PTSD are needed.

Recently, there has been a surge of interest in using 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy for PTSD. MDMA is an amphetamine-like compound that increases the release of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) and various hormones, including oxytocin (Meyer, 2013). MDMA is considered an empathogen/entactogen because of its ability to facilitate empathy, introspection, and personal reflection (Meyer, 2013). It has also been shown to increase openness, feelings of well-being, and prosocial behaviors (e.g., trust; Bedi et al., 2009, Stewart et al., 2014). In relation to PTSD, MDMA appears to enhance fear extinction and/or the reconsolidation of trauma memories (Sarmanlu et al., 2024), which are key processes involved in PTSD treatment. Furthermore, the prosocial effects of MDMA are hypothesized to strengthen the therapeutic alliance, a reliable predictor of outcomes in psychotherapy generally (Ardito & Rabellino, 2011). Supporting its therapeutic potential, Phase 2 and 3 clinical trials of MDMA-assisted psychotherapy for PTSD have demonstrated statistically and clinically significant reductions in PTSD symptomatology and functional impairment (Mitchell et al., 2023, Smith et al., 2022).

Most trials of MDMA-assisted psychotherapy to date have used the psychotherapeutic model developed by the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS) and its affiliated public benefit corporation, Lykos Therapeutics. Briefly, in the MAPS Phase 3 protocol, patients participate in three "preparation" sessions, three MDMA administration sessions, and six "integration" sessions. Preparation sessions focus on discussing the patient's trauma history and experiences, providing psychoeducation and treatment logistics, and establishing a strong therapeutic alliance and sense of safety. During MDMA sessions, the MAPS model is largely "inner-directive," as therapists do not impose a prescribed agenda of psychotherapy methods, but instead encourage and support the patient in following their unfolding internal processes, particularly in relation to their trauma history (Mithoefer, 2017). During MDMA sessions, therapists draw on elements of a wide range of other psychotherapeutic approaches, as indicated and consistent with their own training, to support the patient's inner process (Mithoefer, 2017). Integration sessions aim to help patients make sense of their administration session experiences and integrate insights into their daily lives with the goal of improving well-being and functioning.

The impressive results from clinical trials of MDMA-assisted psychotherapy using the MAPS model led to its receiving Breakthrough Therapy Designation from the US Food and Drug Administration (FDA). Many anticipated that the MAPS model would become the first FDA-approved MDMA treatment for any indication. However, approval was denied by the FDA, which requested additional safety and efficacy data. This decision followed criticisms of the trials' methodology and features of the therapy by the FDA Advisory Committee, the Institute for Clinical and Economic Review, and others (Cristea et al., 2024), including concerns about the lack of standardization across trials and the use of treatment methods without empirical support. These concerns have prompted calls to integrate more established, evidence-based psychotherapeutic approaches with MDMA and psychedelics generally (Yaden et al., 2022). To this end, we propose that Acceptance and Commitment Therapy (ACT) may be an ideal treatment to pair with MDMA to create MDMA-assisted ACT for PTSD.

ACT is an evidence-based, third-wave cognitive behavioral therapy with demonstrated efficacy across a range of conditions, including chronic pain, depression, anxiety, and substance use disorders (Gloster et al., 2020). A central premise of ACT is that unwanted thoughts, emotions, and bodily sensations are inherent aspects of human experience, and that rigid engagement in control strategies, such as behavioral avoidance and thought suppression, often leads to functional impairment and, paradoxically, increased distress (Hayes et al., 2011). Rather than directly attempting to reduce unwanted emotions and sensations or eliminate negative thoughts, ACT promotes psychological flexibility, defined as the ability to be present, adapt ongoing behavior to the situation, and act according to one's values, even when faced with difficult thoughts, emotions, or bodily sensations. The delivery of ACT follows the psychological flexibility model, which involves six interrelated processes designed to increase psychological flexibility and reduce six interrelated processes associated with psychological inflexibility (see Table 1 for a description of psychological flexibility and inflexibility processes; see Hayes et al., 2015, for an in-depth review of the ACT approach).

Although research specifically focused on PTSD is limited, uncontrolled trials show promise (Shea et al., 2020). The largest RCT to date (N = 160 military veterans) demonstrated significant reductions in distress and PTSD symptoms at posttreatment and 1-year follow-up, similar to present-centered therapy, even though the ACT intervention did not specifically focus on PTSD (Lang et al., 2017). Research also supports the role of psychological flexibility in PTSD; studies have found that it mediates trauma-related guilt and PTSD severity in veterans with PTSD and co-occurring alcohol use disorder (Kachadourian et al., 2021), predicts symptom severity in OIF/OEF veterans (Meyer et al., 2019), and accounts for symptom reduction in adolescent inpatients (Schramm et al., 2020). ACT specifically targets multiple aspects of psychological inflexibility that maintain PTSD:

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  Inflexible Attention: Intrusive thoughts, memories, and flashbacks disrupt present-moment awareness (Carpenter et al., 2019, Follette et al., 2004, Martin et al., 2018, Thompson and Waltz, 2010).

  
  


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  Experiential Avoidance: This core feature of PTSD maintains symptoms and perpetuates anxiety and depression (Dulin and Passmore, 2010, Thompson et al., 2018).

  
  


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  Cognitive Fusion: Trauma-related thoughts (e.g., "I could have prevented this") are associated with increased PTSD symptomatology (Ali et al., 2002, O’Donnell et al., 2007, Scher et al., 2017) and reduced functioning (Lyons et al., 2020, Norman et al., 2018).

  
  


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  Self-as-Content: PTSD often involves the development of a negative self-concept (e.g., believing the self/world to be inherently flawed/dangerous), which is a DSM-5 diagnostic criterion for the disorder.

  
  


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  Disruption of Values: Many clients experience moral injury, a loss of meaning resulting from violations of core values (Koenig et al., 2019).

  
  


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  Behavioral Inaction: Reduced values-based action is associated with worse PTSD symptoms, while increased values-based living mitigates the impact of symptoms on functioning (Donahue et al., 20,17).

  
  

Previous articles have described the rationale for integrating ACT with classic psychedelics (e.g., psilocybin; Luoma et al., 2019, Sloshower et al., 2020, Watts and Luoma, 2020). Generally, psychedelics, including MDMA, appear to directly target aspects of psychological flexibility (Close et al., 2020, Davis et al., 2020, Luoma et al., 2022, Watts and Luoma, 2020), suggesting an overlap in therapeutic mechanisms with ACT. Furthermore, because ACT often challenges patients' views of their condition—advocating acceptance of unwanted thoughts, emotions, and bodily sensations to prioritize a focus on meaningful life pursuits—psychedelics and ACT may naturally complement each other and promote greater psychological flexibility than ACT alone. Although clinical trials have paired ACT with classic psychedelics (Barba et al., 2022, Luoma et al., 2019, Sloshower et al., 2020) and with MDMA for social anxiety disorder (Lear et al., 2023), we are unaware of any trials pairing MDMA with ACT for PTSD. In this article, we propose four main reasons why ACT is particularly well suited to integration with MDMA for treating PTSD.

Rationale 1: The Subjective Effects of MDMA Directly Support Core ACT Processes

MDMA's effects on enhancing fear extinction and memory reconsolidation may reduce experiential avoidance and promote greater acceptance of traumatic memories and cues. Indeed, the acute experience of being able to safely approach previously avoided trauma-related memories and experiences may generate new learning that challenges entrenched beliefs about the necessity of avoidance. A central premise of ACT is that experiential avoidance maintains and exacerbates PTSD symptomatology, and thus MDMA may facilitate this core ACT treatment process (i.e., reducing experiential avoidance), even temporarily, which can be built upon during subsequent integration sessions. MDMA's effects on fear extinction and memory reconsolidation may also enhance cognitive defusion by helping patients observe their thoughts and memories rather than becoming caught up in them.

MDMA may also induce self-transcendent states (e.g., a sense of unity, being part of a larger whole; Studerus et al., 2010) and shift perspectives on self-identity and trauma-related beliefs (Feduccia & Mithoefer, 2018). MDMA's empathogenic properties may also foster compassion and love toward oneself and others, feelings that may have long lain dormant in patients with PTSD (Luoma and Lear, 2021, van der Kolk et al., 2024). These effects may both weaken self-as-content and strengthen self-as-context processes (Luoma et al., 2022).

MDMA's prosocial effects include enhanced social closeness and approach behaviors, and increased prosocial mood states (e.g., feeling loving, friendly, talkative), which likely accelerate the development of the therapeutic alliance (Kamilar-Britt & Bedi, 2015). These experiences may also help people clarify and connect more fully with relationship-focused values. This may allow positive changes beyond MDMA sessions, manifesting as improved communication and openness, increased interpersonal connection, and reduced relationship conflict (Barone et al., 2019, Barone et al., 2022, Greer and Tolbert, 1986), which may help motivate relationship-focused committed action. Additionally, the temporary experience of heightened awareness of positive emotions combined with reduced fear may allow patients to reflect on and connect with values more generally, rather than becoming caught up in patterns of avoidance and fusion (e.g., a client motivated to spend more quality time with their child after gaining a greater appreciation of the value of parenting).

In summary, MDMA administration appears to increase psychological flexibility by reducing experiential avoidance, promoting nonjudgmental awareness of internal experiences, facilitating self-transcendent experiences, and enabling clearer recognition of vital life domains—particularly social relationships—all of which align with core ACT processes.

Rationale 2: ACT Offers Several Structured Approaches to Help Prepare Patients for MDMA Sessions, Potentially Enhancing Both Treatment Efficacy and Tolerability

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   Passengers on the Bus Metaphor
   Adapted from Hayes et al. (2011), this core ACT metaphor integrates all psychological flexibility processes and can be introduced during preparation to provide a consistent and accessible point of reference throughout treatment:

   
   

"Imagine a bus, and you are the driver. Your passengers represent thoughts, memories, and emotions collected throughout life, including those arising from traumatic experiences. These passengers often make demands and threats, trying to control where you drive. Complying with their demands brings temporary peace but restricts your journey. How do you relate to this experience? Who are your passengers?"

This metaphor serves several purposes, including helping identify belief systems, narratives, and behaviors likely to arise during MDMA sessions, and illustrating how MDMA may temporarily quiet overwhelming "passengers," allowing easier engagement in treatment. It can also be used to facilitate discussion of all six psychological flexibility processes:

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  Present-Moment Awareness: Focusing on present-moment experience rather than "driving through the rearview mirror" or "planning for future road conditions."

  
  


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  Cognitive Defusion: Contrasting complying with passengers' demands with observing them.

  
  


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  Acceptance: Choosing a direction regardless of passengers' threats rather than giving in for temporary comfort.

  
  


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  Self-as-Context: Recognizing the constancy of the bus driver despite changing passengers.

  
  


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  Values Clarity: Aligning the direction of travel with personal values.

  
  


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  Committed Action: Doing what is needed to reach intended destinations.

  
  


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  Values Clarification Tools Individual intentions or goals for MDMA sessions and treatment overall can be explored and characterized consistently and systematically, either in session or as homework, using established ACT-based measures such as the Valued Living Questionnaire (Wilson et al., 2010) or the Engaged Living Scale (Trompetter et al., 2013). During preparation, these structured tools can help increase clarity about what matters to the client as they enter MDMA sessions. During integration, they can serve as a structured tool for further exploring values-related material that emerged during MDMA sessions.

  
  


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  Skill Building Before MDMA Sessions Targeting all psychological flexibility processes during preparation may be helpful for enhancing outcomes in subsequent MDMA sessions (see Table 2, Panel A). Three examples are described below:

  
  

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   Present-Moment Awareness can be taught through breathing meditation, body scans, and exercises using the five senses. These grounding skills may help clients remain present with difficult experiences that may arise during MDMA sessions.

   
   


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   Acceptance can be taught through the ACT Tug-of-War Metaphor (adapted from Hayes et al., 2011):

   
   

"Imagine you are in a tug-of-war with your own mind. If a vivid memory, emotion, or bodily sensation related to your trauma arises, there may be a tendency to resist or struggle with what you are experiencing. Or perhaps MDMA does not produce as powerful or intense an experience as you would like. Rather than trying to control or dictate how the MDMA session will go or is going, imagine 'dropping the rope'—allowing the experience to unfold naturally."

Increased acceptance has been shown to be associated with more beneficial and tolerable psychedelic experiences (Carhart-Harris et al., 2018). However, increasing acceptance can be difficult for individuals with PTSD, as fear of losing emotional control is a common feature of PTSD. ACT's wide range of techniques for enhancing acceptance offers therapists multiple ways to increase acceptance among avoidant clients in preparation for MDMA sessions.

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   Self-as-Context can be taught using the Sky and Weather metaphor, adapted from Harris (2009):

   
   

"Being able to observe thoughts, memories, and emotions without getting caught up in them is an important part of this treatment. To do this, we want to strengthen our 'observing self.' The observing self is like the sky, and thoughts, memories, and emotions are like the weather. The weather changes, but the sky always stays the same. Even the strongest hurricane cannot harm the sky, and no matter how bad the weather gets, the sky always has room for it. Sometimes the storm becomes so severe and widespread that we forget the sky is there. But if we rise above the storm, we can reach the sky. MDMA may help you access this part of yourself: a place where you can observe and make room for unpleasant thoughts, memories, and emotions, while also feeling the safety within the sky."

Introduced during preparation, this metaphor can be revisited during MDMA and integration sessions to enhance a sense of spaciousness and cognitive defusion from difficult thoughts and emotions. These examples illustrate just a few of the ways that common ACT-based metaphors and exercises can be integrated into MDMA-assisted ACT.

Rationale 3: ACT Provides a "Process-Focused" Approach to Support Clients and Promote Psychological Flexibility During MDMA Sessions

MDMA sessions offer an opportunity to strengthen psychological flexibility. During these sessions, an ACT-consistent approach would be "process-focused" rather than "content-focused," in which the therapist would dictate the content of the session. In this way, an ACT approach would allow MDMA's effects to unfold naturally and, when relevant, permit an internal focus of attention. However, unlike a fully "inner-directive" approach as advocated by the MAPS model, the therapist would use ACT as a therapeutic framework to help guide MDMA sessions in a consistent and replicable manner, as detailed below.

Similar to the MAPS model (Mithoefer, 2017), we envision MDMA-assisted ACT encouraging intentional processing of trauma during MDMA sessions. That is, when the client does not spontaneously process the trauma, the therapist would gently encourage this focus. All ACT processes may be relevant to helping the client process trauma (see Table 2, Panel B). For example, the therapist may help the client gently focus on what is arising in the present moment (present-moment awareness), experience trauma-related thoughts, memories, and emotions with openness and curiosity (acceptance), look at thoughts rather than from them (cognitive defusion), notice personal narratives and worldviews that have emerged as a result of past experiences (self-as-context), and connect with important life domains affected by the trauma(s) (values clarity).

Cognitive defusion exercises may be used if the client has a distressing experience during the MDMA session. For example, the therapist may encourage the client to articulate their thoughts (e.g., "I feel like if I allow myself to feel anger toward the perpetrator, it will never stop") and maintain an observer perspective toward that thought. If the client is fighting the experience or wishing it were different, the therapist may consider offering acceptance as an alternative by "dropping the rope" (referring to the Tug-of-War metaphor completed during preparation sessions).

Identifying values during MDMA sessions can be accomplished by explicitly naming them when they arise spontaneously and referring to the values assessment completed during preparation sessions. The client may indirectly connect with values while processing difficult trauma-related emotions such as grief, guilt, and shame. From an ACT perspective, values are inextricably linked to painful experiences (e.g., shame about being unemployed due to PTSD may reflect the meaningfulness of contributing to society). Thus, identifying the source of emotional pain may be particularly informative for values clarification.

Rationale 4: ACT May Help Integrate MDMA Experiences to Shape Adaptive Functioning

Integration is a critical but challenging phase of treatment that aims to support the client in translating experiences and insights from MDMA sessions into positive changes in daily life (Katzman & Schwartz, 2024). However, the concept of integration has been criticized for being poorly defined and encompassing a wide range of potential practices that can vary considerably across therapists and trials (Cristea et al., 2024). These issues have led to confusion and debate about best practices. ACT would address these concerns by providing a structured and replicable yet flexible framework (see Table 2, Panel C), as well as specific tools and strategies (e.g., case conceptualization, committed action toward values) to help ensure that integration sessions optimally support the client.

Integration typically involves discussing the client's experience during the MDMA session. ACT theory and techniques can be used to support the further development of psychological flexibility. Therapists can listen for temporary increases in psychological flexibility that emerged during MDMA sessions to sustain and build upon them. For example, therapists can explore whether the client noticed: a different aspect of themselves or others (self-as-context), new valued domains or qualities (values), a new awareness of and/or distance from patterns of thinking they usually get caught up in (cognitive defusion), new bodily responses or emotions such as increased safety (present-moment awareness), less struggle with thoughts or emotions they usually avoid (acceptance), and/or any new motivation to take action in their lives (committed action). Assessing each ACT process in this way would further inform ongoing case conceptualization, which could then guide the selection of client-specific exercises, metaphors, and other techniques.

ACT methods introduced during preparation can be revisited during integration, serving as a bridge from the MDMA experience to daily life. For example, the client may explore whether they now have a different perspective on the "passengers" on their bus, or greater clarity about the direction in which they want to drive their metaphorical bus. The Tug-of-War metaphor can be reviewed by validating the extent to which acceptance was experienced during the MDMA session and how this approach to difficult thoughts, emotions, and bodily sensations can be incorporated into daily life. The MDMA experience may have strengthened the observing self such that the Clouds and Sky metaphor takes on new meaning.

Each integration session can conclude by setting clear, values-aligned goals for home practice, which are reviewed in subsequent integration sessions. This iterative process helps refine ongoing ACT case conceptualization by identifying both existing psychological flexibility skills that need reinforcement and areas of psychological inflexibility that need to be addressed, and provides concrete data on the individual's progress in developing new behavioral patterns that support values-based living. To further strengthen committed action, new ACT methods can be introduced as appropriate, such as the Walking the Path metaphor adapted from Stoddard & Afari (2014):

"The work we are doing here is like walking across a grassy hillside. Your MDMA experience may have given you a glimpse of a new path, one that leads to a more meaningful and fulfilling life, less constrained by past trauma. However, this path is new. As you move forward, staying on this path may require deliberate effort. And perhaps you look to your right and see a well-worn path. Walking that path seems much easier than persisting along the route through the tall grass. The thing is, you know exactly where that well-worn path leads, because you have walked it many times before. Where does that path lead in your life? And where might this new, unmarked route lead?"

Importantly, for some clients, the MDMA experience may not provide new perspectives on the self or trauma, help clarify values, or motivate new behavior. Despite the potential of MDMA-assisted therapy for PTSD, no treatment works for everyone. Because of the hype surrounding MDMA and classic psychedelics, clients may feel disappointed if they do not respond to these treatments. In MDMA-assisted ACT, the therapist can process this disappointment through the lens of the psychological flexibility model. For example, did this experience reinforce a particular narrative about the self (e.g., "I am broken")? This may indicate a need for additional work on cognitive defusion and self-as-context processes. The therapist may focus on an ACT technique called "creative hopelessness" to help the client open up to new ways of responding (Hayes et al., 2011). This method involves evaluating the benefits and costs of previous attempts to alleviate PTSD (including MDMA-assisted therapy) and the outcomes of those attempts (e.g., the persistence of PTSD). The aim is to help individuals recognize the unworkability of trying to control thoughts, memories, emotions, and bodily sensations, which may then lead to a powerful turning point toward acceptance and psychological flexibility.

Conclusion

There are high hopes in the scientific and clinical communities that MDMA and other psychedelic compounds can support psychotherapy and help create meaningful and lasting changes in individuals living with difficult-to-treat conditions such as PTSD. We believe that ACT should be considered a viable therapeutic framework for integration with MDMA administration as a treatment for PTSD (and other conditions), and we have outlined four reasons to support our argument. PTSD is a condition that can be characterized by psychological inflexibility, making it well suited to an ACT approach. Psychological flexibility appears to be directly enhanced by MDMA, which may help individuals make direct contact with experiential acceptance, cognitive defusion, self-as-context, and personal values. Additionally, all six psychological flexibility processes can readily be tracked, elaborated upon, and used to help guide preparation, MDMA, and integration sessions. By incorporating a specific set of strategies, methods, and tools already familiar to many clinicians, an MDMA-assisted ACT approach to PTSD treatment would be relatively accessible. Adherence to the treatment model can be monitored using established treatment fidelity measures (O’Neill et al., 2019). Collectively, this would facilitate research, training, and implementation efforts while addressing many of the concerns raised by the FDA and others about the MAPS model. In summary, ACT provides a highly scalable and replicable, evidence-based framework that is well suited to integration with MDMA administration to create a new treatment approach for individuals with PTSD.

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