Couple therapy offers the opportunity to heal, grow and change while in relationship. Given that people do not exist in isolation, it creates the context to change in the milieu in which people live their lives. The current paper offers an examination of the reasons for why, and how, a transtheoretical model of MDMA-assisted couple therapy may be an important contribution to couple therapy treatment options. This mini review provides an overview of MDMA, how MDMA functions in an interpersonal context, including its neurochemical, psychological and subjective effects, and how these effects translate into therapeutic outcomes in a transtheoretical approach to MDMA-assisted couple therapy. Potential pathways of action are introduced, and a model to support the enhancement of these treatment outcomes is outlined.

Couple therapy can be utilized for primarily relationally-oriented presenting problems (e.g., relationship distress, difficulties with communication, relationship enhancement, coping with infidelity, abusive interactions, transgressions of trust, life transitions, intimacy, etc.), for relationship enhancement (e.g., to prepare for a life change, such as the birth of a child or marriage), and for focusing on mental health difficulties in one or both partners (e.g., couple treatment for PTSD, depression, OCD, etc.). Findings from dyadic interventions for specific diagnoses demonstrate improvement in both mental health outcomes (OCD, PTSD, depression), relationship satisfaction and functioning for both partners (Baucom et al., 1998, 2012; Christensen and Heavey, 1999; Benson et al., 2012; Monson et al., 2012; Fischer et al., 2016). Each of these presenting foci can be approached from a variety of therapeutic modalities (e.g., cognitive-behavioral, integrative, emotion-focused, systems-focused, psychodynamic) (e.g., Johnson and Greenberg, 1988; Baucom et al., 1998; Christensen et al., 2020). Common factors among effective couple therapies include objective, shared understanding of the presenting concerns, decreasing emotion-driven dysfunctional behavior, increasing emotion-driven avoided behavior, improving communication and bolstering strengths and gains (Benson et al., 2012). The impact of relational distress has ramifications not only on the relationship, but also each partner's mental health and the functioning of broader family systems (Atkins et al., 2009; Baucom et al., 2012). While couple therapy can reduce relationship distress and increase relationship satisfaction, many couples do not benefit or may not maintain gains over time (Baucom et al., 1998; Christensen et al., 2010). Alternative couple treatment options which can enhance common effective factors are therefore needed.

MDMA (3,4-methylenedioxymethamphetamine) is a ring-substituted phenylisoproylamine derivative that increases the release and prevents reuptake of serotonin, norepinephrine, and dopamine (Liechti and Vollenweider, 2001; Farré et al., 2004; Hysek et al., 2011; Bershad et al., 2016). The 5-HT2 receptor plays a contributing role in its effect (Liechti et al., 2000; van Wel et al., 2011). MDMA elevates serum oxytocin (Wolff et al., 2006; Dumont et al., 2009) and vasopressin (Bershad et al., 2016), as well as cortisol and prolactin (Grob et al., 1996; Mas et al., 1999; Harris et al., 2002). MDMA causes a decrease in cerebral blood flow to the amygdala and hippocampus, an increase in activity in the prefrontal cortex, action in the occipital cortex and insula, and a decrease in functional connectivity between the hippocampus and prefrontal cortex, and an increase between the hippocampus and amygdala (Gamma et al., 2000; Phelps et al., 2001; Carhart-Harris et al., 2014, 2015; Walpola et al., 2017; Feduccia and Mithoefer, 2018).

MDMA-assisted couple therapy was conducted prior to MDMA being made illegal in the mid-1980s. Greer and Tolbert (1986, 1998) conducted a series of cases of MDMA-assisted psychotherapy, including with couples, that demonstrated improvements in fear of emotional hurt and improved communication and introspection. Reports by Sasha and Ann Shulgin describe MDMA's therapeutic use with couples shortly after it was re-synthesized in the mid-1970s (e.g., Holland, 2001), and that it is an excellent tool for communication and to navigate relational issues. Reports suggest that MDMA had broad use by psychotherapists in non-research settings (e.g., Passie, 2018). With recent re-initiation of MDMA-assisted therapy research, long term follow-ups of individual MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) demonstrate that almost two thirds of participants reported improved relationships with loved ones following treatment (Jerome et al., 2020). One pilot trial has been conducted for MDMA-assisted Cognitive Behavioral Conjoint Therapy (CBCT) for PTSD, wherein both partners participated in the entire protocol, including MDMA-assisted sessions. Findings from the study include improved PTSD scores, relationship satisfaction, posttraumatic growth, and improved social intimacy for the partner with PTSD (Monson et al., 2020; Wagner et al., 2021). These pilot trial results are promising, and suggest the potential for non-diagnostic specific MDMA-assisted couple therapy, given the significant improvements in relationally oriented outcome measures.

MDMA's empathogenic qualities have made it a prime candidate as an adjunct to psychotherapy. When considering the couple therapy context, understanding the neurochemical experience related to romantic love illuminates this potentially catalytic combination. The hormones and neurotransmitters most closely associated with the experience of love include oxytocin and vasopressin (linking to attachment and bonding), dopamine and serotonin (causing pleasure and positive mood), and the brain areas most impacted include the amygdala (registering threat, happiness and fear), prefrontal cortex (related to reasoning) and the hippocampus (engagement with thoughts and memories), as well as the caudate nucleus (registering love) and the hypothalamus (registering lust) (e.g., Zeki, 2007; Fisher et al., 2010).

The similarities in these areas of action, and notably the release of oxytocin (which can help facilitate interpersonal trust, attachment, bonding, forming affection) (Kosfeld et al., 2005; Bartz and Hollander, 2006; Domes et al., 2007), notably with its interaction with vasopressin and its context-dependent nature (Carter et al., 2020), and serotonin (increasing positive mood and extraversion, reducing depression and anxiety) (e.g., Hasler et al., 2009; van Wel et al., 2012), demonstrate that similar processes are activated in the neurobiology of love as are with MDMA. Notably, several studies have failed to show a relationship between the social effect of MDMA and oxytocin (e.g., Kuypers et al., 2017), which suggests that the empathogenic effects of MDMA are not unifactorial to the presence of oxytocin. Using the context of an MDMA-assisted psychotherapy session to work with a romantic relationship can therefore allow a potential reactivation or “remembering” of these neurochemical pathways to occur. Additionally, the increase in cortisol and noradrenergic response with MDMA can raise levels of arousal (Mas et al., 1999; Harris et al., 2002; Hysek et al., 2011, 2012a), which may support motivation to engage in therapy and interactions with the partner.

Synthesizing the literature on the psychological, subjective and perceived effects of MDMA, the following offers a distillation of pathways in which MDMA may assist couple therapy. Four broad areas of psychological impact (emotion, cognition, behavior, somatic experience) highlight eight cross-therapeutic outcomes for MDMA-assisted couple therapy: (1) empathy, (2) communication, (3) perception of social connection/support, (4) non-avoidance, (5) openness, (6) attachment/safety, (7) bonding/social intimacy, (8) relationship satisfaction (see Table 1 for synthesis).

The SET Model (Setting, Structure and Safety, Exploration and Experience, Template and Trust) is designed to capture the essential components of MDMA-assisted couple therapy, regardless of theoretical approach and across a range of treatment targets. Principles are derived from effective couple therapy (Benson et al., 2012) and the unique MDMA experience, both from the literature and from the author's experience as an investigator of MDMA-assisted CBCT.

This synthesis of the literature demonstrates the potential usefulness of MDMA as a catalyst to couple therapy, given its neurochemical actions, and emotional, cognitive, behavioral and somatic effects. While preliminary research has been conducted using one model of therapy (CBCT for PTSD) with MDMA (Monson et al., 2020), the SET model proposes a larger, overarching set of principles that can be applied irrespective of therapeutic modality and for different therapeutic targets beyond PTSD. These principles are suggested as common factors that can enhance and guide the MDMA-assisted couple therapy experience, and future research is needed to test this framework in application.

Additionally, future research can investigate, in both interventional and experimental contexts, the neurochemical and subjective experiences of MDMA in a dyadic context, as the majority of research has been conducted with individuals, not as couples. This synthesis also has implications for treatment development, including the testing of MDMA-assisted couple therapy for the reduction of relationship distress and enhancement of relationship satisfaction. In the recent resurgence of MDMA-assisted therapy research, the majority has been to treat psychiatric disorders, such as PTSD, social anxiety and anxiety related to life-threatening illness (Danforth et al., 2018; Mithoefer et al., 2019; Wolfson et al., 2020). MDMA-assisted couple therapy is a prime opportunity to extend these investigations beyond psychiatric diagnosis, while targeting outcomes that have broad and important impact on peoples' lives.

Notably, very limited MDMA-assisted couple therapy has been conducted in a research context, and therefore this mini review and proposed model is limited in scope to theorized mechanisms and pathways of action, and is preliminary in nature.

Altogether, this review suggests that the neurobiological and neurochemical effects of MDMA in a relational context, and the emotional, behavioral, cognitive and somatic effects within a dyadic frame guided by the SET model can be harnessed to facilitate meaningful interpersonal healing and growth.

The author confirms being the sole contributor of this work and has approved it for publication.

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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