Table 1.

Areas of focus for MDMA-assisted couple therapy outcomes.

Area of focus	How MDMA supports	Proposed therapeutic interventions to facilitate
Empathy	Oxytocin release helps increase interpersonal focus, feelings of interpersonal trust, social affiliation (Kosfeld et al., 2005; Bartz and Hollander, 2006; Domes et al., 2007). MDMA associated with seeing others as empathetic and caring (Hysek et al., 2013; Bedi et al., 2014; Wardle and de Wit, 2014), and increases emotional empathy beyond oxytocin alone (Kuypers et al., 2014)	Centering both peoples' experiences, sharing of feelings
Communication	MDMA associated with greater interpersonal focus in language (Bedi et al., 2014), reduction in reactivity to angry facial expressions and greater reward in happy faces (Bedi et al., 2009)	Present and practice skills of sharing and listening with both negative and positive content
Perception of social connection and support	Reduction in feeling of social pain (Frye et al., 2014), decreased feelings of threat, increased feelings of interpersonal trust (Kosfeld et al., 2005; Domes et al., 2007), increased identification of prosocial feelings (Bedi et al., 2010)	Highlight strength in couples' interactions, remind in integration to reduce likelihood of returning to old patterns after MDMA sessions
Non-avoidance	MDMA assists in fear attenuation, allowing for approach of difficult experiences and memories (Young et al., 2015, 2017; Doss et al., 2018; Feduccia and Mithoefer, 2018; Hake et al., 2019)	Explain why non-avoidance is helpful-while difficult initially, is supportive of growth of relationship to not allow difficulties to expand or root over time
Openness	MDMA can assist in increased openness to experience and decreased neuroticism (Wagner et al., 2017). The ability to engage in interactions may be supported by the release of cortisol, and paired with oxytocin (e.g., Mas et al., 1999; Hysek et al., 2011)	Creating shared intentions, and establishing as a value to bring through the process
Attachment/ safety	Decreased feelings of threat, increased feelings of interpersonal trust (Kosfeld et al., 2005; Domes et al., 2007)	Skills to engage in difficult conversations, take breaks and re-engage. Creating a template for future experiences
Bonding/ social intimacy	Oxytocin, which MDMA causes to release, supports feelings of social bonding (Bartz and Hollander, 2006). MDMA helps increase cooperation and feelings of trustworthiness (Stewart et al., 2014; Gabay et al., 2019). Increased experience of social intimacy following MDMA-assisted couple therapy (Wagner et al., 2021)	Couple engaging in the whole process together
Relationship satisfaction	Improved relationship satisfaction, decreased distress in MDMA-assisted couple therapy (Monson et al., 2020; Wagner et al., 2021)	Encouraging shared experiences, engagement together in the therapeutic process