In recent years there has been a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). This renaissance of psychedelic studies opens the door for a new paradigm in psychiatric medicinedrug-facilitated psychotherapy. In this study we report the findings of a randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial (NCT03537014) to test the effects of MDMA-assisted therapy (MDMA-AT) on patients with severe PTSD. The vast majority (85%) of individuals in this study reported having suffered early childhood trauma, which is strongly associated with deficits in emotional coping skills /altered self-capacities, which have been shown to constitute major obstacles to successful completion of currently available evidence-based treatments. Participants were randomized 1:1 to receive manualized therapy with either MDMA or placebo with three preparatory and nine integrative therapy sessions. Symptoms were measured at baseline and at 2 months after the last experimental session with the Clinician-Administered PTSD Scale for DSM-5, the Toronto Alexithymia Scale (TAS_20), the Self Compassion Scale (SCS) and the Inventory of Altered Self-Capacities (IASC). MDMA-AT, compared with psychotherapy alone, significantly altered the domains of alexithymia, self-compassion, and altered self-capacities. These findings suggest that MDMA-AT can substantially improve transdiagnostic mental processes associated with poor treatment response.