Changes in wellbeing, self-compassion and alexithymia in a proof of principle trial with MDMA-assisted therapy for major depressive disorder
Mark Berthold-Losleben, Ivar Walderhaug Goksøyr, Tor-Morten Kvam, Justyna Rog, Lowan Han Stewart, Morgan Scarth, Dan Joseph Stein
Journal of Psychiatric Research November 7, 2026 DOI: 10.1016/j.jpsychires.2026.11.014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label clinical trial Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Adults with moderate to severe major depressive disorder |
| Interventions | MDMA-assisted therapy manualized psychotherapy |
| Duration | Two MDMA sessions with three preparatory and six integration psychotherapy sessions; assessments at baseline, 8 weeks post-treatment, and long-term follow-up of at least 3 months |
| Measures | Toronto Alexithymia Scale (TAS-20), Self-Compassion Scale (SCS), Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), MADRS |
| Topics | Depression MDMA |
| Key findings | MDMA-assisted therapy was associated with lasting improvements in alexithymia, self-compassion, and well-being: TAS-20 fell 11.75 points post-treatment and 16.42 at follow-up, SCS rose 0.73 and 1.07, and WEMWBS improved 17.30 at both timepoints. The authors report these changes were driven by the nine of twelve therapy responders and conclude the approach may support durable psychological recovery beyond symptom reduction. |
Abstract
Background: Transdiagnostic factors such as emotion regulation, self-compassion, and alexithymia influence the development and outcome of psychiatric conditions, including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine-assisted therapy (MDMA-AT) has shown efficacy in reducing PTSD and depressive symptoms. This study examined MDMA-AT effects on alexithymia, self-compassion, and well-being in MDD, assessing durability and links to long-term outcomes.
Methods: Data were drawn from an open-label MDMA-AT trial (EudraCT 2021-000805-26) including twelve participants with moderate to severe MDD (baseline MADRS M(SD)=29.6(4.9)). Participants received two MDMA sessions with manualized psychotherapy (three preparatory, six integration). Outcomes were assessed at baseline, post-treatment (8 weeks), and long-term follow-up (≥3 months) using the Toronto Alexithymia Scale (TAS-20), Self-Compassion Scale (SCS), and Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). Changes were analyzed with linear mixed models; estimated marginal means and post-hoc comparisons explored time effects.
Results: MDMA-AT significantly improved alexithymia, self-compassion, and well-being. TAS-20 decreased by −11.75 post-treatment and −16.42 at follow-up (both p<0.001). SCS increased by 0.73 post-treatment (p=0.017) and 1.07 at follow-up (p=0.001). WEMWBS improved by 17.30 at both timepoints (p<0.001). All SCS subscales improved; common humanity and isolation reached significance only at follow-up. Improvements were driven by therapy responders (9/12). Eight participants had at least borderline alexithymia at baseline; none did at follow-up. Self-compassion shifted from seven low and one high at baseline to seven high and one low at follow-up.
Conclusions: MDMA-AT for MDD produced lasting improvements in alexithymia, self-compassion, and well-being, supporting its potential for durable psychological recovery beyond symptom reduction.