Effects of MDMA-assisted therapy for PTSD on self-experience

Abstract

Introduction: There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores.

Methods: Participants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC).

Results: 90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion.

Conclusion: Compared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology.

Fig 1. Alexithymia change scores in MDMA-assisted therapy.

Least square means (SE) change in Toronto Alexithymia Scale (TAS-20) scores from baseline to follow up by treatment group: MDMA-assisted therapy = -12.06 (1.75) vs Therapy with placebo = -3.39 (1.57), p < .0001.

Fig 2

Self-compassion change scores in MDMA-assisted therapy. Least square means (SE) change in Self-compassion Scale (SCS) from baseline to follow-up by treatment group: MDMA-assisted therapy = 1.08 (0.13) vs. Therapy with placebo = 0.24 (0.12), p < .0001.

Fig 3. Inventory of Altered Self-capacities (IASC) change scores.

Least square means (SE) change from baseline to follow-up by MDMA-assisted therapy vs. Therapy with placebo: (i) “interpersonal conflicts” -0.69 (0.12) vs. -0.25 (0.11), p = .0027; (ii) “idealization disillusionment” -0.70 (0.12) vs. -0.31 (0.11), p = .0095; (iii) “abandonment concerns” -0.62 (0.14) vs. -0.23 (0.13), p = .0293; (iv) “identity impairment” -1.57 (0.25) vs. -0.66 (0.23), p = .0036; (v) “self-awareness” -0.96 (0.16) vs. -0.29 (0.14), p = .0010; (vi) “identity diffusion” -0.61 (0.12) vs. -0.36 (0.10), p = .0757; (vii) “susceptibility to influence” -0.55 (0.10) vs. -0.14 (0.09), p = .0012; (viii) “affect dysregulation” -1.75 (0.30) vs. -0.96 (0.27), p = .0349; (ix) “affect instability” -0.76 (0.15) vs. -0.40 (0.13), p = .0454; (x) “affect skill deficit” -0.98 (0.17) vs. -0.56 (0.15), p = .0424; (xi) “tension reduction activities” -0.42 (0.08) vs. -0.19 (0.07), p = .0206.

Fig 4. Significant differences in CAPS-5 total severity change scores between treatment groups by baseline self-experience levels.

Interaction between treatment and baseline alexithymia subgroup levels was statistically significant to warrant further stratification (p = 0.04); and stratified results also presented for self-compassion and IASC scores. At baseline, being (i) worse-off, having borderline alexithymia/ alexithymia or low self-compassion or (ii) better-off, lower idealization disillusionment, identity impairment, identity diffusion, or susceptibility to influence were associated with statistically significant greater CAPS-5 changes scores in the MDMA-assisted therapy group compared to Therapy with placebo, at alpha p ≤ .05 (*). For all other IASC factors, there were no differences in CAPS-5 change scores by baseline subgroup levels.