Landmark Study Highlights Efficacy of MDMA-Assisted Therapy for PTSD

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In the first of its kind, Bessel van der Kolk, MD, and colleagues found 3,4-methylenedioxymethamphetamine (MDMA)-assisted performed better in improving emotional coping skills in adults with severe posttraumatic stress disorder as compared to therapy plus placebo.¹ The results were published in PLOS ONE.

The results were derived from the MDMA-Assisted Psychotherapy for PTSD (MAPP1) (NCT03537014). The phase 3 randomized, double-blind, placebo-controlled trial was conducted across multiple sites and compared the safety and efficacy of MDMA-assisted therapy with therapy with placebo in individuals who met DSM-5 criteria for severe PTSD, with a Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score of 35 or greater.

Participants (N=90) were randomized to MDMA-assisted therapy (N=46) or therapy with placebo (N=44) across 15 study sites for a series of 3 sessions. In each session, participants received a split-dose of MDMA or placebo, with an initial dose (80 mg MDMA HCl) and then a half-dose (40 mg MDMA HCl)1.5 to 2.5 hours following the initial dose in the first session. The 2 subsequent sessions, the doses were 120 mg followed by 60 mg MDMA HCl 1.5 to 2.5 hours later. Patients received a preparatory session preceding administration and 3 90-minute integration therapy sessions, scheduled 1-week apart, following administration.

Key factors of eligibility was age of at least 18 years, fluency in the language used at the study site, and agree to the conditions of the study. Female patients of childbearing age must have a negative pregnancy test and agree to adequate birth control for the duration of the study and 10 days beyond. Patients were excluded if they had: uncontrolled hypertension; a marked baseline prolongation of QT/QTc interval; a history of risk factors for Torsade de pointes; and a history of significant medical disorders, including symptomatic liver disease and hyponatremia or hyperthermia. Those individuals who weighed less than 48 kg, were pregnant or nursing, or were abusing illegal drugs were also excluded. Psychiatric exclusion criteria included having a primary psychotic, bipolar I disorder, dissociative identity and personality disorders, and current alcohol and substance use disorders.

The majority (84.4%)of participants had histories of developmental trauma, ie, early childhood physical or sexual abuse by their caregivers. Similarly, the majority 87.8% also reported experiencing multiple traumas.

Van der Kolk et al found greater improvements in the self-experience measures, except IASC factor identity diffusion. They also noted that higher baseline alexithymia was associated with greater improvements in PTSD.

MDMA received breakthrough therapy designation in 2017.² Based on research data, Lykos Therapeutics has requested a priority review of the new drug application. Pending the FDA decision and possible approval, the US Drug Enforcement Administration would need to reschedule the agent so it can be used for prescription medical purposes.

Psychiatric Times’ Editor in Chief, John J. Miller, MD, was excited to read about these new findings. In an exclusive interview, he said, “This post-hoc analysis of a previously published phase 3 study demonstrated that in addition to improvement of PTSD symptoms in patients with severe PTSD for patients receiving MDMA-assisted therapy compared to placebo-assisted therapy, there was an independent improvement of self-compassion and self-experience for the MDMA-assisted therapy cohort."

Van der Kolk has previously written about the challenges in supporting patients with PTSD resulting from early childhood experiences. “People who have histories of having been traumatized as children within their caregiving systems are particularly prone to developing major deficits in emotion regulation and often develop a self-identity of being worthless and defective,” he wrote.³ “When these people are being treated for their PTSD, their lack of a sense of safety and difficulties with trust can be major obstacles to successful completion of treatment; these deficits often prevent treatment from being successful. In this study, we observed that MDMA-assisted therapy was more effective than psychotherapy alone in improving a range of problems with self-experience that are associated with treatment failure.”

The authors of the present noted that the data from this study are promising. “Results of this exploratory analysis show both the potential influence of baseline self-experience and MDMA-assisted therapy on self-experience to impact PTSD symptoms, which can be used to guide clinical practice. Further, results found MDMA-assisted therapy improved self-compassion independent of PTSD treatment which warrants further investigation into potential new applications,” they wrote.¹

“More studies are needed to examine the capacity of MDMA to ameliorate post-traumatic symptomatology in a variety of trauma populations, including whether MDMA-assisted therapy is capable of permanently altering a host of psychological processes associated with having been traumatized, including shame, self-blame, the capacity for emotional intimacy, executive functioning and affect regulation” they concluded.

References

1. van der Kolk BA, Wang JB, Yehuda R, Bedrosian L, Coker AR, et al. (2024) Effects of MDMA-assisted therapy for PTSD on self-experience. PLOS ONE 19(1): e0295926.

2. Lykos Therapeutics (Formerly MAPS PBC) Announces Publication Examining the Effects of MDMA-Assisted Therapy on Emotional Coping Skills and Self-Experience in PTSD. Press release. January 10, 2024. Accessed January 10, 2024. https://lykospbc.com/press-releases/lykos-therapeutics-formerly-maps-pbc-announces-publication-examining-the-effects-of-mdma-assisted-therapy-on-emotional-coping-skills-and-self-experience-in-ptsd/

2. Van der Kolk, Bessel A. The body keeps the score: brain, mind, and body in the healing of trauma. Viking; 2014.