Bessel van der Kolk, MD: The Future of MDMA Assisted Therapy in PTSD

Next week, the US Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee (PDAC) will vote to determine whether currently available clinical trial data supports the effectiveness of treating PTSD with midomafetamine (MDMA)-assisted therapy—a determination that will likely influence the FDA’s final determination on a New Drug Application (NDA) from Lykos Therapeutics for the very same indication by August this year.¹

While the third-party meeting and regulatory decision will immediately dictate the established role of psychedelic therapy in the treatment of trauma, experts and investigators remain focused on interpreting greater meaning and further findings from the promising field of care.

In the second segment of an interview with HCPLive prior to the advisory committee meeting,² leading MDMA-assisted therapy investigator Bessel van der Kolk, MD, co-founder and chair of the Trauma Research Foundation, and globally recognized author and researcher of trauma, discussed the further prospects of MDMA clinical research based on his team’s work in the MAPP1 and MAPP2 trials.³ First, he considered whether the identification of a highly efficacious regimen like MDMA-assisted therapy would lend credence to the idea that timelier PTSD screening and diagnosis could potentially optimize treatment outcomes.

“That's an interesting question, actually, because this population is pervasive in psychiatric clinics,” van der Kolk said. “And because they have such complex pathology, they can easily be labeled as bipolar or with chronic depression, severe anxiety or medical problems like fibromyalgia and chronic pain issues. These people have a whole complex set of symptoms.”

Such patients may be more easily undertreated by their clinicians, van der Kolk said—at risk of feeling dismissed while ineffectively treated for their trauma. The findings from MAPP1 and MAPP2 provide newfound optimism that in fact, if these patients are more accurately diagnosed, they can achieve more significant clinical outcomes and reach a higher quality of life.

“But at the same time, many people with this sort of constellation of problems were not included in the study,” van der Kolk said. “For example, we excluded people with dissociative disorder, we excluded people with borderline personality disorder—very specifically, because there are certain difficult people to treat. But this study really opens up the possibility that people on the more severe end of the psychiatric spectrum could actually benefit more than we thought.”

Regarding the potential long-term efficacy of MDMA-assisted therapy for patients with PTSD, van der Kolk was asked whether the clinical measurement for self-compassion scores (SCS)—shown in prior research to impact the efficacy of cognitive reappraisal associated with psychotherapy—was the key barometer to interpreting sustained benefit from the revolutionary treatment. While it may be a critical outcome, he instead suggested that the continued modulation of emotions in treated patients is a more crucial measure.

“Because if the slightest thing can put you in a rage or put you in a state of panic or anxiety, that is a major biological deficit that really interferes with your functioning on many levels,” van der Kolk said. “And if we can change that—that capacity to regulate your emotional control over yourself—that would be a major advance in the treatment of mental illness.”

In terms of next steps in clinical research, van der Kolk highlighted 2 areas of interest: the continued ability to treat symptoms of PTSD including poor emotion regulation, as well as the comorbid physical conditions associated with PTSD including gastrointestinal, musculoskeletal and immunological conditions.

“People who live with chronic trauma tend to die about 10 years earlier than the general population,” van der Kolk said. “So, if we can actually find ways of regulating these physical and hormonal systems, it would be a major advance.”

Reference

1. ^{Kunzmann K. FDA Advisory Committee Meeting to Review MDMA-Assisted Therapy for PTSD. HCPLive. Published May 6, 2024. https://www.hcplive.com/view/fda-advisory-committee-meeting-review-mdma-assisted-therapy-ptsd}
2. ^{Kunzmann K. Bessel van der Kolk, MD: What MDMA-Assisted Therapy Taught us About PTSD. HCPLive. Published May 31, 2024. https://www.hcplive.com/view/bessel-van-der-kolk-mdma-assisted-therapy-taught-ptsd}
3. ^{van der Kolk BA, Wang JB, Yehuda R, et al. Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS One. 2024;19(1):e0295926. Published 2024 Jan 10. doi:10.1371/journal.pone.0295926}