MAPS PBC Announces Frontiers in Psychiatry Published First Study to Evaluate Neural Impact of MDMA-Assisted Therapy in Patients with PTSD

• Results demonstrate a biological correlation between reduction in PTSD severity and treatment with MDMA-assisted therapy in veterans and first responders
• Study sheds light on neurological mechanisms that drive MDMA-assisted therapy in PTSD

SAN JOSE, Calif., Jan. 19, 2023 /PRNewswire/ -- MAPS Public Benefit Corporation ("MAPS PBC"), a private biopharmaceutical company dedicated to the development and commercialization of psychedelic medicines, announced Frontiers in Psychiatry has published the first functional neuroimaging study designed to evaluate the impact of MDMA-assisted therapy in participants with post-traumatic stress disorder ("PTSD"). Results showed that changes in functional connectivity between brain regions implicated¹ in PTSD were associated with a reduction in PTSD severity following treatment with MDMA-assisted therapy. The study also revealed a trend suggesting a strengthening of the resting state functional connectivity between the amygdala and the hippocampus, two regions of the brain that become dysregulated in PTSD.

"This is an important brain imaging study because we can see how MDMA-assisted therapy actually turns down the fear and PTSD circuit in the brain," said Mark S. George, MD, Distinguished Professor of Psychiatry, Radiology and Neuroscience at the Medical University of South Carolina in Charleston and one of the study co-authors. "Although we are not imaging the direct brain regions where MDMA works, we can see, in a dose-dependent fashion, how the therapy may help reduce the fear response in the brain of patients with PTSD while they are remembering their trauma. This is an important early step."

The purpose of this study was to investigate how MDMA may facilitate the therapeutic process by measuring brain activity and functional connectivity between key brain regions thought to be involved in PTSD in veterans and first responders with chronic PTSD before and two months after treatment with MDMA-assisted therapy. Neuroimaging studies have played a critical role in contributing to the understanding of biological changes in the brain that can result from PTSD including the role of the amygdala and hippocampus. The amygdala, known as the fear center of the brain, is associated with threat recognition and heightened response to emotional memories and is often dysregulated in patients with PTSD. The hippocampus also plays a central role in PTSD and is thought to provide contextual information important for the cognitive processing of memories. ^2,3,4

Study Design

This study was part of a randomized, double-blind, dose-response Phase 2 clinical trial, enrolling individuals with moderate to severe PTSD, as measured by the Clinician-Administered PTSD Scale (CAPS-IV), with a chronic duration of six months or more (mean duration of 84 [+/-45] months). Ten participants enrolled in the brain imaging study, and one withdrew due to anxiety in the MRI scanner prior to treatment, leaving nine participants with MRI data at both time points (six male, three female, average age was 41.3 [+/-10.9] years, eight veterans and one first responder). One participant began the trial with mode rate PTSD (CAPS-IV > 39) while the remaining eight presented with severe PTSD (CAPS-IV > 59). Resting state and task-related fMRI data were acquired while participants listened to a trauma-related and neutral audio script they created based on a personal traumatic experience and their normal morning routine. Participants completed three split dose sessions with 125 mg + 62.5 mg MDMA, accompanied by therapy sessions for preparation and integration. All participants were imaged at baseline prior to therapy and then at their follow up visit two months after their final 125 mg MDMA dosing session.

Study Results

Results showed that following treatment with MDMA-assisted therapy, participants experienced a significant reduction in PTSD severity as measured by CAPS-IV (N = 9, t = 6.36, p = 0.00022). Results also showed a trend suggesting that resting state functional connectivity ("FC") between the amygdala and the hippocampus was strengthened after treatment, particularly in the left hemisphere (N = 8; t = -2.91; corrected p = 0.0901). Before treatment, participants had larger activation in areas of the brain involved in self-referential processing and autobiographical memory when they were listening to their individualized trauma audio script compared to when they were listening to their neutral audio script. The study found that two-months after the last treatment session, there was significantly less contrast between the trauma and neutral scripts in the cuneus suggesting decreased visual imagery during traumatic memories after MDMA-assisted therapy. Finally, the study assessed pre- to post-therapy changes in FC during the autobiographical scans and these changes were correlated with PTSD symptom improvements. Of particular interest was the strong correlation between L-amygdala-insula FC changes and symptom improvement (N = 9; R = 0.977, corrected p = 0.0197), as this functional connection is implicated in PTSD symptomology and anxiety.

"These data add to our understanding of the biological rationale for using MDMA combined with therapy in the treatment of PTSD," said Amy Emerson, chief executive officer, MAPS PBC. "The results suggest that treatment with MDMA-assisted therapy may help reset the dysregulation in the brain caused by PTSD and that the effects are durable even two months after treatment."

In 2017 the U.S. Food and Drug Administration ("FDA") granted MDMA-assisted therapy Breakthrough Therapy designation, a process designed to expedite the development and review of drugs intended to treat serious conditions and that demonstrate substantial improvement over available therapies. MAPS PBC expects to submit the new drug application to the FDA in the third quarter of 2023.

MDMA-assisted therapy has not been approved by any regulatory agency. The safety and efficacy of MDMA-assisted therapy have not been established for the treatment of PTSD.

ABOUT PTSD

PTSD is a serious public health issue affecting approximately 12 million Americans each year⁵, yet currently available treatments only provide modest efficacy.⁶ People with PTSD can experience debilitating symptoms that impact nearly all areas of a person's life.⁷ They also frequently suffer from serious comorbidities including anxiety, depression, and substance use disorder.⁸ PTSD has an enormous economic impact resulting in an annual burden of over $200 billion.⁹ Currently available treatments for PTSD are inadequate to address the full spectrum of patients who need treatment and do not provide adequate relief from debilitating symptoms.⁶ These limitations combined with high treatment discontinuation rates¹⁰ underscore the urgent need for novel and effective therapies.

ABOUT MAPS PUBLIC BENEFIT CORPORATION (MAPS PBC)

MAPS Public Benefit Corporation (MAPS PBC) is focused on developing and commercializing prescription psychedelics to bring better treatments to those living with mental health conditions. Founded in 2014, MAPS PBC is a subsidiary of the Multidisciplinary Association for Psychedelic Studies, a 501(c)(3) non-profit organization.

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⁵ VA National Center for PTSD
⁶ Morina N. Remission from post-traumatic stress disorder in adults: a systematic review and meta-analysis of long term outcome studies. Clin Psychol Rev. (2014) Apr;34(3):249-55. doi: 10.1016/j.cpr.2014.03.002.
⁷ The Mayo Clinic, PTSD, Symptoms and Causes www.mayoclinic.org/diseases-conditions/post-traumatic-stress-disorder/symptoms-causes/syc-20355967c
⁸ Grinage B.D. Diagnosis and Management of Post-traumatic Stress Disorder. Am Fam Physician. (2003);68(12):2401-2409.
⁹ Davis LL. The economic burden of posttraumatic stress disorder in the United States from a societal perspective. J Clin Psychiatry. (2022) Apr 25;83(3):21m14116. doi: 10.4088/JCP.21m14116.
¹⁰ Varker T. Dropout from guideline-recommended psychological treatments for posttraumatic stress disorder: A systematic review and meta-analysis. Journal of Affective Disorders Reports (2021) Apr 2021, 100093. doi: 10.1016/j.jadr.2021.100093

SOURCE MAPS PBC