New‐Onset Obsessive–Compulsive Symptoms After MDMA‐Assisted Psychotherapy in a Patient With Refractory PTSD: A Case Report

A 31-year-old woman with chronic PTSD and a history of childhood compulsions developed new-onset obsessive-compulsive disorder (OCD) after undergoing MDMA-assisted psychotherapy (MDMA-AP) in a clinical trial. Her PTSD had been resistant to multiple medications, and she reported significant improvements in flashbacks and suicidal ideation after the first session. Following a delayed second session, she experienced intrusive guilt, scrupulosity, and compulsive urges to confess, leading to a DSM-5 diagnosis of OCD. OCD symptoms persisted for over a year, with a Y-BOCS score of 17 indicating moderate severity, and improved with escitalopram. This case suggests that MDMA-AP may trigger obsessive-compulsive pathology in individuals with complex trauma and prior obsessive-compulsive tendencies, possibly through serotonergic effects on frontostriatal circuits, and highlights the need for screening and long-term monitoring in such protocols.

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Abstract

3,4‐Methylenedioxymethamphetamine (MDMA)‐assisted psychotherapy (MDMA‐AP) has shown promise in treating post‐traumatic stress disorder (PTSD), particularly in treatment‐resistant cases. However, little is known about its potential to precipitate adverse psychiatric outcomes. We present the case of a 31‐year‐old woman with nondistressing childhood compulsions, chronic PTSD, and complex medical comorbidities who developed new‐onset obsessive–compulsive disorder (OCD) following MDMA‐AP. The patient had a history of acute myeloid leukemia (AML), graft‐versus‐host disease (GVHD), avascular necrosis, and lower extremity paralysis secondary to transverse myelitis. Her PTSD had proven refractory to multiple pharmacologic interventions. She enrolled in an MDMA‐AP clinical trial in 2021, reporting significant improvements in flashbacks, suicidal ideation, and functional impairment after the first session. However, following a delayed second session, she developed intrusive guilt, scrupulosity, and compulsive urges to confess, leading to a formal diagnosis of OCD based on DSM‐5 criteria. OCD symptoms persisted for over a year, with a Yale‐Brown Obsessive Compulsive Scale (Y‐BOCS) score of 17 indicating moderate severity. Treatment with escitalopram 7.5 mg daily led to marked improvement of OCD symptoms. This case raises the possibility that MDMA‐AP, while effective in reducing PTSD symptoms, may carry the risk of triggering obsessive–compulsive pathology, particularly in individuals with complex trauma histories and prior obsessive–compulsive tendencies. This risk may be mediated by the serotonergic effects of MDMA, which could disrupt inhibitory control in frontostriatal circuits. Furthermore, current studies may underreport psychiatric side effects of psychedelic‐assisted psychotherapies due to inconsistent safety monitoring. This case, therefore, underscores the need for structured, long‐term follow‐up and pretreatment screening for OCD vulnerability in MDMA‐AP protocols. Despite the adverse outcome, the patient’s significant PTSD improvement highlights the therapeutic complexity of MDMA‐AP and the importance of individualized care. Trial Registration: ClinicalTrials.gov identifier: NCT04077437