ID: 212703 Augmenting rTMS With Psilocybin-Assisted Psychotherapy (PAP) for PTSD: A Proof-of-Concept Study Design

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating mental illness, often with a chronic course and major comorbidities such as treatment-resistant depression (TRD), drug abuse, and suicidality. Current treatments have a long time-to-remission and high nonresponse and recurrence rates; novel and efficacious treatments are necessary. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, FDA-approved, and efficacious treatment for TRD with few side effects. It is emerging as a treatment for PTSD; however, as a monotherapy its efficacy is neither high nor durable1. Recently, our group has combined rTMS with mindfulness therapy (TIMBER) for TRD and PTSD, with promising results2. Other emerging options are psychedelics, especially psilocybin, which has been efficacious for TRD3 and may hold promise for PTSD due to unique properties such as agonism of not only 5-HT2ARs (empathy, openness, creativity), but also 5HT1ARs (anxiolytic) and D1Rs (pro-cognitive) as well, unlike other psychedelics4. These additional properties make it uniquely suitable for psilocybin-assisted psychotherapy (PAP) in PTSD. Psilocybin and rTMS share one common mechanism of action: dampening the overactive default mode network in PTSD1,5. However, unlike MDMA, psilocybin has not yet been studied for PTSD4. We hypothesize that PAP combined with rTMS will have the most robust effects on PTSD, acting synergistically to ameliorate PTSD symptoms and extend the duration of response as well.