Trifecta Research Study

Approximately forty participants took part in a program of experimental interventions and therapies that was created to improve psychological and cognitive health outcomes in a population with severe, treatment-resistant conditions. Participants were obtained from a cohort of SOF veterans who were already seeking these therapies through the Special Operations Care-Fund (SOC-F) and chose to volunteer for the study. Participants were assigned by SOC-F to one of two sequences of interventions through SOC-F's care providers. One group received PS, then MeRT, then IM and 5-MeO-DMT. The other group received PS, then IM and 5-MeO-DMT, then MeRT. PS preceded the other interventions in each condition. The study design includes self-report and informant-report questionnaires and cognitive task assessments, all of which monitor the interventions' impact on health outcomes. The general purpose is to explore the potential for this combination of treatments to improve mental health and cognitive function. A collection of subjective and objective data will allow a comprehensive assessment of therapeutic impact, with the ultimate goal of informing future clinical trials and veteran treatment services. This project was formerly registered on clinicaltrials.gov (NCT06810765). Aims and Hypotheses: Aim 1: Investigate the impact of all interventions on PTSD symptoms and cognitive function in SOF veterans with PTSD and cognitive difficulties. H1.1. Collectively, program interventions will be associated with reduced self-reported PTSD symptoms at 3-month follow-up (3MFU). H1.2. Collectively, program interventions will be associated with improved self-reported cognitive functioning at 3MFU. H1.3. Collectively, program interventions will be associated with improved cognitive inhibition, indexed by the Stroop Squared Task, at Post-treatment. H1.4. Collectively, program interventions will be associated with improved negative emotional memory, indexed by a higher proportion of recalled positive words (see V1.1 in Dependent Variable section) in the Externalizing Free Recall with Emotional Words Task, at Post-treatment. H1.5. Collectively, program interventions will be associated with improved positive emotional memory, indexed by a higher proportion of recalled positive words (V1.2) in the Externalizing Free Recall with Emotional Words Task, at Post-treatment. H1.6. Collectively, program interventions will be associated with improved negative emotional memory, indexed by a higher proportion of negative recall intrusions (V2.1) in the Externalizing Free Recall with Emotional Words Task, at Post-treatment. Aim 2: Investigate the incremental impact of IM and 5-Meo-DMT on PTSD symptoms and cognitive functioning relative to initial intervention with PS and MeRT in SOF veterans with PTSD and cognitive difficulties. H2.1. IM/5-Meo-DMT will be associated with an incremental reduction in self-reported PTSD symptoms at 3MFU, relative to the previous effects of PS and MeRT (measured at Pre-IM/5Meo timepoint). H2.2. IM/5-Meo-DMT will be associated with an incremental improvement in self-reported cognitive functioning at 3MFU, relative to the previous effects of PS and MeRT (measured at Pre-IM/5Meo timepoint). H2.3. IM/5-Meo-DMT will be associated with an incremental improvement in cognitive inhibition at Post-treatment, indexed by the Stroop Squared Task, relative to the previous effects of PS and MeRT (measured at Pre-IM/5Meo timepoint). Aim 3: Investigate whether the sequence of interventions differentially impacts PTSD and cognitive functioning at 3MFU in SOF veterans. No formal hypotheses. Aim 4: Investigate adverse events related to each of the interventions. No formal hypotheses.