This pilot study will examine the safety, tolerability, acceptability, and efficacy of combination psilocybin + psychotherapy to decrease PTSD symptoms. Participants will be randomized into two different treatment groups, allowing the investigators to directly compare PE augmented with psilocybin and psilocybin-assisted psychotherapy.
The Primary objective is to pilot and investigate tolerability, safety, and acceptability of psilocybin-assisted supportive therapy and psilocybin-assisted massed prolonged exposure (PE) therapy and conduct exploratory analyses related to comparative effectiveness of these treatments, including preliminary outcomes from pre-treatment to 1-month follow-up on post-traumatic stress disorder (PTSD) symptoms. Safety and tolerability of the treatment will be assessed and evaluated using the Swiss Psychedelic Side Effects Inventory (SPSI), Psychedelic-assisted Therapy After Effects (PATAE), and the Accessibility Questionnaire (AQ). The study will also evaluate the effect of psilocybin and massed exposure therapy using Subjective Units of Distress (SUDS) during imaginal exposure sessions; to assess self-reported PTSD and depression symptoms across treatment and investigate effect on fear extinction learning and fear extinction recall as assessed via fear potentiated startle. Given that this is a pilot study with small sample, analyses will be preliminary.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
25 mg
Treatment includes non-directive psychological support across the preparatory, dosing, and integration sessions. Preparatory sessions include psychoeducation regarding psilocybin's subjective effects and establish strategies for psilocybin related support, including boundaries around physical touch. Therapists encourage setting intention for dosing day, and practicing experiential exercises. Integration sessions include processing the participant's experience of their psilocybin administration session. Therapists will support participants in identifying activities for ongoing integration outside of sessions. The standard care for supportive therapy will be modeled in this study.
Emory University Hospital
Atlanta, Georgia, United States
Change in PTSD symptoms based on CAPS-5-R total severity score
PTSD symptoms will be evaluated using the Revised Clinician-Administered PTSD Scale for DSM-5, that refers to 20 core symptoms as CAPS-5, each rated on a 0-4 severity scale (0 = absent to 4 = extremely severe), combining frequency and intensity. Total possible score range is 0 to 80 with higher scores correlating with worse outcome.
Time frame: Baseline, 1-month post-intervention
Change in PCL-5 score
The PCL-5 is a 20-item self-report measure of DSM-5 PTSD symptoms. Scores on the PCL range from 0 to 80, with higher scores indicating higher symptom severity, and a cutoff of 33 indicating clinical levels of PTSD symptoms.
Time frame: Baseline, 1, 6 and 12 months post-intervention
Depression symptoms (PHQ-9)
The PHQ-9 is a 9-item self-report measure of depressive symptoms. A score of 10 or above indicative of a possible major depressive episode, and it provides a measure of severity of these symptoms. Total possible score range is 0-29, higher score correlates with worse outcome.
Time frame: Baseline, 1, 6 and 12 months post-intervention
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Prolonged Exposure (PE) Therapy will be conducted for 10 sessions. They will consist of repeated exposures to trauma memories (imaginal exposure) consistent with the manualized protocol for massed exposure therapy. Also consistent with this treatment manual, participants will listen to imaginal exposures and conduct in real life exposures outside of PE sessions for "homework". The standard care for PE therapy will be modeled in this study.