Contemporary clinical trials · 2025
Randomized trial of delta-9-tetrahydrocannabinol (THC) versus placebo to augment the effects of prolonged exposure therapy on fear extinction learning in post-traumatic stress disorder: Study rationale and protocol.
СтатьяПротокол клинического исследованияНазвание и аннотация: Перевод в очереди
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Rabinak Christine A, Kilgore Paul E, Lumley Mark A, Rauch Sheila A M
Аннотация
BACKGROUND: Prolonged exposure (PE) therapy is effective for PTSD, yet dropout and partial response remain concerning. Preclinical and human studies suggest Δ9-tetrahydrocannabinol (THC) enhances fear extinction and recall through brain cannabinoid receptor activation in fear processing.
OBJECTIVE: Examine whether synthetic THC (dronabinol) augments PE effectiveness.
DESIGN: Double-blind, placebo-controlled, trial with treatment-seeking PTSD patients (ages 18-60) randomized to 7.5 mg THC (n = 30) or placebo (n = 30). Randomization after sessions 1-2 (psychoeducation) ensures covariate-adaptive balance before the first medicated session. THC/placebo administered before PE sessions 3-6 of 10 total sessions so dosing coincided with extinction-learning sessions.
SETTING: Wayne State University with remote PE delivery via Emory University.
PARTICIPANTS: Adults with PTSD (CAPS-5 ≥ 25) excluding for severe mental illness, substance use disorders, or contraindications to THC.
INTERVENTIONS: PE therapy (10 sessions, up to 3 times / week) with THC or placebo administered 120 min before sessions to coincide with peak plasma levels.
MAIN OUTCOMES: Primary: PTSD symptom severity (CAPS-5, PCL-5). Secondary: fMRI brain activation during fear extinction paradigms, skin conductance responses, and extinction retention measures pre/post-treatment.
STATISTICAL ANALYSIS: Intent-to-treat linear mixed-effects models accounting for therapist clustering. Neuroimaging analyzed via region-of-interest and whole-brain approaches focusing on ventromedial prefrontal cortex, hippocampus, and amygdala.
DISCUSSION: THC dosing and timing is based on prior mechanistic studies that demonstrated THC-related enhancement of extinction recall and frontolimbic circuit engagement. Aligning peak THC levels with exposure sessions maximizes potential for CB1-mediated augmentation of extinction learning. If effective, this FDA-approved augmentation strategy could be rapidly implemented to improve PE outcomes.
TRIAL REGISTRATION: ClinicalTrials.govNCT04080427.
OBJECTIVE: Examine whether synthetic THC (dronabinol) augments PE effectiveness.
DESIGN: Double-blind, placebo-controlled, trial with treatment-seeking PTSD patients (ages 18-60) randomized to 7.5 mg THC (n = 30) or placebo (n = 30). Randomization after sessions 1-2 (psychoeducation) ensures covariate-adaptive balance before the first medicated session. THC/placebo administered before PE sessions 3-6 of 10 total sessions so dosing coincided with extinction-learning sessions.
SETTING: Wayne State University with remote PE delivery via Emory University.
PARTICIPANTS: Adults with PTSD (CAPS-5 ≥ 25) excluding for severe mental illness, substance use disorders, or contraindications to THC.
INTERVENTIONS: PE therapy (10 sessions, up to 3 times / week) with THC or placebo administered 120 min before sessions to coincide with peak plasma levels.
MAIN OUTCOMES: Primary: PTSD symptom severity (CAPS-5, PCL-5). Secondary: fMRI brain activation during fear extinction paradigms, skin conductance responses, and extinction retention measures pre/post-treatment.
STATISTICAL ANALYSIS: Intent-to-treat linear mixed-effects models accounting for therapist clustering. Neuroimaging analyzed via region-of-interest and whole-brain approaches focusing on ventromedial prefrontal cortex, hippocampus, and amygdala.
DISCUSSION: THC dosing and timing is based on prior mechanistic studies that demonstrated THC-related enhancement of extinction recall and frontolimbic circuit engagement. Aligning peak THC levels with exposure sessions maximizes potential for CB1-mediated augmentation of extinction learning. If effective, this FDA-approved augmentation strategy could be rapidly implemented to improve PE outcomes.
TRIAL REGISTRATION: ClinicalTrials.govNCT04080427.