A Phase 4 interventional study of Buprenorphine and Naltrexone in Major Depressive Disorder and Depression, sponsored by Marta Peciña, MD PhD. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by Marta Peciña, MD PhD · Phase 4, Interventional, and Other
The central goal of this application is to demonstrate the causal contribution of reward learning signals (expected values and reward prediction errors [RPE]) to antidepressant responses (Aim1) by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC (Aim 2) and μ-opioid striatal RPE signal using pharmacological approaches (Aim 3).
The central goal of this study is to demonstrate the causal contribution of reward learning signals (expected values and RPEs) to antidepressant responses (Aim1) by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC (Aim 2) and μ-opioid striatal RPE signal using pharmacological approaches (Aim 3). In a 3x3 factorial double-blind trial, the investigators will randomize 120 unmedicated major depressive disorder (MDD) adults (18-55 years) to one of three between-subject opioid conditions: the μ-opioid agonist buprenorphine (n=40), the μ-opioid antagonist naltrexone (n=40), or the inert pill (n=40). Within each arm, individuals will be assigned to receive three within-subject counterbalanced sessions of TMS targeting the vmPFC-intermittent TBS (iTBS) expected to potentiate the vmPFC, continuous TBS (cTBS) expected to de-potentiate the vmPFC, and sham TBS (sTBS). These experimental manipulations will be used to modulate trial-by-trial reward learning signals and related brain activity during the Antidepressant fMRI Task. Understanding the mechanisms underlying antidepressant responses is essential to identify novel therapeutic targets for depression.
2,741 studies on the registry are indexed under Depressive Disorder, Major; 558 are open to participants now.
This study's enrollment of 120 is above the median of 80 across 2,282 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Marta Peciña, MD PhD is the lead sponsor of 4 studies on the registry; 1 is open to participants now.
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Buprenorphine is a μ-opioid partial agonist and kappa-opioid antagonist that is used to treat moderate to severe pain and opioid dependence. The intramuscular administered opioid agonist which will be used to modulate reward learning signals to understand placebo effects in patients with depression. In the buprenorphine condition, participants will receive one IM injection of 0.3mg/1ML buprenorphine hydrochloride (Buprenex®. Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2006) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~6 hours) and an oral placebo tablet.
Drug: Buprenorphine · Drug: Oral Placebo · Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.
Naltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate reward learning signals to understand placebo effects in participants with depression. In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours) and a saline IM injection.
Drug: Naltrexone · Drug: IM Placebo · Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.
Inert pill and saline injection that have no inherent power to produce an effect. In the inert pill condition, participants will receive one IM arm injection of saline (1ML) and an oral placebo tablet.
Drug: Oral Placebo · Drug: IM Placebo · Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.
Buprenorphine is a μ-opioid partial agonist and kappa-opioid antagonist that is used to treat moderate to severe pain and opioid dependence. The intramuscular administered opioid agonist which will be used to modulate reward learning signals to understand placebo effects in patients with depression. In the buprenorphine condition, participants will receive one IM injection of 0.3mg/1ML buprenorphine hydrochloride (Buprenex®. Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2006) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~6 hours) and an oral placebo tablet.
Naltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate reward learning signals to understand placebo effects in participants with depression. In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours) and a saline IM injection.
Oral placebo: to match the oral naltrexone.
IM saline placebo: to match the i.v. buprenorphine.
Participants will receive two blocks of each TBS form. During the first block, stimulation intensity will be gradually escalated in 5% increments (from 80% to 110% rMT) in order to enhance tolerability. In all conditions, the investigators will apply 600 pulses of theta burst at 110% RMT. Each block of iTBS will consist of 20 trains, each lasting 2s with intertrain intervals of 8s, for a total of 192s. Each block of cTBS will consist of one continuous train of 40s. The sTBS will make use of two surface electrodes placed on the scalp.
Also known as: sham (s), continuous (c) and intermittent (i).
BOLD Responses in the vmPFC-VS circuit
Changes in blood oxygenation level-dependent (BOLD) signal during the Antidepressant fMRI Task.
Time frame: Approximately at day 7, 14, 21.
TBS Effects of BOLD Response
Changes in BOLD signal during the Antidepressant fMRI Task between iTBS vs. sTBS, and cTBS vs. sTBS.
Time frame: Approximately at day 7, 14, 21.
Opioid Modulation Effects on BOLD Responses in the vmPFC-VS circuit
Changes in BOLD signal during the Antidepressant fMRI Task between Buprenorphine vs. inert pill, and Naltrexone vs. inert pill.
Time frame: Approximately at day 7, 14, 21.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Consistent with NIMH Data Archive (NDA) policies, the investigators will obtain relevant GUIDs and experiment IDs in order to upload all relevant data biannually. The investigators will use the Validation and Upload Tool for CSV files from behavior during the fMRI experiment, and NIfTI-formatted images for imaging. The investigators will upload study data cumulatively every 6 months per NDA guidelines, with the exception of imaging data, which are will be uploaded in installments. The final research data will not contain any identifiable information and will be deposited in the Research Domain Criteria Database (RDoCdb) repository in the NDA prior to the acceptance for publication of the main findings from the final dataset. Documentation and code for computational models developed as part of this project will be shared upon request.
Supporting information: Study protocol, Sap, Icf, Analytic code
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Marta Peciña, MD PhD