Attenuating trauma- and cocaine-related intrusions by blocking memory reconsolidation with minocycline: protocol for a transdiagnostic randomized controlled trial

Clinical Snapshot

Key Findings

• P Value: Not available - protocol paper

• Effect Size: Not available - protocol paper

• Primary Outcome: Not available - protocol paper

• Nnt Or Sensitivity: Not available - protocol paper

• Confidence Interval: Not available - protocol paper

Clinical Application

Limited by requirement for specialized neuroimaging facilities and memory reactivation protocols Minocycline is PBS-listed for other indications; would require TGA approval for this novel use. Aligns with RACGP guidelines emphasizing evidence-based PTSD treatment Adults with PTSD or cocaine use disorder experiencing intrusive memories

Abstract

Background: Post-traumatic stress disorder (PTSD) and substance use disorders frequently co-occur, with their comorbidity linked to poorer treatment outcomes. Beyond this epidemiological overlap, PTSD and, in particular, cocaine use disorder (CUD) have also been conceptually linked, as maladaptive memory processes are thought to play a central role in both of their etiopathogeneses. PTSD and CUD are each characterized by intrusive memories - either trauma or cocaine related - that sustain distress and craving, respectively. These parallels have motivated transdiagnostic mechanistic research targeting memory reconsolidation. Matrix metalloproteinase-9 (MMP-9) is critically involved in synaptic plasticity and memory updating, and has been suggested as a pharmacological entry point for modulating reconsolidation-related processes.Objective: This study examines whether pharmacological interference with reconsolidation via MMP-9 inhibition by minocycline modulates trauma- and cocaine-related intrusive memories and their neurobiological correlates in PTSD and CUD.Method: In this monocentric, randomized, double-blind, placebo-controlled trial (NCT05902819), individuals with PTSD (n = 60) or CUD (n = 60) receive a single dose of minocycline - a tetracycline inhibiting MMP-9 - or placebo prior to an individualized, imagery-based reactivation of their most salient intrusive memory. Intrusive memories in day-to-day life are assessed using event-based ecological momentary assessment and pre-post intrusion questionnaires. Neurobiological correlates of maladaptive memory processing are indexed through functional magnetic resonance imaging and magnetic resonance spectroscopy, and peripheral biomarkers are obtained from blood, urine, and hair samples. Diagnostic status and comorbid symptoms are characterized using clinical interviews and standardized self-report measures.Conclusions: This trial adopts a mechanistic framework to investigate whether minocycline-augmented memory reactivation modulates intrusions and associated neurobiological markers in PTSD and CUD. By directly targeting candidate memory mechanisms shared by both disorders, it evaluates a transdiagnostic reconsolidation-based approach and is expected to inform models of intrusive memory persistence and updating. The findings may guide future development of memory-focused interventions in trauma- and addiction-related disorders. This randomized controlled trial evaluates a transdiagnostic, mechanism-focused intervention targeting maladaptive memory processes in PTSD and cocaine use disorder.Minocycline is used as an MMP-9 inhibitor to modulate intrusive trauma- and cocaine-related memories following brief imagery-based memory reactivation.The study integrates multimodal neurobiological assessments (fMRI, MRS, peripheral biomarkers) with ecological momentary intrusion measures to characterize changes in memory-related mechanisms.

References

1. 1.Dietiker, L., Zacher, A., de'Sperati, S., Loosli, M., Schmid, L. B., Wernigg, M., Rühlmann, C., Bavato, F., Zölch, N., Seifritz, E., Quednow, B. B., & Kleim, B. (2026). Attenuating trauma- and cocaine-related intrusions by blocking memory reconsolidation with minocycline: protocol for a transdiagnostic randomized controlled trial. European Journal of Psychotraumatology. https://doi.org/10.1080/20008066.2026.2650920