Blocking memory reconsolidation with minocycline to modulate intrusive memories across diagnoses: first findings from the MEMOCYCLINE trial

Background

Intrusive memories are a hallmark feature of posttraumatic stress disorder (PTSD) and may also contribute to craving and relapse in cocaine use disorder (CUD). We tested whether minocycline administered during guided memory reactivation reduces intrusive-memory expression across PTSD and CUD.

Methods

In this randomized, double-blind, placebo-controlled trial, 35 participants with PTSD and 39 with CUD received minocycline (200 mg) or placebo during two guided imagery-based reactivation sessions of a salient trauma- or cocaine-related memory. At baseline and short- and long-term follow-up, intrusion frequency and phenomenology were assessed retrospectively and repeatedly using ecological momentary assessment (EMA). Retrospective outcomes were analyzed using linear mixed-effects models and EMA outcomes using intervention-aligned piecewise mixed-effects models.

Results

Guided imagery elicited clear memory engagement, with marked increases in distress in PTSD and craving in CUD. Retrospective intrusion frequency and several intensity dimensions decreased over time, with broader and more sustained reductions in PTSD and more selective short-term changes in CUD. However, no consistent medication*time interactions indicated added benefit of minocycline over placebo. EMA intrusion frequency declined significantly more steeply post- than pre-intervention, but this trajectory change did not differ between medication conditions. EMA phenomenology showed no systematic post-intervention shift. Sensitivity, moderator, and mechanistic analyses revealed no coherent hidden treatment effect.

Conclusions

Minocycline did not confer additional benefit over imagery-based memory reactivation alone. Intrusion burden nevertheless changed over time, highlighting the need to distinguish subjective memory engagement from successful destabilization and reconsolidation interference and clarify which memory processes are amenable to therapeutic modification across PTSD and CUD.