Intrusive memories are a hallmark of post-traumatic stress disorder (PTSD) and a key target for early intervention. A new study by Laura Meister, Birgit Kleim and colleagues at UZH and collaborating institutions tested whether doxycycline, a drug known to interfere with memory-related brain processes, could reduce such memories after experimental trauma. The results show that while the drug altered some aspects of memory, it did not reduce intrusive memories – highlighting the complexity of targeting trauma-related memory formation.
Intrusive memories – vivid, unwanted recollections of distressing events – are a core feature of PTSD and often emerge in the days and weeks following trauma. Experimental and animal studies have suggested that memory formation could potentially be pharmacologically modulated during early consolidation phases. In this study, the researchers investigated whether doxycycline, an antibiotic that inhibits matrix metalloproteinase-9 (MMP-9), could disrupt the formation of intrusive memories. Eighty healthy female participants received either doxycycline or placebo before viewing a distressing film designed to model traumatic experience and subsequently recorded intrusive memories over one week.
Funded by the former Clinical Research Priority Program (CRPP) “Synapse, Trauma & Addiction”, the study is part of a broader effort to translate findings from animal and laboratory models into clinically relevant settings. Yet, as the results illustrate, such translation is not always straightforward.
Contrary to expectations, doxycycline did not reduce the frequency, vividness, or distress of intrusive memories. More than 90% of participants reported at least one intrusion, with an average of around three to four memories over the following week, declining similarly over time in both groups. However, the drug did affect other aspects of memory processing: participants who received doxycycline showed stronger physiological responses, such as increased skin conductance, when exposed to reminder cues, indicating heightened arousal. They also recalled details of the film more accurately one week later, suggesting enhanced episodic memory. Together, these findings point to a dissociation: while intrusive memories remained unchanged, conscious recall and physiological reactivity increased rather than decreased.
Instead of supporting a simple memory-blocking effect, the findings point to a more nuanced role of doxycycline in memory processing. In animal studies, memories are often linked to single, tightly controlled events, whereas human trauma memories are typically embedded within broader networks of repeated experiences shaped by personal meaning, context, and prior beliefs. These differences may help explain why pharmacological effects observed in animal research do not readily translate to complex human trauma. The work has also informed ongoing CRPP research exploring alternative compounds and extending these approaches to drug-related memories in substance use disorders.
More broadly, the study highlights the challenge of selectively weakening harmful aspects of memory without impairing adaptive ones. While doxycycline does not appear to prevent intrusive memories, the findings provide important insight into how different memory systems can be modulated and underscore the need for more targeted approaches to preventing PTSD.
Reference: Meister L, Rosi-Andersen A, Bavato F, Xia Y, Bach DR, Kleim B. Effects of doxycycline on intrusive experimental trauma memory: a pre-registered, randomized double-blind placebo-controlled trial. Translational Psychiatry. 2026. https://doi.org/10.1038/s41398-025-03657-0
Useful links:
- CRPP Synapse, Trauma, and Addiction consortium: | CRPP Synapse, Trauma & Addiction | UZH
- A systematic review of pharmacological effects on human aversive memory – ScienceDirect
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