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07. January 2026

New Review Article on Drugs Targeting Human Aversive Memory Publication Alert: New Article on Pharmacological Effects on Human Aversive Memory

Our systematic review, “A systematic review of pharmacological effects on human aversive memory,” is now published in Neuroscience & Biobehavioral Reviews

In this systematic review, we synthesised evidence from 100 studies across 36 compounds and 13 biological systems examining how acute pharmacological interventions influence aversive memory formation, retrieval, reconsolidation, and extinction in healthy humans.

Highlights

  • Assessed effects of 36 compounds targeting 13 signaling systems on aversive memory
  • Most frequently studied compounds are hydrocortisone, propranolol, and D-cycloserin
  • Solid evidence for propranolol inhibiting reconsolidation
  • Fifteen candidate compounds with potential effects for future research identified

Read the pre-proof journal article here (open access): https://doi.org/10.1016/j.neubiorev.2026.106548 

Figure 1
Figure 1 - Literature search summary. (a) Flowchart of the literature search procedure for propranolol as an example. A PRISMA 2020 flowchart for propranolol is available in Supplementary Information. The numbers of articles included in each step for all compounds are summarised in Supplementary Table S1. (b) Distribution of included articles in each transmitter/pathway system. (c) Included articles for the noradrenergic and (d) glucocorticoid systems. The total number of included articles (N = 100) and the sum of the numbers from each system do not add up because some studies investigated multiple products. (e) Risk of bias assessment for the included articles according to revised Cochrane risk-of-bias tool (RoB 2). Most of the concerns are derived from a lack of preregistration of analysis plan in early publications. Two studies were marked as “high risk” due to single-blinding. © Y. Xia et al. 2026
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Abstract:

A large body of work has investigated the effect of various pharmacological compounds on aversive memory formation, retrieval, and modification in humans. A broad overview across signalling pathways and memory models is currently lacking. Here, we systematically review publications that tested the impact of acute pharmacological interventions on aversive memory in healthy humans, following PRISMA-2020. 

We identified 215 candidate compounds from 17 systems and searched Pubmed, Web of Science and Scopus, until 14 June 2024. We identified 100 publications with 36 compounds targeting 13 systems. Three compounds were used by the majority of studies: hydrocortisone (n=25), propranolol (n=19), and D-cycloserine (n=8), while many of the remaining 33 compounds were investigated in single studies only. We summarise the effect of each investigated compound across memory models, according to the targeted memory stage. Solid evidence emerges for an impact of propranolol on reconsolidation, and weak evidence for an impact of propranolol, 3,4-methylenedioxymethamphetamine (MDMA), benzodiazepines, yohimbine, reboxetine, and D-cycloserine on aversive memory encoding/consolidation, and valproic acid on extinction encoding/consolidation. 

Furthermore, 15 compounds showed significant effects in individual studies with no published replication attempts to date. We discuss potential research directions and suggest steps for greater comparability of findings between compounds, memory models, and laboratories.