Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: A systematic review and meta-analysis of clinical and 'sub-clinical' studies
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Abstract
Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This represents a potentially transformative strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, modulation of naturalistic maladaptive memories may be limited by ‘boundary conditions’ imposed on the reconsolidation process by the nature of these memories. We conducted a systematic review and meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward- and threat-related memories in (sub) clinical substance use and anxiety/trauma, respectively. Of 4938 publications assessed for eligibility, 8 studies of substance use and 10 of anxiety (phobia)- and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with most studies favouring the ‘retrieval + treatment’ condition. However, the magnitude of effects was dependent upon the nature of treatment, with pharmacological interventions showing a medium-sized effect ( g = 0.59, p = 0.03) and behavioural treatments, a relatively small effect ( g = 0.32, p = 0.10) in studies of phobia/trauma. Among studies of substance use, post-retrieval behavioural interventions yielded a larger effect ( g = 0.60, p < 0.001) relative to pharmacological treatments ( g = − 0.03, p = 0.91), with treatment type being a statistically significant moderator ( χ 2 (1) = 4.20, p = 0.04). Modification of naturalistic maladaptive memories during reconsolidation appears to be a viable treatment strategy for substance use and phobias/trauma disorders. However, high levels of heterogeneity and methodological variation limit the strength of conclusions that can be drawn from the reviewed studies at this stage.
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The reconsolidation hypothesis has led to interventions for several different clinical populations, with moderate levels of success.
“An alternative to these mechanisms is provided by the reconsolidation hypothesis, which has led to interventions for several different clinical populations, with moderate levels of success [52].”
From Memory and Forgetting (2018) · cites this paper as [52]
The Results (Study and sample characteristics; page unavailable) describe reconsolidation-interfering interventions studied in phobia, trauma-related, and substance-use samples. The Results (Effect size for symptoms of phobia and trauma; page unavailable) report a medium aggregate effect, but the aggregate effect for substance use was small and non-significant. Thus, “moderate levels of success” overstates the findings across the different populations. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPharmacogenomic tools add a complementary layer for medication selection, with multiple blinded trials and meta-analyses showing modest yet reliable gains in response and remission, particularly when switching to genetically congruent agents, thereby enriching strata and reducing futile exposure.
“Pharmacogenomic tools add a complementary layer for medication selection, with multiple blinded trials and meta-analyses showing modest yet reliable gains in response and remission, particularly when switching to genetically congruent agents, thereby enriching strata and reducing futile exposure [409,410].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [409]
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredStudies of propranolol for memory consolidation and reconsolidation have yielded mixed results.
“However, these studies have yielded mixed results (Walsh, Das, Saladin, & Kamboj, 2018).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Walsh, Das, Saladin, & Kamboj, 2018
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Self-citationPostretrieval Extinction Attenuates Alcohol Cue Reactivity in Rats
Cofresí, R. U., Lewis, S. M., Chaudhri, N., Lee, H. J., Monfils, M., & Gonzales, R. A. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13323 · Cited by 29 · see citing works
Das, R., Walsh, K., Hannaford, J., Lazzarino, A. I., & Kamboj, S. K. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.05.001 · Cited by 29 · see citing works
Self-citationJobes, M. L., Aharonovich, E., Epstein, D. H., Phillips, K. A., Reamer, D., Anderson, M. R., & Preston, K. L. (2015) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000000169 · Cited by 27 · see citing works
Das, R., Gale, G., Hennessy, V. E., & Kamboj, S. K. (2018) · Journal of Visualized Experiments · doi:10.3791/56097 · Cited by 24 · see citing works
Self-citationStress disrupts the reconsolidation of fear memories in men
Drexler, S. M., & Wolf, O. T. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.11.027 · Cited by 23 · see citing works
β-Adrenergic signaling is required for the induction of a labile state during memory reconsolidation
Lim, C., Kim, J., Kwak, C., Lee, J., Jang, E., Oh, J., & Kaang, B. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.04.011 · Cited by 18 · see citing works
The chains of habits: too strong to be broken by reconsolidation blockade?
Vousden, G. H., & Milton, A. L. (2016) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.11.010 · Cited by 13 · see citing works
Behavioral and Pharmacological Strategies for Weakening Maladaptive Reward Memories
Kamboj, S. K., & Das, R. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.3937 · Cited by 11 · see citing works
Self-citationDennis, T. S., & Perrotti, L. I. (2015) · Journal of Applied Biobehavioral Research · doi:10.1111/jabr.12031 · Cited by 8 · see citing works
Pavlovian Fear Conditioning Function, Cause, and Treatment
Fanselow, M. S., & Sterlace, S. R. (2014) · eScholarship (California Digital Library) · Cited by 7 · see citing works
Applications of Contemporary Learning Theory in the Treatment of Drug Abuse
McCarthy, D. E., Baker, T. B., Minami, H., et al. (2011) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199735969.003.0079 · Cited by 5 · see citing works
Disrupting Consolidation and Reconsolidation of Human Emotional Memory with Propranolol
Lonergan, M. H., Brunet, A., Olivera-Figueroa, L. A., & Pitman, R. K. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-386892-3.00012-3 · Cited by 3 · see citing works
Meta Analysis via Shiny [R package MAVIS version 1.1.3]
Hamilton, W. K., Aydin, B., & Mizumoto, A. (2017) · Cited by 2 · see citing works
Makkar, S. R., Zhang, S. Q., & Cranney, J. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.16 · Cited by 2 · see citing works
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Sartori, S. B., & Singewald, N. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107402 · Cited by 236 · see citing works
Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories
Das, R. K., Gale, G., Walsh, K., Hennessy, V. E., Iskandar, G., Mordecai, L. A., Brandner, B., Kindt, M., Curran, H. V., & Kamboj, S. K. (2019) · Nature Communications · doi:10.1038/s41467-019-13162-w · Cited by 122 · see citing works
Self-citationAstill Wright, L., Horstmann, L., Holmes, E. A., & Bisson, J. I. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01570-w · Cited by 97 · see citing works
Brewin, C. R. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0950-7 · Cited by 70 · see citing works
Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery
Tanaka, M. (2026) · Biomedicines · doi:10.3390/biomedicines14061265
- Authors
- Walsh, K. H., Das, R. K., Saladin, M. E., & Kamboj, S. K.
- Affiliations
- University College London (GB)
- Medical University of South Carolina (US)
- Corresponding author
- Kamboj, Sunjeev K.
- Venue
- Psychopharmacology
- Published
- 2018-08-08
- Volume
- 235
- Issue
- 9
- Pages
- 2507-2527
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC6132663
- OpenAlex
- W2952702017
- Cited by
- 77
- References
- 112
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 12 · 2023: 5 · 2022: 23 · 2021: 8 · 2020: 10 · 2019: 7 · 2018: 1
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Psychopharmacology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council (MR/M007006/1)
- University College London (PhD Studentship)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- memory reconsolidation, maladaptive memory, substance use disorders, anxiety disorders, phobia, trauma
- MeSH terms
- Memory Consolidation, Adrenergic beta-Antagonists, Animals, Anxiety Disorders, Behavior Therapy, Hormone Antagonists, Humans, Memory, Stress Disorders, Post-Traumatic, Substance-Related Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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