Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories

Journal article

Das, Ravi K., Gale, Grace, Walsh, Katie, Hennessy, Vanessa E., Iskandar, Georges, Mordecai, Luke A., Brandner, Brigitta, Kindt, Merel, Curran, H. Valerie and Kamboj, Sunjeev K.. (2019). Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories. Nature Communications. 10(1), p. 5187. https://doi.org/10.1038/s41467-019-13162-w
AuthorsDas, Ravi K., Gale, Grace, Walsh, Katie, Hennessy, Vanessa E., Iskandar, Georges, Mordecai, Luke A., Brandner, Brigitta, Kindt, Merel, Curran, H. Valerie and Kamboj, Sunjeev K.
Abstract

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical ‘reconsolidation window’ predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders.

Year2019
JournalNature Communications
Journal citation10 (1), p. 5187
PublisherNature Publishing Group
ISSN2041-1723
Digital Object Identifier (DOI)https://doi.org/10.1038/s41467-019-13162-w
Scopus EID2-s2.0-85075624117
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
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Deposited11 Jul 2021
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Howard, Robert, Cort, Elizabeth, Bradley, Rosie, Harper, Emma, Kelly, Linda, Bentham, Peter, Ritchie, Craig, Reeves, Suzanne, Fawzi, Waleed, Livingston, Gill, Sommerlad, Andrew, Oomman, Sabu, Nazir, Ejaz, Nilforooshan, Ramin, Barber, Robert, Fox, Chris, Macharouthu, Ajay, Ramachandra, Pranathi, Pattan, Vivek, ... Gray, Richard. (2018). Amisulpride for very late-onset schizophrenia-like psychosis: The ATLAS three-arm RCT. Health Technology Assessment. 22(67), pp. 1 - 60. https://doi.org/10.3310/hta22670
Ketamine treatment for depression : Opportunities for clinical innovation and ethical foresight
Singh, Ilina, Morgan, Celia, Curran, Valerie, Nutt, David, Schlag, Anne and McShane, Rupert. (2017). Ketamine treatment for depression : Opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry. 4(5), pp. 419-426. https://doi.org/10.1016/S2215-0366(17)30102-5
Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration
Chandni Hindocha, Tom P. Freeman and H. Valerie Curran. (2017). Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration. Cannabis and Cannabinoid Research. 2(1), pp. 217-223. https://doi.org/10.1089/can.2017.0024
Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: A placebo-controlled trial
Hindocha, Chandni, Freeman, T. P., Xia, J. X., Shaban, Natacha D. C. and Curran, Helen V.. (2017). Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: A placebo-controlled trial. Psychological Medicine. 47(15), pp. 2708 - 2719. https://doi.org/10.1017/S0033291717001222
Editorial : Reporting guidelines for psychopharmacology
Steckler, Thomas, Curran, H. Valerie, de Wit, Harriet, Howes, Oliver, Hoyer, Daniel, Lucki, Irwin, Miczek, Klaus A., Morrow, A. Leslie, Price, Lawrence H. and Robbins, Trevor W.. (2016). Editorial : Reporting guidelines for psychopharmacology. Psychopharmacology. 233(7), pp. 1131-1134. https://doi.org/10.1007/s00213-016-4252-7
AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers
Morgan, Celia J. A., Freeman, T. P., Powell, J. and Curran, Helen V.. (2016). AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. Translational Psychiatry. 6(2), pp. 1 - 6. https://doi.org/10.1038/tp.2015.219
Deconstructing the nature of episodic foresight deficits associated with chronic opiate use
Mercuri, Kimberly, Terrett, Gill, Bailey, Phoebe E., Henry, Julie D., Curran, Helen Valerie and Rendell, Peter G.. (2016). Deconstructing the nature of episodic foresight deficits associated with chronic opiate use. British Journal of Clinical Psychology. 55(4), pp. 401 - 413. https://doi.org/10.1111/bjc.12110
Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males
Mokrysz, Claire, Freeman, Tom P., Korkki, S., Griffiths, K. and Curran, Helen V.. (2016). Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males. Translational Psychiatry. 6(11), pp. 1 - 10. https://doi.org/10.1038/tp.2016.225
LSD enhances the emotional response to music
Kaelen, M., Barrett, F. S., Roseman, L., Lorenz, R., Family, N., Bolstridge, M., Curran, Helen V., Feilding, A., Nutt, David J. and Carhart-Harris, R. L.. (2015). LSD enhances the emotional response to music. Psychopharmacology. 232(19), pp. 3607 - 3614. https://doi.org/10.1007/s00213-015-4014-y
Effects of immediate-release opioid on memory functioning: A randomized-controlled study in patients receiving sustained-release opioids
Kamboj, S. K., Conroy, L., Tookman, A., Carroll, E., Jones, L. and Curran, H.. (2014). Effects of immediate-release opioid on memory functioning: A randomized-controlled study in patients receiving sustained-release opioids. European Journal of Pain. 18(10), pp. 1376 - 1384. https://doi.org/10.1002/j.1532-2149.2014.498.x
Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study
Stewart, L. H., Ferguson, B., Morgan, C. J. A., Swaboda, N., Jones, L., Fenton, R., Wall, M. B. and Curran, H.. (2014). Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study. Journal of Psychopharmacology. 28(11), pp. 1001 - 1008. https://doi.org/10.1177/0269881114544775
Prospective memory impairment in long-term opiate users
Terrett, Gillian, McLennan, Skye, Henry, Julie, Biernacki, Kathryn, Mercuri, Kimberly, Curran, Valerie and Rendell, Peter. (2014). Prospective memory impairment in long-term opiate users. Psychopharmacology. 231(13), pp. 2623 - 2632. https://doi.org/10.1007/s00213-014-3432-6
Benzodiazepines: Risks and benefits. A reconsideration
Baldwin, David S., Aitchison, Katherine, Bateson, Alan, Curran, H. Valerie, Davies, Simon, Leonard, Brian, Nutt, David J., Stephens, David N. and Wilson, Sue. (2013). Benzodiazepines: Risks and benefits. A reconsideration. Journal of Psychopharmacology. 27(11), pp. 967 - 971. https://doi.org/10.1177/0269881113503509
Prospective memory and future event simulation in individuals with alcohol dependence
Griffiths, Alison, Hill, Robert, Morgan, Celia, Rendell, Peter Gregory, Karimi, Khashayar, Wanagaratne, Shamil and Curran, Valerie. (2012). Prospective memory and future event simulation in individuals with alcohol dependence. Addiction. 107(10), pp. 1809 - 1816. https://doi.org/10.1111/j.1360-0443.2012.03941.x
Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis (skunk) or on cocaine
Morgan, Celia, Duffin, S., Hunt, S., Monaghan, L., Mason, O. and Curran, Helen. (2012). Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis (skunk) or on cocaine. Pharmacopsychiatry. 45(7), pp. 269 - 274. https://doi.org/10.1055/s-0032-1306310