Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories

Ravi K. Das (), Grace Gale, Katie Walsh, Vanessa E. Hennessy, Georges Iskandar, Luke A. Mordecai, Brigitta Brandner, Merel Kindt, H. Valerie Curran and Sunjeev K. Kamboj
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Ravi K. Das: University College London
Grace Gale: University College London
Katie Walsh: University College London
Vanessa E. Hennessy: University College London
Georges Iskandar: University College Hospital and University College Hospital at Westmoreland Street
Luke A. Mordecai: University College Hospital
Brigitta Brandner: University College Hospital
Merel Kindt: University of Amsterdam
H. Valerie Curran: University College London
Sunjeev K. Kamboj: University College London

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13162-w

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