Journal Article

Assessing the translational feasibility of pharmacological drug memory reconsolidation blockade with memantine in quitting smokers

Freeman, Tom P., Lazzarino, Antonio I., Curran, H. Valerie, Kamboj, Sunjeev K., Das, Ravi K., Hindocha, Chandni

2015

Overview

Rationale Preclinical reconsolidation research offers the first realistic opportunity to pharmacologically weaken the maladaptive memory structures that support relapse in drug addicts. N-methyl D-aspartate receptor (NMDAR) antagonism is a highly effective means of blocking drug memory reconsolidation. However, no research using this approach exists in human addicts. Objectives The objective of this study was to assess the potential and clinical outcomes of blocking the reconsolidation of cue-smoking memories with memantine in quitting smokers. Methods Fifty-nine dependent and motivated to quit smokers were randomised to one of three groups receiving the following: (1) memantine with or (2) without reactivation of associative cue-smoking memories or (3) reactivation with placebo on their target quit day in a double-blind manner. Participants aimed to abstain from smoking for as long as possible. Levels of smoking and FTND score were assessed prior to intervention and up to a year later. Primary outcome was latency to relapse. Subjective craving measures and attentional bias to smoking cues were assessed in-lab. Results All study groups successfully reduced their smoking up to 3 months. Memantine in combination with smoking memory reactivation did not affect any measure of smoking outcome, reactivity or attention capture to smoking cues. Conclusions Brief exposure to smoking cues with memantine did not appear to weaken these memory traces. These findings could be due to insufficient reconsolidation blockade by memantine or failure of exposure to smoking stimuli to destabilise smoking memories. Research assessing the treatment potential of reconsolidation blockade in human addicts should focus on identification of tolerable drugs that reliably block reward memory reconsolidation and retrieval procedures that reliably destabilise strongly trained memories.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Adult / Attention / Biomedical and Life Sciences / Biomedicine / Craving / Cues / Double-Blind Method / Excitatory Amino Acid Antagonists - pharmacology / Excitatory Amino Acid Antagonists - therapeutic use / Feasibility Studies / Female / Humans / Male / Memantine - pharmacology / Memantine - therapeutic use / Memory / Memory - drug effects / Memory Consolidation - drug effects / Middle Aged / Neurosciences / Original Investigation / Pharmacology / Pharmacology/Toxicology / Psychiatry / Receptors, N-Methyl-D-Aspartate / Reward / Smoking - drug therapy / Smoking - psychology / Smoking cessation / Studies / Tobacco Use Disorder - drug therapy / Tobacco Use Disorder - psychology / Translational Medical Research / Young Adult