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

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages3363-3374
Number of pages12
JournalPsychopharmacology
Volume232
Issue number18
Early online date21 Jun 2015
DOIs
StatusPublished - Sep 2015

Fingerprint

Memantine
Smoking
Pharmacology
Pharmaceutical Preparations
Cues
Research
Recurrence
Drug Users
N-Methyl-D-Aspartate Receptors
Reward

Keywords

  • Adult
  • Attention
  • Craving
  • Cues
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists/pharmacology
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Memantine/pharmacology
  • Memory/drug effects
  • Memory Consolidation/drug effects
  • Middle Aged
  • Receptors, N-Methyl-D-Aspartate
  • Reward
  • Smoking/drug therapy
  • Tobacco Use Disorder/drug therapy
  • Translational Medical Research
  • Young Adult

Cite this

Assessing the translational feasibility of pharmacological drug memory reconsolidation blockade with memantine in quitting smokers. / Das, Ravi K; Hindocha, Chandni; Freeman, Tom P; Lazzarino, Antonio I; Curran, H Valerie; Kamboj, Sunjeev K.

In: Psychopharmacology, Vol. 232, No. 18, 09.2015, p. 3363-3374.

Research output: Contribution to journalArticle

Das, Ravi K ; Hindocha, Chandni ; Freeman, Tom P ; Lazzarino, Antonio I ; Curran, H Valerie ; Kamboj, Sunjeev K. / Assessing the translational feasibility of pharmacological drug memory reconsolidation blockade with memantine in quitting smokers. In: Psychopharmacology. 2015 ; Vol. 232, No. 18. pp. 3363-3374.
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abstract = "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.",
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AU - Hindocha, Chandni

AU - Freeman, Tom P

AU - Lazzarino, Antonio I

AU - Curran, H Valerie

AU - Kamboj, Sunjeev K

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N2 - 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.

AB - 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.

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KW - Male

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KW - Middle Aged

KW - Receptors, N-Methyl-D-Aspartate

KW - Reward

KW - Smoking/drug therapy

KW - Tobacco Use Disorder/drug therapy

KW - Translational Medical Research

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