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

Das RK, Hindocha C, Freeman TP, Lazzarino AI, Curran HV, Kamboj SK - Psychopharmacology (Berl.) (2015)

Bottom Line: 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.Brief exposure to smoking cues with memantine did not appear to weaken these memory traces.

View Article: PubMed Central - PubMed

Affiliation: Clinical Psychopharmacology Unit, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK, ravi.das@ucl.ac.uk.

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.

No MeSH data available.


Related in: MedlinePlus

Survival curves for relapse latency by experimental group, adjusted for craving. Curves are censored at 85 days as there was no change in relapse status after this time point
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Fig2: Survival curves for relapse latency by experimental group, adjusted for craving. Curves are censored at 85 days as there was no change in relapse status after this time point

Mentions: Cox regression assessed relapse latency (descriptive statistics of relapse data are shown Table 2) across the three groups. In total, 8 cases were censored due to not having relapsed by their final follow-up [MEM no REACT n = 1; PLAC + REACT n = 5, MEM+REACT n = 2]. Adding group to the basic regression model did not significantly improve model fit [-2LL change = 4.435, χ2 (2) = 0.109]. Contrasts between regression slopes for each group found no significant differences between any group (all ps > 0.1) and entering craving and baseline dependence as covariates did not significantly affect the model (ps > 0.1). A survival plot for these data is shown in Fig. 2. Curves are plotted to 85 days as there was zero variance in relapse status up to 365 days in all participants who were abstinent at this time point.Fig. 2


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

Das RK, Hindocha C, Freeman TP, Lazzarino AI, Curran HV, Kamboj SK - Psychopharmacology (Berl.) (2015)

Survival curves for relapse latency by experimental group, adjusted for craving. Curves are censored at 85 days as there was no change in relapse status after this time point
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537501&req=5

Fig2: Survival curves for relapse latency by experimental group, adjusted for craving. Curves are censored at 85 days as there was no change in relapse status after this time point
Mentions: Cox regression assessed relapse latency (descriptive statistics of relapse data are shown Table 2) across the three groups. In total, 8 cases were censored due to not having relapsed by their final follow-up [MEM no REACT n = 1; PLAC + REACT n = 5, MEM+REACT n = 2]. Adding group to the basic regression model did not significantly improve model fit [-2LL change = 4.435, χ2 (2) = 0.109]. Contrasts between regression slopes for each group found no significant differences between any group (all ps > 0.1) and entering craving and baseline dependence as covariates did not significantly affect the model (ps > 0.1). A survival plot for these data is shown in Fig. 2. Curves are plotted to 85 days as there was zero variance in relapse status up to 365 days in all participants who were abstinent at this time point.Fig. 2

Bottom Line: 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.Brief exposure to smoking cues with memantine did not appear to weaken these memory traces.

View Article: PubMed Central - PubMed

Affiliation: Clinical Psychopharmacology Unit, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK, ravi.das@ucl.ac.uk.

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.

No MeSH data available.


Related in: MedlinePlus