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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

Schematic of testing order on study day 1. Day 8 followed an identical testing order, without drug administration or waiting period. The visual probe was performed as the last task on this day
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Fig1: Schematic of testing order on study day 1. Day 8 followed an identical testing order, without drug administration or waiting period. The visual probe was performed as the last task on this day

Mentions: Before the videos, the on-screen instructions read as follows: “In front of you is a box, please open the box now and take note of its contents and leave it open until you are told to close it. In the box there is [a lighter, cigarettes and ashtray/ a deck of numbered cards, paper and a pencil]. These are for a task that you may be required to perform after watching a series of short videos. This task will be performed outside of the building, with a different experimenter. When you are watching the videos, try to imagine being in the depicted scenes as much as possible, imagining the sights, smells, sensations and sounds as if they were really there. You will be told whether or not you need to complete the task after the videos finish.” The videos then played and after their conclusion participants were informed that they would not complete the task, to close the box and alert the experimenter. Another blood pressure and single item VAS craving measure was then recorded, and a 5-min period of heart rate post-video collected. To ensure engagement with the reactivation procedure, participants were then given space to write a summary of the procedure that had happened, what they had seen in the videos, what the videos and box reminded them of and what they believed the task involved. Finally, participants guessed whether they received drug or placebo. A schematic of the testing order and timing on day 1 is shown in Fig. 1.Fig. 1


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)

Schematic of testing order on study day 1. Day 8 followed an identical testing order, without drug administration or waiting period. The visual probe was performed as the last task on this day
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Schematic of testing order on study day 1. Day 8 followed an identical testing order, without drug administration or waiting period. The visual probe was performed as the last task on this day
Mentions: Before the videos, the on-screen instructions read as follows: “In front of you is a box, please open the box now and take note of its contents and leave it open until you are told to close it. In the box there is [a lighter, cigarettes and ashtray/ a deck of numbered cards, paper and a pencil]. These are for a task that you may be required to perform after watching a series of short videos. This task will be performed outside of the building, with a different experimenter. When you are watching the videos, try to imagine being in the depicted scenes as much as possible, imagining the sights, smells, sensations and sounds as if they were really there. You will be told whether or not you need to complete the task after the videos finish.” The videos then played and after their conclusion participants were informed that they would not complete the task, to close the box and alert the experimenter. Another blood pressure and single item VAS craving measure was then recorded, and a 5-min period of heart rate post-video collected. To ensure engagement with the reactivation procedure, participants were then given space to write a summary of the procedure that had happened, what they had seen in the videos, what the videos and box reminded them of and what they believed the task involved. Finally, participants guessed whether they received drug or placebo. A schematic of the testing order and timing on day 1 is shown in Fig. 1.Fig. 1

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