Exploring Post-Retrieval Strategies to Reduce Drug Craving in Methamphetamine Use Disorders

Abstract

Post-retrieval interventions based on memory reconsolidation have shown promise in reducing addiction-related memories. However, research on methamphetamine (MA) use, particularly in humans, remains limited. This study aimed to evaluate the efficacy of a post-retrieval intervention paradigm in managing methamphetamine use disorder (MUD) with 46 individuals from a compulsory drug rehabilitation centre. A single-blind design was employed, with participants randomly assigned to one of three groups: (1) retrieval-no intervention, (2) retrieval-extinction and (3) retrieval-cognitive task. The study involved baseline testing, followed by memory retrieval using MA cues, and one of the three interventions during the memory reconsolidation window. The interventions were as follows: (1) no further intervention after retrieval, (2) extinction training and (3) playing Tetris after memory reactivation. Relapse was assessed through physiological and psychological indicators, with a focus on both spontaneous and cue-induced relapse of MUD memory. The results showed that both retrieval-extinction and retrieval-cognitive task showed benefits in reducing cravings and preventing relapse in MUD compared to retrieval alone. Physiological and psychological indicators of MA memory relapse showed weak correlation and differed across several dimensions. These findings suggest new strategies for MUD intervention and provide valuable insights for clinical treatment. Limitations of the study are also discussed.

Keywords: cognitive task; craving; methamphetamine use disorder; post‐retrieval intervention; retrieval–extinction.

FIGURE 1

Schematic overview of the experimental design and procedure, consisting of three phases: baseline testing, memory retrieval intervention and relapse testing. After memory reactivation on Day 2, participants were randomly assigned to one of three groups, each with a different intervention strategy: G1 (retrieval–no intervention, R), G2 (retrieval–extinction, R‐E), and G3 (retrieval–cognitive task, R‐CT). The procedure on Day 3 mirrored that of Day 2. Abbreviations: BP, blood pressure; HR, heart rate; m, minutes; SCR, skin conductance response; VAS, Visual Analogue Scale.

FIGURE 2

Results of Day 1 baseline testing for (a) skin conductance response and (b) subjective craving. (c) Extinction phase in G2 using drug‐related photos across trial blocks on Days 2 and 3. Each block consists of 5 photos, totalling 8 blocks across 40 trials. B, blocks. Pre, prevideo measurements; *p < 0.05, ***p < 0.001.

FIGURE 3

Skin conductance response during the model extinction phase on Days 2 and 3 in G2. Note: ‘First’, ‘mid’ and ‘end’ refer to the first 15 s, middle 15 s and last 15 s of exposure to the MA models, respectively. M1–M5 represent the first through fifth MA models.

FIGURE 4

(a) Left panel: SCR induced by drug‐related photo cues on the fourth day of relapse testing. Right panel: SCR induced by drug video cues on the fourth day of relapse testing. (b) SCR changes over time in response to video cues during the Day 4 relapse test across groups. Subjective cravings were assessed on Day 4 (c) and Day 11 (d) during the relapse test and follow‐up, with measurements for spontaneous recovery (SR) without cues and video cue‐elicited VAS. Abbreviations: NV, novel video; OV, old video; SR, spontaneous recovery. *p < 0.05.

FIGURE 5

Subjective craving at a 1‐month follow‐up. During spontaneous recovery without cues, G1 showed significantly higher VAS scores than G2. No significant differences were observed in VAS scores triggered by old or novel videos. Abbreviations: NV, novel video; OV, old video; SR, spontaneous recovery. *p < 0.05.

FIGURE 6

Physiological (SCR) and psychological (VAS) indicators in each group on Days 4, 11 and 34. (a) Time course of SCR changes in response to drug cues throughout the relapse tests in each group. (b) Mixed linear model (MLM) analysis results, with group and cue type (photo and video) as fixed effects and tracking time as a random effect. (c) Time course of craving across different test types during the relapse tests in each group. (d) The change of subjective cravings from baseline to tests in G1–G3. (e) Overall relapse of subjective craving during the test period in each group. Abbreviations: NV, novel video; OV, old video; SR, spontaneous recovery. *p < 0.05, ***p < 0.001.