Effect of conditioned stimuli-triggered memory retrieval-extinction in patients with methamphetamine use disorder

• Published in: Translational psychiatry Vol. 15; no. 1; pp. 249 - 14
• Main Authors: Yue, Jing-Li, Wang, Ru-Jia, Chen, Si-Jing, Lin, Xiao, Fang, Qing, Guo, Xiao-Jie, Sun, Ye-Kun, Yuan, Kai, Bao, Yan-Ping, Shi, Jie, Xue, Yan-Xue, Wu, Ping, Lu, Lin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.07.2025; Nature Publishing Group
• Subjects: 631/477/2811; 692/699/476/5; Abstinence; Addictions; Adult; Amphetamine-Related Disorders - physiopathology; Amphetamine-Related Disorders - psychology; Amphetamine-Related Disorders - therapy; Anxiety; Behavior modification; Behavioral Sciences; Biological Psychology; Blood pressure; Clinical trials; Conditioning, Classical - physiology; Craving - physiology; Cues; Data analysis; Evidence; Extinction, Psychological - physiology; Female; Heroin; Hormones; Humans; Hydrocortisone - analysis; Hydrocortisone - metabolism; Hypertension; Intervention; Male; Medicine; Medicine & Public Health; Memory; Mental disorders; Mental Recall - physiology; Methamphetamine; Methamphetamine - adverse effects; Nervous system; Neurosciences; Pharmacotherapy; Psychiatry; Saliva - chemistry; Sociodemographics; Young Adult; United States > US; China
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-025-03474-5

Methamphetamine (METH) is a widely abused stimulant that affects the central nervous system. The persistent maladaptive conditioned stimuli (CS, drug cues)-drug associative memories represent a primary factor precipitating relapse. Interfering with the reconsolidation of these memories may help disrupt and modify these maladaptive CS-drug associations, potentially reducing their influence on drug-seeking behavior. The present study explored the effect of CS-triggered memory retrieval-extinction on METH craving, potentially offering a new treatment strategy for addiction. This was a single-center, randomized, controlled trial involving individuals with METH use disorder (MUD). Participants completed one of three interventions on consecutive days (days 2 and 3): CS-triggered memory retrieval followed by extinction after a 10-min interval, CS-triggered memory retrieval followed by extinction after a 6-h interval, or extinction without prior retrieval. Self-report cue-induced craving for METH, salivary cortisol and sympathetic responses were measured at baseline (day 1), post intervention (day 4) and two follow-up timepoints (days 34 and 184), with cue-induced craving and salivary cortisol as primary outcomes. Ninety-eight MUD individuals (mean age 28.15 ± 6.31) were analyzed. After two-day’s interventions, cue-induced METH craving (time × cue interaction: F (1,94)  = 60.02, p  < 0.001) reduced in all groups. Results from follow-up data indicated, when the extinction was performed 10 min, but not 6 h after memory retrieval or no retrieval, the intervention decreased experimental cue-induced METH craving (intervention × time × cue: F (2,94)  = 14.32, p  < 0.001; intervention: F (2,94)  = 24.28, p  < 0.001) and saliva cortisol increases (F (2,90)  = 9.51, p  < 0.001), with effects lasting up to 6-month follow-up. The results revealed a substantial reduction in cue-elicited craving and saliva cortisol in the retrieval-10 min-extinction group over the 6-month follow-up. These findings provide compelling evidence that a brief reconsolidation-based intervention can effectively diminish METH-related craving and cortisol levels, underscoring its potential as a supportive measure in METH treatment. Salivary cortisol is a readily accessible and sensitive biomarker for evaluating intervention effects.