The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study
Summary: Background: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinica...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422004650 |
| _version_ | 1828098464558350336 |
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| author | Jing-Li Yue Kai Yuan Yan-Ping Bao Shi-Qiu Meng Le Shi Qing Fang Xiao-Jie Guo Lu Cao Ye-Kun Sun Tang-Sheng Lu Na Zeng Wei Yan Ying Han Jie Sun Jie Shi Thomas R. Kosten Yan-Xue Xue Ping Wu Lin Lu |
| author_facet | Jing-Li Yue Kai Yuan Yan-Ping Bao Shi-Qiu Meng Le Shi Qing Fang Xiao-Jie Guo Lu Cao Ye-Kun Sun Tang-Sheng Lu Na Zeng Wei Yan Ying Han Jie Sun Jie Shi Thomas R. Kosten Yan-Xue Xue Ping Wu Lin Lu |
| author_sort | Jing-Li Yue |
| collection | DOAJ |
| description | Summary: Background: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP. Methods: In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate. Findings: Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80) = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F (12, 63·3) = 2.41, p = 0.01). Interpretation: The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse. Funding: National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800) |
| first_indexed | 2024-04-11T08:03:05Z |
| format | Article |
| id | doaj.art-d54d5c796e024312ab0c9539a72e5c7f |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-11T08:03:05Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-d54d5c796e024312ab0c9539a72e5c7f2022-12-22T04:35:40ZengElsevierEBioMedicine2352-39642022-11-0185104283The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational studyJing-Li Yue0Kai Yuan1Yan-Ping Bao2Shi-Qiu Meng3Le Shi4Qing Fang5Xiao-Jie Guo6Lu Cao7Ye-Kun Sun8Tang-Sheng Lu9Na Zeng10Wei Yan11Ying Han12Jie Sun13Jie Shi14Thomas R. Kosten15Yan-Xue Xue16Ping Wu17Lin Lu18NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, ChinaNHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, ChinaNational Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, ChinaNational Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, ChinaNHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, ChinaDepartment of Clinical Psychology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaNHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, ChinaNHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, China; Peking-Tsinghua Centre for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, ChinaSchool of Psychology and Mental Health, North China University of Science and Technology, Tangshan 063210, Hebei, ChinaNHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, China; National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, ChinaNational Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, ChinaNHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, ChinaNational Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, ChinaDepartment of Anesthesiology, Center for Pain Medicine, Peking University Third Hospital, Beijing 100191, ChinaNational Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, ChinaDepartment of Psychiatry, Pharmacology, Neuroscience, Immunology, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author.National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China; Chinese Institute for Brain Research, Beijing 102206, China; Corresponding authors at: National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing 100191, China.National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China; Corresponding authors at: National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing 100191, China.NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, China; National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China; Peking-Tsinghua Centre for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; Corresponding authors at: National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing 100191, China.Summary: Background: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP. Methods: In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate. Findings: Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80) = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F (12, 63·3) = 2.41, p = 0.01). Interpretation: The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse. Funding: National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800)http://www.sciencedirect.com/science/article/pii/S2352396422004650Opioid use disorderRelapseMethadoneCravingMemory reconsolidation updating |
| spellingShingle | Jing-Li Yue Kai Yuan Yan-Ping Bao Shi-Qiu Meng Le Shi Qing Fang Xiao-Jie Guo Lu Cao Ye-Kun Sun Tang-Sheng Lu Na Zeng Wei Yan Ying Han Jie Sun Jie Shi Thomas R. Kosten Yan-Xue Xue Ping Wu Lin Lu The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study EBioMedicine Opioid use disorder Relapse Methadone Craving Memory reconsolidation updating |
| title | The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study |
| title_full | The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study |
| title_fullStr | The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study |
| title_full_unstemmed | The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study |
| title_short | The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study |
| title_sort | effect of a methadone initiated memory reconsolidation updating procedure in opioid use disorder a translational study |
| topic | Opioid use disorder Relapse Methadone Craving Memory reconsolidation updating |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422004650 |
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