{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:11:31Z","timestamp":1768569091168,"version":"3.49.0"},"posted":{"date-parts":[[2025,4,30]]},"group-title":"Addiction Medicine","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Drug-related memories can hinder abstinence goals in drug addiction. Promoting non-drug memories via ventromedial prefrontal cortex- (vmPFC) and amygdala-guided extinction yields mixed success. Post-retrieval extinction (RE) destabilizes and updates memories during reconsolidation, improving extinction. Supplementing RE, we tested methylphenidate (MPH), a dopamine-agonist that promotes PFC-dependent learning and memory in cocaine use disorder (CUD). In an Early Phase 1 double-blind randomized clinical trial using a within-subjects design, participants received oral MPH (20 mg) or placebo before the retrieval of some of the conditioned stimuli (i.e., reminded CS+ vs. non-reminded CS+) followed by extinction; lab-simulated drug-seeking was measured the following day.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Lower vmPFC activity following non-reminded CS+ (standard extinction) under placebo replicated the putative impairments in CUD; separately, RE (trend) and MPH conditions recruited the vmPFC, and RE\u2019s vmPFC-reliance correlated with drug-seeking only under placebo. Crucially, MPH-combined RE normalized cortico-limbic processing, bypassing the vmPFC and its amygdala connectivity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Pharmacologically-enhanced drug memory modulation may inform intervention development for addiction recovery.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.29.25326658","type":"posted-content","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T23:35:19Z","timestamp":1746056119000},"source":"Crossref","is-referenced-by-count":0,"title":["The neural signature of methylphenidate-enhanced memory disruption in human drug addiction: a randomized clinical trial"],"prefix":"10.64898","author":[{"given":"Ahmet O.","family":"Ceceli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah G.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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