{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T02:49:16Z","timestamp":1771901356005,"version":"3.50.1"},"posted":{"date-parts":[[2024,11,18]]},"group-title":"Addiction Medicine","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"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":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To study the sex and hormonal effects on cortico-striatal engagement during drug cue-reactivity and its regulation focusing on drug reappraisal.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Forty-nine men (age=41.96\u00b19.71) with heroin use disorder (HUD) and 32 age-matched women (age=38.85\u00b19.84) with HUD (n=16) or cocaine use disorder (CUD; n=16) were scanned using functional MRI, with a subgroup of women scanned twice, during the late-follicular and mid-luteal phases, to examine sex and menstrual phase differences in cortico-striatal drug cue-reactivity and its cognitive reappraisal and their correlations with ovarian hormones and drug craving.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Women showed higher medial prefrontal cortex (PFC) drug cue-reactivity while men showed higher frontal eye field (FEF)\/dorsolateral PFC (dlPFC) drug reappraisal as associated with lower cue-induced drug craving. In the women, drug cue-reactivity was higher during the follicular phase in the FEF\/dlPFC, whereas drug reappraisal was higher during the luteal phase in the anterior PFC\/orbitofrontal cortex. The more the estradiol during the follicular vs. luteal phase (\u0394), the higher the \u0394drug cue-reactivity in the vmPFC, which also correlated with higher \u0394drug craving (observed also in the inferior frontal gyrus). The more this \u0394estradiol, the lower the \u0394drug reappraisal in the vmPFC, anterior PFC and striatum. Conversely, \u0394progesterone\/estradiol ratio was positively associated with \u0394drug reappraisal in the dlPFC.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Compared to men, women with addiction show more cortico-striatal reactivity to drug cue exposure and less PFC activity during drug reappraisal, driven by the follicular compared to luteal phase and directly related to craving and fluctuations in estrogen and progesterone with the former constituting a vulnerability and the latter a protective factor. This study provides insights for developing precisely timed and hormonally informed treatments for women with addiction.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.11.18.24317491","type":"posted-content","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T22:05:16Z","timestamp":1731967516000},"source":"Crossref","is-referenced-by-count":1,"title":["Sex and hormonal effects on drug cue-reactivity and its regulation in human addiction"],"prefix":"10.64898","author":[{"given":"Yuefeng","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo R.","family":"Butelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet O.","family":"Ceceli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Kronberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah G.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie E.","family":"McClain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yui Ying","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie","family":"Boros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K Rachel","family":"Drury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajita","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly","family":"Alia-Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita Z.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024112008302961000_2024.11.18.24317491v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23963"},{"key":"2024112008302961000_2024.11.18.24317491v1.2","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.121.000361"},{"key":"2024112008302961000_2024.11.18.24317491v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1183-2"},{"key":"2024112008302961000_2024.11.18.24317491v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.107657"},{"key":"2024112008302961000_2024.11.18.24317491v1.5","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.121.000367"},{"key":"2024112008302961000_2024.11.18.24317491v1.6","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/s41386-023-01601-8","article-title":"Overdose mortality rates for opioids and stimulant drugs are substantially higher in men than in women: state-level analysis","volume":"48","year":"2023","journal-title":"Neuropsychopharmacol"},{"key":"2024112008302961000_2024.11.18.24317491v1.7","doi-asserted-by":"publisher","DOI":"10.1037\/1064-1297.7.3.274"},{"key":"2024112008302961000_2024.11.18.24317491v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-001-0944-7"},{"key":"2024112008302961000_2024.11.18.24317491v1.9","doi-asserted-by":"crossref","first-page":"e12918","DOI":"10.1111\/adb.12918","article-title":"Increases in endogenous progesterone attenuate smoking in a cohort of nontreatment seeking women: An exploratory prospective study","volume":"26","year":"2021","journal-title":"Addiction Biology"},{"key":"2024112008302961000_2024.11.18.24317491v1.10","first-page":"259","article-title":"Can neuroimaging help combat the opioid epidemic?","volume":"44","year":"2019","journal-title":"A systematic review of clinical and pharmacological challenge fMRI studies with recommendations for future research. 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