{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:47:56Z","timestamp":1785419276808,"version":"3.56.0"},"reference-count":83,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Recreational ketamine use has increased globally and is associated with psychiatric and cognitive concerns. The hippocampus in preclinical models shows damage and working\u2010memory disruption with repeated dosing. However, whether specific hippocampal subregions may differ in people with chronic ketamine use remains unclear. In Taiwan, ketamine is predominantly consumed by smoking ketamine mixed with tobacco, producing smoking\u2010related behavioral profiles like non\u2010ketamine tobacco use participants (TUs). We therefore examined individuals with urine\u2010confirmed ketamine as the only detected substance who reported predominantly smoking\u2010administered recreational use (KUs) and used TUs as controls. This study aimed to: (1) characterize ketamine\u2010use patterns and psychiatric symptoms; (2) compare working\u2010memory and affective\u2010behavioral measures between KUs and TUs; (3) quantify group differences in hippocampal subregion volumes; and (4) assess group differences in functional connectivity (FC) of identified subregions and relationships with neurotransmitter receptor distributions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Cross\u2010sectional case\u2010control study with cognitive testing and neuroimaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Community\u2010based recruitment in Taiwan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>58 KUs (44 males; mean age\u2009=\u200921.00\u2009\u00b1\u20094.57) and 73 TUs (52 males; mean age\u2009=\u200924.34\u2009\u00b1\u20095.86).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>Ketamine\u2010use patterns (Addiction Severity Index), psychiatric symptoms [Symptom Checklist\u201090\u2010Revised (SCL\u201090\u2010R)], working\u2010memory (N\u2010back), affective\u2010behavioral measures [Barratt Impulsiveness Scale (BIS\u201011), Buss and Perry Aggression Questionnaire (BPAQ), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ)], hippocampal subfield volumes (FreeSurfer) and functional connectivity (FC) of identified subregions (seed\u2010based analysis). Spatial correspondence with N\u2010methyl\u2010D\u2010aspartate (NMDA) receptor density was evaluated using JuSpace.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Heavier ketamine use was associated with greater psychological distress [Global Severity Index (GSI) r\u2009=\u20090.343,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.011], particularly anxiety (r\u2009=\u20090.457,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and hostility (r\u2009=\u20090.442,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Although self\u2010reported impulsivity, aggression and reward\/punishment sensitivity did not differ between groups, KUs showed reduced accuracy under higher working\u2010memory load [2\u2010back: F(1, 124)\u2009=\u20094.16,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04, partial\n                      <jats:italic>\u03b7<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.03; 1\u2010back: F(1, 124)\u2009=\u20098.10,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.005, \u03b72\u2009=\u20090.06]. KUs displayed reduced left hippocampal volume [F(1, 119)\u2009=\u20094.23,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04, \u03b72\u2009=\u20090.03], most marked in the hippocampal\u2010amygdaloid\u2010transition\u2010area [HATA; F(1, 119)\u2009=\u200910.52,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002, \u03b72\u2009=\u20090.08]. KUs also showed increased FC between left HATA and frontal, cingulate, temporal, subcortical, insular and cerebellar regions (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05, AlphaSim corrected), which correlated with NMDA\u2010receptor distributions (z\u2009=\u20090.30,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.005, false discovery rate corrected).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Recreational smoking\u2010administered ketamine use appears to be associated with dose\u2010dependent psychiatric symptoms, load\u2010dependent working memory impairment, selective hippocampal subregion volumetric differences and altered network connectivity aligned with N\u2010methyl\u2010D\u2010aspartate\u2010 (NMDA) receptor distribution.<\/jats:p>\n             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