{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:10:31Z","timestamp":1791259831715,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NCCIH","award":["R01AT011463"],"award-info":[{"award-number":["R01AT011463"]}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"crossref","award":["R01AT011463"],"award-info":[{"award-number":["R01AT011463"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Cannabidiol (CBD) is increasingly used for pain management, including in transplant recipients with limited analgesic options. Its immunomodulatory effects in humans are not well defined at a single-cell level at CBD steady state with concomitant tacrolimus treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In a phase I ex vivo study, peripheral blood mononuclear cells from 23 participants who received oral CBD (Epidiolex) up to 5 mg\/kg twice daily for 11 days were collected before CBD (pre-CBD) and at steady state (post-CBD). Lymphocytes were isolated and stimulated with anti-CD3\/CD28 antibodies, with or without tacrolimus (5 ng\/mL). Pharmacodynamic responses were assessed using CellTiter-Glo proliferation, single-cell and single-nucleus RNA sequencing, cytokine assays, and flow cytometry. Steady-state plasma concentrations of CBD were quantified via tandem mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We identified an increased proportion of T effector memory (TEM) cells post-CBD (22% increase), which correlated with CBD plasma concentrations (\n                      <jats:italic>R<\/jats:italic>\n                      = 0.77,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.01). CBD reduced proliferation of T (37% decrease) and CD70\n                      <jats:sup>hi<\/jats:sup>\n                      B (17% decrease) lymphocytes with additive immunosuppressive effects to tacrolimus. Single-cell RNA sequencing revealed reduced\n                      <jats:italic>IL2<\/jats:italic>\n                      and\n                      <jats:italic>TNF<\/jats:italic>\n                      signaling and altered receptor-ligand networks in TEM cells. Post-CBD cytokine assays revealed elevated proinflammatory IL-6 protein levels and antiinflammatory IL-10 levels, with reduced TNF-\u03b1, LTA, and IL-2. In flow cytometry, the proportion of TEM and TEMRA cells increased post-CBD with tacrolimus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>CBD exerts mixed immunomodulatory effects in humans, combining antiproliferative and pro- and antiinflammatory responses. Understanding the clinical safety of CBD use is important given the paucity of pain control options available for immunocompromised transplant populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT05490511<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>NIH\/National Center for Complementary and Integrative Health (R01AT011463); NIH\/National Institute of General Medical Sciences (NIGMS) (R35GM145383); Intramural Research Program of the NIH; NIH\/NIGMS (T32GM008425).<\/jats:p>\n                  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