{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:37:34Z","timestamp":1791859054191,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848120001"],"award-info":[{"award-number":["848120001"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cannabidiol (CBD), the main non\u2010intoxicating compound from the cannabis plant, is regularly used by patients with chronic pain who also take analgesics. CBD has previously been shown to inhibit CYP\u2010mediated drug metabolism. This study aimed to characterize the potential pharmacokinetic interaction of CBD with amitriptyline and tramadol, two commonly used analgesics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was an open\u2010label, fixed\u2010sequence, 2\u2010way crossover study in 13 healthy participants. On Day 1, 25\u2009mg amitriptyline and 50\u2009mg tramadol were co\u2010administered orally in a fasted condition, followed by a 7\u2010day washout period. On Day 8, 30\u2009mg CBD was administered orally 1\u00a0h prior to amitriptyline and tramadol. Pharmacokinetic sampling was performed for CBD, amitriptyline, tramadol and their respective active metabolites nortriptyline and O\u2010desmethyltramadol for up to 24\u2009h post\u2010dose. The areas under the curve (AUCs) were compared between visits using a mixed effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twelve participants (4M\/8F) completed the study; one participant (M) dropped out for personal reasons. CBD significantly increased the AUC\n                      <jats:sub>0\u201024h<\/jats:sub>\n                      (least square means [LSM] ratio 1.13, 95% CI: 1.01, 1.26,\n                      <jats:bold>p\u2009=\u20090.033)<\/jats:bold>\n                      and the C\n                      <jats:sub>max<\/jats:sub>\n                      (LSM ratio 1.17, 95% CI: 1.01, 1.36,\n                      <jats:bold>p\u2009=\u20090.041<\/jats:bold>\n                      ) of amitriptyline. CBD did not significantly change the AUC\n                      <jats:sub>0\u201024h<\/jats:sub>\n                      and C\n                      <jats:sub>max<\/jats:sub>\n                      of nortriptyline and tramadol, and the C\n                      <jats:sub>max<\/jats:sub>\n                      of O\u2010desmethyltramadol.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A single dose of 30\u2009mg CBD significantly influenced the metabolism of amitriptyline in healthy volunteers. In patients, CBD\u2010induced drug interactions may be more pronounced in chronic dosing and dependent upon prandial status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70415","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T04:21:00Z","timestamp":1765858860000},"page":"1595-1606","source":"Crossref","is-referenced-by-count":4,"title":["Low\u2010dose cannabidiol increases plasma concentrations of amitriptyline: A clinical drug\u2013drug interaction study"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5917-7888","authenticated-orcid":false,"given":"Andriy A.","family":"Gorbenko","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Centre  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4844-6402","authenticated-orcid":false,"given":"Titiaan E.","family":"Post","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2525-2323","authenticated-orcid":false,"given":"Pamela K.","family":"Strugala","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-1846","authenticated-orcid":false,"given":"Erica S.","family":"Klaassen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-9744","authenticated-orcid":false,"given":"Linda E.","family":"Klumpers","sequence":"additional","affiliation":[{"name":"Verdient Science LLC.  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