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In this exploratory study, we aimed to evaluate the PK and PD in a probable steady state of CBM in neuropathic pain and spasticity in a population of patients with multiple sclerosis (MS). Of 134 patients participating in a randomized, double\u2010blinded, placebo\u2010controlled, trial, 23 patients with MS (17 female) mean age 52\u2009years (range 21\u201367) were enrolled in this substudy. They received oral capsules containing \u0394<jats:sup>9<\/jats:sup>\u2010tetrahydrocannabinol (THC, <jats:italic>n<\/jats:italic>\u2009=\u20094), cannabidiol (CBD, <jats:italic>n<\/jats:italic>\u2009=\u20096), a combination (THC&amp;CBD, <jats:italic>n<\/jats:italic>\u2009=\u20094), or placebo (<jats:italic>n<\/jats:italic>\u2009=\u20099). Maximum doses were 22.5\u2009mg (THC) and 45\u2009mg (CBD) a day divided into three administrations. PD parameters were evaluated for pain and spasticity. Blood samples were analyzed using an ultra\u2010high\u2010performance liquid chromatography\u2013tandem mass spectrometer after protein precipitation and phospholipid removal. PK parameters were estimated using computerized modeling. The variation in daily dose and PK between individuals was considerable in a steady state, yet comparable with previous reports from healthy controls. Based on a simulation of the best model, the estimated PK parameters (mean) for THC (5\u2009mg) were C<jats:sub>max<\/jats:sub> 1.21\u2009ng\/mL, T<jats:sub>max<\/jats:sub> 2.68\u2009h, and half\u2010life 2.75\u2009h, and for CBD (10\u2009mg) were C<jats:sub>max<\/jats:sub> 2.67\u2009ng\/mL, T<jats:sub>max<\/jats:sub> 0.10\u2009h, and half\u2010life 4.95\u2009h, respectively. No effect was found on the PD parameters, but the placebo response was considerable. More immediate adverse events were registered in the active treatment groups compared with the placebo group.<\/jats:p>","DOI":"10.1111\/cts.13685","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T10:02:48Z","timestamp":1701856968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacokinetics and pharmacodynamics of cannabis\u2010based medicine in a patient population included in a randomized, placebo\u2010controlled, clinical trial"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9133-2769","authenticated-orcid":false,"given":"Julie Schj\u00f8dtz","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus 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Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-9623","authenticated-orcid":false,"given":"Finn","family":"Sellebjerg","sequence":"additional","affiliation":[{"name":"Danish Multiple Sclerosis Center, Department of Neurology Copenhagen University Hospital \u2013 Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Kasch","sequence":"additional","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-7743","authenticated-orcid":false,"given":"Peter Vestergaard","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanna Brix","family":"Finnerup","sequence":"additional","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"},{"name":"Danish Pain Research Centre, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Aggerholm","family":"S\u00e6dder","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina Bacher","family":"Svendsen","sequence":"additional","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus 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