Pharmacokinetics and pharmacodynamics of cannabis-based medicine in a patient population included in a randomized, placebo-controlled, clinical trial

Julie Schjødtz Hansen*, Fernando Boix, Jørgen Bo Hasselstrøm, Lambert Kristiansen Sørensen, Mads Kjolby, Stefan Gustavsen, Rikke Middelhede Hansen, Thor Petersen, Finn Sellebjerg, Helge Kasch, Peter Vestergaard Rasmussen, Nanna Brix Finnerup, Eva Aggerholm Saedder, Kristina Bacher Svendsen

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabis-based medicine (CBM) in capsule formulation in patient populations is sparse. 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-blinded, placebo-controlled, trial, 23 patients with MS (17 female) mean age 52 years (range 21-67) were enrolled in this substudy. They received oral capsules containing Δ 9 -tetrahydrocannabinol (THC, n = 4), cannabidiol (CBD, n = 6), a combination (THC&CBD, n = 4), or placebo (n = 9). Maximum doses were 22.5 mg (THC) and 45 mg (CBD) a day divided into three administrations. PD parameters were evaluated for pain and spasticity. Blood samples were analyzed using an ultra-high-performance liquid chromatography-tandem 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 mg) were C max 1.21 ng/mL, T max 2.68 h, and half-life 2.75 h, and for CBD (10 mg) were C max 2.67 ng/mL, T max 0.10 h, and half-life 4.95 h, 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.

OriginalsprogEngelsk
Artikelnummere13685
TidsskriftClinical and Translational Science
Vol/bind17
Nummer1
Antal sider14
ISSN1752-8054
DOI
StatusUdgivet - jan. 2024

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