Pharmacokinetics and pharmacodynamics of cannabis-based medicine in a patient population included in a randomized, placebo-controlled, clinical trial
Julie Schjødtz Hansen 1 2, Fernando Boix 3, Jørgen Bo Hasselstrøm 4, Lambert Kristiansen Sørensen 4, Mads Kjolby 5 6, Stefan Gustavsen 7, Rikke Middelhede Hansen 8, Thor Petersen 9 10, Finn Sellebjerg 7, Helge Kasch 1 2, Peter Vestergaard Rasmussen 1, Nanna Brix Finnerup 1 11, Eva Aggerholm Saedder 5 6, Kristina Bacher Svendsen 1 2
- 1Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
- 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
- 3Section for Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.
- 4Department of Forensic Medicine, Aarhus University, Aarhus, Denmark.
- 5Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
- 6Department of Biomedicine, Aarhus University, Aarhus, Denmark.
- 7Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, Denmark.
- 8Spinal Cord Injury Center of Western Denmark, Viborg, Denmark.
- 9Department of Neurology, Hospital of Southern Jutland and Research Unit in Neurology, Aabenraa, Denmark.
- 10Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
- 11Danish Pain Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Affiliationer
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 Δ9 -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 Cmax 1.21 ng/mL, Tmax 2.68 h, and half-life 2.75 h, and for CBD (10 mg) were Cmax 2.67 ng/mL, Tmax 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.
