Novel approaches in clinical development of cannabinoid drugs

Leiden Repository

Novel approaches in clinical development of cannabinoid drugs

Title: Novel approaches in clinical development of cannabinoid drugs
Author: Klumpers, Linda Elvira
Publisher: Centre for Human Drug Research, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2014-01-21
Keywords: Cannabinoids
THC
CB1 antagonists
Pharmacokinetics
Clinical pharmacology
Pharmacodynamics
Feeling high
PK-PD modelling
Resting state FMRI
Rimonabant
Abstract: The endocannabinoid system has only been discovered during the last few decades, and scientific progress in understanding the relevance of this system in health and disease has been limited and slow. CB1 antagonists were considered a ‘miracle drug’ for the treatment of obesity and smoking with ‘blockbuster’ potential. But due to central side effects (such as depression and suicidal behaviour) and a lack of systematic clinical pharmacologic research, market access of a CB1 antagonists failed. In this thesis, we explored some improvements in the early development of cannabinoids, and by systematically investigating, we found that the new cannabinoid antagonist TN38837 seems effective with a reduced propensity for central side effects, and that a new oral THC formulation enhances the pharmacological activities by its seemingly superior pharmacokinetics. Also, we experiment with new methodology to optimise effect measurement, including resting state-FMRI which we found suitable for early phase cannabinoid research, and including new concentration-effect models to improve the simulation and prediction of future studies. The research in this thesis shows that a revival of research on the cannabinoid system requires novel approaches to the administration of cannabinoids, to the measurements and the study designs, and to the analyses of the effects. This reflects the complexity of the highly integrated endocannabinoid system, but also sets the stage for other innovative drug development programs
Description: Promotores: J.M.A. van Gerven, A.F. Cohen
With summary in Dutch
Faculty: LUMC
Citation: Klumpers, L.E., 2014, Doctoral thesis, Leiden University
Handle: http://hdl.handle.net/1887/23050
 

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