Novel approaches in clinical development of cannabinoid drugs

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 programsUBL - phd migration 201

Pharmacokinetic/pharmaco-dynamic modelling and simulation of the effects of different cannabinoid receptor type 1 antagonists on (9)-tetrahydrocannabinol challenge tests

Stress-related psychiatric disorders across the life spa

Peripheral selectivity of the novel cannabinoid receptor antagonist TM38837 in healthy subjects

Stress-related psychiatric disorders across the life spa

Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits 9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans

Stress-related psychiatric disorders across the life spa