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Marc Baggelaar graduates cum laude on body’s own marijuana

PhD candidate Marc Baggelaar of the Leiden Institute of Chemistry (LIC) graduated cum laude on Thursday 6 April. His thesis on the endocannabinoid system in the brain is very comprehensive and of high quality, according to the jury. ‘A very talented young scientist, that definitely belongs to the top five percent'.

Fundamental and practicable

Baggelaar’s thesis is both fundamental and applied. He designed and synthesised compounds that enable visualisation, and modulation of the activity of diacylglycerol lipases. These are proteins that produce the endocannabinoid 2-AG (2-arachidonoylglycerol). This endocannabinoid has the same effect as THC, the active substance in marijuana. They both activate the cannabinoid CB1 receptor in the brain. Activation of the CB1 receptor is related to energy metabolism. Therefore, influencing the signaling process of this receptor is very promising in drug development for diseases such as obesity and diabetes.  

The role of the body’s own marijuana

Next to 2-AG, the brain produces another kind of endocannabinoid, namely anandamide. The specific role of both neuromodulators is currently unclear. Understanding their role is essential for drug development; Baggelaar looked at which endocannabinoid is responsible for the different biological processes. These include the regulation of appetite, pain sensation, memory and anxiety. An enhanced insight in these processes could lead to alternatives for existing antagonist for the cannabinoid CB1 receptor in the brain. Previous compounds worked well against heavy overweight and type 2 diabetes, but had a major drawback that they induced severe psychiatric side effects, including suicidal ideation.

Chemical toolbox

To study a biological system such as the endocannabinoid system, chemical tools are highly important. Efficient tools to study the role of diacylglycerol lipases were lacking. In the Molecular Physiology group of Mario van der Stelt, Baggelaar developed a new tool set and methods to measure the activity of diacylglycerol lipases. This enabled him and his colleagues to explore the regulation of endogenous marijuana. With this new method, Baggelaar identified and optimised new inhibitors of diacylglycerol lipase. The discovery of these new inhibitors is of high importance to neuroscience, and the field of endocannabinoids in particular. These studies could lead to more insight in the exact functions of the endocannabinoid system and could lead to novel drugs.

Full of praise

Promotor Hermen Overkleeft is full of praise for Baggelaar: ‘Besides his large number of publications, Marc is social and took the lead in several collaborations with experts in the Netherlands and abroad. As first PhD student in de group of Mario van der Stelt he laid the foundation for the technologies that his successors now use. What I admire, is that he changed from an excellent organic chemist into an all-round chemical biologist with an eye for detail, in only a short period of time. In addition, he has an exceptional problem solving ability: with his creative way of thinking he individually developed original molecules and concepts. 

Ongoing research

Researchers in the molecular Physiology group of Mario van der Stelt are currently working on further development of the chemical tools to study the specific roles of the various types of the body’s own marijuana. More insight in the exact role of different components of the endocannabinoid system is likely to result in novel therapeutic strategies without the psychiatric side effects. At the end of this summer, Baggelaar will continue his research as a Marie Curie fellow in the lab of Professor Ed Tate at the Imperial College London.