FOR 926:  Physiology and Pathophysiology of the Endocannabinoid System

• Subject Area: Medicine
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 42860621

The term cannabinoids originally described the active ingredients in the hemp plant Cannabis sativa, including the well-known psychoactive substance ?9-Tetrahydrocannabinol (THC). THC activates the G-protein-coupled receptors CB1 and CB2. The physiological endogenous ligands of these receptors, the endocannabinoids, are lipids that are produced by many different cells.
Recent results, to which the principle investigators of this Research Unit have contributed to a major extent, strongly suggests that the endocannabinoid system plays a crucial role in the physiological responses to internal and external stressors and thus contributes to the maintenance of the homeostasis.
The short-term activation of the endocannabinoid system represents thus an important protective stress response and promotes the following protective physiological responses:
(1) to relax (reduction of locomotor activity, reduction of the blood pressure, analgesia, stimulation of the reward system),
(2) to eat (appetite stimulation, enhancement of energy conservation),
(3) to forget (inhibition of short-term memory, stimulating extinction of stress-related memory contents),
(4) to protect (inhibition of excessive neuronal activity, reduction of hormonal stress responses, stimulation of neurogenesis, stimulation of anti-inflammatory processes).
A long-term or even chronic activation of the endocannabinoid system is, according to our current understanding, rather detrimental and may in fact contribute to the development of several important common disorders, including addiction, chronic pain, obesity, psychiatric disorders, coronary heart disease, neurodegenerative disorders, osteoporosis and allergies. Because the underlying mechanisms are not well understood, we aim in this multidisciplinary Research Unit to further elucidate the role of the endocannabinoid system in physiological stress responses and pathological processes. The improved understanding of these mechanisms shall enable us to test novel therapeutic approaches that are based on the modulation of endocannabinoid system activity in appropriate model systems.

• DFG Programme: Research Units

Projects

• Analysis of the detrimental effects of Cnr1-/- mice in an Alzheimer's mouse model and of the interplay between CB1 receptor function and amyloid precursor protein processing (Applicant Behl, Christian )
• Characterization of cell type-specific endocannabinoid signaling at biochemical and behavioral level (Applicant Lutz, Beat )
• Common resources of the research unit (Applicant Zimmer, Andreas )
• Detection and quantification of endocannabinoids by LC-MS/MS (Applicant Lutz, Beat )
• Function of the endocannabinoid system in normal and pathological ageing processes of the brain (Applicants Bilkei-Gorzo, Andras ;  Schlicker, Eberhard )
• Impact of the developing endocannabinoid system in rats on the modulatory influence of stress on adolescent ethanol intake (Applicant Schneider, Miriam )
• Modulation of the exocytotic and carrier-mediated transmitter release by endogenous and exogenously added cannabinoids (Applicant Schlicker, Eberhard )
• Role of the cannabinoid receptor 2 (CB2) in neuroinflammation (Applicant Alferink, Judith )
• Role of the endocannabinoid system in homeostasis and adaptation to pathological conditions in the cardiopulmonary system (Applicant Dewald, Oliver )
• Role of the endocannabinoid system in human pain sensitivity, pain plasticity, pain habituation, and neurogenic and non-neurogenic inflammation (Applicant Magerl, Walter )
• The role of the CB2 receptor and human CB2 receptor variants in neuropathic pain (Applicant Zimmer, Andreas )
• The role of the endocannabinoid system in the regulation of cellular immune responses in the skin (Applicant Tüting, Thomas )

• Spokespersons: Professor Dr. Beat Lutz; Professor Dr. Andreas Zimmer