Marijuana (Cannabis sativa L.) and its derivatives have been used both medicinally and recreationally for at least fifty centuries. However, the chemical structure of their active components – the cannabinoids – was not elucidated until the early 1960s. Pharmacological studies conducted at that time led to the conclusion that, among all the cannabinoids present in the plant, one of them, D9-tetrahydrocannabinol (THC), is especially relevant owing to its high abundance and potency. Three decades later the mechanism of THC action was unravelled. Thus, in the early 1990s it was found that THC affects our body because it is similar to (and therefore mimics the effects of) a family of molecules produced by our organism that were so called endocannabinoids - anandamide and 2-arachidonoylglycerol being their main representatives. THC and endocannabinoids act by engaging specific proteins located on the surface of our cells and called cannabinoid receptors, two of which have been well characterized: CB1 y CB2. Nowadays it is known that those receptors are expressed preferentially in areas of the central nervous system that control processes such as motor activity, memory and learning, pain, appetite, vomiting, emotions and sensorial perception, which obviously explains that these processes are modulated by both the endocannabinoids generated at those locations and the THC that gains access to them owing to marijuana consumption. Cannabinoid receptors are also present at many other sites in our body, for example the peripheral terminals that innervate the skin and the digestive, circulatory and respiratory tracts, as well as in the immune system, the reproductive organs, the eye and the vascular endothelium. All these discoveries have contributed not only to an extraordinary expansion of the basic knowledge on how cannabinoids act in our body, but also to the renaissance of the study of their therapeutic properties, that constitutes a current topic of debate with ample scientific and clinical consequences.
Lines of research
1. Neuroprotection
Mechanisms of cannabinoid neuroprotective action in neurodegenenerative and de-myelinating diseases and acute brain injury. Design of experimental therapies based on endocannabinooid system modulators for those neuropathologies.
2. Cytotoxicity
Mechanisms of cannabinoid cytotoxic action in malignant brain tumours. Design of experimental therapies based on endocannabinooid system modulators for those tumours.
3. Medicinal Chemistry
Design, synthesis and optimization of new compounds with therapeutic potential on the endocannabinooid system.
Other items
Activities: education and outreach
In this context, our consortium studies the mechanisms by which endogenous and plant-derived cannabinoids act in the brain and their potential physiological and therapeutic implications. Specifically, one of our major interests focuses on unravelling whether these compounds impact neural cell generation, growth and survival. Understanding these processes is a pivotal issue for characterizing the aetiology and progression of neurodegenerative diseases (characterized by a loss of neural cells) and oncologic processes (characterized by an uncontrolled cell proliferation) and, therefore, for designing rational therapies for their treatment. Along these years we have observed for example that, upon activation of their specific receptors, cannabinoids modulate key cell signalling pathways, thereby eliciting effects such as progenitor cell proliferation, neuron and glial cell survival, and, on the contrary, apoptosis of cancer cells. These cellular events have a clear physiological relevance in laboratory animals, in which we have observed that cannabinoids, for example, control brain development, contribute to the regeneration and protection of nervous tissue upon damage, and inhibit the growth of malignant tumours. Overall, these studies support the notion that cannabinoid receptors are involved in the control of basic cell decisions and may thus constitute new pharmacological targets. However, further basic and preclinical research as well as thorough clinical trials are required to allow us to know whether cannabinoids could be used – aside from their palliative actions – as therapeutic agents in the treatment of neurodegeneration and cancer.
The endocannabinoid system (ECS) constitutes an inhibitory neuromodulatory system that controls a wide array of central and peripheral functions. It includes receptors that are also targeted by delta-9-tetrahydrocannabinol (THC) and other active constituents of the hemp plant Cannabis sativa L. The major goal of the research groups that participate in this program, coordinated by Universidad Complutense and finantially supported by Comunidad de Madrid, is the neuropharmacological characterization and the study of the therapeutic potential of the ECS by using a multidisciplinary approach. This would allow deciphering the physiological and pathological actions of cannabinoids (both endogenous and plant-derived) in the body, especially in the central nervous system; the molecular mechanisms underlying those actions; the interactions of the ECS with various drugs of abuse; and the therapeutic implications of the pharmacological manipulation of the ECS. The present program is based on the experience and repute in this field of the applying research groups. Our aim is gathering efforts in order to improve the use of the available resources and therefore to obtain a better scientific yield. This would allow us developing more efficient interaction strategies among all the groups, not only to take more profit of our current potential, but also to gain common objectives aimed at implementing convergent lines of research for more ambitious and impacting projects.
The development of this collaborative program will be carried out by a multi-disciplinary consortium that comprises eight experienced research groups belonging to various Universities, Hospitals and CSIC Institutes located within the Madrid Region.