Oren Ostersetzer-Biran Ph.D.  Rami Yaka Ph.D. Esther Shohami Ph.D,

1) Dept. of Plant and Environmental Sciences, Institute of Life sciences, The Hebrew university of Jerusalem, Israel.
2) School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Israel.

Natural products (i.e. metabolites) are derived from various sources, including bacteria, fungi, animals, and are particularly plentiful in plants. It is estimated that plants produce between 70~80% of all known metabolites in nature. Generally, the metabolites are categorized into two main categories, termed as ‘primary’ and ‘secondary’ metabolites. Here, we focus on a specific class of plant-metabolites, the (phyto) cannabinoids, and their effects in curing brain trauma. Cannabinoids are a large group of ‘secondary metabolites’, which in an opposite manner to the ‘primary metabolites’ (i.e. natural chemicals required to the plant's survival that are directly involved in the growth and development of the plants) are not essential to the functioning of the plant under ‘normal’ growth conditions. Numerous different plant metabolites have been exploited for medicinal, agricultural and industrial uses. According to the ‘World Health Organization’ about 25% of drugs used are derived from plants. Still, these represent only a tiny fraction of the diversity of plant metabolites (estimated to be in the range of hundreds of thousands). The current proposal focuses on a specific class of diverse terpenophenolic compounds, phyto-cannabinoids, which are produced in the cannabis plant (also termed marijuana). It is becoming obvious that both plant and animal cannabinoids have important and diverse medicinal properties, including as anti-depressants, anti-anxiety, anti-emetic effects, or anti-inflammatory effects. Phyto-cannabinoids produced in plants and their related compounds produced in the brain (endocannabinoids) have shown significant promise in basic experiments on pain and brain activities. For example, the phyto-cannabinoid tetrahydrocannabinol (THC) has been shown to possess a high binding affinity with CB1 receptors located throughout the brain and central nervous systems. Our work focuses on Traumatic Brain Injury (TBI). Brain injuries can range in scope from mild to severe.  Quite often, traumatic brain injuries can result in permanent neurobiological damage that can produce lifelong deficits (to varying degrees). Accordingly, the main aims of our research are designed to establish the roles of a specific phyto-cannabinoid, cannabidiol (CBD) in curing/reducing traumatic brain injury (TBI).