Grant: Project Grant

Cannabinoids are a broad class of molecules that act on nerve cells, affecting pain sensation, appetite, mood, learning and memory. There are 3 classes of cannabinoids: (1) endocannabinoids produced naturally by the body, (2) phytocannabinoids from some plants, and (3) synthetic cannabinoids. Cannabinoids may provide effective treatments for addiction, pain, epilepsy, major mood disorders, anxiety, post-traumatic stress disorder, spasticity in multiple sclerosis, Parkinson's disease, and Huntington's disease. However, to use them, without negative effects on learning and memory, we must understand exactly how they affect nerve function. Cannabinoids bind to Cannabinoid receptors (CBRs). However, activating CBRs cannot directly change the firing of nerve cells, since CBRs do not generate electrical signals on their own. Instead, electrical signals are controlled by ion channels, which allow for the movement of charged "ions" from one side of a membrane to the other. My lab focuses on hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. HCNs are important for nerve function, learning and memory, pain sensation, and vision. The endocannabinoid WIN55,212-2 effects memory by activating CB1R, which leads to changes in electrical currents through HCNs. However, cannabinoids can also bind ion channels directly, or alter their membrane environment. In addition, different cannabinoids (for example, THC and cannabidiol from marijuana) have different effects on people's mood, pain sensations, and memory. Since HCN channels are involved in all of these processes, we are asking, do cannabinoids have a direct effect on HCNs, independent of CBRs? If so, are these effects specific to the type of cannabinoid? These findings will help us to develop therapeutic approaches to the treatment of numerous neuronal disorders. Also, our results will also help in the development of novel nootropics or "smart drugs" that can enhance memory, creativity, or motivation.