Cannabis sativa is one of the oldest herbal plants in the history of medicine. It
was used in various therapeutic applications from pain to epilepsy, but its psychotropic
effect has reduced its usage in recent medical practice. However, renewed interest
has been fueled by major discoveries revealing that cannabis-derived compounds act
through a signaling pathway in the human body. Here we review recent advances showing
that endocannabinoid signaling is a key regulator of synaptic communication throughout
the central nervous system. Its underlying molecular architecture is highly conserved
in synapses from the spinal cord to the neocortex, and as a negative feed-back signal,
it provides protection against excess presynaptic activity. The endocannabinoid signaling
machinery operates on demand in a synapse-specific manner; therefore, its modulation
offers new therapeutic opportunities for the selective control of deleterious neuronal
activity in several neurological disorders.
