Phytocannabinoids and endocannabinoids

Progress in understanding the molecular mechanisms of cannabis action was made after discovery of cannabi- noid receptors in the brain and the finding of endogenous metabolites with affinity to them. Activation of cannabinoid re- ceptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity. Neu- romodulation of synapses by the cannabinoids is proving to have a wide range of functional effects, making them poten- tial targets as medical preparations in a variety of illnesses, including some mental disorders and neurodegenerative ill- nesses. Cannabis contains a large amount of substances with affinity for the cannabinoid receptors. The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of impor- tant findings about the role of membrane lipids and fatty acids in nerve signal transduction. Plant, endogenous and syn- thetic cannabinoids are using in these studies. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid, an important membrane constituent. The study of structure-activity relationships of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis.