CANNABINOIDS, ENDOCANNABINOID SYSTEM AND COGNITIVE FUNCTIONS: FOES OR FRIENDS?

Cannabinoids are natural compounds found in hemp (Cannabis sativa). Scientific interest in cannabinoids arose after the discovery of the main psychoactive component in cannabis, Delta 9-tetrahy-drocannabinol. Subsequently, receptors on which it acts were identified in the brain, as well as ligands of these receptors, endogenous cannabinoids (ECs), which together with the enzymes of their synthesis, transport and degradation form the endacannabinoid system (ECS). Interest in ECs has steadily increased in recent years, especially after the discovery of their important role in cognitive functions. They are regulators of synaptic transmission in the brain, mediate numerous forms of plasticity and control neural energy metabolism. They exert their influence through a number of mechanisms and interactions with neurotransmitters, neurotrophic factors and neuropeptides. The main function of ECs in the brain is to perform retrograde synaptic signaling and neuromodulation, owing to which cell homeostasis is maintained. Information on the effect of cannabinoid drugs on cognitive functions is very contradictory. The reasons for the contradictions may lie in the fact that strict scientific data from clinical and socio-logical studies are not yet sufficient, and in experiments on animals, different authors use different methods and approaches for influencing the EC system. Thus, the effects may vary depending on the drugs used, their dose and method of administration, as well as on the tasks and experimental conditions selected for testing. There is extensive literature indicating the protective effect of the ECS activation in neurodegenerative diseases in humans and in models of cognitive deficiency in animals. This review discusses evidence of the effects of (endo)cannabinoids and activation of the EC system on cognitive functions in the normal brain and in neurodegenerative diseases, Alzheimer's disease and temporal lobe epilepsy. Possible causes of inconsistencies in available data are also discussed.