Cannabinoid and Other Neurotransmitter Systems

Endogenous cannabinoid neurotransmitter systems, which are the main target of cannabinoids, have recently become the subject of fundamental research by neurochemists, neuropharmacologists, narcologists, and immunologists. The designation of the systems comes from the name of the exogenous ligand of cannabinoid receptors ∆9 -tetrahydrocannabinol, the most active alkaloid isolated from cannabis. At the end of the 80s of the 20th century, the idea of the presence of specific cannabinoid receptors was formed and subdivided into two subtypes: CB1 and CB2 receptors. The former is found in the CNS, while CB2 receptors are located in peripheral organs. CB1 and CB2 receptors belong to the metabotropic family, including muscarinic-sensitive, dopamine, serotonin, opioid, α- and β-adrenergic. Cannabinoid receptors of the first and second subtypes were cloned in the early 90s. At the same time, endogenous ligands of cannabinoid receptors were identified in the CNS and peripheral tissues: arachidonoyl ethanolamide (anandamide, an agonist of CB1 receptors) and 2-arachidonoylglycerol (an agonist of CB2 receptors).

The endogenous cannabinoid system is the collection of cannabinoid receptors and their endogenous ligands. Its primary function is to modulate the transmission in synapses of a different chemical affiliation by changing the release of neurotransmitters (inhibition of exocytosis). This is mainly due to the presynaptic localization of cannabinoid receptors. Cannabinoid receptors of the first subtype are localized mainly on the axons of neurons. On dendrites and bodies of nerve cells, their concentration is significantly lower. CB1 receptors, like other metabotropic receptors, can form homo- and heterodimers.

Cannabinoid receptors belong to the class of metabotropic receptors coupled to guanine nucleotide-binding proteins. Their similarity lies in transmitting information into the cell using transduction systems (cyclase, phosphoinositide, calcium, and nitric oxide systems). Excitation of the metabotropic receptor activates the G-protein, which interacts with the effectors of the transduction system (enzymes, calcium channels, and others). The resulting secondary messengers modulate the functional state of the cell by phosphorylation of various proteins. The polypeptide chain of the CB1 receptor includes an NH2 terminal (extracellular), seven transmembrane domains (TM I – VII), a carboxyl-terminal (intracellular), and extra- and intracellular loops.

The main difference between CBD and THC is that the former is non-narcotic, unlike the latter. This is because CBD does not directly interact with the human endocannabinoid system – the body’s unique system that regulates elements of life such as sleep, appetite, and the immune system. It is this direct interaction that gives the person the feeling of being drugged. THC initiates a psychological response via the cannabinoid CB1 receptors, primarily in the central nervous system and brain. When the CB1 receptor is activated, it produces a psychoactive effect.

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