Serotonergic System - Endourage


Serotonergic System

Serotonin System and its Function

The serotonin system is a major neuronal system that plays a role in various mental functions, including the regulation of anxiety, mood, cognition, perception and pain. Serotonin works by binding to 5-HT receptors, of which 14 variants have been identified, though full understanding of what each one does has not yet been fully understood. Stimulation of 5-HT1a receptors has shown prominent antidepressive effects, while the inhibition of these receptors has been correlated with depression-like behaviors. Alternatively, 5-HT2a receptors, the most abundant ones found in the prefrontal cortex, have been associated with mood disorders, psychosis and drug addiction. Inhibition of these receptors has been observed in several neurological disorders, including Alzheimer’s disease, depression, anxiety, addiction and schizophrenia. 


Most research into the relationship between cannabinoids and serotonin comes from preclinical animal models, specifically rodent subjects. Contradicting studies indicate some kind of interaction with 5-HT receptors when CB1 receptors are stimulated with either THC, CP55940 or WIN55212-2, though this relationship has not yet been clearly defined. Some studies turned up 5-HT suppression anywhere from 17 – 49%, while others found no change at all, and a few recent studies have indicated an up-regulation in 5-HT receptors following microdosing of THC. In human cases, it’s been discovered that CBD, CBDa and THCV can partially bind to 5-HT1a receptors, assisting in antidepressive and antipsychotic effects. Furthermore, a 2013 study made the interesting discovery that among cannabis users, only those who carried two specific genotypes, COMT val/val and serotonin-transporter-linked polymorphic region (5-HTTLPR) s/s, have shown serotonin impairments compared to control subjects and cannabis users who carried a different genotype. This suggests that issues arising between cannabis use and serotonin binding, presumably with 5-HT2a receptors, come from a genetic predisposition. Still, the exact relationship between cannabinoids and the serotonergic system needs to be further explored.


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