Foreword.
The serotonin system plays through various means a major role in human cognitive and behavioral functions. In the world of recreational drug use the serotonin system is commonly considered to be mainly responsible for feelings of euphoria and well being. However the full scope of the serotonin or 5-HT system for short, and it’s functions are very complex indeed. Besides playing a part in normal human physiology. In this thread I will attempt to explain it’s psychopharmacological significance.
5-HT receptors
There are a couple of different types of serotonin receptors, namely; 5-HT1 through 7 which are mostly involved in increasing or decreasing cellular levels of cAMP (Cyclic adenosine monophosphate). It might be argued that activation of these recepetors contributes directly to the overall effects profile of the exogenous or endogenous substances, that can either agonise or antagonise these receptors. However to get a more complete picture of these mechanisms you must understand that every 5-HT receptor has it’s own set of subtypes with it’s own functions within the CNS.
5-HT Receptor subtypes
While the actual subtypes are quite numerous i will only go into specific detail about those that play a significant role in contributing to the effects of recreational and some medicinal drugs. Mostly to keep this thread psychopharmacology related and not a lesson in human physiology.
An overview of some 5-HT receptor subtypes and their functions.
5-HT1A
Cognitive funtion: Mood, sociability, appetite, sexual arousal, anxiety, aggresion, memory, sleep, analgesia and impulsivity.
Mode of operation: Agonising 5-HT1A receptors increases dopamine release, which is exhibited by an increase in mood, sociability and a decrease in aggresion and anxiety. Along with these effects 5-HT1A agonism also induces secretion of multiple hormones such as oxytocin, which most likely, also contribute to the effects i described above.
5-HT1A receptor agonism also results in decreased levels of glutamate and acetylcholine which has a negative effect on learning and memory formation.
Finally, some 5-HT1A receptors are co-localized with NK1 receptors. These NK1 receptors play an important part in the perception of pain. However when 5-HT1A receptors (That are co-localised with this other type of receptor.) are agonised, they inhibit the release of SP which is the endogenous ligand for NK1 receptors, thereby decreasing NK1 activation and promoting analgesia.
5-HT2A
Cognitive function: Perception, imagination, general cognition, mood, sleep, anxiety.
Mode of operation: These receptors are widely distributed through the CNS and are generally considered the most important when it comes to the mechanism of action of various psychedelics. The areas of the brain that are most densely populated by this type of receptor are the apical dendrites of the pyramidal cells of the cortex. Apical dendrites are the branched apex of the neurons of the pyramidal cells and pyramidal cells are the main type of excitatory neurons found within the brain. As such 5-HT2A receptors have the ability to significantly modulate cognitive processes. Via certain mechanisms 5-HT2A agonism results in increased glutaminergic activity and a decrease in the effectiveness of inhibition through GABAA receptors. Furthermore, a signaling cascade occurs through a series of complex interactions, which combined with the effects i described above, ultimately results in a decreased ability of the thalamus to proces sensory information and relay it properly to the cortex, where the faulty information is intergrated as psychedelic effects such as; colours, fractals, closed eye visuals, etcetera.
5-HT2C
Cognitive function: Mood, sexual arousal, sexual behavior, anxiety and sleep.
Mode of operation: 5-HT2C plays an important role in the release of dopamine in certain parts of the brain, however it primarily has an inhibitory funtion and to increase dopamine levels via 5-HT2C receptors we must use an antagonist. Psychedelics of the phenethylamine class are, besides partial agonists of 5-HT2A receptors, also antagonists of 5-HT2C receptors which influences the effects percieved by a someone while under the influence of this type of drug.
Antagonism of 5-HT2C receptors also results in increased levels of nor-epinephrine which may have a cardiovascular effect.
Agonism of 5-HT2C receptors also results in increased levels of certain hormones, primairly oxytocin and vasopressin.
Conclusion
With all this information in mind it is easy to see why the serotonin system plays an important part when it comes to psychoactive drugs. Mood, perception and general cognition are mostly governed by the serotonin system which consequentially contributes to the effects of drugs such as MDMA, LSD, 2c-B and various others.
Thank you for reading! Should you have any questions feel free to post them, also if you found any flaws in my explanation please feel free to point them out as well!
