How Do Nootropics Work?
Many people ask us how nootropics work. This is a very complicated question since there are many different types of nootropics with different methods of action. We recommend that you read about the types of nootropics before reading this article.
Neurotransmitters & Receptors
In order to understand how nootropics work, you must first have a basic understanding of neurotransmitters and the brain. Neurotransmitters are grouped with receptors to make up a system. There are many different types of neurotransmitters and each has its own unique set of characteristics.
Basically, a neurotransmitter is a cell signalling chemical in the brain that binds to a receptor through a synapse. This binding action allows for the receptor to activate and complete its function(s). Each neurotransmitter system has its own set of specific actions in the nervous system. Nootropics work by increasing the efficiency of systems related to cognitive function.
A “system” refers to a neurotransmitter and its associated receptors. Neurotransmitters have their own receptors and there are different types of receptors in a group that can be targeted selectively. Read below to see the types of nootropic neurotransmitter/receptor systems.
Cholinergic System
The cholinergic system refers almost entirely to acetylcholine. Acetylcholine is an abundant neurotransmitter in the brain that is important in: learning, memory, decision-making, focus and sensory perception.
The cholinergic system has two types of acetylcholine receptors, nicotinic and muscarinic. Nicotinic receptors get their name because they can be activated by both nicotine and acetylcholine. Nicotine is a nootropic drug but is short acting and addictive.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659740/ – Ach receptors and memory
Acetylcholine Synthesis
Acetylcholine has many precursors but is usually synthesized from choline found in a natural diet. Not all choline sources will result in Acetylcholine conversion and it is a complicated process. Certain supplements like Alpha GPC and Citicoline are better at converting into Acetylcholine. There are also supplements that aid in conversion of choline and phospholipids to acetylcholine as well as supplements that reduce the enzyme that breaks it down.
Usually, increasing the amount of Acetylcholine will not result in noticeable nootropic results. The effects are often very subtle and for this reason Acetylcholine precursors are often combined with acetylcholine agonists for a synergistic effect. Racetams will also reduce the demand for Acetylcholine and lower levels in the brain. When headaches occur with racetams it is believed that it may be caused by lowered or depleted AcH levels.
http://www.ncbi.nlm.nih.gov/pubmed/7301036 – Study combining racetams with a choline source
Acetylcholine Agonists
Acetylcholine agonists are supplements or drugs that encourage a synapse to take place in the cholinergic system. Racetams are acetylcholine agonists. They work to increase these synapses but do not increase levels of acetylcholine. Increasing acetylcholine levels alone will not have a direct effect on encouraging receptor activity and this is why racetams are often stacked with acetylcholine precursors. Having too much or too little acetylcholine may influence the results and side effects of racetams.
Glutamatergic System
Glutamate receptors are activated by Glutamate which is the most abundant neurotransmitter in the brain. The neurotransmitter glutamate by iteself cannot be considered nootropic because it can also be converted into GABA and excess amounts can result in excitoxicity. Glutamate to receptor binding is considered nootropic and is a function of ampakines and racetams.
Excess glutamate levels can accumulate outside of cells and cause toxicity in the brain. Glutamate receptor malfunctions in the brain are thought to be a factor in neurological diseases like Parkinson’s and Alzheimer’s. ADHD and autism are also thought to be caused in part, by a malfunction of the glutamatergic system
Glutamate Receptors
There are two types of glutamate receptors that can be considered nootropic, NDMA and AMPA. These two types of glutamate receptors are divided into different subunits. Overall NDMA and AMPA receptor activation is an overall goal in nootropic supplementation. Ampakines and racetams are both known to stimulate the NDMA and AMPA receptors. Certain racetams have more of an affinity with activating either of these receptor groups or certain subunits.
www.sinauer.com/rudy/samples/rudy_ch08_lecture.ppt – NDMA & AMPA memory functions (microsoft powerpoint)
Dopaminergic & Serotonergic Systems
Dopamine and Serotonin are both very important monoamine neurotransmitters. Both are very important in the central nervous system for mood, motivation, reward as well as areas of memory and focus. Nootropics don’t use dopaminergic or serotonergic systems as a primary method of action but effects of these systems can contribute to overall results.
Certain nootropics do affect certain dopamine and serotonin receptors which add to overall cognitive benefits (some more than others). Drugs and supplements that involve dopamine are often very addictive and therefore should not be considered as nootropics or substances to use every day. On the flipside, drugs and supplements that influence or modulate serotonin, usually involve the areas of mood and are not mainly nootropic.
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