Nootropics Primer

There are many means by which to increase ones intelligence and cognition. Smart drugs attempt to increase the biochemical processes by which memory formation, speed of processing, and focus are made possible. In order to understand the mechanism by which Nootropics work, one first needs to understand how the brain works. Humans have studied fields of science such as physics, chemistry, and geology for hundreds, if not thousands of years. While attempts to study cognition from the perspective of physiology and anatomy have existed for nearly as long, the tools needed for breakthroughs in this field have existed for less than one hundred. Even simple light microscopes did not exist until 1665. Humans are only just beginning to understand the complexities of the brain. According to Nootriment, self augmentation of cognition through supplementation is not a process one can think of like a cookbook. Finding the right combinations is often trial and error. Although humans are far from understanding the mechanisms of thought, this primer will attempt to explain the components that are well understood.

Nervous System

The nervous system is the quick response communication method of the body. Neurotransmitters act as extracellular messengers to initiate a physiological response in the target cell. Generally, this will be another neuron, although the nervous system also controls skeletal muscles and even interacts with the endocrine system at the hypothalamus. Neurotransmitters don't only cause other neurons to fire, but neuron to neuron interaction is simple to understand and lays the ground work for understanding the effects of nootropics.


There are two important perspectives by which to understand neurons. The first, histological, allows one to view each part of a neuron while the second, physiological, allows one to understand what occurs when neurons are active. Finally, one must also understand the Neuroglia, or support cells of the brain.

Most neurons have many dendrites. Exceptions include neurons that are modified for sensory functions, such as photoreceptors or thermoreceptors. Dendrites are short extension that branch away from the soma, or cell body. They have many Ligand gated sodium channels. Neurotransmitters are the ligands that activate these channels and allow sodium to stream into a neuron. All neurons have an axon, which is the long extension which ends in a synaptic knob. While there is only one axon per neuron, it can have many collateral branches. The synaptic knob attaches to a dendrite of another neuron. The small gap between is called a synapse, or synaptic gap. It is into this gap that neurotransmitters are released from the knob, which activate the Ligand gated sodium channels on the next neuron. The axons is insulated by a material called myelin, which is produced neuroglia, which are accessory cells which assist neurons. In the soma of the a neuron, there is an axon hillock. The hillock is where the axon emerges, and is where graded potential are summated in order to cause an action potential to occur. All of these components are specialized parts of the neuron that allow a process call synaptic transmission. The "take home message" of the neuron histology, is that dendrites receive neurotransmitters, Axons release neurotransmitters, and that the hillock in the soma summates. The rest becomes simple once the physiological perspective is explained.
The physiological perspective of neurons is essentially a step by step explanation of synaptic transmission. This is a chemical-electrical event by which neurons communicate with each other, as well as how they stimulate the various effectors of the body (i.e muscle,). For simplification, I will number he steps. Keep in mind this is an oversimplification, and the number of steps that are listed are arbitrary. There is much more going on within a neuron than will be explained, but this should be enough for a general understanding.

1. A neuron has electrical potential. This is due to the cell membrane. Within a neuron, there is less sodium than outside. Sodium has a positive charge, so the intracellular fluid is negative relative to the charge of the extracellular fluid. There is a higher quantity of pottasium, which is also positive, in the intracellular fluid than there is in the extracellular fluid. This raises the charge within the cell to an extent, but it is still overall negative. Both sodium (Na+) and pottasium (K+) are ions. The cell membrane is permiable enough that some of these ion diffuse through, but this change in charge is offset by Na+/K+ pumps which keep the electrical potential.

2. A Ligand gated sodium channel on the dendrite is activated by a neurotransmitter. These channels have high specificity so they are only activated by one type of neurotransmitter. They allow Na+ to stream into the neuron, which changes the charge of the cell. Be cause the charge rises towards that of the extracellular fluid, this can be thought of as a type of depolarization, but it is called a Graded Potential. The many small and localized depolarization effects are called Graded Potentials. The neurotransmitter is soon broken down, and the small region within the dendrite returns to equilibrium.

3. If enough LGSCs are activated at once, the Graded potential spreads, and threshold is met. Threshold is when many LGSC are opened and a certain charge indicates to the hillock to initiate an action potential.

4. Along the Axon, VGSCs are stimulated by the voltage change. They allow massive amounts of sodium to stream into the cells. This is called depolarization.

5. At a very high charge, the VGSCs inactivate, and the VGPCs open. The VGPCs allow K+ to stream out of the neuron, which drops its charge to a level below it intitial rest state. This is called repolarization, and once the charge drops below rest, its called hyperpolarization. These steps are very important because they cause a "refractory period" when the neuron is incapable of firing.

6. During the peak of the Action Potential, the charge reaches the VGCCs at the synaptic knob. These allow calcium to stream into the neuron. This calcium binds to vessicles of neurotransmitters and cause them to release into the synaptic gap.

7.These neurotransmitters bind to the LGSC on the dendrites of the next neuron, and start the process again.

Neuroreceptors and Responses


Neurotransmitters are a type of signaling molecule that communicates extracellularly to initiate responses between cells. There are two functions that a neurotransmitter can accomplish, stimulation or inhibition. There are many neurotransmiter systems, such as: Noradrenergic, Dopaminergic, Serotonergic, Cholinergic, and Gaba-ergic.

Inhibiting Enzymes

So that leaves the question of, how do we regulate these neurotransmitters? The answer is through enzymatic inhibition. Heres an example. The Neurotransmitter Acetylcholine activates skeletal muscle contractions. At the neuromuscular junction, acetylcholine is released. It croses the synaptic gap and activates events that lead to muscle contraction. This is great. Now our muscles are activated, right? The problem is that now your muscle will remain in a state of tetanus. To stop a muscular contraction, an enzyme called Acetylcholine Esterase is released, that breaks down the Acetylcholine and stops the muscle from contracting. So we have neurotransmitters that give, and we have enzymes that taketh away. In the brain, constantly destroying or degrading neurotransmitters would be too wasteful. Many neurotransmitters instead of being destroyed are instead simply "taken back up" into vesicles. This is a very effective process. In fact, sometimes to effective. Clinical depression for example is a result of a person not have enough Seratonin present. To combat depression, the most commonly described class of drug is a seratonin reuptake inhibitor. This drug serve to "inhibit the inhibitor." Inhibiting the inhibitor, is the means by which many of the most effective drugs and nootropics function. Cocaine for example, inhibits the reuptake of dopamine. Another way to alter the way alter neurotransmitter function is add a molecule that competes for either a neuroreceptor or for an enzyme that breaks down a transmitter.

An example of this would be when Adenosine receptors in the brain cause depression of pacemaker functions and causes a general lethargic state. When a person feels tired it is due to adenosine stimulation. Caffeine is molecule that does not stimulate adenosine receptors, but binds to them so that adenosine cannot stimulate them either. This is an example of competetive inhibition. A very similar method is called allosteric (or non-competitive) inhibition. The molecule in allosteric regulation binds not to the active site of the enzyme or receptor, but rather to another portion of the protein, causing it to change shape so that it cannot bind to a nerotransmitter. Both competitive and allosteric regulation are considered to be reversible inhibitions, because after a period of time the enzyme or receptor will go back to a state where it can again be stimulated.

The final categorie of inhibitors are those that are irreversible. We've already discussed acetylcholine and how it causes muscle contraction. There is a molecule called DIPF that irreversibly bonds to Acetylcholine Esterase and prevents it from breaking down Acetylcholine. DIPF is a strong Nerve Gas that leads to uncontrollable muscle spasm and death in large amounts. Another example is Botulinum toxin. It works to prevent Acetylcholine from being released in the first place, and thus causes death from cessation of breathing. While these sound terrible, the reason they are called irreversible is because they permanently deactivate the enzyme they effect. The fact that they lead to death has nothing to do with it. Most people are familiar with "Botox." In small amounts, botulinum toxins causes facial relaxation and assists in the treatment of wrinkle. Along the same line, a nootropic called THA is homologous to DIPF. It inhibits Acetylcholine Esterase permanently, leading to higher levels of Acetylcholine in the brain. In small amounts it can be beneficial.

Most Nootropics fall under these categories. They enhance brain function by inhibiting the break down of the chemical messengers. One other common mechanism is sensitization. The racetam group for example, works by activating receptors that are connected to cholinergic receptors. While they don't activate the cholinergic receptor, they do make them far more susceptible towards stimulation. When dealing with Nootropics, the goal is to assemble your perfect "stack." A stack is the right combination of Nootropics, vitamins, and supplements in order to balance your brain chemistry to the condition that a person feels is optimal. The first step towards this is understanding the mechanisms of the nootropics taken. The list of nootropics below have a description that will help you understand exactly how they work on your brain. This should help, but it is not enough. First understand how each nootropic is said to function, and then keep a record of its actual effect on you. Brain enhancement is knowing not only the drug, but knowing yourself.

Endocrine System





The racetams are a common group of nootropic drugs that work on the Acetylcholine system. Commonly racetams like the Piracetam or Aniracetam are stacked with a Acetycholine choline precursor like Choline Bitrate. These racetam supplements begin to work on the Glutamate and Acetylcholine receptors upon ingestion. Common receptor sites racetams work on are the NDMA and AMPA receptor sites.

Certain racetam nootropics also have function on the dopamine, acetylcholine nicotine and serotonin receptors. Aniracetam and Noopept (not technically a racetam) have these effects.


Ampakines are another class of nootropic drugs and supplements. Ampakines act primarily on the glutamate receptors. Racetams also act on the glutamate receptors however not to the same extent of the ampakines.

Ampakines are a newer form of nootropic. The safety and efficiency has not yet been proven. Sunifiram is a nootropic that is currently being used by the public. It is said to be 1000-1500x stronger than piracetam