How nootropics work: A beginner’s guide to pharmacology

Before I get into the specifics of nootropics I’m going to provide an overview into how drugs actually work on the brain. Essentially I’m giving a short guide to pharmacology. That way when you are doing your own research and coming across descriptions of drugs and certain terms, you fully understand what is being said. In addition, if you are planning on consuming relatively unheard drugs and supplements, it’s a good idea to actually know what is happening to your body and brain.

How the brain communicates

In order to understand how drugs work, you need to know what they are affecting. In this case, the drugs are primarily affecting the communication between brain cells.

In the most basic description, the brain communicates via the connections between neurons. Essentially, when one neuron becomes activated, it releases chemicals that then act on another neuron to either activate or inhibit it. These chemicals are called neurotransmitters. Different neurotransmitters tend to represent different overall functions in the brain and are therefore targeted by nootropics.

What are neurotransmitters?

Neurotransmitters primarily allow neurons to communicate with each other. Nootropics are mainly used to enhance, inhibit, mimic or reverse the effects of neurotransmitters that control cognition.

The main neurotransmitters include dopamine, noradrenaline, serotonin, acetylcholine, histamine, GABA, and glutamate.

Dopamine. This neurotransmitter is thought of as the “reward” molecule. This is because it is involved in the reward pathway, or mesolimbic pathway, in the brain. However it also has important roles in physical movement and executive function. It’s relevance to nootropics is for motivation, drive, concentration and executive function. It also helps modulate neuroplasticity.

Noradrenaline. This neurotransmitter is primarily involved with focus and concentration. It has a more prominent role than dopamine in concentration and is therefore the primary target for ADHD drugs. It is also involved in neuroplasticity modulation.

Serotonin. This is called the “happy” molecule, which is mainly due to the fact that is the main target for antidepressants. This is misleading as antidepressants aren’t very effective and altering serotonin levels don’t actually have any direct effect on mood. It has many roles, the most notable being for sensory perception and general cognitive activity. Due to the non-specificity of its role, this neurotransmitter generally isn’t targeted by nootropics.

Acetylcholine. This neurotransmitter is probably the most versatile in terms of cognition. It is known to have a prominent effect on memory, attention, and communication between different parts of the brain. Nicotine activates an acetylcholine receptor, therefore causing increases in cognitive performance. It is the main target of Alzheimer’s disease drugs as a way to improve memory.

Histamine. The primary role of histamine in the brain is to induce wakefulness. This is why certain antihistamines are known to cause substantial drowsiness. Increasing histamine enhances alertness and attention. It can also act to modulate the release of other neurotransmitters such as dopamine and noradrenaline. Therefore, histamine can indirectly cause the same effects as these neurotransmitters by increasing their release.

GABA. This neurotransmitter is primarily used to suppress the activity of neurons. Globally this causes depression of all neural activity and can cause reduction of anxiety, the feeling of relaxation, loss of inhibition, sedation and sleepiness. Alcohol directly activates the GABA receptor and therefore causes each of these effects. Due to its inhibitory effect it is not usually targeted for cognitive enhancement.

Glutamate. This neurotransmitter is the primary excitatory neurotransmitter in the brain. It has the opposite effect to GABA by causing activation of neurons. It is the main chemical involved in neuroplasticity and long term potentiation. For this reason, it is hugely important for the ability to store memories.

How do neurotransmitters affect cells?

Neurotransmitters bind to and change the functioning of receptors, which in turn change the functioning of a cell. This can be by activating or inhibiting a cell, altering its metabolism, changing how excitable the cell is, changing what proteins are produced by the cell, and much more.

Common receptors include channel receptors; G-protein coupled receptors; enzyme coupled receptors; and steroid receptors.

Channel receptors (ionotropic receptors) alter the excitability of cells. They are bound to ion channels and directly change the voltage of the cell, therefore causing it to become more or less excitable.

G-protein coupled receptors (metabotropic receptors) are the most versatile and can essentially do anything to the cell when activated. They can open or close ion channels to change cell excitability, activate enzymes to change cell metabolism and initiate intracellular changes, initiate gene transcription to influence the production of certain proteins and much more.

Enzyme coupled receptors can activate enzymes that cause changes within the cell to alter its functioning.

Steroid receptors exist within the cell and can therefore be only activated by certain molecules that can pass through the cell wall first. Once activated, they then bind to DNA to influence the activation of certain genes and induce protein production.

How drugs affect receptors in the brain

Most drugs, including nootropics, act on receptors to enhance, mimic, or inhibit the effects of neurotransmitters. The main types of drugs include agonists, antagonists, inverse agonists and allosteric modulators.

Agonists. Agonists bind to receptors and activate them. In this way they are mimicking the neurotransmitter. In fact, most agonists share very similar structures to the neurotransmitters they are mimicking. An example of an agonist is alcohol, which is a GABA receptor agonist.

Antagonists. Antagonists bind to receptors and prevent them from being activated by the neurotransmitter. However, this doesn’t mean they are the opposite of agonists, stopping activity of the receptors. Certain receptors operate without any neurotransmitter binding. When a neurotransmitter does bind and activate the receptor, it simply produces a stronger effect. With these types of receptors the antagonist does not stop the basal activity, but instead prevents the enhanced activity caused by the neurotransmitter. An example of an antagonist is beta-blockers used for hypertension. These drugs inhibit the beta noradrenergic receptor.

Inverse agonists. The type of drug that produces the opposite effect to agonists is the inverse agonist. The inverse agonist not only causes the same effect of the antagonist by preventing the neurotransmitter from having an effect, but it also stops all activity of the receptor. In fact, many drugs that were once thought to be antagonists are actually inverse agonists.

Allosteric modulators. An allosteric modulator is different in that it does not activate or inhibit a receptor, but alters the strength of its effect when activated. A positive allosteric modulator enhances the effects of the neurotransmitter binding, while a negative allosteric modulator suppresses the effects. An example of a positive allosteric modulator is benzodiazepine, which is a sleeping pill. This drug acts at the GABA receptor to enhance the effects of GABA.

As you can see, drugs can alter the functioning of receptors as a way of eliciting specific changes to the functioning of the brain. Nootropic drugs also follow these rules and affect the receptors in the brain in the same way but with the sole purpose of enhancing your mental performance.


As you can see, the brain operates in a very complex way. I hope that through this article you have developed a basic understanding of how neurons communicate in the brain and how drugs operate to alter communication and therefore alter function. Using this new information and understanding of terminology relating to pharmacology, you should have all the resources you need to pursue your own research into nootropics. That way when you decide to experiment with cognitive enhancement though the use of nootropics, you will have full confidence about what it is you are taking and how it is actually affecting you.

Posted in Experience, Mind
One comment on “How nootropics work: A beginner’s guide to pharmacology
  1. Claribel says:

    Wow, amazing blog layout! How long have you been blogging
    for? you make blogging look easy. The overall look of your
    site is fantastic, as well as the content!

Leave a Reply

Your email address will not be published. Required fields are marked *


Subscribe to Cultivated Self

Enter your email address to subscribe and receive notifications of new posts by email.