NeurotransmittersThe chemical messengers that create mood, motivation and calm, and on which almost all drugs act

1What are neurotransmitters?

Nerve cells in the brain do not touch each other directly; a very tiny gap separates them. For a message to cross this gap it needs a chemical “messenger”: small molecules released by the first cell and picked up by the second. These molecules are neurotransmitters, the language the brain uses to talk to itself and to the body.

Cleveland Clinic’s health library describes neurotransmitters as chemical messengers used by the nervous system to carry messages between nerve cells, and from nerve cells to muscles and glands. With them a person breathes, their heart beats, they move, learn, and feel fear, reassurance or desire. Scientists know of at least a hundred neurotransmitters and believe others exist that have not yet been discovered.

The difference between a neurotransmitter and a hormone is explained in detail on the main brain chemistry page. In short: a neurotransmitter is a very fast, short-range message between two neighboring cells, while a hormone travels in the blood. Some substances, such as norepinephrine and endorphins, play both roles, which is why we have placed them here, since their neural role is the more important one for mood and addiction.

2How does a neurotransmitter carry a message between two cells?

A nerve message goes through successive steps that all happen in a small fraction of a second, and understanding them is the key to understanding how psychiatric medications and drugs work, because each of them interferes in one or more of these steps:

1. Making and storing: the cell makes the neurotransmitter from raw materials, such as amino acids from food, and stores it in tiny vesicles at its tip.
2. Release: when an electrical signal reaches the tip of the cell, the vesicles open and release the neurotransmitter into the synaptic gap.
3. Binding to the receptor: the neurotransmitter binds to special proteins on the surface of the facing cell called receptors; each neurotransmitter has its own receptors, and may have more than one type of them.
4. Response: depending on the type of receptor, the receiving cell becomes active, quiets down, or changes its sensitivity to other messages.
5. Ending the message: the message has to stop, so either the neurotransmitter disperses into the surroundings, or it is taken back up into the cell that released it to be reused, or specialized enzymes break it down.

The last step in particular matters a great deal to readers of this guide. Many antidepressants work by slowing reuptake, cocaine blocks dopamine reuptake far more powerfully, and an older group of drugs works by inhibiting the enzymes that break down neurotransmitters. The mechanism is roughly the same, but the difference in intensity, speed, medical supervision and outcome is enormous.

3How are neurotransmitters classified?

Scientists classify neurotransmitters in two complementary ways: by their effect on the receiving cell, and by their chemical structure. The first is more useful for understanding mood and addiction:

By chemical structure, medical references list several groups, most notably: amino acids such as glutamate, GABA and glycine; monoamines such as dopamine, serotonin, norepinephrine and histamine; peptides, which are short chains of amino acids, such as endorphins; in addition to acetylcholine, which is usually listed in a separate category.

This classification is approximate and useful for understanding, but it is not strict. The same neurotransmitter may be excitatory in one place and inhibitory in another, depending on the type of receptor it binds to. Dopamine, for example, has two large families of receptors with different effects, which is why it is hard to describe any neurotransmitter in a single phrase such as “the happiness chemical” or “the calming chemical.”

4Types of neurotransmitters in the Eradah guide

From dozens of neurotransmitters we chose six that are most closely tied to mood, motivation, stress, pain and addiction, each with a full guide and separate pages. Here is a short card for each neurotransmitter:

5What is the difference between dopamine, serotonin, GABA and the other neurotransmitters?

The following table summarizes the main role of each neurotransmitter in this group and the addictive substances most closely tied to it. It is a summary for comparison only; the detailed information is on each neurotransmitter’s page:

The table shows that the six neurotransmitters work in pairs and networks: glutamate and GABA are the fuel and the brakes for most neural activity; dopamine directs motivation toward what the brain learns is rewarding; serotonin takes part in regulating mood and impulsivity; norepinephrine raises alertness and readiness; and endorphins ease pain and give a feeling of comfort after exertion.

6What other neurotransmitters are worth knowing?

There are important neurotransmitters we have not dedicated separate guides to at this stage, but mentioning them completes the picture, especially since some are directly tied to substances common in Egypt:

• Acetylcholine: the first neurotransmitter discovered historically, it carries commands from nerves to muscles and takes part in attention and memory. Nicotine in cigarettes acts on one type of its receptors, and this is where its effect on the reward circuit begins.
• Histamine: known for its role in allergy, but in the brain it is a neurotransmitter of wakefulness, which is why some older allergy medications cause drowsiness.
• Glycine: an inhibitory neurotransmitter that works mainly in the spinal cord and brainstem, and it also joins glutamate in activating NMDA receptors.
• Endocannabinoids: molecules the body makes itself that bind to receptors on which the active ingredient in hashish also acts, while synthetic drugs such as Strox bind to the same receptors far more powerfully, and this is part of their danger.

This reminds us that what is written online about “the four happiness neurotransmitters” is a drastic oversimplification of a network of dozens of overlapping substances whose roles science is still discovering.

7How do psychiatric medications act on neurotransmitters?

Most well-known psychiatric medications affect one or more neurotransmitters, and this has made neurotransmitters the focus of psychiatric pharmacology since the middle of the last century. This is only an overview of drug classes, without names or doses, because choosing a medication is an individual medical decision:

But one point must be clear: that a drug acts on a neurotransmitter does not mean the illness is caused by a “deficiency” of that neurotransmitter. A comprehensive review published by Moncrieff and colleagues in 2022 concluded that the evidence does not consistently support the idea that depression results from low serotonin, yet antidepressants remain useful for many patients, and scientists are still studying their full mechanism. That is why we discuss this controversy fairly on the serotonin deficiency symptoms page.

8How do drugs change neurotransmitters?

The US National Institute on Drug Abuse explains that drugs interfere with the way nerve cells send, receive and process messages, in three main ways, to which we add a fourth way known in pharmacology:

Substances differ in which neurotransmitters they hit first, but they converge in the end on the reward circuit: most of them raise dopamine in this circuit directly or indirectly, faster and stronger than any natural reward does. This circuit is explained in the reward system section.

9Why do tolerance and withdrawal happen at the neurotransmitter level?

The brain is an organ that always seeks balance. When a substance floods a neural system with an excessive signal day after day, the brain responds with counter-adjustments: it reduces the number or sensitivity of receptors, or reduces what it makes of the natural neurotransmitter, or strengthens the opposing system. The result is that the person needs a larger amount to get the same effect, and this is tolerance.

When the substance is suddenly absent, these counter-adjustments remain alone with nothing to balance them, and withdrawal appears as a mirror image of the substance’s effect. A person used to a sedative that enhances GABA faces, on stopping suddenly, anxiety, insomnia and tremor, and seizures may occur, because the excitatory glutamate system is left without enough brakes. A person used to opioids faces a surge of norepinephrine that causes sweating, diarrhea, a fast pulse and tension.

• Alcohol and sedative withdrawal: an imbalance between GABA and glutamate, which can be dangerous and needs medical supervision. Details are in GABA and addiction.
• Opioid withdrawal: absence of natural pain relief and a surge of norepinephrine. Details are in endorphins and addiction.
• After stimulants: dulled pleasure and motivation, exhaustion and low mood. Details are in dopamine and addiction.
• Cravings and relapse: a strong memory cemented by glutamate links the substance to places and people. Details are in glutamate and addiction.

The reassuring side is that the same flexibility that let the brain adapt to the substance lets it adapt to its absence. With abstinence and treatment, receptors and neurotransmitter systems gradually move back toward balance, and the time varies from one substance to another and from person to person. This is why the first weeks need patience, support and a clear treatment plan, not judging oneself a failure.

10What are the common myths about neurotransmitters?

11When should you see a doctor about symptoms linked to neurotransmitters?

No one needs to know which neurotransmitter is “off” in order to ask for help, and there is no blood test in the clinic that measures neurotransmitters inside the brain. Seek a psychiatric medical assessment if you notice the following. This list is for awareness and is not a diagnosis.

• Loss of pleasure and motivation, or sadness or anxiety, lasting more than two weeks and affecting your daily life.
• Cravings for a substance, a sedative or a painkiller, or needing an increasing amount of it for the same effect.
• Distressing physical and psychological symptoms whenever you try to stop a substance or medication.
• Tremor, slowness or stiffness in movement that you cannot explain.
• Suspicion, hearing voices or strange thoughts, especially after using stimulants or hashish.
• Any thoughts about death or harming yourself; in this case, seek help immediately by calling 123 or the mental health support line 16328.

At Eradah, the doctor begins with a comprehensive assessment of symptoms, medical history, and the substances and medications used, then builds a plan combining medication when needed, psychotherapy and family support, with safe medical supervision of withdrawal when required, in complete confidentiality.