Brain chemistry and hormonesHow do tiny chemical messages shape our moods and desires, and how does addiction hijack them?

1What is brain chemistry?

Every thought you have, and every feeling of fear, comfort or longing, begins with an electrical signal travelling along a nerve cell, which is then converted into a chemical message that crosses to the next cell. These chemical messages, together with the hormones released by glands into the blood, are what we simply call "brain chemistry."

The brain contains tens of billions of nerve cells, and each one connects to thousands of others through tiny meeting points called synapses. At each synapse, the cell releases chemical molecules that cross a very small gap and bind to receptors on the neighboring cell, like a key fitting a lock, delivering a message: become active, calm down, or adjust your response.

Scientists have so far identified at least a hundred neurotransmitters and more than fifty hormones in the body, according to the Cleveland Clinic health library. But a limited number of them are the most relevant to mood, motivation, sleep, stress and addiction, and these are the ten substances for which we have written a full guide in this section.

It is important to understand from the start that brain chemistry is not a tank that fills up or empties of a single substance. It is closer to an orchestra: each instrument has its role, and the meaning comes from how they play together, from the circuits they play in, and from the experiences that retune them every day.

2What is the difference between a neurotransmitter and a hormone?

Both are chemical messengers, and the main difference lies in the route they take, the distance they travel and the speed at which they work. A neurotransmitter is released from the end of a nerve cell directly to its neighbor, while a hormone is released from a gland into the blood and travels to any organ that carries its receptors.

But the boundary between the two categories is not sharp. The same substance can be a neurotransmitter inside the brain and a hormone in the blood: norepinephrine is released by nerves in the brain and also secreted by the adrenal gland; oxytocin is a hormone released into the blood during childbirth and breastfeeding and, at the same time, a chemical messenger inside the brain; and endorphins work both ways. For this reason we have classified each substance here by its best-known role, and we mention its other roles on its own page.

3What is the brain's reward system?

The reward system is a set of deep neural circuits, the most important of which is a pathway that starts in a region of the midbrain and ends in areas involved in motivation and learning, within what the US National Institute on Drug Abuse calls the "basal ganglia." Its job is to make us repeat what helps our survival: eating when we are hungry, sleeping, connecting with people we love, and getting work done.

The best-known messenger in this circuit is dopamine. But the common belief that it is the "pleasure chemical" is inaccurate; research suggests that a burst of dopamine is closer to a learning signal that tells the brain: "This matters, remember it and repeat it." That is why dopamine rises with the anticipation of a reward, not only with receiving it.

1. Cue: the smell of food, a phone notification, or a place associated with a pleasant experience.
2. Anticipation: dopamine signals rise, and the person feels desire and the drive to act.
3. Reward: the person gets the thing, and other substances such as endorphins join in to produce a sense of relief and satisfaction.
4. Learning: the brain links the cue, the behavior and the reward, making the behavior easier to repeat next time.

The reward system works under the supervision of the prefrontal cortex at the front of the brain, the area for planning, decision-making and impulse control, and in parallel with the stress circuit, in which substances such as cortisol and norepinephrine are active. The balance among these three circuits is what allows us to want something and then decide rationally whether or not to pursue it.

4Which kinds of brain chemistry do we explain here?

In the Eradah guide we have divided the ten substances into two groups: neurotransmitters that work mainly inside the brain, and hormones that glands release into the blood and that affect the brain and body together. Each substance has a full guide explaining what it is and what it does, followed by pages on the symptoms of low or high levels, natural ways to support it, and its relationship to addiction where relevant.

5Neurotransmitters

Fast messages between nerve cells: dopamine, serotonin, GABA, glutamate, norepinephrine and endorphins. This is the arena in which almost all drugs act.

The complete neurotransmitter guide →

6Hormones

Gland messages that travel in the blood: cortisol, oxytocin, melatonin and adrenaline. They regulate stress, bonding, sleep and emergencies, and are strongly affected by substance use and withdrawal.

The complete hormone guide →

7Comparisons and frequently asked questions about brain chemistry

Stand-alone answers to questions that come up often about the brain's neurotransmitters and hormones:

8How do brain chemicals work together?

No substance works alone. Glutamate is the brain's main accelerator, GABA is its main brake, and most nerve activity is the result of the balance between them. Dopamine, serotonin and norepinephrine are closer to tuning dials that adjust the strength and direction of signals in the circuits for mood, motivation and attention.

• Sleep: involves melatonin, which signals nighttime, and GABA, which calms activity, along with a drop in norepinephrine and cortisol at night.
• Stress: the brain releases norepinephrine, then the adrenal gland quickly releases adrenaline and, after it, cortisol through the HPA axis.
• Mood: influenced by serotonin, dopamine and norepinephrine, but also by inflammation, sleep, hormones, circumstances and thoughts.
• Pain and comfort: endorphins relieve it, and oxytocin strengthens the sense of safety around people we trust.

That is why affecting one substance, with a medication or a drug, inevitably moves others. Alcohol, for example, enhances the effect of GABA and weakens glutamate, while at the same time raising dopamine in the reward circuit; and when it is stopped suddenly after long-term use, this balance is disrupted in the opposite direction.

9Can brain chemistry be measured with a blood test?

This is one of the questions we receive most often, and the honest answer is: neurotransmitters inside the brain cannot be measured by a blood or urine test in routine medical practice. The brain is protected by a blood-brain barrier that separates it from the circulation, and many of these substances are also made and act outside the brain. About 90% of the body's serotonin is made in the gut, so its level in the blood does not tell us what is happening in the mood circuits.

10Are mental illnesses just a "chemical imbalance" in the brain?

For years the claim spread that depression is caused by "low serotonin" or a "chemical imbalance." The truth is more complicated. A comprehensive review published by Moncrieff and colleagues in Molecular Psychiatry in 2022 concluded that the available research does not provide consistent evidence that depression results from lowered serotonin, while the researchers cautioned that many of the studies they reviewed were of limited quality.

Harvard Medical School summarizes the picture by saying that depression does not arise simply from too much or too little of one particular chemical, but from the interaction of many factors: how the brain regulates mood, genetic predisposition, life stresses, physical illnesses, and certain medications and substances. Thousands of chemical interactions take part, not one substance.

The practical lesson here is that brain chemistry is an important part of the picture, but it is not the whole story. That is why good treatment usually combines medication when needed, psychotherapy, better sleep and activity, and family support. The details are in the depression guide and on the page about symptoms of serotonin deficiency, which discusses this debate fairly.

11How do drugs change brain chemistry?

Almost every drug affects one or more of these chemical messages. According to the National Institute on Drug Abuse, some substances, such as heroin and cannabis, resemble the body's natural neurotransmitters in structure and activate receptors directly, while others, such as cocaine and amphetamines, force cells to release huge amounts of neurotransmitters or block their reabsorption.

With repetition the brain adapts: the number or sensitivity of receptors falls, so tolerance appears; the stress circuit becomes active, so distress and anxiety appear when the substance is absent; and the prefrontal cortex's control over impulses weakens. These changes are what make addiction a brain disease and not merely "weak willpower." Each substance has a page explaining its role in detail, such as dopamine and addiction, GABA and addiction and cortisol and addiction.

Even so, the brain remains capable of recovery. With abstinence and treatment, the circuits regain a large part of their balance gradually, and the time needed varies from one substance to another and from one person to another. That is why we tell people in recovery that a dulling of pleasure and mood in the first weeks is an expected stage and not a permanent state, and it improves with regular sleep, activity, treatment and support. The reward system is also affected by behaviors, as in gambling addiction.

12How is brain chemistry related to mental illness?

Most mental disorders are linked to changes in the brain's circuits and chemical messages, but a link does not mean a single substance is the cause. Here are examples of what science knows today, worded cautiously:

• Attention-deficit/hyperactivity disorder: linked to differences in dopamine and norepinephrine circuits, and its stimulant medications act on both.
• Schizophrenia and psychosis: linked to increased dopamine activity in certain pathways, with roles for glutamate, and antipsychotics act on dopamine receptors.
• Depression and anxiety: the serotonin, norepinephrine and GABA systems and the stress axis take part, along with psychological and social factors that are no less important.
• Insomnia: melatonin and the body clock interact with stress, habits and mental state.
• Drug-induced psychosis: a clear example of how an outside substance can upset dopamine balance within a short time.

Mental illness and addiction often meet in the same person, which is called dual diagnosis, because the two share the same circuits: someone with anxiety may turn to a substance that calms them, and the substance in turn changes brain chemistry and increases the anxiety in the longer term.

13Common myths about brain chemistry

14Can lifestyle support brain chemistry?

Yes, to a reasonable degree and without exaggeration. Regular sleep, physical activity, daylight exposure, supportive relationships and a balanced diet all affect the brain's chemical systems in ways proven to varying degrees. But they complement treatment and do not replace it when there is a mental illness or an addiction.

Each substance has a page that assesses the evidence frankly and separates what is proven from what is popular without evidence, such as ways to increase dopamine naturally, ways to increase melatonin naturally and ways to lower cortisol naturally. In none of them do we mention doses of supplements or medications, because that is an individual medical decision.

15When should you see a doctor about a problem with mood, energy or sleep?

You do not need to know which chemical is "out of balance" in order to ask for help; that is the doctor's job. Ask for an assessment if you notice any of the following in yourself or someone close to you. This list is for awareness and is not a diagnosis.

• Sadness, loss of pleasure or anxiety lasting more than two weeks and affecting work or study.
• Persistent insomnia or excessive sleep, or a major change in appetite and weight without a clear reason.
• Depending on a substance, sedative or painkiller to feel "normal."
• Cravings for a substance or behavior that keep returning despite repeated attempts to stop.
• Palpitations, sweating and repeated panic attacks, or an unexplained rise in blood pressure.
• 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 psychiatrist assesses the full picture: symptoms, medical history, and the substances and medications used, with general tests to rule out physical causes, and then sets a treatment plan combining medication, psychological and family support, in complete confidentiality.