Histamine in the brain

One of histamine’s many functions in the body is as a neurotransmitter, where it helps regulate important brain functions such as alertness, attention, learning, memory, stress response, sleep-wake cycles, and sexual function. When the body’s histamine levels get out of control, many behavioral and psychological symptoms manifest.

While there is no solid evidence to prove a connection between histamine and mental disorders, symptoms such as hyperactivity, obsessive-compulsive behavior, panic, anxiety, and depression are often seen among those suffering from histamine imbalance.

This is a bit puzzling, since histamine does not cross the blood-brain barrier—that is, no matter how much histamine is in the blood, none of the excess is likely to enter the brain.

Histamine in the Brain

If histamine does not cross the blood-brain barrier, then the explanation for how it causes behavioral and psychological symptoms is quite simple: the brain produces its own histamine. According to studies, histamine is produced in a specific area of ​​the brain called the hypothalamus and is stored in the so-called histaminergic neurons, where it is released after stimulation.

The brain has receptors for histamine, and mental disorders result when there is an abnormality of these receptors. In general, histamine has four types of receptors, designated as H1R, H2R, H3R and H4R. Only the first three are present in the brain.

H1R excites neurons in the brain and is responsible for the sleep-wake cycle. The activation of these receptors by histamine explains why insomnia is one of the most common symptoms of histamine intolerance and how antihistamines that act on them produce a sedative effect. These receptors are also known to trigger the body's danger response, resulting in the release of the chemical norepinephrine. Norepinephrine plays a role in anxiety and depression.

H2R, like H1R, is also excitatory, but its role is primarily in perception, memory, learning, reward, pleasure and pain. This explains why antihistamines that act on H2 receptors affect our perception of pain. Addiction and compulsive disorders also have something to do with these receptors, as addictive substances such as alcohol and illicit drugs have been found to interfere with histamine's activity at H2R. Meanwhile, compulsive behaviors such as anorexia and bulimia are linked to histamine's effect on the brain's reward systems. H3R, on the other hand, inhibits neurons from releasing histamine. These receptors are also responsible for regulating the release of other neurotransmitters in the brain. Experts see drugs that target H3 receptors as a promising solution to address the effects of histamine on the brain.

Histamine and Adrenaline

    An alternative explanation for most of the behavioral and psychological symptoms of histamine intolerance, especially anxiety, is that they are generated in the body rather than the brain. This is through histamine’s ability to trigger the release of adrenaline, the main player in the body’s fight-or-flight response. Adrenaline, like histamine, cannot cross the blood-brain barrier, but it can trigger a wide range of panic symptoms, such as rapid heartbeat, sweating, shaking, shortness of breath, nausea, and anxiety.