December 22, 2021 9:00 pm


Despite its crucial role, histamine’s impact on the nervous system often goes unnoticed.

The nervous system, composed of the central and peripheral nervous systems, controls essential body functions to restore health.  The autonomic nervous system is part of the peripheral nervous system.

It quickly sends signals to ensure the body responds to stimuli, maintaining homeostasis and restoring health. One of those signals is histamine.  This explains why histamine symptoms appear so diversely throughout the body.

Therefore, managing histamine levels is vital to restoring health.

In this blog post, I explore the fascinating interplay between histamine and the nervous system, revealing how this molecule unexpectedly impacts your health.

Nervous System

The Nervous System: A Hidden Source of Histamine

Histamine is crucial in the body’s evolutionary protective system, responding to danger or the cell danger response.

It regulates various body functions, and when physiological stress occurs—such as dehydration, prolonged fasting, blood loss, or severe infection—the body releases histamine.

Similarly, during emotional stress, histamine mediates the release of hormones and other neurotransmitters, like norepinephrine, as part of the stress response.

Consequently, this response arouses the body, conserves energy, and disables pain and reward learning, allowing the body to focus solely on responding to the perceived danger.

Typically, the histamine system maintains tight regulation.

However, the system can become dysregulated if stressors exceed the nervous system’s capacity to process them. In such cases, the nervous system, along with histamine release under its control, acts as if there is danger when there is none.

This misresponse leads to various symptoms associated with histamine intolerance

Therefore, understanding the complex interaction between the nervous system and histamine is essential for managing conditions related to this dysregulation and maintaining overall health and well-being.

How The Nervous System and Histamine Affects Brain Function

Histamine produced in the body does not pass the blood-brain barrier. 

Instead, the brain synthesises histamines from histidine in the bloodstream and deactivates any excess through methylation. Afterwards, histamine is stored inside neurons and released upon stimulation.

Furthermore, histamine acts as a neurotransmitter in the brain, sending signals throughout the central nervous system. The autonomic nervous system delivers histamine to targeted areas. Consequently, these target sites determine the type of symptoms an individual with histamine intolerance will experience.

Importantly, research in 2024 identified that diamine oxidase, traditionally known for regulating histamine in the gut, also affects the brain. This research suggests that the interplay between the nervous system and the brain is more complex than previously thought. 

Histamine receptors, H1, H2, H3, H4, Histamine Intolerance, Nervous system, Alison Vickery, Health,. Australia

Understanding Histamine's Key Players: The Four Receptors

Four known receptors for histamine are H1R, H2R, H3R, and H4R. The first three are widely present in the brain, while H4R is not.

Firstly, H1R excites neurons in the brain and is mainly responsible for arousal and awakening. This explains why H1R antihistamines that cross the blood-brain barrier (though not all do) sedate the brain.

Additionally, H2R excites neurons and is primarily responsible for perception, learning, pain, reward, and neuroplasticity. This is why H2R histamines crossing the blood-brain barrier can affect a person’s pain perception.

In contrast, H3R is inhibitory and controls the release of neurotransmitters, including histamine, from brain neurons. Consequently, H3R drugs, along with methylation, are promising targets for addressing histamine dysregulation in the brain.

Moreover, H4R is excitatory and controls the release of neutrophils from the bone marrow and white blood cells. It is not found within the brain but communicates with it via the nervous system.

Therefore, these histamine receptors, H1, H2, and H3, play vital roles in assessing danger. They communicate via the nervous system, involving the H4 receptor and the immune system. In turn, they also explain the wide-ranging role of histamine in the body. 

Histamine, Nervous system

How the Nervous System and Histamine Impact the Body

Wide-ranging symptoms characterize histamine intolerance due to the effects of histamine signaling throughout the body via the nervous system. Common histamine symptoms include:

Allergic Reactions

Firstly, histamine plays a crucial role in the body’s immune response. It is released by mast cells and basophils during allergic reactions and helps to mediate inflammation and other immune responses.

Stomach Acid Regulation

Next, histamine regulates stomach acid production by binding to H2 receptors in the stomach lining. This action is crucial for digestion, helping break down food and kill harmful bacteria. Taking H2 antihistamines blocks the production of stomach acid, exposing us to infections.

Gastrointestinal Motility

Additionally, histamine influences gastrointestinal motility. It stimulates smooth muscle contraction in the intestines, affecting the movement of food through the digestive tract.

Adrenal Fatigue

Moreover, histamine regulates the adrenal glands and hormone release under stress, leading to adrenal fatigue in histamine intolerance.

Estrogen Dominance

Furthermore, histamine and estrogen promote each other’s release, worsening histamine intolerance before menstruation and during peri-menopause.

Thyroid Issues

Additionally, histamine controls thyroid hormone release, affecting energy metabolism and causing thyroid issues.

Cardiovascular Issues

Moreover, histamine increases blood pressure and decreases heart rate, often causing tachycardia.


Importantly, histamines regulate sleep, causing insomnia or hypersomnia. Histamine levels vary with the sleep-wake cycle, making insomnia a dominant symptom.


Histamine also affects noradrenaline and serotonin release in the brain, potentially leading to depression. Many antidepressants block histamine receptors. Recent research shows that people with major depressive disorder have low diamine oxidase levels.


Similarly, histamine causes anxiety and signals danger. People with histamine intolerance often feel “free-floating anxiety.”

Addictions and Compulsive Behaviours

Histamine further influences addiction and compulsive behaviors. Addictive substances interfere with histamine activity, and withdrawal can cause severe symptoms.

Metabolic Syndrome

Moreover, histamine regulates leptin, which affects appetite. As a result, histamine levels can influence obesity, insulin resistance, and high cholesterol.

Appetite Control

Additionally, brain histamine regulates appetite. H3R antagonists suppress food intake, while H1R antagonists stimulate appetite, affecting weight management.

Pain Perception

Furthermore, histamine mediates itching and pain. It promotes pain relief through H2R and increases pain through H1R. Blocking H3R can have analgesic effects.

Airway Constriction

Moreover, histamine can cause airway constriction, which is the narrowing of the airways in the lungs. This action is significant in conditions like asthma and allergic reactions.

Motion Sickness

Lastly, histamine plays a role in motion sickness and vomiting. Anti-histamines effectively treat these symptoms.

By recognizing these diverse symptoms and their causes, you can better manage histamine intolerance and improve your overall health and well-being.

infections, histamine intolerance, mast cell activation, diamine oxidase, autoimmunity, Alison Vickery, Health, Australia


In conclusion, understanding the profound relationship between histamine and the nervous system opens new pathways to restoring health.

Histamine’s role extends beyond allergic reactions; it influences our mood, digestion, and overall well-being.

You can better manage symptoms and restore your health by recognising the intricate dance between histamine and the nervous system, particularly the autonomic nervous system.

As you navigate your health journey, remember histamine’s vital role and explore ways to maintain balance within your body.

Ultimately, your well-being is worth it.

You can learn more about managing histamine intolerance on these blog posts.

Follow me on Instagram and Facebook to continue the conversation.

Additional Reading