Elevated histamine levels may contribute to symptoms that resemble or worsen ADHD in some individuals.
Histamine isn’t just involved in allergies; it also acts as a neurotransmitter in the brain, influencing attention, wakefulness, mood, and cognition. When histamine levels are too high—either due to overproduction or poor breakdown (as in histamine intolerance)—it can lead to symptoms like:
- Brain fog
- Hyperactivity
- Difficulty concentrating
- Sleep disturbances
- Mood swings or irritability
Some researchers have noted that these symptoms overlap with those of ADHD, and there’s growing interest in how histamine dysregulation might play a role in neurodevelopmental conditions. For example, the H3 histamine receptor in the brain helps regulate the release of other neurotransmitters like dopamine and norepinephrine—both of which are central to ADHD.
That said, histamine isn’t considered a primary cause of ADHD, but it may be a contributing factor in some people, especially those with histamine intolerance, mast cell activation syndrome (MCAS), or food sensitivities.
There have been some intriguing case studies and clinical observations suggesting that antihistamines may help reduce ADHD-like symptoms in certain individuals—especially those with histamine intolerance or mast cell activation issues.
While antihistamines aren’t a standard treatment for ADHD, some people with overlapping symptoms—like brain fog, hyperactivity, or poor focus—have reported improvements when using:
- H1 blockers (like cetirizine or loratadine)
- H2 blockers (like famotidine)
- Or by following low-histamine diets.
These interventions seem to help by calming neuroinflammation and reducing histamine overload, which can affect neurotransmitters like dopamine and norepinephrine—key players in attention and impulse control.
That said, this is still an emerging field. Most of the evidence is anecdotal or from small-scale studies, so more rigorous research is needed before antihistamines could be considered a mainstream ADHD treatment.
There’s growing evidence that histamine plays a role in schizophrenia, particularly through its function as a neurotransmitter in the brain.
Histamine interacts with several brain systems that regulate mood, cognition, and perception—all areas affected in schizophrenia. Here are some key insights:
- Histamine receptors (H1, H2, H3, H4) are found throughout the brain. Alterations in these receptors—especially H1 and H3—have been observed in people with schizophrenia.
- Some antipsychotic medications block H1 receptors, suggesting that histamine signaling may influence symptoms like agitation or sleep disturbances.
- There’s emerging research into H2 receptor antagonists (like famotidine) as potential adjunct therapies for schizophrenia. Some early studies showed positive effects on symptoms, though the exact mechanisms are still being explored.
- The H3 receptor, which regulates the release of other neurotransmitters like dopamine and serotonin, is of particular interest because of its role in modulating cognition and arousal—areas often disrupted in schizophrenia.
In short, while histamine isn’t the main player in schizophrenia, it’s part of a complex neurochemical web that researchers are still untangling.
https://www.medcentral.com/behavioral-mental/adhd/histamine-and-psychiatric-disorders
https://link.springer.com/article/10.1007/s12264-023-01122-w
https://mthfrgenehealth.com/histamine-activity-of-the-nervous-system-mechanisms-and-effects/
A person can have elevated histamine levels without having high cortisol. While both histamine and cortisol are involved in the body’s stress and immune responses, they operate through different systems and don’t always rise or fall together.
- Histamine is released primarily by mast cells and basophils in response to allergens, infections, or certain foods. If the body can’t break it down efficiently—due to enzyme deficiencies (like DAO or HNMT), gut issues, or genetic factors—it can build up and cause symptoms like headaches, rashes, anxiety, or digestive problems.
- Cortisol, on the other hand, is a hormone produced by the adrenal glands in response to stress. It generally has an anti-inflammatory effect, and in some cases, it can actually suppress histamine release.
So, someone with histamine intolerance or mast cell activation might experience high histamine symptoms even if their cortisol levels are normal—or even low. In fact, chronic stress or adrenal fatigue can lead to low cortisol, which might reduce the body’s ability to counteract histamine’s effects.
If you're noticing histamine-related symptoms but your cortisol levels seem fine (or even low), it could be worth exploring histamine metabolism, gut health, or mast cell activity.
There are tests that can measure histamine levels in your body—typically through blood or urine samples.
1. Blood Test: This measures the concentration of histamine in your plasma. It’s often used when doctors suspect conditions like mast cell activation syndrome (MCAS), anaphylaxis, or histamine intolerance. Timing is important—especially if symptoms are acute—because histamine levels can spike and fall quickly.
2. Urine Test: A 24-hour urine collection can detect histamine metabolites, which may give a broader picture of histamine activity over time. This is useful for identifying chronic imbalances.
3. DAO Enzyme Testing: Since the enzyme diamine oxidase (DAO) helps break down histamine, some tests also measure DAO activity to assess whether your body can properly metabolize histamine.
These tests aren’t always part of standard panels, so they’re often ordered by specialists—like allergists, immunologists, or functional medicine practitioners.
If you’re experiencing symptoms like flushing, headaches, hives, or digestive issues, testing might help pinpoint whether histamine is playing a role.
Some people who were diagnosed with ADHD and other mental health problems, completely recovered after learning what their allergies were and treated the allergies or changed their diets. Same is true for IBS.
However, we’re only talking about a segment/portion of patients. Many other people have IBS, ADHD, schizophrenia and other conditions without having problems with histamine. But I firmly believe that histamine testing and allergy testing should become standard for many conditions.
In addition to too much histamine, another major cause of these same health problems and many other health problems is mineral and vitamin deficiency caused by poor intestinal health, lack of healthy gut bacteria, over consumption of unhealthy foods/drinks and not enough consumption of healthy foods/drinks.
We can also add to this list, lack of natural sunshine, exercise, fresh air and human interaction.