Histamine, perimenopause, and ADHD: What’s the connection?
When we think of histamine, most of us picture allergies, hay fever, hives, or reactions to food. But histamine is far more than just a trigger for itchy eyes or sneezing.
For some women with ADHD, particularly during perimenopause, histamine may play an unexpectedly important role in how symptoms show up and fluctuate.
This emerging area of research is offering new insights into why ADHD might feel different, or harder to manage, during midlife, and it could help women feel more empowered to understand and support their bodies in a more holistic way.
What is histamine?
Histamine is a naturally occurring chemical that acts as a neurotransmitter (a chemical messenger in the brain) and a signalling molecule in the immune system. It helps regulate a wide range of bodily functions including:
sleep–wake cycles
mood and cognition
digestion and appetite
immune response and inflammation
oestrogen balance
When histamine levels become dysregulated, it can result in a wide range of symptoms, many of which overlap with ADHD or worsen it. This includes things like anxiety, irritability, brain fog, disrupted sleep, headaches, gut issues, and even sensory overload.
Why does this matter in ADHD?
ADHD is often described as a condition of executive function, but we now understand it’s also closely linked to neurotransmitter imbalances, especially dopamine and norepinephrine. But histamine is also involved in regulating alertness, attention, and arousal, and its role in ADHD is gaining attention in the research community.
Recent studies have found that changes in the histamine H2 receptor in the brain may lead to hyperactivity, impulsivity, and difficulties with attention. Animal models show that histamine receptor deficiencies produce ADHD-like behaviours (An et al., 2025; Kaneko et al., 2024).
There’s also growing evidence that people with ADHD may have increased mast cell activation, a process that releases histamine during immune responses, and associated neuroinflammation, which can impact memory, emotional regulation, and cognitive clarity (Shirasaka et al., 2020).
Histamine intolerance and genetic factors
Some individuals with ADHD may have difficulties breaking down histamine, often due to genetic variations in enzymes such as diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT). When these enzymes don’t function properly, histamine can build up in the body and contribute to what’s known as histamine intolerance.
Symptoms of histamine intolerance can include:
bloating, diarrhoea, or reflux
headaches or migraines
low mood or anxiety
sleep disturbances
skin flushing or itching
These issues can easily be mistaken for unrelated problems, but in women with ADHD, they may be part of a much broader picture of neuroimmune dysregulation (Duelo, 2022; Campbell, 2022).
Hormones, perimenopause, and histamine
This becomes particularly important during perimenopause, when oestrogen levels begin to fluctuate. Oestrogen stimulates the release of histamine and also inhibits the DAO enzyme, which is responsible for breaking histamine down. This means that during midlife, some women may become more sensitive to histamine without realising why.
So, if you’re noticing more ADHD symptoms like:
increased brain fog
poor sleep
heightened anxiety
worsening gut symptoms
irritability or overwhelm
…it could be worth considering whether histamine is contributing to the picture, particularly if you also experience allergy symptoms or food sensitivities.
Links with MCAS
Mast Cell Activation Syndrome (MCAS) is a condition where mast cells release excessive or inappropriate amounts of histamine and other inflammatory mediators. It’s increasingly being explored in connection with neurodevelopmental conditions, including ADHD. For some individuals, especially women in perimenopause, MCAS may be part of the puzzle behind chronic inflammation, hypersensitivity reactions, and fluctuating cognitive or emotional symptoms. Symptoms of MCAS can mirror or exacerbate ADHD traits such as brain fog, anxiety, sleep disturbances, and sensory issues.
Emerging research also suggests that mast cell instability may contribute to neuroimmune dysregulation, particularly when combined with hormonal shifts and impaired histamine breakdown (Critchfield et al., 2021). While MCAS is still under-recognised and often misdiagnosed, awareness is growing in both allergy and neurodivergent communities. If symptoms appear multisystemic or unpredictable, MCAS may be worth discussing with a knowledgeable practitioner.
What can help?
There’s still a lot we don’t know, and more high-quality research is needed. However, some women find relief by:
Tracking histamine-rich foods (e.g. fermented foods, aged cheeses, wine, cured meats)
Looking for patterns in ADHD symptoms around hormonal shifts or allergy flare-ups
Discussing DAO/HNMT testing or mast cell involvement with a knowledgeable GP or specialist
Seeking support for gut health and histamine metabolism alongside ADHD care
Most importantly, recognising that ADHD isn’t just about dopamine or attention, it’s about the whole body. And for many perimenopausal women, that includes complex interactions between the brain, hormones, immune system, and gut.
If your ADHD symptoms have changed as you’ve got older, or if you’ve noticed increasing sensitivities to food, weather, or stress, you are not imagining it. The interplay between histamine and ADHD is a growing field that may help explain why things feel harder, and also offer new avenues for support.
As always, it’s important to speak with a qualified healthcare professional if you’re experiencing significant symptoms or suspect histamine intolerance.
And remember, you are not broken. You’re navigating a beautifully complex, interconnected system, and the more we understand it, the more compassion and clarity we can bring to ourselves and others.
References
An, D., Kaneko, S., Sudo, H., Sugimoto, Y. & Yanai, K. (2025). Histamine H2 receptor deficiency causes hyperactivity and inattention in mice: Implications for ADHD. Neuron, 113(6), 1054–1068. https://doi.org/10.1016/j.neuron.2024.06.004
Shirasaka, Y., Yamashita, M., Hashimoto, K., et al. (2020). Neuroinflammation and mast cell activation in neurodevelopmental disorders. Experimental and Therapeutic Medicine, 20(2), 1255–1262. https://doi.org/10.3892/etm.2020.8807
Duelo, A. (2022). DAO enzyme and ADHD: Histamine’s hidden role in executive dysfunction. Retrieved from https://www.adrianaduelo.com/en/dao_adhd_histamine
Campbell, B. (2022). Histamine intolerance and ADHD: The connection. Retrieved from https://drbeckycampbell.com/histamine-intolerance-and-adhd-the-connection
Kim, S. Y., Kim, B. N., Kim, J. W., et al. (2023). Allergic diseases and ADHD in children: A population-based study and treatment response to antihistamines. Journal of Clinical Medicine, 12(6), 1659. https://doi.org/10.3390/jcm12061659
Critchfield, J. W., Wilcox, A., & Laidlaw, T. M. (2021). Mast cell activation and neuropsychiatric symptoms in mast cell activation syndrome (MCAS): A potential role in neurodevelopmental and mood disorders. Frontiers in Neuroscience, 15, 671138. https://doi.org/10.3389/fnins.2021.671138