Individuals suffering from hay fever understand that histamine stimulates an immune response in various parts of the body. Interestingly, recent research shows that histamine plays a distinct role in the brain, where elevated levels can enhance memory accuracy by approximately 10%.

“We believe it enhances something known as excitement associated with novelty,” explains
Michael Colwell from Oxford University. “It affects how alert we are when encountering new stimuli in our environment.”

There’s substantial evidence that the brain contains receptors specifically for histamine. “These receptors are concentrated around areas crucial for learning and memory,” Colwell notes. Animal studies further support the correlation between
histamine and learning.

This link may clarify some side effects associated with early antihistamines, as elaborated in
academic research. “Many older antihistamines penetrated the brain,” Colwell explains. “Consequently, they appeared to impair memory, which is a common issue for long-term users.”

But what happens when histamine levels rise in the brain? Previously, there was no method to examine this in humans until Colwell and his team discovered that an existing narcolepsy medication, pitolisant, could achieve this. It binds to histamine-3 receptors, raising histamine levels throughout the brain.

In their study, the team enlisted 60 volunteers, administering pitolisant to half of them, while the others received a placebo. MRI scans revealed that subjects treated with pitolisant exhibited enhanced connectivity between the histamine-producing regions and the hippocampus, an essential area for memory. These volunteers were also 11% more accurate in recalling learned information during scanning.

However, Colwell cautions against using pitolisant as a “smart drug.” “It significantly impacts sleep, and I suspect that prolonged use might ultimately worsen memory.”

Roland Seifert
from Hannover Medical University in Germany suggests the rarity of pitolisant misuse as a cognitive enhancer, given the difficulty in accessing it. He emphasizes that findings in animal models likely reflect similar trends in humans, signaling potential for targeting histamine receptors in treating neurological disorders.

Those using pitolisant for genetic conditions such as narcolepsy or Prader-Willi syndrome have reported increased alertness.
Holger Stark, who collaborated on the drug’s development at Heinrich-Heine University in Düsseldorf, states, “In cases where cognitive function suffers due to illness, pitolisant has shown promise in reversing cognitive decline and enhancing alertness. However, in most scenarios, the goal was to normalize function rather than to exceed typical cognitive levels.”

The dual effects of histamine in the body illustrate evolution’s resourcefulness. “This reflects how economical the human body can be,” Colwell concludes.