Polarised light micrograph of crystals of the chemical histamine
ALFRED PASIEKA/SCIENCE PHOTO LIBRARY
In most of the body, histamine triggers an immune response, as people with hay fever know only too well. But in the brain, it seems to have a completely different role, with a small experiment demonstrating that boosting histamine levels improves the accuracy of our memory by around 10 per cent.
“We think it’s changing something called novelty-linked arousal,” says Michael Colwell at the University of Oxford. “So, how alert we feel when we see new things in the environment.”
It’s long been known that there are receptors in the brain for detecting histamine. “They are densely packed around areas of the brain which are involved in learning and memory,” says Colwell. Animal studies support the idea that histamine is involved in learning.
This might explain some of the memory-related side effects of early antihistamine drugs, says Colwell. “A lot of those older ones got into the brain,” he says. “They would have made people less able to remember things, which you often see when people were taking those antihistamines for a long time.”
But what happens if the levels of histamine in the brain increase? There hadn’t been a way of testing this in people, but Colwell and his colleagues realised an existing drug used to treat narcolepsy, called pitolisant, has this effect. It binds to what are known as histamine 3 receptors and raises the molecule’s levels throughout the brain, he says.
To put it to the test, his team recruited 60 volunteers and gave half of them pitolisant and half a placebo. They then imaged their brains in an MRI scanner while they did various memory tests. The scans showed that in those given pitolisant, there was greater connectivity between the parts of the brain where histamine is made and the hippocampus, an area involved in memory. These people were also 11 per cent more accurate in retrieving information learned while they were in the scanner.
But it would be a mistake to try to use pitolisant as a “smart drug”, says Colwell. “I would imagine it’s going to really affect sleep, and that’s going to make your memory much worse in the long term.”
Roland Seifert at Hannover Medical School in Germany says there’s little danger of pistolisant being abused as a smart drug, as it should be very difficult for people to get hold of. He adds that the findings confirm that the results in non-human animals apply to people, too, and that this may boost interest in treating various brain conditions by targeting histamine receptors.
People who take pitolisant to help treat narcolepsy or a genetic condition called Prader-Willi syndrome have previously reported improved attention and alertness, says Holger Stark at Heinrich Heine University in Düsseldorf, Germany, who helped create the drug. “A recurring finding has been that pitolisant can help restore impaired cognitive function and improve attention when these are compromised by disease,” he says. “In most cases, however, the effect has been to normalise impaired function rather than to enhance cognition beyond normal levels.”
The fact that histamine has two such different effects in the body also shows how evolution repurposes things. “I think the bigger picture is that this shows how economical the human body is,” says Colwell.
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