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Feeling shy, afraid of strangers? Hormone under study may help

Imagine yourself cuddled up in a warm embrace, protected, beloved, at peace with the world. Now imagine you could put that feeling in a bottle of nasal spray and sniff it when, say, you had to give a speech or go to a party full of strangers.

''It could be like social Viagra," said Andreas Meyer-Lindenberg, an investigator at the National Institute of Mental Health.

He was talking about oxytocin, a hormone long known for its effects in the human body; it helps spur labor contractions, breastfeeding, and orgasm. It has also long figured in research on bonding in animals, including landmark findings that it encourages monogamy and parental love in rodents.

Researchers now report that they can boost oxytocin in the human brain using a nasal spray. And when they do, trust seems to rise and social fear seems to abate, raising the possibility that oxytocin-based drugs might eventually help people with mental illnesses that involve exaggerated fear of others, from crippling shyness to autism and schizophrenia.

This month, Meyer-Lindenberg and others reported in The Journal of Neuroscience that when young men snorted oxytocin -- allowing it to cross the blood-brain barrier -- brain scans showed that fear centers became less responsive to threatening faces.

And this summer, the journal Nature published research showing that when subjects played a game that hinged on trust, those who had snorted oxytocin were much likelier to trust other players than those who had not.

The two studies fit nicely together and with other recent research, said Thomas Insel, director of the National Institute of Mental Health and one of the pioneers in research on oxytocin and rodent bonding. For example, he said, brain scans suggest that the fear centers in the brains of autistic people are hypersensitive in social situations, so perhaps oxytocin could help quiet them.

''I think one take-home from this is that it would be worth a try," he said.

Oxytocin research has been reaching the kind of critical mass that all but guarantees that pharmaceutical companies will be seeking to develop oxytocin-based drugs, said Robert Ring, a neuroscientist and oxytocin researcher at Wyeth Pharmaceuticals in Princeton, N.J.

Ring reported at last month's Society for Neuroscience conference that oxytocin or a similar molecule reduced anxiety in mice subjected to a variety of stressful situations, such as standing on an open, elevated platform.

''These results suggest that the development of oxytocin-like drugs may offer a novel way to treat anxiety disorders in humans," he said. Oxytocin ''has been shown to reduce anxiety, to increase pain thresholds, and to lower levels of stress hormones. It is truly one of the body's most amazing molecules."

He declined to say whether Wyeth was developing an oxytocin-like drug but noted that oxytocin in the form used in the recent experiments was far from ideal: People tend to prefer a pill to a spray, and the effects of the spray are short-lived.

On the other hand, he said, most panic attacks and phobias involve acute situations, so a quick, short-acting substance may be useful.

The synthetic oxytocin used in the experiments has been around so long that it is available as a generic drug. It is no longer sold in the United States, though European women still use it to boost breastfeeding, said Paul Zak, one of the authors of the trust paper in Nature.

The dose needed to produce effects on trust was large -- subjects took about three teaspoonsful up their noses. But it appears to be quite safe, said Zak, who is director of the center for Neuroeconomic Studies at Claremont Graduate University in California.

The biggest side effect is that perhaps 20 percent of the men who take it get erections, he said, and, of course, pregnant women would want to avoid it because it could trigger contractions.

Zak agreed that oxytocin seems to hold promise for psychiatric patients but argued that it might be best to harness the brain's own oxytocin -- through methods like petting animals -- or to use an oxytocin-like drug in conjunction with therapy to retrain a patient's oxytocin responses. It may not be wise to raise base-line oxytocin levels, he said, because it might make a person too gullible and a ''target for predation."

On that score, a body spray on the market called ''Liquid Trust," is advertised as containing oxytocin that will induce unconscious trust in all who encounter you. But Zak said it's ''totally bogus," because sniffing oxytocin from someone's shirt collar will not get enough of the hormone to the brain. It's also available without a prescription -- unlike the real stuff -- he said, and overpriced: ''Liquid Trust" costs $49.95 for a two-month supply, while Zak and his colleagues made their inhalers for about $5 each.

The new work on oxytocin is spurring other warnings.

Some researchers note that it may have potential as a date-rape drug, since oxytocin is involved both in trust and in sexual arousal.

In Nature, the prominent neuroscientist and author Antonio Damasio spun an imaginary scenario in which politicians sprayed the crowds at political rallies with oxytocin to inspire trust. But he countered that current methods in marketing and political persuasion probably already manipulate natural oxytocin levels anyway.

For now, researchers are much more interested in the potential good that oxytocin can do.

Some speculate that oxytocin might be able to help new mothers who have trouble bonding with their babies or orphans whose psychic scars from neglect make it hard for them to love adoptive parents.

Markus Heinrichs, one of Zak's Swiss collaborators on the Nature letter, is already testing oxytocin on patients with social phobias, including one study that combines the hormone spray with cognitive behavioral therapy. Results should be in next spring, he said in an e-mail from the University of Zurich.

Meyer-Lindenberg said that he and others were preparing to try oxytocin on autistic people. ''We've never had even an inkling of a drug that might be able to treat a core symptom of autism," he said, ''so there's at least a hope that might be possible."

Carey Goldberg is reachable at goldberg@globe.com.

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