Runner's High?

Richard Friedman, a psychopharmacologist at Weill Medical College of Cornell University, had a runner's high -- once.

"When I was young and foolish, I ran a marathon in the Smoky Mountains," he said. "I have never before or since had that kind of high, and maybe it was just the result of a near-death experience."

Bill Fox, a recreational bicyclist and an IBM research lab technician, says his exercise highs do not come easily.

"You've really got to work for this high," Fox explained, saying he usually needed two hours or more of sweaty, intense, vigorous exercise. But when the feeling comes, he said, it is just like cocaine, a drug he knows from his days as an addict.

"It has that well-being kind of feeling, that Superman kind of feeling," said Fox, of Middletown, N.Y.

Others say they never get such a feeling, no matter how hard or how much they exercise. Despite a widespread belief in the so-called runner's high, a feeling of intense euphoria that is supposed to come with vigorous exercise, the experience is not consistent or predictable. Some researchers have asked whether it exists at all.

Many say its supposed genesis, a rush of endorphins into the brain, is without scientific evidence and some say the whole endorphin-runner's-high hypothesis is the scientific version of an urban legend.

"I believe this endorphin-in-runners is a total fantasy in the pop culture," said Huda Akil, an endorphin researcher at the University of Michigan, who is president-elect of the Society for Neuroscience.

Yet only now are a few researchers rigorously examining exercise as an addictive behavior. They are finding that exercise, in rats at least, may actually be addictive but that it is not at all clear that the crucial brain chemical is an endorphin.

Pinpointing endorphins

The hypothesis that there is a runner's high and that it is caused by endorphins emerged in the 1970s, when scientists found a new class of brain chemicals that act just like morphine.

"We had meetings to decide what to call it," said Solomon Snyder, a neurobiologist at Johns Hopkins University, with a committee deciding on "endorphin." The word is an amalgam of endogenous, meaning made by the body, and morphine.

Scientists eagerly looked for evidence that the chemicals mediated any and all sorts of pleasure. Meanwhile, Snyder said, a running craze had begun, with enthusiasts exalting in the wonderful feelings they said exercise elicited.

"Jogging was first becoming popular in the United States, and everyone was talking about the runner's high," Snyder said. "They said: `Well, I have a high. It must be endorphins.' "

Indeed, scientists noted that endorphin levels in the blood rose with exercise. But that finding is meaningless, they say. "Endorphins in the blood are irrelevant," Snyder said. They do not pass from the circulating blood into the brain.

An alternative approach may be to give volunteers drugs to block brain endorphins, said Gavril Pasternak, a neurologist at Memorial Sloan-Kettering Cancer Center in Manhattan.

But, he said, if the subjects do not get the runner's high, is it because the drugs are blocking endorphins, because the subjects are not exercising vigorously enough, because the runner's high itself is so unpredictable, or because there are a variety of endorphins contained in a variety of nerves?

If they did get a runner's high, would that be because endorphins found alternative ways to exert their effects or because molecules other than endorphins were involved? Or was it perhaps because the drugs did not block the right endorphins or that they acted in the wrong part of the brain?

That leaves researchers with another option for studying runners' highs -- rats.

Virginia Grant, a psychologist at the Memorial University of Newfoundland, said rats seemed to get addicted. The evidence, she says, is that rats that are allowed to run seem unable to stop. And in studies asking if running rats behave like rats addicted to cocaine or morphine or other addictive drugs, the answer seems to be yes.

Rats love running to the extent that they can actually run themselves to death. That happened in experiments in which rats, which usually nibble all day long, were offered food for only an hour a day.

Animals that were left in their cages, without running wheels and without food, for the other 23 hours did fine; they quickly learned to eat all their day's calories in one hourlong session. But those that had running wheels for those 23 hours ran so much that they could not eat enough to compensate, actually eating less and less as they ran more and more, reaching distances of 12 miles by running non-stop. In a week or two, nearly all were dead of starvation.

Place matters

Grant and her colleague Bow Tong Lett recently asked another question: How long does runner's high last in rats?

They took advantage of a striking effect, elicited both by addictive drugs such as morphine and by running: the animals learn to prefer a place they associate with feeling high. So when Grant and Lett allow rats to run and then put them in a special room, such as one with horizontal stripes, the animals learn to like that room.

Given a choice, they will enter the room with the stripes and wait there. It is as though they associate the room with a good feeling and so the room itself starts to please them.

But what if the rats have to wait before going into the special room? If they still feel high when they enter it, they will learn to like the room, Grant said. If not, the conditioning will fail. That led Grant and Lett to ask how long the running high lasts.

"We tried a 10-minute delay," Grant said, taking the rats out of the wheel and making them wait in their home cages before putting them in the special room. They were conditioned. But when she made the animals wait half an hour in the home cage, the conditioning failed. Given a choice, the rats did not hang out in the room with the horizonal stripes.

Addictive running

The question is: What is going on in the brains of these rats that seems to make running irresistible? Some clues are now emerging from the laboratory of Stefan Brene, a neurobiologist at the Karolinska Institute in Stockholm, Sweden.

They build on a growing body of science indicating that many addictions are, at their core, the same, with a final common pathway. No matter what else drugs such as morphine, cocaine, alcohol, nicotine, amphetamines, cannabis and painkillers like Darvon do in the brain, eventually they precipitate a chemical signal that arrives at the nucleus accumbens, a structure toward the front of the brain. And that chemical signal is always the same: a flood of the nerve hormone dopamine.

"A reward is something you work for," said Roy Wise, an addiction researcher at the National Institute of Drug Abuse. "It makes you want to go back for more."

The dopamine that rushes to the brain's reward center attaches itself to a group of cells, the medium spiny neurons. These in turn can make other nerve hormones, the small proteins, or peptides, known as enkephalin, dynorphin and substance P.

Brene and his colleagues reported that if they gave rats free access to a running wheel, they would run about about six miles a day. In that time, he finds, the three hallmark chemicals of addictive drugs -- enkephalin, dynorphin and substance P -- are produced in the reward centers of their brains.

The interpretation is that the same brain systems are affected by running and by addictive drugs, Brene said. "It is the same brain circuitry that is activated and it is possible that you can have the same pathology in the brain, the same addictive nature of the behavior."

That is one reason Akil is so skeptical of the endorphin-runner's high hypothesis. She is willing to believe that exercise may elicit a sense of well-being sometimes, in some people, and she is willing to believe that some endorphins, somewhere in the brain, may be involved, although that is yet to be shown.

"I think it is really simplistic to make one hormone the heart of it all," she said, adding, "I would think it is a cocktail of goodies and that it probably is a delicate mix."