July 1, 2002 -- It's a leaf in East Africa, a nut in the Far East, and in the United States, a fine powder mixed into a drink.

By differing degrees, they keep the eyes of the world open. Chewed, smoked or chugged, the kick is similar.

They give soldiers, diplomats and housewives alike the energy to make it through a long day and night.

They are a generation removed from the world's most frequently prescribed medications, and distant relatives to its most outlawed drugs. Herbal stimulants represent one of the largest trends in the legal and illegal drug market worldwide.

Caffeine and nicotine are the most common. Cocaine and methamphetamines are the most illicit. And between the two extremes is a group of herbal stimulants — ephedra, khat, betel nuts — that are gaining in popularity around the world and raising debate about the tolls of their use.

Last year, the NFL became the first professional sports league to ban ephedra. As of today, any player who fails the random testing for the stimulant will face a four-game suspension.

The Drug Enforcement Administration this week is expected to release a comprehensive statement on khat and its place in North America, echoing the longtime concerns of countries like Ethiopia, where it is commonly chewed.

And health officials in South Asia are beginning to describe a new cancer epidemic among consumers of betel nuts.

It's a crackdown on a product once common, now controversial, and it's happening to similar stimulants across the globe.

The Ephedra Debate

Taken from an evergreen plant found in Central Asia and used for centuries to treat the region's asthmatics, ephedra is now a major ingredient in dozens of sport drinks and dietary supplements produced in the United States.

Manufacturers of drinks containing ephedra say they can help the consumer reach "a new level of muscle blasting workout intensity," build "lean muscle mass quicker and faster," and enhance "mental acuity."

Though drinks and supplements featuring the herbal stimulant have only boomed in the United States in the last decade, Americans have been depending on ephedra in one form or another since the early 20th century.

Today, athletes looking for a quick jolt of energy can pick up drinks like Ripped Fuel or Ultimate Orange, both of which contain ephedra, before they hit the field, to get a kick from an ancient Chinese formula.

Of course, that's as long as they aren't playing in the NFL, the Olympics or collegiate athletics.

Since 1997, the NCAA has barred its member athletes from consuming ephedra. A survey of athletes in 2001 showed an increase in the supplement's use. The Olympics has banned ephedra's use for more than a decade. Until last year, NFL players were endorsing sports drinks with ephedra, and its use remains widespread in Major League Baseball.

In a May news release, the NFL said it banned ephedra after experts said it "can cause seizures, strokes and even death."

In June 2001, the Canadian government warned its citizens not to use products with ephedra, and the following June, Canada's federal health agency urged a recall of ephedra products that advertise weight loss or improved athletic performance.

The Stance of the FDA

The U.S. Food and Drug Administration has received hundred of notices of ephedra's adverse effects and has conducted multiple investigations into its safety but so far has held that supplements with the stimulant are safe if taken as recommended.

Just two weeks ago, Health and Human Services Secretary Tommy Thompson said it was unclear whether ephedra was dangerous and commissioned a new top-to-bottom analysis of the stimulant.

But Public Citizen, a consumer advocacy group, labeled the HHS and FDA "cowards" and called for everyone involved in the decision to be fired for not taking a stronger stance.

"It should not require further deaths or strokes in soldiers or anyone else in this country for the FDA and HHS to abandon their cowardly position and ban ephedra alkaloids," said Dr. Sidney Wolfe in a statement released by Public Citizen.

Wes Siegner, a Washington-based lawyer for an industry group called the Ephedra Education Council, has the task of defending ephedra's battered image. The council promotes ephedra's safe but continued use on behalf of the multibillion-dollar industry.

Siegner said the stimulant has been criticized in the press based on complaints filed to the government, but these reports are largely unscientific.

"It's a sexy story and it can help sell newspapers or magazines, but it's not science," Siegner said. "Consumers know the products work, and that's why they continue to sell."

Siegner said he welcomes the government's upcoming review of ephedra, and is confident the stimulant's clinical data will speak for itself.

Dr. Neal Benowitz, chief of clinical pharmacology at the University of California-San Francisco, said ephedra has a chemical structure similar to that of amphetamines, only less potent. However, Benowitz and colleagues are doing research, some of which will be published next month, to describe the stronger effects of ephedra when combined with other stimulants, such as caffeine.

"[Ephedra and amphetamines] have a similar effect in that both have a direct effect on the release of hormones," said Benowitz, who has been studying stimulant drugs for more than 30 years.

Benowitz said he plans to petition to the National Institutes of Health in the fall to begin his own comprehensive, controlled study of ephedra's adverse effects.

Taking the Blame

Ephedra's use was brought to national attention in August 2001 when Rashidi Wheeler, a football player at Northwestern University, collapsed and died during a workout with teammates. Investigators acknowledged that Wheeler drank the ephedra-based sports mix Ultimate Punch and Xenadrine with teammates before taking the field. An autopsy ruled the cause to be an asthma attack, but Wheeler's family has filed a wrongful death suit against the companies that produce and distribute the drinks.

Wheeler's case isn't the only one. A small network of personal injury lawyers has made a cottage industry of pursuing litigation against companies that sell products with ephedra, and in the past two years, more than 100 people have filed lawsuits. Sites such as www.ephedraattorney.com, www.ephedrainjury.com and www.ephedra-lawsuit.com list possible side effects ranging from depression to paranoid psychosis to death.

Siegner said only a few of the many suits filed in lower courts against ephedra companies have been won, largely because there is no legal consensus on its safety.

The FDA does regulate some uses of ephedra, depending on how it's marketed. Though labeled safe as an ingredient in sports drinks and dietary supplements, ephedra falls under the law when packaged as what the government calls "street drug alternatives."

Such alternatives were aimed at a younger, hipper crowd that took to rave drugs like Ecstasy in the late 1990s. Products like "Hextasy" and "Herbal Koke" promise a natural high similar to that provided by their illegal namesakes, but because they are promoted for recreational use, the FDA red-flagged them as having potential for abuse.

A Milder Effect

Other herbal stimulants designed for recreational use get an OK from the U.S. government.

Like ephedra, betel nuts had their first use in Central Asia centuries ago. Popular today in Thailand, Indonesia and Taiwan, the olive-size nuts are either chewed whole or served with tobacco. Again, the effect is similar to a mild amphetamine: A user has more energy, more alertness and sometimes, euphoria.

Proponents of alternative medicine count on betel nuts as a miracle cure for common illnesses, but its primary use among its more than 200 million users worldwide is as a pick-me-up. Men and women stroll the busy streets of many Asian cities with the nuts tucked in their lips, drinking the red juice they produce and spitting the residue on the sidewalk. The red-tinted tongue the person is left with is considered attractive in some cultures.

But the nuts are also available in the United States. In the Jackson Heights neighborhood of Queens, N.Y., customers can purchase all the ingredients needed to make the betel-derived delicacy paan — betel leaves, betel nuts, pepper and rose-petal preserves.

Because they contain "a poisonous or deleterious substance," primarily arecoline, betel nuts were outlawed in the United States in 1992. The ban was lifted partially in 2000.

A Larger Concern

Benowitz said the arecoline in betel nuts has a chemical structure similar to nicotine rather than amphetamine, but its effects and propensity for addiction are alike.

Though legal, there still are many concerns about the effects of betel nuts. In Taiwan, where betel nuts are the nation's second-most-important crop and a national symbol, government officials are looking into concerns that the stimulants are causing mouth cancer among the nation's many users.

Like ephedra in the United States, regulating betel nuts has become the goal of a small number of medical experts who foresee an epidemic. These experts quote recent statistics showing that annual deaths from mouth cancer in Taiwan doubled in less than a decade. Recent studies from King's College Hospital in London have backed their suspicion.

Betel nut consumption in the United States is much smaller. A bag of the tiny nuts goes for $3 a bag in Queens, though the New York Department of Health's Web site lists Betel Nut Palm as a poisonous substance.

Banned in the U.S.A.

Harder to come by in the United States is the international upper khat. Popular in East Africa and made famous recently in the Somalia-set book and movie Black Hawk Down, khat is a small leaf that the user chews, like betel nuts, to unleash its herbal stimulants.

Chewing khat is a centuries-old ritual in Ethiopia and is legal in many Western countries, such as the United Kingdom. But in the United States, it's illegal and possession is as punishable as carrying around heroin or cocaine.

In its earliest stages, khat contains the Schedule I narcotic cathinone. After three days the substance breaks down into the less harmful — and less punishable — cathine, a Schedule IV narcotic.

Officials with the DEA say use of khat largely is confined to certain pockets of the country. According to the agency's Web site, DEA officers seized 24 metric tons of the illegal stimulants in 1999.

"It's not something we spend a lot of time working with," said DEA Special Agent Will Gaspy.

Like ephedra or betel nuts, khat produces an amphetamine-like buzz in the user, increasing alertness at the cost of stress to the body. Side effects include a rapid heartbeat, increased blood pressure and breathing problems.

Abuses Abroad

American soldiers battling in Somalia in the 1993 said they found it more difficult to fight in the afternoon when the Somali soldiers were more agitated and aggressive from chewing khat.

Khat was traditionally chewed by older men, but during Somalia's years of civil unrest, residents reportedly were chewing for as many as 20 hours a day, creating a wave of addiction.

In April, federal narcotics agents intercepted a 60-pound FedEx package of the plant roots in Maine. Though rare in the United States, khat is found most often in East African immigrant communities. Many states, including Maine, don't have laws banning khat, so only federal officers enforce the ban.