Ephedra

What Kind of Drug Is It?

Ephedra plants are yellow cone-bearing bushes that grow in desert areas. The Chinese herbal remedy ma huang (ma-HWANG) is made from the twigs of the ephedra bush. It has been used to treat asthma (AZ-muh), a lung disorder, for thousands of years. Asthma is a disease that involves swelling and congestion in the lungs, which makes it difficult to breathe.

Ephedra is a natural source of ephedrine, just as coffee beans are a natural source of caffeine. For nearly a decade prior to its ban by the U.S. government in 2004, ephedra was associated with very serious side effects, including strokes, heart attacks, and even death in some users.

Overview

The Chinese herbal remedy ephedra, also called ma huang, has generated a whirlwind of debate since the mid-1990s, when some of its users became seriously ill. Reports of adverse events, or negative side effects, related to ephedra use raised considerable concern among physicians and legislators. Until it was banned by the U.S. Food and Drug Administration (FDA) in 2004, ephedra was most often taken by young and middle-aged adults for weight loss, increased energy, and bodybuilding. Chinese herbalists argue that ephedra should not be used for these purposes.

The earliest known use of ephedra was in ancient China, where it was used as an herbal remedy to treat a variety of ailments. In the 1920s, Dr. K. K. Chen studied ephedra and isolated its active ingredient—ephedrine. An active ingredient is the chemical or substance in a compound known or believed to have a therapeutic, or healing, effect.

Official Drug Name: Ephedra (ih-FEH-druh) Ephedra sinica, ephedrine (ih-FEH-drinn), ephedrine alkaloids

Also Known As: Ma huang, mahuang, Mormon tea

Drug Classifications: Not scheduled; dietary supplement

Ephedrine alkaloids act as powerful stimulants on the heart, causing an increase in heart rate and a rise in blood pressure. (Stimulants are substances that increase the activity of a living organism or one of its parts.) Ephedrine also helps dilate, or open up, the breathing passages in the lungs.

Soon after the discovery of ephedrine alkaloids, physicians in the United States began prescribing ephedra as a decongestant for stuffy noses. It was also used as a bronchodilator—a drug that relaxes

breathing muscles, allowing air to flow more easily through the tubes that lead to the lungs.

Serious side effects associated with ephedra include high blood pressure, irregular heart rate, seizures, heart attacks, and strokes. Extensive research and analysis have linked the use of this herbal stimulant to 155 deaths. One tragedy involved a healthy sixteen-year-old high school student from Lincoln, Illinois. In September of 2002, Lincoln Community High School football player Sean Riggins died of heat stroke after taking a strength-boosting ephedra supplement he had purchased at a gas station. As of early 2005, the controversy surrounding ephedra—and its ban—raged on.

Bulking Up and Slimming Down

Before ephedra was banned by the FDA in 2004, products containing the herb were used primarily for weight reduction. Health food stores, supermarkets, drugstores, convenience stores, and even gas stations sold products containing ephedrine alkaloids. These included products with names such as Easy Trim, Diet Max, Xtreme Lean, Metabolife 356, Xenadrine RFA-1, Ultimate Orange, Yellow Jacket, Quick Shot, Stacker 2, and Ripped Fuel. The products' labels promised they would fight fat, build lean muscle mass, curb the appetite, boost energy, and help users lose weight.

Under the U.S. Dietary Supplement Health and Education Act (DSHEA), which was passed in 1994, herbs are treated as foods rather than drugs. The act allowed dozens of brands of supplements containing ephedrine alkaloids to flood the market without being tested for safety. As a rule, herbal supplements do not have to undergo the extensive testing required for over-the-counter (OTC) medications and prescription drugs. In fact, it is up to the FDA to show that an herbal supplement is unsafe. As Snigdha Prakash explained in a National Public Radio (NPR) story on ephedra, "the FDA must prove that problems associated with ephedra supplements are caused by them."

As far back as April of 1996, the FDA issued a consumer warning about ephedra. The government agency noted that ephedra may have been connected with a dozen deaths and several hundred complaints of adverse reactions. From that point on, the reports of complications linked to ephedra use kept climbing. In an article published in the Virginian Pilot in 2000, Dr. Neal L. Benowitz of the University of California at San Francisco noted that heart attacks, strokes, seizures, and deaths were occurring in "otherwise healthy young people" who had taken the herbal stimulant. He and fellow researcher Dr. Christine Haller concluded: "Dietary supplements that contain ephedra alkaloids pose a serious health risk to some users."

The Ephedra Education Council, a group backed and supported by the herbal products industry and supplement manufacturers, has always insisted that ephedra is completely safe when taken as directed. They blame adverse reactions to ephedra on: 1) improper dosing; 2) preexisting health problems among users; and 3) the combined effects of caffeine or other drugs taken along with the herbal supplement.

Tragedy on the Ball Field

On February 16, 2003, the ephedra controversy became front-page news when twenty-three-year-old Steve Bechler, a pitcher with the Baltimore Orioles, collapsed during a preseason workout in Florida. He died the next day.

Bechler was trying to lose about ten pounds that he had put on between seasons. He had not eaten regular meals for several days and was reportedly taking a weight-loss supplement that contained ephedra and caffeine. By speeding up body processes, ephedra and ephedrine alkaloids create more heat within the body. The substances also act to constrict, or narrow, the blood vessels, making it harder for the body to release the pent-up heat through the skin in the form of sweat. In addition, experts note that the energy-enhancing effect of ephedra may prompt users to exercise longer and harder than they normally would or should.

Aside from being overweight, Bechler had other health problems, including an enlarged heart, higher blood pressure than he should have had, and trouble with his liver. On the day of his fatal spring training workout, he is said to have taken three ephedra-containing supplement pills—one pill more than the recommended dosage. Bechler later collapsed on the field from severe heat stroke. His organs simply stopped working. According to a New York Times article by George Vecsey, "conditions in Florida on Sunday were 81 degrees" with "74 percent humidity, far below the danger level" for heat stroke. Still, Bechler's body temperature rose to 108.4 degrees Fahrenheit before his death.

In March of 2003, reports from the medical examiner in Broward County, Florida, stated that ephedra "played a significant role" in Bechler's death. This tragedy followed earlier reports of ephedra-related fatalities among young athletes. One and a half years earlier, twenty-two-year-old Northwestern University cornerback Rashidi Wheeler died during a workout. The cause of death was listed as an asthma attack, but Wheeler had been taking a powdered performance-enhancing dietary supplement containing ephedra and caffeine. The company that manufactured the supplement had discontinued the product and all other ephedra supplements shortly before Wheeler died.

Athletic Associations Take Action

In September 2001, just one month after Wheeler's death, the National Football League (NFL) joined the National Collegiate Athletic Association (NCAA) and the International Olympic Committee (IOC) in banning its players from using ephedrine. The ephedrine ban allows for the random testing of NFL players for ephedrine use.

Drugs and Baseball

The controversy surrounding the death of Steve Bechler in 2003 prompted Major League Baseball (MLB) to take a good look at its drug-testing policy. Ephedra and ephedrine alkaloids had already been banned in minor league baseball, as well as by the International Olympic Committee (IOC), the National Collegiate Athletic Association (NCAA), and the National Football League (NFL). Suspected steroid use among professional baseball players had sparked arguments about the prevalence of drugs in the league as well. "Both ownership and the players have been widely criticized for not facing up to the use of legal muscle-building drugs that gave new muscles to Mark McGwire and many other sluggers," noted George Vecsey in the New York Times.

Mounting Evidence of Health Risks

Authorities in Canada were equally concerned about the safety of ephedra. Health Canada, the agency that regulates Canadian health care, requested a voluntary recall of products containing ephedra or ephedrine in 2002. The agency's Web site posted an advisory stating: "A risk assessment concluded that these products pose a serious risk to health." Health Canada received sixty reports of adverse events and a report of one death related to ephedra use. The agency noted that it would "continue to monitor reports of adverse events" and "take further action if necessary."

By January of 2003, 7-Eleven stores announced that they would stop selling ephedra-containing products such as Metabolife. The General Nutrition Centers (GNC) retail chain followed suit in May. Meanwhile, the makers of Metabolife announced the release of a new formula of their supplement—one that did not contain ephedra. At the time, Metabolife International, the San Diego-based maker of Metabolife, was being investigated by the U.S. government following claims that the company had lied about the safety of its ephedra product.

At the end of 2003—six years after the safety of the herbal supplement was first called into question by the U.S. government—the administration of President George W. Bush took steps to ban ephedra. This decision was based on an in-depth investigation of the situation by RAND, a nonprofit research institute. An expert panel of researchers from RAND was hired by the government to analyze the data surrounding the ephedra controversy. The group examined the results of 20 clinical trials and 284 case reports of adverse events. RAND researchers admitted that they did not have much data to work with but stated they were able to compile "enough evidence to reach fairly confident conclusions." The results of the study were released in March of 2003. Highlights include findings that:

• Ephedrine-containing supplements increased the average weight loss of dieters in the short term by 0.4 to 2.2 pounds per month
• The athletic benefit from supplements containing ephedrine and caffeine was limited to a "20-30 percent increase in short-term performance" only
• "There may be a causal relationship between taking the substances and suffering rare serious adverse events. Catastrophic effects of ephedra, including death, cannot be ruled out."

Research from the University of California at San Francisco supports these findings. Dr. Stephen Bent and his colleagues set out to compare the health risks of ephedra with the dangers of other herbal products. The results of their study were published in the Annals of Internal Medicine in March of 2003. The researchers found that even though ephedra products amounted

to less than 1 percent of herbal supplement sales in the United States, more than 64 percent of all adverse reactions to herbal supplements were linked to their use. Bent and his colleagues concluded: "Ephedra use is associated with a greatly increased risk for adverse reactions compared with other herbs, and its use should be restricted."

FDA Bans Ephedra in 2004

In February of 2004, the FDA prohibited the sale of ephedra supplements. The agency issued a consumer advisory that stated, in part: "After a careful review of the available evidence about the risks and benefits of ephedra in supplements, the FDA found that these supplements present an unreasonable risk of illness or injury to consumers." The ban went into effect on April 12, 2004. During the weeks leading up to that date, diehard users were "reportedly stocking up" on their favorite ephedra supplements, commented Mary Duenwald in the New York Times. In some cases, users bought a large enough supply to last one to two years.

With ephedra gone from the shelves, dieters and athletes began looking for a product to take its place. "Critics … remained concerned because so little was known about the other herbal ingredients being used as substitutes," reported Christopher Drew and Ford Fessenden in the New York Times. One such substance is an ephedrine-like stimulant called synephrine (sih-NEH-frinn), also known as the bitter Seville orange (Citrus aurantium) or simply bitter orange. The substance is supposed to be safer than ephedra but has not undergone studies to prove that claim. According to the New York Daily News, bitter orange "has been linked to seven deaths."

Back in the News in 2005

The Utah-based supplement company Nutraceutical International was the first in the industry to be successful in challenging the FDA's ban on ephedra. In the spring of 2005, federal judge Tena Campbell ruled in favor of Nutraceutical, saying the FDA had failed to prove that the company's product "posed a significant health risk," wrote Penni Crabtree. The judge's ruling applies only to so-called "low-dose" supplements such as the one produced by Nutraceutical. A "low dose" supplement contains 10 or fewer milligrams of ephedrine alkaloids per daily dose.

The Utah ruling made it hard to predict the future legal status of ephedra. Under Judge Campbell's order, the FDA cannot stop Nutraceutical from selling its ephedra supplement. In addition, the FDA must determine what constitutes a "safe level" of ephedrine.

Metabolife Lawsuits

In June of 2004, just two months after ephedra supplement products were banned in the United States, Metabolife International lost a major court case that centered on the health risks connected with its product Metabolife 356. Rhea McAllister, a thirty-five-year-old Texas woman who took Metabolife 356 for about a month, suffered a stroke in 2002. She was trying to lose some weight and thought the product would help her burn off a few pounds. A jury awarded her $7.46 million in damages. The award would have been larger if McAllister had not been found partly to blame for the extent of the damage. "Jurors found McAllister 30 percent liable for failing to tell her doctors she was using Metabolife when she first complained of symptoms," noted Beth Gallaspy in an article for the Beaumont Enterprise.

This was not the first time Metabolife International had been taken to court over Metabolife 356. "In November 2002," wrote Penni Crabtree in the San Diego Union-Tribune, "a federal jury in Alabama awarded $4.1 million in damages to four people who suffered heart attacks or strokes" after taking the product.

What Is It Made Of?

The ephedra bush grows in the desert regions of Asia, North America, and other parts of the world. Not all ephedra plants contain ephedrine alkaloids. It is the alkaloid content of the plant that gives it a medicinal effect. The Asian ephedra plant typically has the highest concentration of ephedrine alkaloids.

The chemical formula for ephedrine is C₁₀H₁₅NO, which is very similar to the structure of amphetamine or "speed," a widely abused stimulant that gives people a lot of energy. (A separate entry on amphetamines is available in this encyclopedia.) Like amphetamine, ephedrine alkaloids can have a powerfully stimulating effect on the heart. Former FDA commissioner David A. Kessler told the New York Times in 2003 that substances like ephedra are really drugs "masquerading as nutritional supplements."

How Is It Taken?

Ephedra has been sold in the form of tablets, capsules, a powder that can be combined with water to make a shake, and as a key ingredient in energy boosting bars. Asthma treatments include sprayable mists and injectable liquids containing ephedrine.

The twigs of the ma huang plant are dispensed by traditional Chinese herbalists. Tea made from the twigs is used to treat asthma, coughs, and the common cold. Herbalists caution that ephedra is a strong herb and that it should not be used for more than a week at a time.

Ephedrine starts to take effect about an hour after ingestion and, after kicking in, lasts about three to four hours. The recommended dosage of ephedrine is a maximum of 8 milligrams in 6 hours, or 32 milligrams per day. In Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy, Cynthia Kuhn and her coauthors caution that it is hard to regulate the dosage of herbal remedies because "the amount and purity of what you buy is unknown."

Are There Any Medical Reasons for Taking This Substance?

Ephedra has been used to treat a variety of ailments for thousands of years. Because it can dilate breathing tubes and ease congestion in the nasal passages, it has been used as an ingredient in some over-the-counter decongestants and cough and cold products. Until it was banned in 2004, ephedra was used in the United States mainly as a weight-loss aid, a body-building product, and a booster for improved athletic performance.

In a report on Chinese herbal medicine published in the Dallas Morning News, Esther Wu interviewed experts in the field of herbal remedies. One of these experts, Dr. Richard Tao of the Dallas College of Oriental Medicine, commented: "In the United States, the herb has been abused. Ma huang is not traditionally used for losing weight."

Usage Trends

The Knight Ridder/Tribune Business News estimated that 12 million Americans used ephedra products at the height of their popularity. Ephedra sales fell from $1.3 billion in 2002 to $510 million in 2003, according to the New York Times.

Before the ban on ephedra and ephedrine alkaloid supplements, manufacturers claimed that the products enhanced athletic performance and helped build lean muscle mass. That made ephedra supplements especially appealing to both male and female athletes. Frank Uryasz of the NCAA told Houston Chronicle reporter Janny Hu that young athletes run the greatest risk of suffering ephedra-related problems. "The age group we work with thinks they're going to live forever…. When we educate athletes about banned drugs, we say, 'Stimulant, plus exercise, plus heat and humidity, equals death."'

Government studies reveal that most drug use, including ephedrine use, begins in high school. In fact, 62 percent of student athletes in a 2001 NCAA survey reported that they had started using nutritional supplements in high school.

Effects on the Body

Ephedra supplements have amphetamine-like effects on the user. Side effects may include dizziness, headache, tiredness, shaking, nausea, and trouble sleeping. Higher dosages can cause an unusually fast heartbeat, chest pain, extremely high blood pressure, and even seizures. Health officials point out that ephedra can be dangerous even at recommended doses because the potency, or strength, of each dose varies so much from one manufacturer to another and from one batch to another. Users have been known to double or triple the recommended dosage in an attempt to lose weight faster or perform better in athletic events.

Ephedrine and Meth

The U.S. Drug Enforcement Administration (DEA) has been monitoring ephedrine powder and tablet production because these substances can be used to make methamphetamine, an illicit drug more commonly known as "meth" or "speed." Methamphetamine is highly addictive, often abused, and extremely dangerous. Illegal labs can produce about 1.5 pounds (0.68 kilograms) of meth from 2.2 pounds (1 kilogram) of ephedrine. Pseudoephedrine, a substance found in cold medicines, can be used for the same purpose.

Opponents of ephedra claim that the product is legal methamphetamine, or speed. (An entry on methamphetamine is available in this encyclopedia.) Mental side effects of ephedrine such as euphoria, agitation, irritability, and anxiety were noted in the RAND report. Personality changes, depression, and paranoid psychosis (a severe mental disorder that can lead to a total loss of touch with reality) could not be ruled out. These types of side effects commonly occur with the use of illicit, or illegal, stimulant drugs, including amphetamines and methamphetamine.

Ephedra users also face an increased chance of seizures, heart attack, stroke, and possibly death. The use of ephedra by pregnant women and people with high blood pressure is especially risky.

Reactions with Other Drugs or Substances

Ephedra supplements typically contain caffeine. Users may already be consuming caffeine in carbonated beverages, coffee, or tea. Mixing caffeine with ephedrine increases the stimulant effects on the heart, making the user more anxious and edgy. "Ephedrine/caffeine/aspirin combinations are often 'stacked' by weight lifters, and used for weight loss," noted Kuhn prior to the substance's ban. Ephedra is especially dangerous when used in combination with over-the-counter or prescription decongestants, any other stimulants, and certain drugs used to treat depression.

Treatment for Habitual Users

Although the FDA recognizes that ephedra and ephedrine alkaloids may cause adverse health events or serious side effects, they are not considered addictive, habit-forming drugs. "Quitting abruptly is safe and does not bring on withdrawal symptoms," wrote Duenwald in the New York Times. "But people who have used the supplement to lose weight may see the pounds return."

Consequences

Healthy individuals have been known to suffer serious consequences following ephedra use. As of early 2005, ephedra was the only dietary supplement banned by the FDA. Possession and use of a banned substance can lead to trouble with the authorities. According to MSNBC.com, ephedra consumption can actually "result in a false-positive for amphetamines in urine tests." Athletes will incur a doping suspension if they test positive for ephedra.

The Law

The FDA's ban on ephedra went into effect on April 12, 2004. The ban "specifically excludes uses of the herb in traditional Asian medicine," explained Duenwald. It is aimed instead at supplements marketed for weight loss, muscle building, and enhanced athletic performance. The sale and distribution of ephedra and ephedrinecontaining supplements is against the law. It is illegal for users in the United States to obtain ephedrine supplements from countries that have not banned it. As of mid-2005, federal authorities were cracking down on Internet sites that continued to sell ephedra in the United States. It is hard to predict whether the federal ban on ephedra will remain in place.

For More Information

Books

Chang Huang, Kee. The Pharmacology of Chinese Herbs, 2nd ed. Boca Raton, FL: CRC Press, 1998.

Kuhn, Cynthia, Scott Swartzwelder, Wilkie Wilson, and others. Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy, 2nd ed. New York: W.W. Norton, 2003.

Rotblatt, M., and I. Ziment. Evidence-Based Herbal Medicine. Philadelphia: Hanley & Belfus, 2002.

Weil, Andrew, and Winifred Rosen. From Chocolate to Morphine. New York: Houghton Mifflin, 1993, rev. 2004.

Periodicals

Abramovitz, Melissa. "Ephedra: An Herbal Danger." Current Health (December, 2002): pp. 26-28.

Bent, Stephen, Thomas N. Tiedt, Michelle C. Odden, and Michael G. Shlipak. "The Relative Safety of Ephedra Compared with Other Herbal Products." Annals of Internal Medicine (March 18, 2003): pp. 468-471.

Crabtree, Penni. "Ephedra Ruling Puzzles the Industry." San Diego Union-Tribune (April 16, 2005).

Crabtree, Penni. "GNC to Remove All Ephedra Products from Its Shelves." San Diego Union-Tribune (May 3, 2003).

Crabtree, Penni. "San Diego Dietary Supplement Firm Loses Second Suit, Must Pay $7.46 Million." San Diego Union-Tribune (June 24, 2004).

Drew, Christopher, and Ford Fessenden. "Expert Panel Finds Flaws in Diet Pill Safety Study." New York Times (July 23, 2003): p. A16.

Duenwald, Mary. "Despite FDA Ban, Ephedra Won't Go Away." New York Times (February 17, 2004): p. F5.

Duenwald, Mary. "Slim Pickings: Looking Beyond Ephedra." New York Times (January 6, 2004): p. F1.

"Ephedra Ban Weighs Heavily on Diet Pills." Knight Ridder/Tribune Business News (April 26, 2004).

Gallaspy, Beth. "Crosby, Texas, Woman Wins $7.4 Million in Ephedra Case." Beaumont Enterprise (June 26, 2004).

Gelles, Jeff. "The Ephedra Question: To Take or Not to Take." Philadelphia Inquirer (February 24, 2003).

Harris, Gardiner, and Jay Schreiber. "Judge's Decision Lifts Ban on Sale of Ephedra in Utah." New York Times (April 15, 2005).

"Herbal Stimulant Deadly." Virginian Pilot (November 7, 2000): p. A1.

Hu, Janny. "Bringing Ephedra's Risk to Light." Houston Chronicle (February 23, 2003): p. 1.

"A Major League Loss." Time (March 3, 2003).

Manier, Jeremy, and Manya Brachear. "U.S. Moves to Ban Dietary Ephedra." Chicago Tribune (December 30, 2003).

McVicar, Nancy, and Ardy Friedberg. "Autopsy Finds 'Significant' Role for Diet Aid Ephedra in Bechler's Death." South Florida Sun-Sentinel (March 13, 2003).

O'Keefe, Michael. "Ban on Ephedra Now in Effect." New York Daily News (April 12, 2004).

Somers, Terri. "Metabolife Founder in San Diego Pleads Not Guilty in Ephedra Case." San Diego Union-Tribune (July 28, 2004).

"Two Firms Shed Ephedra Herbal Stimulant from Product Lines." Knight Ridder/Tribune Business News (January 23, 2003).

"U.S. to Prohibit Supplement Tied to Health Risks." New York Times (December 31, 2003).

Vecsey, George. "Baseball Has Failed to Confront Drugs." New York Times (February 23, 2003).

Wu, Esther. "Chinese Herb Spurs Ephedra Confusion." Dallas Morning News (January 17, 2004).

Web Sites

"Consumer Advisory: Ephedra" (April 2004). National Institutes of Health, National Center for Complementary and Alternative Medicine.http://nccam.nih.gov/health/alerts/ephedra/consumeradvisory.htm (accessed July 6, 2005).

"Ephedra and Ephedrine Alkaloids for Weight Loss and Athletic Performance." National Institutes of Health, Office of Dietary Supplements.http://ods.od.nih.gov/factsheets/ephedraandephedrine.asp (accessed July 6, 2005).

"FDA Issues Regulation Prohibiting Sale of Dietary Supplements Containing Ephedrine Alkaloids and Reiterates Its Advice That Consumers Stop Using These Products" (February 6, 2004). U.S. Food and Drug Administration, FDA News.http://www.fda.gov/bbs/topics/NEWS/2004/NEW01021.html (accessed July 7, 2005).

"Health Canada Requests Recall of Certain Products Containing Ephedra/Ephedrine" (January 9, 2002). Health Canada Online.http://www.hc-sc.gc.ca/english/protection/warnings/2002/2002_01e.htm (accessed July 7, 2005).

"Judge Strikes Down Ban on Ephedra." MSNBC.com, April 14, 2005. http://www.msnbc.msn.com/id/7504443/ (accessed July 7, 2005).

McBroom, Erica. "Ethnobotanical Leaflets: Ephedra (Ma Huang)." Southern Illinois University.http://www.siu.edu/~ebl/leaflets/ephed1.htm (accessed July 6, 2005).

Prakash, Snigdha. "The Secret of Ephedra's Questionable Success." National Public Radio, November 22, 2002. http://www.npr.org/templates/story/story.php?storyId=850679 (accessed July 6, 2005).

Shekelle, Paul G., Margaret Maglione, and Sally C. Morton. "Preponderance of Evidence: Judging What to Do about Ephedra." RAND Review.http://www.rand.org/publications/randreview/issues/spring2003/evidence.html (accessed July 6, 2005).

See also: Amphetamines; Caffeine; Dextroamphetamine; Diet Pills; Diuretics; Herbal Drugs; Methamphetamine; Over-the-Counter Drugs; Steroids

EPHEDRA

OFFICIAL NAMES: Ephedra, Ephedra sinica

STREET NAMES: Mahuang, ma huang, desert tea, Mormon tea, American ephedra, European ephedra, Pakistani ephedra, ephedrine, ephedrine alkaloids, pseudoephedrine

DRUG CLASSIFICATIONS: Not scheduled, dietary supplement

OVERVIEW

Ephedra has a long, varied, and global history. Most varieties of the drug or herb are legal as of 2002. Despite its legal status, however, ephedra is not safe in large quantities. In fact, some non-profit groups, lawyers, and even some physicians and state and federal health agencies claim that ephedra can be harmful. They have sought to ban or at least more strictly regulate products containing ephedra, because these supplements have been associated with some very serious side effects, including strokes and heart attacks.

The earliest known use of ephedra was in ancient China, where it was used as an herbal remedy to treat a variety of ailments. Physicians in the United States began prescribing ephedra in the early part of the twentieth century as a decongestant for stuffy noses and a bronchodilator to open blocked airways.

Today, products containing ephedra and its synthetic or chemical equivalent are primarily used for two purposes in the United States. Ephedra is found in many dietary supplements and energy bars for weight loss and body builders. Ma huang, or ephedra, may also be found in so-called energy-boosting drinks. Both health food stores and supermarkets sell products containing ephedra, such as Easy Trim, Diet Max, Metabolife, Ripped Fuel, and Quick Shot. Some ephedrine supplements such as Ecstasy and Black Beauties have the same name as illegal street drugs. The labels of products containing ephedra may claim that the product will fight fat, build lean muscle mass, curb appetite, boost energy, increase metabolism, and help lose weight. Such claims, however, are not necessarily true.

Ephedra is subject to the Dietary Supplement Health and Education Act (DSHEA), which was passed in 1994. The act essentially protects dietary supplements like ephedra. That is, while U.S. federal agencies can regulate prescription drug and food additives, DSHEA exempts herbal products and supplements from federal regulation. The law states that the United States Food and Drug Administration (FDA) cannot regulate dietary supplements unless, or until, they are proven to be unsafe and pose a risk to users. The United States Drug Enforcement Administration (DEA) monitors ephedrine because it can be used to make methamphetamine.

Today, supplements containing ephedra are at the center of a controversy, with opponents claiming that they are dangerous and should be banned. Supplement makers and the herbal products industry, however, maintain that ephedra is safe and reports of adverse effects are overblown, exaggerated, and inaccurate. The Food and Drug Administration (FDA) has received hundreds of reports of adverse effects of ephedra, including strokes, heart attacks, heart rate irregularities, seizures, psychoses, and death. Dating back to the early 1990s, reports of ephedra-related adverse events raised concern among physicians and legislators. In 1997, the FDA proposed a new rule about ephedra, which would have considered some products containing ephedra as adulterated supplements, making them subject to FDA regulation. The FDA based its adulterated claim on the fact that ephedrine alkaloids resemble amphetamine and, like amphetamine, stimulate the heart and nervous system. However, this attempt to subject ephedra products to regulation failed.

Since 1997, a number of groups have lined up on each side of the ephedra battle. A non-profit group called Halt Ephedrine Abuse Today has spoken out about the dangers of ephedra. On the other side of the battle is the Ephedra Education Council, a group backed and supported by the herbal products industry and supplement manufacturers. Many of the companies that sell products containing ephedra do not want any further restrictions on the products.

A big concern about ephedra is that drug traffickers and laboratory operators are using ephedrine to make methamphetamines (speed). Consequently, in the United States, ephedrine is subject to regulatory laws. The Drug Enforcement Administration (DEA) carefully monitors medications containing ephedrine.

The United States is not the only country concerned about the safety of ephedra. Health Canada, the Canadian health regulatory agency, requested a voluntary recall of products containing both natural and chemical ephedra in 2002, because it received 60 reports of adverse events related to ephedra use.

CHEMICAL/ORGANIC COMPOSITION

Ephedra is available in both natural and synthetic forms. The Asian version of natural ephedra comes from a 1.5–4 ft (0.45–1.2 m) high shrub-like plant that grows in desert regions of Asia from northern China to Inner Mongolia. There are three Asian species of ephedra— Ephedra sinica, E. intermedia, and E. equisetina. Chinese and other early users of ephedra dried the green stems of the plants and ground them into a powder for medicinal use. The Asian version of the plant generally has the highest concentration of ephedrine. The ephedra plant is also grown in North America and other parts of the world, but some of these ephedra species have no alkaloid content, and it is the alkaloid content of the plant that causes its medicinal effects.

In the United States, ephedrine alkaloids are derived from the Ephedra sinica, or ma huang plant. Most ephedra supplements contain a standard extract of 6–8% ephedrine alkaloids. Other herbs and ingredients, including caffeine, may also be added to ephedra supplements.

The molecular structure of ephedra resembles that of amphetamine, a stimulant. Dietary supplement product manufacturers often mixed caffeine with ephedra. Some experts believe that caffeine probably enhances or heightens ephedra's stimulant effects. Ephedra may also be combined with other herbs in supplements, depending on the desired effects.

INGESTION METHODS

Ephedra is available in multiple forms. It is a common ingredient in energy boosting bars, sold as "Herbal Ecstasy" in some health food stores, and is also available as powder that can be mixed with water. Health food stores may sell powdered ephedrine stems, which can be used in a tea, or they may sell infusion, extracts, tinctures, or tablets of ephedra. Health food stores may also sell ephedra as the ma huang herb. Many manufacturers tend to advertise or market ephedra supplements as natural or as a botanical herb, because some consumers equate natural with safe. In China, ephedra may be boiled with cinnamon twig, licorice root, and almond to treat the common cold.

THERAPEUTIC USE

Ephedra has been used to treat a variety of ailments for thousands of years. Five thousand years ago the Chinese used ephedra as a medication to treat sweating, lung and bronchial constriction, water retention, coughing, shortness of breath, the common cold, and fevers.

Ephedra was introduced in the United States in the earlier part of the twentieth century when physicians began prescribing it for its bronchodilating and decongesting properties. Ephedra alkaloids stimulate certain receptors in the body, such as the airways in the lungs. By stimulating the airways, ephedra may open the blocked airways or nasal passages that occur with the common cold and asthma. This may help alleviate symptoms of the common cold. Ephedra can also affect other parts of the body. It also stimulates other receptors in the body, including receptors in the heart. This can increase the heart rate of ephedra users, and it may also increase blood pressure and decrease circulation. The end result may be very serious health consequences for some ephedra users.

Today, ephedra is primarily used in the United States for two purposes. It is used as a weight-loss aid or bodybuilding product and as a nasal decongestant. As a relative of methamphetamine, ephedra can affect the body in many of the same ways. Ephedra can stimulate the nervous system, dilate bronchial tubes, elevate blood pressure, and increase heart rate. Manufacturers of weight-loss products containing ephedra claim that it suppresses the appetite and increases metabolism. Because ephedra can dilate bronchial tubes and decongest the nasal passages, it is also used an ingredient in some over-the-counter decongestants and cough and cold products.

As of January 2002, the maximum allowable dosage of ephedra is 8 mg per dose, or 32 mg per day. Most ephedra supplement products advise users to take two or three doses per day. What the product label says and what the actual content of the product is may be different. A research study published in 2000 tested the amount of ephedra alkaloids in dietary supplements and compared the results to the product label. The researchers found that more than half of the supplements did not list the ephedra alkaloid content or had a significant difference between the amounts listed on the label and the actual ephedra alkaloid content. The labels of most ephedra supplements state that the product is not intended for users less than 18 years old.

USAGE TRENDS

Despite the growing health concerns about ephedra, products containing ephedra remain popular in the United States. Studies indicate that use of ephedra may begin in the high school years. High school and college athletes may purchase products containing ephedra because they believe that the supplements can build muscle mass and enhance performance, while teenaged and adult weight-conscious consumers may purchase supplements as a diet aid. And finally, some users may turn to ephedra products as a legal high.

Scope and severity

Exact data about the scope of ephedra use is unavailable, but the Ephedra Education Council estimates that more than three billion servings of ephedra products are consumed each year, and it claims that use increased dramatically between 1997 and 2002. But a New England Journal Medicine article about ephedra

points out that actual consumption may be higher. That is, if ephedra supplements were used as directed, at three doses a day for 12 weeks, 12 million Americans used ephedra supplements in 1999. These figures refer only to ephedra supplements, not over-the-counter nasal decongestants and cough and cold remedies.

Age, ethnic, and gender trends

Because ephedra manufacturers claim that the product enhances athletic performance and builds lean muscle mass, ephedrine supplements are especially popular among both male and female athletes. A 2001 survey of National College Athletic Association (NCAA) student athletes revealed that 42% of college athletes use nutritional supplements. Not all of these supplements contain ephedrine, but many do. According to the survey, 3.9% of NCAA student athletes use ephedrine. This is an increase from a similar survey completed in 1997, which showed that 3.5% of athletes used ephedrine. Products containing ephedrine are particularly popular among women gymnasts. In 2001, 8.3% of NCAA women gymnasts used ephedrine products. In 1997, 1.1% of women gymnasts used ephedrine. On the other hand, ephedrine use among NCAA wrestlers fell from 10.4% in 1997 to 4.3% in 2001.

The NCAA survey also revealed that most drug use, including ephedrine use, begins in high school. In fact, 62% of student athletes in the NCAA survey reported that they had started using nutritional supplements in junior or senior high school.

MENTAL EFFECTS

Opponents of ephedra claim that the product is legal methamphetamine, or speed. In February 2000, medical experts raised concerns about mental side effects of ephedrine such as nervousness and irritability. The group Halt Ephedrine Abuse Today completed an on-line survey of 355 people who had taken ephedra products; more than 60% of respondents reported feeling mental side effects such as nervousness, headaches, insomnia, and paranoia. The 2000 ephedra study published in the New England Journal of Medicine also listed mental side effects, including anxiety, tremulousness, and personality changes. Other possible mental side effects associated with ephedra are depression and paranoid psychosis. Lawyers representing clients who have been allegedly harmed by ephedra have reported that the victims suffer from depression and paranoid psychosis. These types of side effects, as well as some of the other physiological side effects reported by ephedra users, commonly occur with illicit stimulant drugs.

PHYSIOLOGICAL EFFECTS

There are a number of physiological effects related to ephedra consumption, and it is these side effects and reports of adverse events that are causing both the FDA and several state regulatory bodies to consider regulating it.

Some medical experts have testified about ephedrine's physiological side effects, which include hypertension and an increased risk of heart attack or stroke. The Halt Ephedrine Abuse Today survey found that more than 60% of respondents reported feeling physiological side effects such as a rapid heartbeat, nervousness, headaches, insomnia, shortness of breath, and chest pain. Physiological effects reported in the New England Journal of Medicine include palpitations and insomnia.

At higher doses, ephedra may be toxic. An overdose of ephedra can cause nausea, vomiting, fever, palpitations, tachycardia, hypertension, psychosis, respiratory depression, convulsions, and coma.

The FDA has been receiving reports of adverse effects related to ephedra use since the early 1990s. Many of the initial concerns were linked to one ephedra product—Formula One. However, when state and federal agencies investigated the product, they could not prove that it contained ephedra, and after the manufacturer of Formula One reformulated the product, reports of adverse events linked with the product ceased. But there have been many reports of adverse events associated with ephedra since 1994. The severity of those events spurred the FDA to action, which sought an independent review in an attempt to determine if ephedra had been the cause. Another purpose of the independent review was to determine the risks of consuming ephedra.

The researchers determined that ephedra posed serious risks to users. In addition, the ephedra research study published in 2000 in the New England Journal of Medicine claimed that ephedra could cause heart attacks, strokes, seizures, and death.

According to the researchers, nearly half of the adverse events definitely, probably, or possibly caused by ephedra were cardiovascular side effects. The most common cardiovascular side effect was hypertension, or high blood pressure. Other reported cardiovascular events were palpitations, tachycardia (an abnormally fast heartbeat), stroke, and seizures. The researchers stated that 10 of the adverse events definitely, probably, or possibly caused by ephedra resulted in death, and 13 of the events caused permanent disability. In one-fifth of the cases, there was not enough evidence or information about the incident, and the remaining complications were not related to ephedra.

Researchers found that the majority of the complications in the study occurred in young, healthy ephedra users. Victims did not need to be long-time users of ephedra to experience complications; some adverse events occurred in people who took ephedra for days or weeks. Two women who became pregnant while using ephedra had miscarriages. It was concluded that supplements containing ephedra might pose a serious health risk to some users. Moreover, it was suggested that a better understanding of the risks of ephedra use is required. With a better understanding of the incidence of adverse events and the at-risk population, the FDA can recommend appropriate dosing guidelines, and it can warn users about the potentially serious side effects of ephedra.

Adverse event reporting

It is important to note that the FDA's MedWatch reports, or reports of adverse events, do not include all adverse events associated with ephedra. Some studies indicate that less than 15% of adverse events are reported to the FDA. Furthermore, the rate of adverse event reporting for herbal products or supplements may be even lower than 15%, as people do not make the connection between an herbal product they believe is safe and an adverse event. As a result, there may be more adverse events linked with ephedra use than the FDA or medical experts are aware of. Consequently, users may actually run a greater risk of adverse events.

Manufacturers of dietary supplements take a different stance when it comes to adverse events reporting. They claim that adverse events are anecdotal records and do not prove that ephedra caused the side effect or adverse event. The ephedra manufacturers' trade group also contends that victims may not recall which product they took or when. While these points are worth considering, they are made by companies and groups that have a vested interest in keeping ephedra on the market with as few regulations as possible.

Harmful side effects

Potential harmful side effects associated with ephedra include nervousness, irritability, headaches, insomnia, palpitations, depression, and paranoia. Other possible side effects are hypertension and rapid heartbeat. Ephedra users also face an increased risk of seizures, heart attack, and stroke. A heart attack or stroke caused by ephedra can result in death.

Long-term health effects

The long-term health effects of ephedra use are unknown; however, users who suffer a heart attack or stroke face the long-term health consequences of those ailments.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Ephedra supplements typically contain caffeine, and users may consume caffeine in carbonated beverages, coffee, or tea. Researchers suspect that caffeine may enhance ephedra's stimulant effects on cardiovascular and/or central nervous system responses. This may account for the types of adverse events that have been reported by ephedra users.

When ephedra is used in combination with decongestants or other nervous system stimulants, the effect on the nervous system may be increased.

Ephedra has negative interactions with cardiac heart glycosides, halothene, guanethidine, MAO inhibitors, and secale alkaloid derivatives or oxytocin.

TREATMENT AND REHABILITATION

Although the FDA, some medical authorities, and some states recognize that ephedra and its relative, phenylpropanolamine (PPA), may cause adverse health events or serious side effects, ephedra is not considered an addictive, habit-forming drug. Drug treatment and rehabilitation programs, therefore, do not address ephedra or PPA use.

PERSONAL AND SOCIAL CONSEQUENCES

Statistics and research do not yet connect ephedra use with adverse personal or social consequences. However, if an ephedra user does suffer a serious adverse effect after taking ephedra, there may be personal and social consequences with which to contend.

Even if serious health consequences do not follow ephedra use, users may experience other personal consequences. College athletes may incur a doping suspension if they test positive for ephedra, because the National College Athletic Association (NCAA) bans ephedrine.

LEGAL CONSEQUENCES

Like most herbal supplements, the federal regulation that applies to ephedra is the Dietary Supplement Health and Education Act (DSHEA). This law was first passed in 1994 and allows supplement manufacturers to market and sell products without federal regulation. The FDA can only step in to regulate ephedra or other herbal supplements when they are proven to be unsafe or pose a risk to users.

Although DSHEA essentially tied the FDA's hands with regard to ephedra, individual state governments do have the power to enact laws about it. In the 1990s, there were reports of potential problems and serious ephedrarelated health consequences such as heart attacks and strokes. Some states decided to pass their own legislation. In 1994, Ohio became one of the first states to pass a law restricting ephedra, which in fact banned the sale of products containing ephedrine. Texas also passed a similar ban in 1994, although the law was overturned a few weeks after it was passed.

More and more states are passing laws to regulate ephedra sales and labeling. By 2001, nearly half of the states in the United States had passed laws to regulate sales or labeling of ephedra products. Essentially, legal restrictions on ephedra fall into a few categories. A state may regulate how a product is formulated. This type of law might mandate that ephedra must occur naturally, that is, it is not produced synthetically in a laboratory. Another type of restriction is a dosage restriction.

States may also restrict labeling and marketing of ephedra products. In a few states, the law requires that labels of ephedra products comply with DSHEA or federal laws. Other states prohibit the term ephedrine on the label. Some states require exact dosing information on the product label, while other states require that the label inform users of potential risk and adverse health consequences, particularly with improper use. In New York, the Department of Health forbids manufacturers to market ephedra as a legal stimulant or legal alternative to illegal drugs. The FDA's Medwatch phone number must be printed on the label of any product containing ephedra that is sold in Texas. A few states prohibit the sales of ephedra to consumers under the age of 18. Finally, in some states if a product indicates the term ephedrine (vs. ephedra) on the label, it must be sold as prescription instead of an over-the-counter supplement.

Ephedra has been the subject of a number of lawsuits in the United States. As users report adverse events, lawyers have started to champion their causes and sue product manufacturers. Some lawyers advertise on the Internet and seek clients who believe that they have been harmed by ephedra. An ephedra lawsuit can garner a lot of money for a lawyer and a client.

Legal history

Ephedra has a long history of legal use in the United States and around the world. Today, the laws that apply to ephedra cover sales, formulation, and labeling by manufacturers; they do not outlaw its use by consumers as with street drugs such as marijuana and cocaine. Because ephedrine can be used to manufacture methamphetamine, companies that sell bulk ephedrine and ephedrine tablets are subject to laws designed to halt the conversion of ephedrine into methamphetamine.

Federal guidelines, regulations, and penalties

Since clandestine lab operators use ephedra to make methamphetamine, the DEA monitors supplements containing ephedrine. One kilogram of ephedrine, the equivalent of 48,000 25-mg ephedrine tablets, can be used to produce anywhere from 1.1 to 1.6 lbs (.5 to 0.75 kg) of methamphetamine in a drug lab. Pseudoephedrine can be used for the same purpose.

In the late 1980s, drug traffickers and clandestine laboratory operators began to purchase bulk ephedrine powder to make methamphetamine. The government responded in 1988 and passed the Chemical Diversion and Trafficking Act (CDTA) to control the import, export, and distribution of bulk ephedrine powder. The drug traffickers then turned to ephedrine tablets to make methamphetamine, which were exempt from the CDTA. Drug traffickers and lab operators found that they could buy large quantities of ephedrine tablets and convert them to methamphetamine. A number of mail-order companies even advertised 1,000-count bottles of ephedrine tablets in national magazines. Although the CDTA allowed for criminal prosecution of companies selling tablets if they knew the tablets were being used to make an illegal substance, the companies were able to claim they had no knowledge of their products' ultimate use.

In 1993, Congress passed a new law, the Domestic Chemical Diversion Control Act (DCDCA), to include ephedrine tablets in the first law. According to the law, all distributors, importers, and exporters who sell List 1 chemicals, such as ephedrine, must register with the DEA. The DEA can deny registration or revoke registration to companies whose actions threaten public health and safety. Thus, if the company sells ephedrine tablets that are then converted into illegal substances, its registration may be denied. By 1994, lab operators responded by using pseudoephedrine to make methamphetamine.

See also Methamphetamine

RESOURCES

Books

Kee, Chang Huang. The Pharmacology of Chinese Herbs. Boca Raton, FL: CRC Press, 1992. Scanlon, William, and Nye Stevens. Dietary Supplements: Uncertainties in Analyses Underlying FDA's Proposed Rule on Ephedrine Alkaloids. Collingdale, PA: DIANE Publishing Company, 1999.

Periodicals

Cho, Arthur K. "Ice: A New Dosage Form of an Old Drug." Science 249 (August 10, 1990): 631-634.

Sager, Mike. "The Ice Age." Rolling Stone (February 8, 1990): 53-116.

Organizations

Ephedra Educational Council, 2000 K St., NW, Suite 801, Washington, DC, USA, 20006, <http://www.ephedrafacts.com>.

Halt Ephedrine Abuse Today, P.O. Box 1103, Novi, MI, USA, 48376-1103.

Healthcare Reality Check, <http://www.hcrc.org>.

Institute of Traditional Medicine, 2127 SE Hawthorne Blvd., Portland, OR, USA, 97214, (503) 233-4907, <http://www.itmonline.org>.

National Center for Drug Free Sport, 810 Baltimore, Suite 200, Kansas City, MO, USA, 64105, (816) 474-8655, <http://www.drugfreesport.com>.

Lisa A. Fratt

Ephedra

Description

Ephedra, also known as Ma Huang, is an herb utilized by Chinese medicine for more than 2,500 years due to its ability to remedy symptoms of asthma and upper respiratory infections . A member of the Ephedracae family of herbs (Ephedra sinica ), ephedra is native to northern China and Inner Mongolia where it thrives in desert areas as a jointed, barkless plant with branches that bear few leaves and tiny yellow-green flowers that bloom in summer. While varieties of ephedra grow throughout the world, the United States version flourishes in the dry southwest.

Ephedra became popular to Mormon settlers in the early 1800s as a stimulant consumed in the form of tea in place of the coffee and black tea from which they abstained, giving the plant one of its many names, Mormon Tea. Other folk names that have resulted over time include Desert Tea, Desert Herb, and Squaw Tea. The herbal drink was named Whorehouse Tea after it was served in brothels during the 1800s due to unproven beliefs that it cured gonorrhea and syphilis .

The medicinal herb Ma Huang is made of the dried, young branchlets of ephedra. Harvested in the autumn, ephedra is reproduced from seed or by root division and the stems are dried in the sun throughout the year for production. The herb should be stored away from light. Ephedra gains its strength primarily from the alkaloid ephedrine, pseudephedrine, and norpseudephedrine. These active ingredients produce central nervous system stimulation. Other key components of ephedra include:

• tannin, an acidic substance found in the bark
• saponin, originating in the roots
• flavone, the chemical from which natural colors of many plants originate
• volatile oil

General use

A bitter-tasting herb that has been relied upon by the Chinese throughout centuries to heal ailments from fevers and chills , to nasal and chest congestion, ephedra also maintains its prominence as a strong stimulant. Contrary to its reputation, Zen monks used the herb to promote calm concentration during meditation . However, larger amounts can make a person jittery. Today, ephedra is used in the United States as an herbal medicine to treat asthma and hay fever , and the beginnings

of colds and flu. The herb is also used to raise blood pressure, cool fevers, and ease the pain of rheumatism.

While ephedrine was used in various decongestant and bronchodilator products in the United States beginning in the late 1920s through the 1940s, its potential for causing dangerous side effects led to the creation of a chemical substitute. Scientists created the equally effective, but safer, pseudephedrine that remains the active ingredient in many over-the-counter (OTC) products such as Sudafed. Primatene Mist, an OTC that contains ephedrine, is used regularly to treat asthma.

The body responds to ephedra as one of its key ingredients, ephedrine, opens bronchial passages, activating the heart and raising blood pressure while increasing metabolism. Due to its stimulating effect on the nervous system, many weight loss and energy products contain ephedra. Ephedrine increases basal metabolic rate (BMR), causing the body to burn calories faster. Dieters use ephedra-based products because they suppress the appetite and stimulate metabolism. While these diet products prove to be effective, their results are rarely permanent, and long-term use can be quite harmful. Chinese sources only recommended its use for acute situations.

As an "energy" product, ephedra increases alertness and perception. The use of ephedra in this way dates back to bodyguards of Genghis Khan, who, legend has it, fearful of being beheaded if they fell asleep on duty, consumed tea containing ephedra to stay alert. Caffeine products, such as coffee, tea, chocolate, and cola drinks, enhance the effect of energy products containing ephedra. Additional medicinal uses of ephedra include the promotion of menstruation , the decreased desire for cigarettes, and the promotion of uterine contractions. Ma Huang is also known for its ability to increase sexual sensation.

Some controversy surrounds the extended use of ephedra. It is recommended that products containing ephedra be taken only for short periods of time. Tachyphylaxis, or becoming immune to a drug's effectiveness due to overuse, and dependence on the drug may develop when taken consistently over time. Both ephedrine and Ma Huang are considered doping substances. In April 1996, the United States Food and Drug Administration (FDA) issued a warning on dietary supplements containing ephedra that were labeling themselves as safe substitutes for "street drugs," such as the illegal drug ecstasy. The FDA stated that these products could have "potentially dangerous effects on the nervous system and heart."

Ephedra is classified as a dietary supplement, and unlike pharmaceutical companies that must follow strict rules regarding safety, efficacy, and quality set by the FDA, manufacturers of supplements are not held to these guidelines. In 1994, the regulation of herbal medicine-type products in the United States changed with the passage of the Dietary Supplement Health and Education Act (DSHEA). At this time, herbal products were reclassified, along with vitamins and minerals, as dietary supplements. When classified in this grouping that falls somewhere between food and over-the-counter drugs, herbal supplement manufacturers were then able to begin making "structure-function" claims for a product on its label if there is scientific evidence supporting these claims. When appropriate, supplement manufacturers are allowed to use three types of claims: nutrient-content claims, disease claims, and nutrition support claims. These claims are made to guide the buyers of supplements, but supplement manufacturers may use the claims without FDA authorization, and are not required by law to conduct scientific studies on their products. In March 1999, the placement of a "Supplement Facts" panel became a requirement on the labels of most dietary supplements. In January 2002, The United States Pharmacopeial Convention announced it would launch a dietary supplement verification program. Though voluntary, the program would allow supplement manufacturers to provide documentation that they had a quality standard system in place, the organization would audit that system, then verify the quality of the supplement as long as the manufacturer continued to meet the criteria.

While questions surround the correct use of ephedra in the United States, the German government's Federal Institute for Drugs and Medical Devices (Commission E) certifies that ephedra herba, ephedra, and Ma Huang is an approved remedy for diseases of the respiratory tract with mild bronchospasms. Approval from Commission E, however, is not equivalent to the FDA's higher standards of drug approval. Some states in the United States have limited the use of ephedra, or banned the drug completely.

Preparations

Ephedra is available over the counter as a fluid extract, in tablet form, or as a dried bulk herb at Chinese pharmacies, Asian markets, and health food stores where it is permitted throughout the United States. When purchasing the herb, be certain to avoid those that look dry or have a greenish-brown cross section.

Chinese herbalists prepare ephedra for use by combining one part honey, four parts dried herb in combination with other herbs, and a small amount of water in a wok. The herbs are simmered over low heat until the water has evaporated and the herb begins to turn brown. Other forms of preparation include frying ephedra in vinegar or wine to improve its tonic effect on blood circulation, and toasting it to an ash so that it may increase its ability to stop bleeding.

To treat fever and chills, Chinese herbalists recommend combining ephedra with cinnamon twig and other herbs. Coughing and wheezing are remedied with a mixture of ephedra and apricot seed , while licorice is added to the herb for stomachaches . An upper respiratory infection, or congestion, is treated with a combination of ephedra and ginger . The powder form, mixed with rehmannia, is also used by the Chinese to treat kidney energy (yin) deficiency. It is recommended to consult a Chinese medicine practitioner, or physician for detailed information on mixtures of ephedra and doses of the herb.

As the United States has adopted the herb for its healing properties, the variety of ephedra preparations has increased. The average single dose of ephedrine for adults is 15–30 mg, with a maximum allowed daily dose of 300 mg per day. When consumed as a tea, 1 teaspoon (5 ml) of ephedra is boiled with 1 cup (250 ml) water for 15–20 minutes, with up to 2 cups (500 ml) of the tea allowed per day. This tea (also known as a decoction) is prescribed by herbalists for asthma. The tincture preparation is used in treatments to ease the aches and joint pains caused by rheumatism. The amount of tincture recommended is 1/4 teaspoon (1.25 ml)–1 teaspoon (5 ml) in combination with other herbs, up to three times a day.

As a dietary supplement, there is no FDA control over the manufacturing of ephedra, including what is in the pill, additional ingredients added to the pill, how it is produced, or what part of the plant it is made from. For example, when the whole ephedra plant is used for treatment, the side effects are minimal. When key ingredients, such as ephedrine, are isolated from the herb, the strength of the drug increases, therefore increasing the side effects. The potencies and purity within supplements vary greatly by brand and by bottle, resulting in the difficulty of exact dosage recommendations. It is recommended that directions on the product's label are followed exactly for proper use.

Precautions

While ephedra may be taken safely in the correct doses, the supplement has shown to be harmful to children, adolescents, older or chronically ill people, and pregnant women or women who are breastfeeding. Those with heart disease , high blood pressure, prostate enlargement , pheochromocytoma, diabetes, glaucoma , thyrotoxicosis, overactive thyroid gland (hyperthyroidism ), nervousness, anorexia, insomnia , suicidal tendencies, stomach ulcers, or bulimia should not take ephedra. It is also recommended that the herb be avoided by those with diarrhea or abdominal bloating.

It should be noted that ephedra is an ingredient in many weight-loss aids. While it is effective for a dieter's purpose as it accelerates his/her metabolism, the excess stimulation can cause dangerous consequences. The strength of the herb is extremely powerful as a stimulant, with its active ingredient epinephrine mimicking the effects of adrenaline. The molecular structure of epinephrine is close to methampetamine, also known as speed, and the use of ephedra can result in a positive test for amphetamines in the urine. Regular use of ephedra has shown to lead to dependence on the herb.

Many cases of Ma Huang toxicity have been reported to the FDA and possibly serious cardiovascular effects have been associated with its use. Health Canada issued a recall for products containing more than recommended levels of ephedra in early 2002 because of serious, possibly fatal, side effects. The dose limits set by Canadian authorities were more than 8 mg of ephedrine or a label that recommended more than 8 mg per dose or 32 mg per day. It also included products recommended use exceeding seven days.

A 2002 study concluded that use of Ma Huang could be associated with serious complications including increased risk of stroke, heart attack or even sudden death and that the effects were not limited to massive doses.

Side effects

Side effects of ephedra include insomnia, dry mouth , nervousness, irritability, headache , and dizziness . The following side effects are considered serious: increased blood pressure, increased heart rate, and heart palpitations. If these develop, the use of ephedra should be stopped and a physician should be consulted immediately.

In 2000, the FDA reported that the herb ephedra when used as a weight-loss product could result in serious side effects, including heart attack, stroke, and high blood pressure. These potentially life-threatening outcomes, especially to those people with heart problems, are a result of those products that combine ephedra with other stimulants, such as caffeine. At this time it is estimated that four million people safely use products that contain the combined ingredients of ephedra and caffeine.

Ephedra may be life threatening if taken in very high dosages (over 100 g, lethal dosage when taken orally corresponding to approximately 1–2 g L-ephedrine). Signs of poisoning by the herb include severe outbreaks of sweating, enlarged pupils, spasms and elevated body temperature, with heart failure and asphyxiation causing death. To treat the symptoms of poisoning caused by ephedra, seek medical attention immediately.

Interactions

While ephedra may be taken safely on its own, several adverse effects may result from taking the herb along with other drugs.

Drugs that may cause adverse effects if combined with ephedra include:

• methyl xanthines, such as caffeine
• beta blockers
• Dexamthasone
• Reserpine
• Amitriptyline
• urinary alklinizers, such as sodium bicarbonate
• unrinary acidifiers, for example, ammonium chloride
• monoamine oxidase inhibitors, such as heart glycosides
• secale alkaloid derivatives, such as oxytocin
• Yohimbine
• Gaunethidine, which leads to the enhancement of the sympathomimetic effect, or stimulation of the nervous system

Those who are taking any of the aforementioned drugs should avoid ephedra. The isolated drug ephedrine (the active ingredient of ephedra) has also been shown to cause side effects if combined with other drugs, including: antidepressants that increase the overall effect of ephedrine; methyldopa, due to possible increased blood pressure; and ergot preparations that may lead to serious blood pressure problems. Other substances that may cause alarming circumstances if combined with any form of ephedra include cocaine, marijuana , and caffeinated drinks. While it is known that Ma Huang taken with certain drugs and other substances may causes adverse effects, overall drug interactions with the supplement ephedra have not been thoroughly studied. It is recommended that a physician be notified before beginning the use ephedra in any form, or of any herbal supplement.

Resources

BOOKS

Chevallier, Andrew. "Ephedra sinica." In The Encyclopedia of Medicinal Plants. New York: DK Publishing Inc., 1996.

The Editors of Time-Life Books. "Conventional and Natural Medicines." In The Medical Advisor: The Complete Guide to Alternative & Conventional Treatments. Richmond, VA: Time-Life Inc., 1996.

Fleming, Thomas. "Ephedra sinica." In PDR for Herbal Medicines. Montvale, NJ: Medical Economics Company Inc., 1998.

Griffith, H. Winter. "Ephedrine." In Complete Guide to Prescription & Nonprescription Drugs. New York: Berkley Publishing Group, 1998.

PERIODICALS

Binkley, Alex. "Health Canada Issues Ephedra Recall." Food Chemical News 43, no.49 (January 21, 2002):19.

Kurtzwell, Paula. "An FDA Guide to Dietary Supplements." FDA Consumer no. 99 (September/October 1998): 2323.

Levy, Sandra. "Watch for New Seal of Approval on Dietary Supplements." Drug Topics 146, no.29 (January 7, 2002):29.

Samenuk, David. "Adverse Cardiovascular Events Temporarily Associated with Ma Huang, an Herbal Source of Ephedrine." JAMA, Journal of the American Medical Association 287, no. 12:1506.

Taylor, David. "Herbal Medicine at a Crossroads." Environmental Health Perspectives 104, no.9 (September, 1996).

ORGANIZATIONS

American Botanical Council. PO Box 201660, Austin, TX 78720–1660.

Food and Drug Administration, Office of Consumer Affairs. HFE-88, Rockville, MD 20857.

Herb Research Foundation. 1007 Pearl Street, Suite 200, Boulder, CO 80302.

OTHER

Drug Digest. http://www.drugdigest.org (January 17, 2001).

The Ephedra Site. http://ephedra.demon.nl/index.html

WebMD. http://WebMD.com

Beth Kapes

Teresa G. Odle

Ephedra

Definition

Purpose

Description

Ephedra and the Law

Precautions

Interactions

Complications

Parental concerns

Resources

Definition

Ephedra is a genus of plants found worldwide. One species, Ephedra sinica or Chinese ephedra, has a long history of use in complementary and alternative medicine (CAM). In the late twentieth century, ephedra gained popularity as a weight-loss supplement. The herb can cause life-threatening side effects, and since April 2004, sale of products containing ephedra have been banned in the United States. In Traditional Chinese Medicine (TCM) ephedra is called ma huang.

Purpose

Ephedra (ma huang) has been used in TCM for about 5,000 years primarily to treat sneezing, runny nose, coughing and other symptoms of a cold,

influenza, bronchitis, and allergy. In the 1990s ephedra was marketed in the United States as a dietary supplement that stimulated weight loss. It was also marketed to adolescents as a mood-altering “herbal Ecstacy” and to athletes to improve performance. In 2005 use of ephedra-containing supplements in the United States was banned.

Description

Ephedra is an evergreen plant with tiny leaves that grows to a height of about 12 in (30 cm). Many species of ephedra are found worldwide, but E. sinica used in herbal medicine grows mainly in dry, rocky areas of Mongolia and northern China. The stems and roots of the plant are used medicinally. Many other species of ephedra, for example, E. nevadensis or Mormon tea that grows in the western United States, do not have the same active ingredients as E. sinica

The active ingredients in ephedra are the alkaloids ephedrine and pseudoephedrine. These chemicals have effects similar to amphetamines. They stimulate the central nervous system and affect the heart and circulatory system. Ephedra causes blood vessels to narrow, increases heart rate, and raises blood pressure. These effects are enhanced when ephedra is taken with caffeine . Ephedra also expands the airways, making breathing easier. Researchers generally agree that ephedra is effective in treating cold and allergy symptoms

Standardized amounts of manufactured ephedrine and pseudoephedrine, the active ingredients found in ephedra, are used in many cold and allergy products made by traditional pharmaceutical companies and approved for sale by the FDA. For years, these drugs were sold in the United States over the counter without restrictions. Beginning in the early 2000s, a movement developed to limit access to these drugs by placing them behind the counter at the pharmacy, limiting the amount an individual could buy, and requiring identification to purchase the drugs. This came about more because ephedrine and pseudoephedrine are used in the manufacture of illicit methamphetamines (e.g., crystal meth) than because of safety concerns about the drugs

Ephedrine and pseudoephedrine are also effective appetite suppressants, especially when combined with caffeine. Many people who took diet pills containing ephedra or a combination of ephedra and caffeine did lose weight. However, they also experienced an increased risk of dangerous, sometimes fatal, side effects. Ephedra was brought to the attention of the FDAin the mid-1990sby alarge increase inthe number of reports from poison control centers and health care providers about serious adverse effects related to ephedra-containing weight-loss supplements. These side effects included dangerously high blood pressure, fast heart rate, stoke, and heart attack. By 2003, at least 155 deaths were linked to ephedra use, including that of Baltimore Oriole’s pitching prospect Steve Belcher. That same year, an analysis of side effects related to herbal therapy published in the Annals of Internal Medicine found that ephedra accounted for less than 1% of all herbal supplement sales, but was responsible for 64% of all reported negative events caused by herbs.

Ephedra and the Law

The FDA regulates ephedra and other dietary supplements under the 1994 Dietary Supplement Health and Education Act (DSHEA). At the time the act was passed, legislators felt that because many dietary supplements come from natural sources such as plants and because they have been used for hundreds of years by practitioners of CAM, these products did not need to be regulated as rigorously as prescription and over-the-counter drugs used in conventional medicine. The legislators decided that dietary supplements should be regulated the same way food is regulated. As a result, manufacturers of ephedra supplements, just like the manufacturers of cheese or cereal, did not have to prove that ephedra was either safe or effective before it could be sold to the public. They also were not required to tell the public about possible side

KEY TERMS

Alternative medicine— A system of healing that rejects conventional, pharmaceutical-based medicine and replaces it with the use of dietary supplements and therapies such as herbs, vitamins, minerals, massage, and cleansing diets. Alternative medicine includes well-established treatment systems such as homeopathy, traditional Chinese medicine, and Ayurvedic medicine, as well as more-recent, fad-driven treatments

Amphetamine— A drug that stimulates the central nervous system and can be physically and psychologically addictive

Complementary medicine— Includes many of the same treatments used in alternative medicine, but uses them to supplement conventional drug and therapy treatments, rather than to replace conventional medicine

Conventional medicine— Mainstream or Western pharmaceutical-based medicine practiced by medical doctors, doctors of osteopathy, and other licensed health care professionals

Dietary supplement— A product such as a vitamin, mineral, herb, amino acid, or enzyme, that is intended to be consumed in addition to an individual’s diet with the expectation that it will improve health

Traditional Chinese Medicine (TCM)— An ancient system of medicine based on maintaining a balance in vital energy or qi that controls emotions, spiritual, and physical well being. Diseases and disorders result from imbalances in qi, and treatments such as massage, exercise, acupuncture, nutritional and herbal therapy are designed to restore balance and harmony to the body.

effects of the herb. (Conventional pharmaceuticals must include potential side effects in their packaging.)

With ephedra and all other dietary supplements, the burden of proof falls on the FDA to show that the supplement is either unsafe or ineffective before the supplement can be restricted or banned. Information about a supplement’s safety and effectiveness is normally gathered only after people using the product develop health problems or complain that the product does not work

The FDA involvement with ephedra in weight-loss supplements began in 1996 after receiving more than 800 reports of adverse events in people taking products containing ephedra. In 1997 the FDA proposed regulating ephedra by requiring that the product carry a warning on the label stating that adults should take no more than 8 mg of ephedra at one time and no more than 24 mg in one day. The proposed regulation was fought by the diet supplement industry. During the course of public comment about the regulation, it became clear that there was little or no standardization of ephedra content among products or even within different batches of product from the same manufacturer. This lack of standardization made it difficult for consumers to know and control how much ephedra they were taking from day to day

In 2002, the FDA commissioned and independent organization to study ephedra-related complications and deaths. As a result of this study, the FDA banned the uncontrolled sale of dietary supplements containing ephedra based on the what the FDA called an “unreasonable risk of illness or injury.” The ban took effect on April 14, 2005

Several supplement makers have challenged the ban on ephedra containing supplements in federal and state courts. They argue that the FDA did not test supplements containing low doses of ephedra for safety and effectiveness and that a total ban on ephe-dra supplements based only on high-dose products was illegal. The FDA took the position that it was unethical to do more human testing of ephedra given the findings that ephedra-containing supplements increase the risk of stroke, heart attack, irregular heart beat, and similar serious cardiovascular events. On October 18, 2006, after several legal challenges, the United States Court of Appeals Tenth Circuit upheld the FDA ban on all ephedra-containing supplements regardless of dose. Nutraceutical Corporation, the plaintiff in the case, vowed to file another a petition for review with the United States Supreme Court

The ban on ephedra-containing supplements continues to be controversial. There is general agreement that ephedra does treat cold symptoms and does help people with short-term weight loss. However, these benefits do not, in the opinion of FDA scientists, outweigh the health risks associated with the ephedra-containing products. Ephedra continues to be legal in countries such as Germany, Japan, India, and China where it is widely used. Ephedra-containing supplements are easily available over the Internet, and it is estimated that several million Americans continue to use them.

Precautions

The FDA warns that no one should take dietary supplements that contain ephedra because they can cause serious, sometimes fatal, side effects. Some individuals choose to ignore this warning. In that case, people with high blood pressure, heart problems, thyroid problems, enlarged prostate , and glaucoma, should avoid ephedra because there is a high risk the supplement will worsen their condition and could cause serious complications. Ephedra-containing supplements should not be given to children, pregnant women, or breastfeeding women.

Interactions

Studies have shown that ephedra interacts with many drugs used in conventional medicine, especially those used to treat heart problems and monoamine oxidase inhibitors (MAOI) used to treat mental depression, anxiety, and phobias.

Complications

At low doses, adverse side effects include headache, restlessness, anxiety, sleeplessness, nausea, difficulty urinating, and racing heart. At high doses, adverse reactions include sweating, enlarged pupils, fever, spasms, and death, usually through heart failure or stroke.

Parental concerns

Ephedra is a dangerous herbal supplement and should not be given to children. Accidental use of ephedra by children can result in serious side effects. In the case of accidental poisoning in the United States, call the national poisoning hotline at 1-800-222-1222, the local hospital emergency room, or emergency services.

Resources

BOOKS

Fillon, Mike. Ephedra Fact and Fiction: How Politics, the Press and Special Interests are Targeting Your Rights to Vitamins, Minerals, and Herbs. Orem, UT: Woodland Pub., 2004

PDR for Herbal Medicines, 3rd ed. Montvale, NJ: Thompson Healthcare, 2004

Pierce, Andrea. The American Pharmaceutical Association Practical Guide to Natural Medicines New York: William Morrow, 1999.

PERIODICALS

Bent, S., et al. “The Relative Safety of Ephedra Compared With Other Herbal Products.” Annals of Internal Medicine 138, no. 6 (March 18, 2003): 468-71

Harrison, Todd. “Ephedra: The Real Story.(INDUSTRY NEWS).” Nutraceuticals World 9, no. 9 (2006): 24-25

Shekell, P., S. Morton, M. Maglione, et al. “Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects.” Evidence Report/Technology Assessment No. 76 AHRQ Publication no. 03-E022, (February 2003).

ORGANIZATIONS

Alternative Medicine Foundation. P.O. Box 60016, Potomac, MD 20859. Telephone: (301) 340-1960. Fax: (301) 340-1936. Website: <http://www.amfoundation.org>

National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gathersburg, MD 20898. Telephone: (888) 644-6226. TTY: (866) 464-3615. Fax: (866) 464-3616. Website: <http://nccam.nih.gov>

Natural Standard. 245 First Street, 18th Floor, Cambridge, MA 02142. Telephone: (617) 444-8629. Fax: (617) 444-8642. Website: <http://www.naturalstandards.com>

Office of Dietary Supplements, National Institutes of

Health. 6100 Executive Blvd., Room 3B01, MSC 7517, Bethesda, MD 20892-7517 Telephone: (301)435-2920. Fax: (301)480-1845. Website: <http://dietary-supplements.info.nih.gov>.

OTHER

“Ma Huang.” Drugs.com February 13, 2004. [cited May 3, 2007]. <http://www.drugs.com/mtm/ma_huang.html>

Mayo Clinic Staff. “Ephedra (Ephedra sinica)/Ma Huang.” MayoClinic.com [cited May 3, 2007]. < http://www.mayoclinic.com/health/ephedra/NS_patient-ephedra>

Medline Plus. “Ephedra (Ephedra sinica).” U.S. National Library of Medicine, December 1, 2006. [cited May 3, 2007]. <http://www.nlm.nih/gov/medlineplus/druginfo/natural/patient-ephedra.html>

“Ephedra Consumer Advisory.” National Center for Complementary and Alternative Medicine. October 2004. [cited May 3, 2007]. <http://nccam.nih.gov/health/alerts/ephedra/consumeradvisory.htm>

Tish Davidson, A.M.

Ephedra

Ephedra, a short form for the scientific name ephedra sinica, is also known as ma huang, Mormon tea, and other descriptions. Ephedra leaves have been a component of the holistic practices known as traditional Chinese medicine (TCM) for over 3,000 years. The healing and recuperative qualities of the ephedra leaves have been highly valued in the treatment of numerous physical conditions.

Ephedra is a green shrub-like plant native to various parts of China, Japan, and eastern Asia. A similar species was discovered by the settlers to the western United States in the early 1800s, and the plant is now cultivated in various parts of the world. Ephedra is particularly effective in the reduction of swelling in the mucous membranes of the nose and the breathing passages leading to the lungs. Breathing disorders such as asthma and hay fever have proven especially responsive to ephedra treatments. Ephedra leaves, when administered either as a tea or in combination with other herbs, were also known to create a general stimulant effect on the heart and the central nervous system. Ephedra remains a popular natural supplement in both sports specific formats as well as those intended to promote general health and wellness.

The substance that provides ephedra with its therapeutic properties are the alkaloids (a nitrogen-based substance that is neutralized by acids) known as ephedrine and pseudo-ephedrine. Both ephedrine and pseudo-ephedrine are stimulants, each very similar in chemical composition to the other, and each possessing properties similar to those of the natural hormone and stimulant adrenaline. Depending upon the source of the ephedra, ephedrine will comprise between 30% and 90% of the active stimulant in ephedra. Ephedrine is extracted from ephedra leaves to produce crystals that are highly soluble in water; for this reason ephedrine may be readily added to powdered solutions or used in the manufacture of tablets.

The important effects of ephedrine upon the systems of the human body are: central nervous system stimulation; a restriction of blood vessels in the extremities of the body; an increase in heart rate; a corresponding increase in blood pressure; an opening of the bronchial passages and ease of breathing.

Since the 1970s, ephedra has attracted significant attention in North America for its perceived enhancement of athletic performance as a stimulant and its weight loss capabilities. It also acts as an agent to induce thermogenesis, which is the utilization of body fat stores as an energy source. All of these applications have generated controversy centering on the safety of ephedrine usage.

Ephedrine, as a component of over-the-counter cold medications, enjoyed a strong underground reputation as a stimulant among athletes in many sports. National Hockey League (NHL) players have been reputed to be among the most persistent ephedrine users, who consume the substance in the form of Sudafed, an over-the-counter cold medication. Hockey players are on the ice in shifts lasting no more than 60 seconds at a time, and the players have found that the ephedrine seems to provide an edge in their performance. The World Anti-Doping Agency (WADA) lists ephedrine as a prohibited substance, rendering an athlete liable to disqualification from an international sporting event and accompanying suspension, if the ephedrine found present in the athlete's system exceeds 10 micrograms per milliliter (mcg per ml). There is a consensus in the international sport science community that ephedrine is a reasonably effective performance-enhancing drug. Given the wide availability of ephedrine in commercially available formulations, elite athletes who are subject to rigorous drug testing and formidable consequences for a positive test, must themselves be very cautious regarding what supplements they consume as part of their preparation for competition, as the chance of an inadvertent consumption of ephedra or ephedrine is always present.

Ephedrine has generated controversy in a number of countries for its effects in addition to those regarding athletic performance. Ephedra, in its herbal form (and refined ephedrine) were long-time staples in various weight-loss formulations. Stimulants of all types are known to depress appetite; research—including that conducted by the U.S. Food and Drug Agency (FDA)—tended to demonstrate an increase risk of heart attack among some type of ephedra users, particularly those with pre-existing high blood pressure. The FDA moved to ban the sale of all ephedra supplements in the United States in 2004, in the face of significant public protests.

Thermogenesis (expenditure of energy by the body) became a popular athletic training concept, particularly among body builders seeking to reduce body fat content. Thermogenesis supplements sought to force the body, in some circumstances, to utilize fat stores for the production of energy during exercise as opposed to carbohydrate stores. A number of supplements were formulated using ephedrine, often in combination with caffeine, to stimulate the body. The true effectiveness of thermogenetic products is not well established; the use of stimulants, especially in combination, poses risks to persons with pre existing heart or circulatory problems.

see also Caffeine; Doping tests; Nervous system; Stimulants; World Anti-Doping Agency (WADA).