Ephedra

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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.