Ephedra

Ephedra

Common names: ma huang, epitonin

Background

Ephedra is an herbal medication obtained from the woody stems of Ephedra sinica, a shrub native to the semiarid and desert areas of Asia, Europe, and Africa. Ephedra sinica is the most commonly used species for medicinal purposes, but other species have also been described. This herbal medication has a long history in traditional Chinese medicine in which it is known as ma huang.

Uses

Ephedra was traditionally given to induce perspiration and treat respiratory conditions including asthma, bronchitis, allergic rhinitis, and upper respiratory tract infections. Today, it is still used to treat respiratory disorders. The German Commission E has approved ephedra for "diseases of the respiratory tract with mild bronchospasm in adults and children over the age of 6." The World Health Organization has determined its effectiveness in treating nasal congestion and asthma. The known pharmacological effects of ephedrine, the major active alkaloid in ephedra, suggest that ephedra is an effective bronchodilator.

Recently, ephedra has gained popularity as a weight loss aid. In 1998, 2% of obese Americans and 1% of the general population took over-the-counter weight loss products containing ephedra. These figures are likely to increase in the future, particularly in light of an FDA proposal in 2001 to withdraw approval of phenylpropanolamine, another popular over-the-counter drug for weight loss. Ephedrine is often combined with caffeine to promote weight loss by increasing thermogenesis and reducing appetite. In a randomized controlled trial, an ephedra/caffeine preparation produced significant weight loss in obese subjects. However, in this study, 23% of the actively treated subjects withdrew because of side effects.

Ephedra has also gained popularity as an ergogenic (physical performance enhancing) aid. Individual ephedrine alkaloids did not affect physical performance, but the combination of ephedrine and caffeine improved physical performance as determined by exercise time to exhaustion. This combination of ephedrine and caffeine may be unsafe because it also causes greater tachycardia than either placebo or ephedrine alone. Moreover, ephedrine is a banned substance in amateur sporting events and is likely to disqualify athletes in drug-tested events.

"Herbal ecstasy" preparations that are advertised as safe alternatives to illegal street drugs contain ephedra. The labels of such preparations claim or imply that they produce euphoria and increase awareness, energy, and sexual sensation.

Phytochemistry and pharmacology

Unlike those in many herbs, the pharmacologically active constituents in ephedra are well characterized. They consist of ephedrine and ephedrine-related alkaloids, primarily pseudoephedrine, norephedrine, methylephedrine, and norpseudoephedrine. Commercial preparations may be standardized to ephedra alkaloid content, but content can vary considerably among manufacturers.

Ephedrine, the primary alkaloid in ephedra, is a noncatecholamine sympathomimetic agent that exhibits α1, β1, and β2 activity by acting directly at adrenergic receptors and by indirectly releasing endogenous norepinephrine. Ephedrine caused dose-dependent increases in blood pressure and heart rate. However, ephedra inconsistently increased heart rate and blood pressure in healthy, normotensive volunteers after a single dose.

The pharmacokinetics of ephedrine have been studied in humans. It has an elimination half-life of 4.85-6.47 hr and is excreted unchanged in urine. The pharmacokinetics of ephedrine do not depend on whether it is taken alone or in unprocessed ephedra.

Safety

The use of ephedra has raised serious safety concerns. Its sympathomimetic effects have been associated with adverse events in the central nervous and cardiovascular systems including hypertension, arrhythmias, stroke, seizures, and death. Most of these adverse events have occurred in healthy young or middle-aged adults who used ephedra for weight loss and increased energy. In at least one case, ephedra was also been associated with eosinophilic myocarditis. As a result, ephedra should be avoided by those with hypertension, cardiovascular disease, cerebrovascular disease, seizure disorders, thyrotoxicosis or pheochromocytoma. It should not be taken with caffeine or other stimulants. It should also be avoided by pregnant or nursing patients and by those taking MAO inhibitors and cardiac glycosides.

The long-term abuse of dietary supplements containing ephedrine has been reported to cause radiolucent kidney stones that by some estimates, account for 0.064% of all cases of nephrolithiasis.

In 1997, the FDA proposed to (1) restrict the amount of ephedrine alkaloids in dietary supplements to 8 mg or less, (2) limit intake of ephedra alkaloids to 8 mg in a 6-hour period and 24 mg in a day, (3) require a warning against use for more than 7 days, (4) require the label statement "Taking more than the recommended serving may result in heart attack, stroke, seizure, or death," and (5) prohibit the combination of ephedrine alkaloids with other stimulants. These proposals were subsequently withdrawn due to criticisms by the General Accounting Office that the scientific evidence supporting them was weak. In spite of the criticism, some states have individually adopted regulations similar to the ones proposed by the FDA.

For detailed safety information, please read U.S. government agencies website.

Preparations and dosage

Ephedra should be used with caution, especially when it is in combination with caffeine. It should not be taken for prolonged periods. Daily doses of ephedra alkaloids should be limited to 24 mg per day.