Drugs & Medication

Species of Ephedra have traditionally been used by indigenous people for a variety of medicinal purposes, and are a likely candidate for the Soma plant of Indo-Iranian religion. Also known as ma huang, it was used in Traditional Chinese Medicine up to 5,000 years ago for the treatment of asthma and hay fever, as well as for the common cold.^[1].

In recent years attention has been focussed on the safety of ephedra by the Food & Drug Administration and critics in the biomedical community due to the use of the herb as a stimulant and a dieting aid. As a result of adverse effects of ephedra overdose to the cardiovascular system, Western medical professionals recommend against the consumption of any ephedra.[2] Despite these warnings, ephedra is a safe herbal medicine when prescribed in appropriate doses by trained practitioners of Traditional Chinese Medicine^[3].

Contents 1 Chemistry 2 Effects 3 Safety 4 Regulatory history in the United States 5 In professional sports 6 External links 7 References

Chemistry

The alkaloids ephedrine and pseudoephedrine are the active constituents of the plant. Pseudoephedrine is used in over-the-counter decongestants. Ephedrine is used to treat low blood pressure, but alternatives with reduced cardiovascular risk have replaced it for treating asthma. It is also considered a performance-enhancing drug and is prohibited in most competitive sports. Some species in the Ephedra genus have zero alkaloid content and are therefore essentially inert, however the most commonly used species, Ephedra sinica, has a total alkaloid content of 1–3% by dry weight. Ephedrine constitutes 40–90% of the alkaloid content, with the remainder consisting of pseudoephedrine and the demethylated forms of each ^[4].

Effects

Ephedra is both a stimulant (similar to adrenaline) and a thermogenic. It stimulates the brain, increases heart rate, constricts blood vessels (increasing blood pressure), and expands bronchial tubes (making breathing easier). Its thermogenic properties cause an increase in metabolism, evidenced by an increase in body heat.

In traditional Chinese herbology, ephedra is most notably included in many herbal formulas that treat cold and flu such as ma huang tang (ephedra decoction) or ma xing shi gan tang (ephedra, apricot kernel, gypsum, and licorice decoction). Ephedra is used therapeutically as a diaphoretic to help expel exterior pathogens and regulate the proper functioning of the lung.^[5].

Side effects of ephedra overdose may include irritability, nervousness, dizziness, trembling, headache, insomnia, profuse perspiration, dehydration, itchy scalp and skin, vomiting and hyperthermia.

Safety

Just like other stimulants such as Ritalin[6], in high doses ephedra can cause heart attacks, stroke, and seizures[7]. The sale of ephedra is now regulated by the FDA due to the abuse of the herb by dieters and athletes who take it in excessively large doses with the intent of losing weight and enhancing athletic performance.

The FDA maintains that "[ephedra] is dangerous at any dose"^[8]. But there are many people including experienced users of ephedra^[9] who don't agree with the FDA. One popular website with a focus on ephedra questions the FDA's recommendation, asking, "If ephedra is as dangerous as the FDA claims it is, given that the Chinese have been using it for 5,000 years, shouldn't they have experienced enough adverse events to be wary of it? If the FDA is so forceful in its opinion that any amount of natural ephedra is harmful, why does it allow you to buy Big Pharma's synthetic versions of ephedra, 240mg pseudoephedrine^[10] and 25mg ephedrine^[11] without a prescription? Unless natural ephedra is more dangerous than its synthetic form, it's disingenuous to prohibit the sale of natural ephedra if the synthetic form can be sold without a prescription!"^[12]

Ephedra and pseudoephedrine are precusors to methamphetamine. After ephedra was restricted, sales of pseudoephedrine soared (which can be used instead of ephedra in the production of the drug methamphetamine). Sales of decongestants such as Sudafed now have restrictions and are monitored in the United States. However it should be stated that decongestants were popular for the making of methamphetamine prior to the restrictions placed on ephedral products.

Regulatory history in the United States

Beginning in the 1990s, concerns about the safety of Ephedra and Ephedra-based products began to be publicly raised in the United States. Concentrated mixtures were found in weight control products marketed as "dietary supplements". Sympathomimetic amines such as ephedrine raise heart rate and blood pressure and can be particularly hazardous to those with pre-existing cardiac problems. After receiving over 800 reports of "adverse events", the country's federal Food and Drug Administration (FDA) proposed regulations in 1997 for a warning label, and a limited dose of 8mg (no more than 24mg per day).^[13]

After various petitions for and against the regulations, (including complaints about the accuracy of dosage and lack of quality control in the dietary supplement industry ^[14]) the FDA hired the RAND Corporation to do a study in 2002, [15] and eventually linked 155 deaths to Ephedra, most of them caused by cardiac problems and strokes.

In May 2003, the health food store General Nutrition Center announced that they would stop carrying ephedra-containing products as of June 2003. [12]

The FDA must approve all drugs before they may be sold in the United States. It considers the risks and benefits of medications for specific medical conditions, may require a doctor's prescription, make labeling requirements, or ban the drug entirely. The burden of proof for safety is on the manufacturer. The Dietary Supplement Health and Education Act of 1994 creates a class of substances known as dietary supplements, which are not subject to pre-approval, and for which the burden of proof is on the government if it wishes to restrict availability. As a traditional herb, Ephedra qualifies as a dietary supplement.

On December 30, 2003, the FDA announced a ban (effective 12 April 2004) on the uncontrolled sale of dietary supplements containing Ephedra, citing "an unreasonable risk of illness or injury" from the use of the drug. The active ingredients ephedrine and pseudoephedrine remained available as an ingredient in some over the counter (OTC) medications that are clearly labeled in accordance with FDA regulations. Chemicals created in a laboratory do not qualify as dietary supplements, even if they are the same as those found in natural products.

Many advocates maintained that Ephedra was safe in low doses typical of traditional herbal preparations, and that the adverse cardiovascular effects were associated with higher doses.

The Nutraceutical Corporation of Park City, Utah, which had been selling a relatively low dose (10mg, compared to 40mg-100mg doses also on the market) sued the FDA. On 14 April 2005, Utah federal district judge Tena Campbell ruled in favor of the company.^[16] The ruling stated that because of the 1994 law and Ephedra's status as a dietary supplement, the FDA did not have the statutory authority to require the manufacturer to prove that the product offered a benefit, and that it had failed to meet its burden of proof that the 10mg dose posed a sufficient risk. Nutraceutical said that it did not plan to re-introduce Ephedra, and that it had brought the suit merely to protect its other product lines from overzealous regulation by the FDA. The FDA said that it considered further research into the dose-dependent safety of Ephedra to be unethical, given the lack of benefit (other than for short-term weight loss ^[17]) and potential risk.^[18] Critics renewed calls to reform the 1994 dietary supplement law.^{[19] [20]}

The state of California has reinstated Ephedra dietary supplements in January 2006, followed by New York and Illinois. These laws are not affected by the federal court decision. ^[21]

On August 17, 2006 a three judge panel of the United States Court of Appeals for the Tenth Circuit overruled a lower United States District Court decision by Judge Tena Campbell for the District of Utah. ^[22]

On August 18, 2006, Jonathan Emord, the attorney representing Nutraceutical Corporation announced "On or before September 29, 2006, Plaintiff Nutraceutical Corporation will file a petition for rehearing en banc by the entire 10th Circuit." ^[23]

In professional sports

In the 1994 FIFA World Cup, the Argentine footballer Diego Armando Maradona tested positive for ephedrine in a doping control for using one dietary supplement product containing the substance. The Japanese motorcycle racer Noriyuki Haga tested positive for it in 2000, being disqualified from two races and banned from two more as a result.

The U.S. National Football League banned players from using ephedra as a dietary supplement in 2001 after the death of Minnesota Vikings offensive tackle Korey Stringer. The substance is also banned by the National Basketball Association.^[24]

Baseball pitcher Steve Bechler of the Baltimore Orioles died in 2003 after taking the supplement that same year. [13] Later that year, his widow filed a $600 million wrongful death lawsuit against the manufacturer.^[25]

NFL player Todd Sauerbrun of the Denver Broncos was suspended for the first month of the 2006 season after testing positive for the banned supplement ephedra.

External links

• United States FDA links to actions
• FDA Rule
• United States NIH Factsheet regarding weight loss and athletic performance
• About Ephedra Information About Ephedra
• Rootdown.us Information About the traditional Chinese medical use of ma huang and ma huang gen (Ephedra)

References

1. ^ [[1]]
2. ^ [2]
3. ^ [[3]]
4. ^ [4]
5. ^ [[5]]
6. ^ http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682188.html
7. ^ [6]
8. ^ http://www.sltrib.com/portlet/article/html/fragments/print_article.jsp?article=3800052
9. ^ http://health.groups.yahoo.com/group/ephedraforum
10. ^ http://www.sudafed.com/products/24hour.html
11. ^ http://www.drugstore.com/products/prod.asp?pid=152878&catid=9327&trx=29384&tab=0#0
12. ^ http://www.ephedra.com/ephedra-opinion.htm
13. ^ http://injury.findlaw.com/ephedra/ephedra-overview(1).html
14. ^ http://www.webmd.com/content/article/23/1728_56810.htm
15. ^ http://injury.findlaw.com/ephedra/ephedra-overview(1).html
16. ^ [7]
17. ^ http://www.nutraingredients-usa.com/news/printNewsBis.asp?id=60687
18. ^ "Judge's Decision Lifts Ban On Sale of Ephedra in Utah." Gardiner Harris and Jay Schreiber. New York Times. April 15, 2005. [8]
19. ^ http://www.steroidlaw.com/?pageID=49
20. ^ "Experts debating scope of decision." San Diego Union-Tribune. Penni Crabtree. April 16, 2005. [9]
21. ^ [10]
22. ^ http://www.kscourts.org/ca10/cases/2006/08/05-4151.htm
23. ^ http://ephedra.com/news.htm
24. ^ [11]
25. ^ http://injury.findlaw.com/ephedra/ephedra-overview(1).html