Ephedrine

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See also Ma Huang

Pronunciation: e-FED-rin (also pronounced EF-uh-dreen)

Chemical Abstracts Service Registry Number: 299-42-3. (Hydrochloride form 5098-6; sulfate form 134-72-5) Formal Names: Broncholate Syrup, Elsinore, Kie Syrup, Letigen, Marax, Pretz-D,

Primatene, Rynatuss Informal Names: Chinese Speed, Herbal Ecstasy, Herbal XTC Type: Stimulant (amphetamine class). See page 12 Federal Schedule Listing: Unlisted

USA Availability: Varies by state and by product formulation Pregnancy Category: C

Uses. Although natural products containing the drug have a long history, ephedrine was not isolated from ma huang until the 1880s. Ephedrine is found in other plants as well. It can be refined from plants or synthesized in a laboratory. Despite ma huang's familiar use as a medicinal herb, Western medicine did not accept ephedrine until the 1920s. Ephedrine has found usage in standard medicine, alternative medicine, and recreation. Responding to a survey, 14 companies reported they sold the equivalent of 425 million individual doses in 1995, 976 million in 1997, and 3 billion in 1999.

Some early uses have since become outmoded, such as against leprosy and whooping cough. Weight loss experiments have found ephedrine, alone or in combination with caffeine or aspirin, to be more effective than placebos and also more effective than dexfenfluramine (see fenfluramine). A study found ephedrine useful in helping heavy smokers to reduce the number of cigarettes they consume. Standard medicine has also exploited ephedrine's urinary retention effect to help incontinent persons. The drug has been employed against asthma, runny noses, narcolepsy, painful menstruation, and depression.

In alternative medicine ephedrine is marketed for losing weight, increasing muscle mass, facilitating intellectual concentration, and promoting vigor. A scientific study found that ephedrine in combination with caffeine (but not by itself) significantly improves endurance in physical exercise. Many sports organizations ban use of ephedrine by athletes.

Although not a true amphetamine, ephedrine has qualities reminiscent of that stimulant class and has been commonly used to manufacture illicit meth-

cathinone and methamphetamine. Indeed, ephedrine's chemical relationship to amphetamine and methamphetamine is so close that urine tests can mis-identify ephedrine as those drugs. In an experiment where people received a substance without knowing what it was, ephedrine produced the same physical and mental effects as phenmetrazine, methylphenidate, dextroamphetamine, and methamphetamine. Ephedrine's legal status was in flux as this book was written: Depending on the federal or state jurisdiction, ephedrine might be Schedule IV or a freely available unscheduled substance; commerce as a medical drug might be legal, but commerce as a raw chemical might be a crime.

Drawbacks. Amphetamine was designed in a laboratory to provide a substitute for ephedrine because of the latter's drawbacks. A double dose of ephedrine can be poisonous, in comparison to other drugs with the same therapeutic effects but that require 10 or 20 times the regular dose to become severely toxic. For that reason many physicians prefer to avoid prescribing ephedrine.

Ephedrine can cause skin rash, nausea, diarrhea, constipation, hepatitis, rise in body temperature, jitteriness, insomnia, hyperactivity, irregular heartbeat, high blood pressure, heart attack, stroke, seizures, kidney stones, visual and auditory hallucinations, and paranoid psychosis. Ephedrine can worsen muscle tics; animal experimentation shows the drug causing brain damage that can lead to the tics seen in Parkinson's disease. During strong physical exertion, such as bodybuilding, ephedrine may increase danger of heart attack. Suspicion exists that persons who stop taking ephedrine may be more sensitive to it if they start using the drug again.

Many reports of adverse events come from cases in which a person was using ephedrine diet supplements commonly found in health food stores. Perhaps people regard such products as inherently "healthy" and fail to realize that an ephedrine food supplement can produce a drug overdose or be hazardous if used moderately but for too long.

The U.S. Food and Drug Administration (FDA) became particularly alarmed at the prevalence of medical problems developed by young healthy users, and regulatory efforts were increasing when this book was written. Some scientists say the FDA's concerns are unfounded and that many physical problems after ephedrine ingestion derive from a person's prior medical history or massive overdose. Nonetheless, the FDA believes that ephedrine may harm people who already have the following conditions: prostate trouble, psychological afflictions (including depression and nervousness), high blood pressure, diabetes, glaucoma, and ailments of thyroid, kidney, or heart.

Alcohol is an ingredient in some ephedrine inhalers and can influence readings in breathalyzer tests for drunk driving. That problem can be avoided by a 15-minute wait between using the inhaler and administering a test.

Abuse factors. Historically ephedrine has seldom been abused, but in the 1990s it was cited as growing in popularity among youths, as a recreational stimulant with euphoric and aphrodisiac effects. Such characteristics have allowed illicit dealers to market ephedrine falsely as cocaine, methampheta-mine, and MDMA. Some cocaine users find ephedrine less satisfying but still a satisfactory substitute. Reports of ephedrine addiction exist.

Drug interactions. Caffeine boosts ephedrine's power and can transform a normal dose into a dangerous one. Aspirin and yohimbine (from yohimbe) may also strengthen some ephedrine effects. Dangerous interactions can occur with monoamine oxidase inhibitors (MAOIs, typically antidepressants). Less serious adverse effects may occur if ephedrine is taken with the antiasthma medicine theophylline.

Cancer. The FDA has noted research indicating that substances like ephed-rine may promote lung cancer, especially among tobacco smokers.

Pregnancy. Safety for use during pregnancy is unestablished. The drug is known to raise fetal heart rate, and fetal blood levels can reach about 70% of the pregnant woman's blood level of ephedrine. The drug is transferred to breast milk in sufficient quantity to affect nursing infants, making them grouchy and interfering with their sleep. Chicken experiments with ephedrine produce defects in embryos, but such testing is considered inconclusive regarding human impact. Rabbit experiments find a mix of ephedrine, theophylline, and phenobarbital to cause birth defects similar to those observed in the child of a woman who took that drug combination while pregnant. The same drug combination is suspected in another birth defect case. Although a study of 373 human pregnancies found no malformations attributable to ephedrine even when used in the first trimester, the drug is associated with a small increase in likelihood of birth defects and is not recommended for use during pregnancy.

Additional information. Many nonprescription remedies for common colds include pseudoephedrine (CAS RN 345-78-8), which is related to ephedrine and has similar effects, both desired and undesired. Depending on actions being measured, pseudoephedrine may have from 25% to 50% of ephedrine's strength. Pseudoephedrine can be used to make methamphetamine and meth-cathinone.

Pseudoephedrine is believed to promote a dangerous bowel disease called ischemic colitis, particularly in women around the time they go into menopause. A case report indicates that taking pseudoephedrine with serotonin reuptake inhibitor antidepressants may create a medical emergency called "serotonin syndrome." Typical signs of that condition are hyperactivity, confusion, nervousness, vomiting, fast heartbeat, excessive body temperature, shivering, tremors, weakness, or losing consciousness. Caution is advised about using pseudoephedrine shortly after receiving vaccinations, which temporarily increase body temperature. Nonetheless, in the 1980s research on more than 100,000 individuals using prescription pseudoephedrine found no hospitalizations caused by the drug.

Influence on fetal development is uncertain, although pseudoephedrine is suspected of causing birth defects when used in the first trimester. The drug is known to accelerate fetal heartbeat but has no particular effect on fetal blood flow, nor does the substance seem to hinder passing nutrients and gases between woman and fetus. Although excreted into human milk, the amount of excretion is so slight as to be considered safe for infants of nursing mothers.

Additional scientific information may be found in:

"Adverse Events Associated with Ephedrine-Containing Products—Texas, December 1993-September 1995." Morbidity and Mortality Weekly Report 45 (1996): 689-93.

Astrup, A., et al. "The Effect and Safety of an Ephedrine/Caffeine Compound Compared to Ephedrine, Caffeine and Placebo in Obese Subjects on an Energy Restricted Diet. A Double Blind Trial." International Journal of Obesity and Related Metabolic Disorders 16 (1992): 269-77.

"Dietary Supplements Containing Ephedrine Alkaloids; Proposed Rule." Federal Register 62 (1997): 30677-724.

Gruber, A.J., and H.G. Pope, Jr. "Ephedrine Abuse among 36 Female Weightlifters." American Journal on Addictions 7 (1998): 256-61.

James, L.P., et al. "Sympathomimetic Drug Use in Adolescents Presenting to a Pediatric Emergency Department with Chest Pain." Journal of Toxicology. Clinical Toxicology 36 (1998): 321-28.

Pipe, A., and C. Ayotte. "Nutritional Supplements and Doping." Clinical Journal of Sport Medicine 12 (2002): 245-49.

Whitehouse, A.M., and J.M. Duncan. "Ephedrine Psychosis Rediscovered." British Journal of Psychiatry 150 (1987): 258-61.

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