Ephedra

Chad Bradshaw

General Description:

Ephedra is an erect branching shrub that can be found in arid regions all over the world. The shrubs can be anywhere from 1 and 1/2 to 4 feet tall and generally grow on dry, rocky, or sandy slopes. The branches are slender and have two very small leaf scales at each node. In the fall, the mature, double-seeded cones are visible. The nodes of the ephedra plant are said to be toxic.

Chemical Composition:

Most significant is the alkaloid content, which can reach 3.3%. 40-90 percent of this content is ephedrine and the remaining alkaloids are primarily pseudoephedrine and norpseudoephedrine.

History and Folk Use:

Ephedra has a history of medicinal use which dates back to 2800 BC. The stem and branch (Ma Huang) was used to treat the common cold, asthma, hay fever, bronchitis, edema, arthritis, fever hypotension, and urticaria. The root and rhizome (Ma Huanggen) was used to treat profuse night sweating. Western medicine's interest in ephedra began in 1923 and was first synthesized in 1927. It is now used extensively in over-the-counter cold and allergy medications.

Pharmacology:

Ephedrine:

Ephedrine's basic pharmacological action resembles epinephrine (adrenaline), but is considerably less active. Ephedrine can also be absorbed orally, unlike epinephrine. Ephedrine also has a longer duration of action and more pronounced effects on the brain and central nervous system. These CNS effects resemble amphetamines, but are less potent. Ephedrine increases blood pressure, cardiac output, and heart rate, but these effects last about ten times longer than epinephrine. Ephedra will also increase heart, brain, and muscle blood flow - thus compromising blood flow to the kidney and intestine. Ephedrine also relaxes bronchial and uterine muscle.

Pseudoephedrine:

Pseudoephedrine also relaxes bronchial muscle, but its effects on the heart and and CNS are weaker. It may also possess some antiinflammatory effects.

Clinical Applications:

Asthma and hay fever:

Ephedra and its alkaloids are effective bronchodilators. Peak bronchodilation effect occurs in 1 hour and lasts about 5 hours after administration. Ephedra is often prescribed in combination with substances that support the adrenal glands such as licorice, ginseng, vitamin C, magnesium, zinc, vitamin B6, and panthothenic acid. This is done because many believe that tachyphylaxis develops to ephedra with long-term use. However, APhA does not believe that this is a "significant problem [as evidenced by the] scientific literature." A 1977 JAMA study of ephedrine in pediatric asthma therapy concluded: "Ephedrine is a potent bronchodilator that, in appropriate doses, can be administered safely along with therapeutic doses of theophylline without the fear of progressive tolerance or toxicity."

Expectorants such as licorice, grindelia, euphorbia, sundew and senega may also be prescribed along with ephedra to improve the quality and quantity of bronchial secretions.

Weight Loss Aid:

Ephedra does not suppress appetite, but it will promote weight loss by increasing the metabolic rate of adipose tissue. The effects are greatest in individuals with a low basal metabolic rate and/or decreased diet-induced thermogenesis.

Diet-induced thermogenesis is the direct conversion of ingested food into heat. A lean individual may produce a 40% increase in heat production, whereas an obese individual may only produce a 10% increase in heat production. In these people, the food energy is stored instead of converted to heat. The degree of heat production is controlled by the sympathetic nervous system. Ephedrine can activate the sympathetic nervous system, thereby increasing the metabolic rate and thermogenesis. The result is weight loss.

Substances such as methylxanthines (coffee, tea, cola nut, guarana) and salicylates (aspirin, mint, oak) can enhance the thermogenic effects of ephedrine. In one animal study, ephedrine used alone produced a 14% loss in body weight and a 42% loss in body fat. When ephedrine was combined with theophylline or coffee, a loss of 25% body weight and 75% body fat was observed. Caffeine or theophylline used alone produced no significant loss of body weight.

Clinical Trials:

Ephedrine Only:

Studies examining ephedrine as a sole weight loss agent have yielded inconsistent results. One study gave overweight individuals either placebo, 25 mg ephedrine, or 150 mg ephedrine TID. Caloric intake was restricted to 1000 calories for women and 1,200 calories for men. Weight loss was similar in all groups, but the ephedra group displayed significantly more side effects than the other groups.

Another study treated 10 obese women with diet therapy (1,000-1,400 calories/day) and either ephedrine (50 mg TID) or placebo for 2 months and then crossed over. Results showed that weight loss was significantly greater during the ephedrine period (5.3 lbs) than during the placebo period (1.4 lbs).

The reason for these difference seems to be that ephedrine is effective primarily in people who have defects in diet-induced thermogenesis. In addition, it appears that ephedrine alone is not as effective as when it is used in combination with other products.

Ephedrine with methylxanthines:

One study treated 180 overweight patients with diet and either an ephedrine-caffeine combination (20mg/200mg), ephedrine alone (20 mg), caffeine alone (200 mg) or placebo TID x 24 weeks. Mean weight loss at 24 weeks was significantly greater in the group given the ephedrine-caffeine combination (average=36 lbs weight loss) compared to the placebo group (29 lbs weight loss). Groups receiving ephedrine or caffeine only showed similar results to the placebo group. Side effects such as tremor, insomnia, and dizziness were transient and by week 8 there was no difference in side effects between the groups. Both systolic and diastolic blood pressures fell similarly in all four groups, indicating the weight loss promoted by ephedrine and caffeine counteracts any increase in blood pressure these substances may promote.

Ephedrine and aspirin:

One study investigated the effect of ephedrine (30 mg) and aspirin (300 mg) on the acute thermogenic response to a liquid meal of 250 kilocalories in lean and obese women. Following the meal-only treatment, the mean increase in metabolic rate was 0.17 kcal (lean) and 0.13 kcal (obese) per minute. With the meal-plus-ephedrine treatment, the corresponding rises were 0.21 and 0.19 kcal/minute. Finally, with the meal-plus-ephedrine and aspirin treatment, the rise was 0.23 kcal/min in both groups.

Another study examined the safety and efficacy of a mixture of ephedrine (75-150 mg), caffeine (150 mg), and aspirin (330 mg) in divided premeal doses, compared to placebo in 24 obese humans. Dietary intake was not restricted. Overall 8-week weight loss was 4.84 lbs for the combination group versus 1.5 lbs for the placebo group. Eight placebo individuals returned 5 months later and received the combination treatment. 8-week weight loss for these participants was 7 lbs compared to 2.86 lbs for the period which they were on placebo. After 5 months on ephedrine-caffeine-aspirin combination, the average weight loss in 5 subjects was 11.44 lbs. In all studies, no significant changes in heart rate, blood pressure, blood glucose, insulin, and cholesterol levels, and no differences in the frequency of side effects, were found between groups.

Dosage:

The appropriate does depends on the alkaloid content. The average total alkaloid content of ephedra is 1-3%. For asthma or weight loss, the dose should contain an ephedrine content of 12.5-25.0 mg and be taken BID-TID. For the crude herb, this would require a dose of 500-1000 mg TID. Some extracts are standardized to an alkaloid content of 10%, which would make 125-250 mg TID an effective dose.

Toxicity:

Side effects are the same as ephedrine (increased blood pressure, increased heart rate, insomnia, and anxiety). The FDA recommends that ephedrine not be taken by patients with heart disease, hypertension, thyroid disease, diabetes, or urinary retention due to prostate enlargement. It should also not be taken by patients using antihypertensives or antidepressants.

Ephedra and ephedrine are often abused drugs. They can be found under multiple brand names and are named "the poor man's speed." They are frequently consumed in very high doses to produce euphoria and to increase energy. These high doses can be dangerous due to the tremendous cardiovascular effects of ephedrine.

References:

Murray Michael T: The Healing Power of Herbs. Prima Publishing, California, 1995, pp. 108-115.

Jones, Andrea and Arlen Rash.  Ephedra.  Presentation Handout, Pharmacy 100, Fall Semester 1997; UNC School of Pharmacy, Chapel Hill, NC.