For many, the word thalidomide conjures up tragic images of babies born without normal arms and legs. An over-the-counter sedative, thalidomide was used by several thousand pregnant women in Europe, Canada, Japan and Australia between 1958 and early 1960 to ease their morning sickness. But many who took the drug in the early stages of pregnancy gave birth to babies with severe birth defects. The manufacturer withdrew the drug from the market in late 1960 after it was associated with these unexplained fetal abnormalities.

Manufactured in Germany, the drug was never approved by the Food and Drug Administration (FDA) for use in the United States because of concerns about peripheral neuropathy — a functional or structural change in the nerves of the arms and legs — and other concerns about its safety in humans.

By the time thalidomide was banned worldwide, more than 10,000 children had been born with major thalidomide-related problems. A common pattern of limb deformities emerged, including shortened or missing arms with hands extending from the shoulders, absence of the thumb and the adjoining bone in the lower arm, and similar problems with the legs and feet. The drug also caused abnormalities in the eyes, ears, heart, genitals, kidneys, gastrointestinal tract — including the lips and the mouth — and nervous system.

In short, thalidomide proved to be a very powerful agent in causing physical defects in an embryo or fetus. But researchers are now taking a second look at this notorious drug as a potential treatment for certain severe or life-threatening diseases, such as leprosy, lupus and complications of AIDS.

After the sale of thalidomide was banned, the drug remained a focus of research. In the early 1960s, an Israeli dermatologist, Jacob Sheskin, found that thalidomide was effective in treating a particularly disfiguring complication of leprosy called erythema nodosum leprosum (ENL). Thalidomide was approved in 1998 by the FDA for the treatment of ENL.

"Because of its well-known potential for causing birth defects, thalidomide will be among the most tightly restricted drugs ever to be marketed in the United States," the FDA said in its approval statement.

During the 1990s, other aspects of thalidomide suggested it had therapeutic potential.

• Immunomodulatory properties. Thalidomide has an apparent ability to regulate the immune system, says Angela Dispenzieri, M.D., a hematologist at Mayo Clinic, Rochester, Minn. "Thalidomide's effectiveness in leprosy and autoimmune diseases like rheumatoid arthritis and Behcet's syndrome are likely due to the drug's effect on the immune system."

  Specifically, thalidomide has been shown to inhibit the production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a cell protein that can directly stimulate inflammation. Normally your body contains only traces of TNF-alpha, but its levels are significantly higher in chronic inflammatory conditions.

  Such anti-inflammatory effects may be of benefit in treating such diseases as lupus, Crohn's disease, graft-versus-host disease, Sjogren's syndrome and certain AIDS-related problems.

• Anti-angiogenic properties. Angiogenesis is the medical term for the formation of new blood vessels. Thalidomide is anti-angiogenic, meaning it has the ability to stop blood vessels from forming. This property may explain the drug's ability to cause birth defects, says Dr. Dispenzieri.

  "I don't think thalidomide is a mutagen (a substance that increases frequency of genetic mutations) in the standard sense," says Dr. Dispenzieri. ''What it seems to have done in those babies exposed to it during fetal development was prevent the vessels from sprouting out and guiding the growth or development of the limbs. This matter, however, remains controversial."

  Tumors also require blood vessels to grow and spread. If thalidomide is anti-angiogenic, then it's possible it could stop the growth and spread of some cancers. It also might be helpful in treating macular degeneration, a condition that leads to the loss of central vision when the growth of abnormal new blood vessels occurs in the central portion of the retina.

Diseases and conditions for which thalidomide is being studied include:

• Lupus erythematosus
• AIDS-related disorders such as wasting syndrome, Kaposi's sarcoma and severe mouth ulcers
• Mouth and genital ulcers related to Behcet's disease
• Cancers such as multiple myeloma and advanced colon cancer
• Crohn's disease
• Chronic graft-versus-host disease
• Sjogren's syndrome
• Rheumatoid arthritis
• Macular degeneration
• Leprosy
• Reflex sympathetic dystrophy

"I work with people who have myeloma (bone marrow cancer), and in some cases we prescribe thalidomide," says Dr. Dispenzieri. "About 25 percent to 40 percent of the people with hard-to-treat myeloma respond to it as a single agent. When it is combined with a corticosteroid, responses are seen in about half of patients treated. There is similar activity in patients with newly diagnosed myeloma."

Dr. Dispenzieri says that ongoing clinical trials of thalidomide include people who have advanced myeloma and early-stage disease. "We're seeing some very nice responses," says Dr. Dispenzieri. "The duration of the response is about one year. Though it's an exciting new treatment for myeloma, it's not a cure."

Dr. Dispenzieri says it's too early to say whether treatment with thalidomide increases the overall life expectancies of those who take it. "Until you do a randomized, controlled study you can't say that with 100 percent certainty. So far, the data show only that we're helping some people for a period of time. It is progress."

Although thalidomide is receiving attention in the scientific community, the drug is still in the investigative and trial stages and must be used cautiously to prevent potential side effects. Side effects include:

• Sleepiness
• Constipation
• Skin rash
• Peripheral neuropathy
• Mood changes
• Dry mouth
• Nausea
• Headache
• Constipation
• Increased appetite
• Puffiness of the face and limbs (edema)
• Dry skin
• Itching
• Irregular menstrual period
• Low white blood cell count
• Thyroid problems
• Blood sugar that is too high or too low
• Slow heartbeat

Thalidomide often causes drowsiness. If you take thalidomide, avoid drinking alcohol or taking other medications that make you drowsy. Thalidomide can reduce your ability to drive or operate machinery. It can reduce your alertness and ability to think clearly.

Thalidomide might also cause nerve damage. It isn't known whether this nerve damage is reversible after the drug is stopped. Symptoms of nerve damage include burning, numbness or tingling in your arms, hands, legs or feet. Call your doctor if you have any questions or experience any of these or other troubling symptoms.

Your doctor may do special laboratory tests to check for nerve damage. If nerve damage is found, you and your doctor will decide whether the benefit you might be receiving from thalidomide outweighs the risk of possible permanent damage to your nerves.

Take your medication exactly as prescribed by your doctor. If there's anything you don't understand, ask your doctor to explain it. Check with your doctor before taking any other prescription or over-the-counter medication. If you develop a skin rash with or without a fever, rapid heart beat or low blood pressure, immediately stop taking thalidomide and contact your doctor.

The Food and Drug Administration (FDA) urges you to follow these rules if taking thalidomide:

• Don't take thalidomide if you're pregnant.
• Take a blood or urine pregnancy test before starting treatment. Test results must show you aren't pregnant. The test should be conducted and interpreted by your doctor. The test must be repeated every month while you're taking thalidomide and 4 weeks after your last dose. More frequent pregnancy tests may be needed if you have an irregular menstrual period, vaginal bleeding or you miss a period.
• Abstain from sexual intercourse or use two highly effective birth control methods at the same time for at least 1 month before receiving thalidomide. Continue these methods until 1 month after the last dose of thalidomide. Ask your doctor about birth control options.
• Don't take thalidomide if you're breast-feeding.

Stop taking thalidomide immediately and inform your doctor if:

• You have a late or an irregular menstrual period
• You stop practicing abstinence
• You stop using birth control
• You think you're pregnant
• You become pregnant. Contact your doctor to discuss whether to continue your pregnancy.

Males

Abstain from sexual intercourse or use a condom during intercourse while taking thalidomide and for 1 month afterward. It's not known if thalidomide is present in male ejaculate (semen).