James Locke, a flight surgeon at NASA's Johnson Space Center in Houston, has made dozens of people sick in the name of science. When he puts subjects in a spinning chair designed to induce motion sickness, roughly 70 percent of them succumb—and at nearly the exact same point on each ride. Locke has used this research and his work with shuttle astronauts to determine which medications and doses best prevent the nausea and vomiting associated with motion sickness.

Unfortunately, while the chair always goes through precisely the same motions, the real world is less predictable. In a ship at sea or on a small plane in turbulence, for example, the type and amount of motion can vary dramatically—and so can its effects on people.

Researchers like Locke, and those who work with pilots and the military's most frequent flyers, are especially keen to find better ways to treat motion sickness. And the many civilians who face nausea in cars, planes, boats or even the tamest amusement park rides would welcome a cure without the common side effects of current medications, such as sleepiness, or the questionable efficacy of alternative treatments, such as pressure bracelets. The path to those ends remains bumpy and filled with more than a few green faces, but new research is closer to finding the best treatments to keep both side effects and lunch down.

Eyes vs. ears

Despite decades of research, scientists are still not sure exactly why motion sickness occurs—or how. The currently accepted theory is that sensory conflict is to blame.
"Information from both our visual and vestibular systems is processed by the brain to match it all up. Your vestibular system—your inner ear—is tuned to a terrestrial, 1G environment," Locke says. "When you move [yourself] around, changes in your vestibular system match up with what you're seeing. But [riding] in an airplane or car, your inner ear signals that you're moving, but your eye says you're sitting still" because your body is not moving in relation to its immediate environment—such as the seat you're sitting in, the back of the seat in front of you and the floor beneath your feet.

Why this conflicting input actually causes symptoms such as vomiting is also fairly unclear, says Edwin Park, a neurologist at the Naval Aerospace Medical Institute in Pensacola, Fla.. "Most research has only revealed bits and pieces, and it's all speculation on how it goes together."

A number of neural pathways apparently can activate the brain's vomiting center, thought to be located in the medulla. Studies have shown that certain medications—antihistamines, anticholinergics, amphetamines and serotonin agents—are effective in treating motion sickness, which suggests that it involves the related neurotransmitters: histamine, acetylcholine, noradrenalin and serotonin. Locke says some agents used to treat nausea from other causes, such as food poisoning and chemotherapy, curiously fail to work on motion sickness. Thus, these reactions likely do not involve the same brain pathways as motion-induced nausea.

Locke's data suggest that roughly 30 percent of the population is naturally immune to motion sickness, at least in most conditions. Studies as to why some people are susceptible and others are not have been inconclusive, he says: "So far, we're unable to predict who gets it and who doesn't." Most research has focused, instead, on what helps those who do succumb in controlled conditions, which may also help scientists better manage the condition in the real world.
Drugs and other treatments
Unimpressed with the effectiveness of over-the-counter meds, NASA researchers have experimented with combinations of more heavy-hitting drugs to strengthen astronauts' stomachs, so to speak. Through trial and error, Locke has found that a combination of oral scopolamine, to suppress vomiting, and dextroamphetamine, to counteract scopolamine's potential to induce drowsiness, reduced the incidence of motion sickness from 70 percent to about 12 percent among passengers in the "Vomit Comet"—a DC-9 aircraft used to achieve brief periods of zero gravity as part of NASA's Reduced Gravity Program. Oral or injected scopolamine takes effect more quickly and can be administered in higher doses than the patches commonly used by the general public, but the drug is not as readily available to the public in those forms (NASA orders its own supply).

Multiple studies have shown that people with a history of suffering from migraines are more susceptible to motion sickness. Joseph Furman, a professor in the department of otolaryngology at University of Pittsburgh, recently published a study showing that patients who were prone to migraines that are accompanied by dizziness responded to rizatriptan, a serotonin agonist that is often prescribed to help stop migraine headaches in their early stages. But like motion sickness, scientists do not really know why people get migraines, Furman says. And determining whether the drug would have the same vertigo-alleviating effect on people who do not would require a larger study of rizatriptan's application specifically to motion sickness.    

Additional factors might complicate the full biophysiology of motion sickness, some experts argue. "To say a certain percentage of the population is susceptible to motion sickness is probably an oversimplification," Park says. "There are so many variables involved, including the type and frequency of motion, and a range of tolerance and frequency." In fact, testing motion sickness in the real world is so difficult precisely because conditions and individuals vary so much on a case-by-case and incident-by-incident basis.

Park thinks anxiety makes people more susceptible, for instance, and having a sense of control over a situation makes them less so—which might explain why people are more likely to get sick riding in a car or aircraft than when they are driving or at the controls. He has used desensitization training, exposure to motion in an artificial environment (the same type of spinning chair Locke uses), and biofeedback, in which subjects learn to control their own breathing, heart rate and other physical responses, to help flyers deal with motion sickness.

Park, who works with those in training to be U.S. Navy flyers, relies on conditioning more than medication and says most of his subjects develop increased tolerance after a few wild flights. "One of the best countermeasures for motion sickness is adaptation," says Catherine Webb, a research psychologist with the U.S. Army Aeromedical Research Laboratory in Fort Rucker, Ala. She notes that about 95 percent of people will eventually adapt to a motion environment, citing single-day intervals between brief motion sessions as the optimal pacing.

Locke agrees desensitization can work—you can "get your sea legs," he says—but the time that such training requires has proved impractical given astronauts' busy premission schedules. It would also be tough, he suspects, for the typical civilian's sailing excursion or dive trip, and unpredictable conditions could work against the desired outcome. And as Webb notes, adaptation can be quickly lost if exposure or training are not continued.

Also, Locke is not convinced that being in control or using biofeedback are effective. In experiments with the motion sickness–inducing chair, he has not seen any difference in results based on a subject's well-being or mental state. "It doesn't matter how they feel before the test," he says. "An individual hits the point [of feeling sick] at the same time every test."
Studies of nondrug remedies such as consuming ginger and wearing wristbands that have pressure pads on them have not provided clear results. "The trick is that you have to test properly under controlled conditions to find out what works," Locke says. And so far, in his opinion, these alternative treatments have not been rigorously tested.

Sick or sleepy
Currently available medications to treat motion sickness suppress vestibular sensations or other brain processes, so as a rule, they make people drowsy or otherwise impaired. Scopolamine, for example, can cause drowsiness and dry mouth. It also affects vision, although a recent study reported that these effects did not seem to be clinically important. Scopolamine's side effects increase with repeated use and with age; Locke says elderly people can become delirious or even psychotic when taking it.
Side effects of rizatriptan can include fatigue, sleepiness, dizziness and nausea. Promethazine, or Phenergan, a traditional antinausea medication Locke has studied, is also sedating. In tests, people who took it were fairly impaired but did not seem to be aware that they were.   
The type of medication, its dosage and the timing of its administration are key to maximizing effectiveness and minimizing side effects. But, Locke says, most physicians are not well versed in such details in the treatment of motion sickness.   
"There's not a lot of information out there, and much of what does exist is wrong," Locke says. "So far, there's no magic bullet." Future studies could develop algorithms for the most effective and least side effect–inducing strategies for dosing, he says. Also, more research is needed on other fronts, including more conclusive studies to test theories on why motion sickness occurs; treatment for unpredictable situations translated from controlled ones; well-designed studies to test the efficacy of alternative treatments. In addition, studies could fine-tune methods of administrating medicines and develop guidelines for medical practitioners; evaluate the effects of age on motion sickness susceptibility; and identify new and better agents for treating motion sickness, including non-pharmacologic ones. "We could gain a lot from work to identify better agents," Locke says, "and to look specifically at more effective use of existing medications."