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Stanford Report, July 23, 2003

Ongoing study explores effects of alcohol, nicotine, donepezil on pilots


Researchers at the medical center and the Veteran’s Affairs Palo Alto Health Care System have found that pilots who take nicotine or an Alzheimer’s drug called donepezil fly better than those in a control group, while those who have consumed alcohol are impaired when flying.

Martin Mumenthaler, PhD, a senior research scientist in the Department of Psychiatry and Behavioral Sciences, analyzed results of previous trials done over a 10-year period on the effects of alcohol, nicotine and donepezil on pilots. The trials, conducted at the Stanford Aviation Safety Laboratory, focused on how the various drugs affected pilot skill in a flight simulator. Results appeared in this month’s issue of the journal Neuropsychopharmacology.

In the nicotine trials, pilots were given either nicotine gum or a placebo before flying in a simulator that mimicked a single-engine propeller plane. Pilots in the donepezil trial took the drug or a placebo for 30 days between two simulator flights. (Donepezil is normally prescribed to help Alzheimer’s patients function better.) Pilots in the alcohol portion of the trial drank either four alcoholic drinks or four placebo drinks. They took one test flight immediately after drinking, when their blood alcohol level was about one-tenth of 1 percent, and another test flight eight hours after their last drink.

Pilots given nicotine or donepezil flew better in the simulator than the control group. Pilots who flew immediately after drinking, however, did much worse in the simulator. Eight hours later, the flight performance of pilots in the alcohol group was still much worse than that of the pilots in the control group. Also, pilots on nicotine or donepezil were better at the same flight tasks, especially on approach to landing. "Pilots are getting tired at that point and landing requires a high amount of sustained attention," Mumenthaler said. "That’s where the drug benefits them most."

Nicotine and donepezil both affect the cholinergic system of the brain, which is involved in human cognition. But the degree of the drugs’ similar effects was a surprise because they work in different ways. Acetylcholine, the main neurotransmitter in the cholinergic system, binds to nicotinic receptors. Nicotine works just like acetylcholine, directly binding to these receptors. But donepezil works indirectly by inhibiting the metabolism of acetylcholine. People with fewer nicotinic receptors may be less able to pay attention, learn and remember; patients with Alzheimer’s disease may have fewer of these receptors, Mumenthaler said.

Mumenthaler cautioned that pilots shouldn’t rely on nicotine or donepezil to improve their flying. Nicotine is addictive and "donepezil can make people dizzy and cause nausea," he said. "You wouldn’t want to be up in the air and have those side effects even if they’re rare."

Several researchers in the Aviation Safety Laboratory are also pilots. The head of the lab, Jerome Yesavage, MD, professor of psychiatry and behavioral sciences, is a licensed commercial pilot. Mumenthaler is licensed for recreational flying. The study, he added, is not pro-smoking despite its findings on nicotine’s effects.

The findings have inspired additional research on nicotine and flying. Now that smoking is prohibited on most commercial flights, pilots who smoke have to endure without cigarettes. On a flight across the Atlantic or Pacific, that could mean more than 12 hours without nicotine. Mumenthaler said pilots who smoke might chew nicotine gum or wear a nicotine patch to help them on such long flights.

The Aviation Safety Laboratory is now recruiting pilots who are smokers for a study on the effects of nicotine withdrawal on flight performance. Prospective volunteers can contact Lisa Wilson at [email protected] or call 493-5000, ext. 66040. The nicotine withdrawal study is being funded by California cigarette taxes through the Tobacco-Related Disease Research Program.

Researchers discover nicotine stimulates growth of new blood vessels (7/11/01)

Grand rounds lecture covers new thinking on nicotine (5/14/03)