Drug: Melatonin
N/A

Jet lag resulting from rapid flight across several time zones is a common complaint of travelers. The symptoms of jet lag are primarily described as daytime sleepiness, fatigue, and impaired mental efficiency and can also include weakness and irritability. It is considered to be due to the desynchronization between the internal circadian rhythm and the new local day-night cycle at the traveler's destination. A means of rapidly resynchronizing the circadian rhythm to the local time would benefit people who suffer severely from this syndrome.

What actually underlies jet lag is a question that has not been fully answered. Various endogenous hormones, including cortisol and melatonin, have a natural circadian rhythmicity and play a role in maintaining the body's internal clock. Cortisol is produced by the hypothalamic- pituitary-adrenal axis in a circadian manner and in response to stress. Normal cortisol has a diurnal rhythm with a maximum level in the morning and a nadir during the night. While a time shift does not change the total daily amount of cortisol that is secreted, the temporal organization of the cortisol secretions is disrupted and the circadian rhythm does not re-entrain for several days. Thus, the first few mornings in a new time zone can be considered relatively cortisol-deficient because the traveler does not experience the peak of cortisol at the time of awakening. Taking exogenous glucocorticoids at the proper time may help re-entrain the circadian rhythm faster and result in less jet lag.

Melatonin is a hormone that is secreted nocturnally by the pineal gland. Exposure to bright light diminishes its release while darkness triggers it. A recent meta-analysis has shown that taking melatonin can alleviate symptoms of jet lag.

The aim of the present study is an attempt for the first time to attenuate jet lag symptoms with hydrocortisone, melatonin, a combination of both hydrocortisone and melatonin or placebo.

Forty-eight normal volunteers will be randomized in blocks of eight to one of four treatment arms: hydrocortisone (25 mg) alone, melatonin (5 mg) alone, hydrocortisone (25 mg) and melatonin (5 mg) in combination, and placebo. Volunteers will travel in an eastwardly direction across 6-8 time zones. Upon morning arrival at the new destination, volunteers will obtain a saliva sample and then take 25 mg hydrocortisone (or placebo). At the target bedtime of (10 pm to midnight local time) they will take 5 mg of melatonin (or placebo). Volunteers will wake up at 7 am-10:30 am (local time) and take 25 mg hydrocortisone (or placebo). Subjects will repeat these dosages for 3 days for a total of four days. Participants also will obtain salivary samples of cortisol and melatonin on awakening and at bedtime on one day before travel and at the new destination for days 1 - 4, 7 and 10 after arrival. The primary outcome measure will be subjective rating of jet lag and components or correlates of this such as fatigue and daytime tiredness. Subjects will keep sleep logs and fill out a symptoms questionnaire daily for 3 days before and 4 days after the flight and on days 7 and 10. Secondary outcomes will be the measurement of salivary cortisol and melatonin. The data obtained from this study will provide an assessment of effective treatment of jet lag syndrome and will provide a better understanding of the role of hormones in the disruption of the circadian rhythm.