A benzodiazepine hypnotic facilitates adaptation of circadian rhythms and sleep-wake homeostasis to an eight hour delay shift simulating westward jet lag

Sleep. 2000 Nov 1;23(7):915-27.


Study objectives: To determine whether appropriately timed administration of a short-acting benzodiazepine hypnotic, which has proven effective in an animal model of jet lag, also facilitates adaptation of circadian rhythmicity and sleep-wake homeostasis in a human model of jet lag.

Design: Subjects participated in two double-blind, placebo-controlled studies of adaptation to an 8-hr delay shift of sleep-wake and dark-light cycles simulating westward travel. Each 9-day laboratory study began with a 3-day habituation period followed by a 24-hr study to obtain basal hormonal and sleep profiles (23:00-07:00). Subjects were then kept awake until 07:00 the next day and slept in darkness 07:00-15:00 for the next five 24-hr spans post-shift.

Setting: N/A.

Participants: 6 normal, healthy men 24-31 years of age.

Interventions: Oral Triazolam (0.5 mg) or placebo given at 04:00 before the first shifted sleep/dark period (3 hours before bedtime) and at 07:00 (at bedtime) on days 2-5 post-shift.

Measurements and results: Sleep recordings and 24-hr cortisol and growth hormone profiles were obtained at baseline and on the first, third, and fifth days post-shift. Global measures of treatment efficacy were calculated for multiple endpoints representing circadian rhythmicity and sleep-wake homeostasis. With placebo, the shift induced disturbances of sleep and hormonal secretion, and a gradual re-entrainment of circadian rhythmicity. Triazolam significantly facilitated adaptation by accelerating re-entrainment of circadian rhythms (chronobiotic effect) and normalizing markers of sleep/wake homeostasis (hypnotic effect).

Conclusions: Appropriately timed administration of a benzodiazepine hypnotic appears to facilitate the adaptation of both circadian rhythmicity and sleep-wake homeostasis to a shifted dark/sleep cycle. Compounds with combined chronobiotic/hypnotic properties may be useful in conditions of jet lag or night work.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological / drug effects*
  • Adult
  • Anti-Anxiety Agents / pharmacology*
  • Anti-Anxiety Agents / therapeutic use*
  • Circadian Rhythm / drug effects*
  • Double-Blind Method
  • Growth Hormone / metabolism
  • Homeostasis / drug effects
  • Humans
  • Hydrocortisone / metabolism
  • Male
  • Polysomnography
  • Sleep Disorders, Circadian Rhythm / diagnosis
  • Sleep Disorders, Circadian Rhythm / drug therapy*
  • Sleep, REM / drug effects
  • Sleep, REM / physiology
  • Time Factors
  • Triazolam / pharmacology*
  • Triazolam / therapeutic use*


  • Anti-Anxiety Agents
  • Triazolam
  • Growth Hormone
  • Hydrocortisone