Studies on the chronopharmacology of ethanol

Male subjects (n = 10) were given ethanol (0.75 g/kg) at four equally spaced times in the 24 hr cycle (9 am, 3 pm, 9 pm 3 am) in random order. Blood ethanol concentrations were monitored by breath analysis and measurements were made of the blood or plasma levels of ethanol, acetaldehyde, acetate, pyruvate, lactate and cortisol. Blood pressure, heart rate and body temperature were measured before and at 60 and 120 min after ethanol administration and the effects of ethanol on a number of behavioural parameters and mood were studied. After ethanol ingestion, there was a significant decrease in body temperature, systolic blood pressure, plasma cortisol and pyruvate levels, whilst acetate levels and the lactate:pyruvate ratio were significantly increased. Standing steadiness, critical flicker fusion threshold and divided attention tracking control were significantly impaired under ethanol and self-report data indicated a significant decrease in alertness, co-ordination, concentration and attentiveness. Although a significantly higher peak blood ethanol concentration was attained at the 9 am session, other time-of-day differences did not reach significance and the pharmacokinetics of ethanol were essentially unchanged. Since the only significant diurnal variations in the response to ethanol identified in this study (apart from the subjective results) were for plasma cortisol concentrations and body temperature (both of which are well known to exhibit diurnal rhythmicity), it appears that major circadian variability in the metabolic and/or behavioural effects of ethanol is unlikely to occur.