Hypnotic activity of melatonin.
OBJECTIVE
To establish the effect of melatonin upon nocturnal and evening sleep.


METHODS
Experiment I: The effect of melatonin (0.1, 0.5, 1.0, 5.0, and 10 mg), ingested at 23:30, was studied on nocturnal sleep (23:30-07:30) and core body temperature in 8 healthy volunteers. Performance was measured 8.5 h post-ingestion. On completion of the experiment dim light melatonin onsets (DLMO) were determined. Experiment II: The effect of melatonin (0.5, 1.0, 5.0, and 10 mg), ingested at 18:00, was studied on evening sleep (18:00-24:00) and core body temperature in 6 healthy volunteers. Performance was measured 6.5 h post-ingestion. Each experiment was placebo-controlled and double-blind with a cross-over design with temazepam (20 mg) as an active control.


RESULTS
Experiment I: Melatonin (5 mg) reduced the duration of stage 3 in the first 100 min of sleep. Melatonin (0.1 mg) reduced body temperature 6.5 to 7 h post-ingestion. Temazepam increased stage 2, reduced wakefulness and stage 1, and increased the latency to REM sleep. Temazepam reduced body temperature 4.5 to 6.5 h post-ingestion. There were no changes in performance compared with placebo. DLMO occurred between 20:40 and 23:15. Experiment II: Melatonin (all doses) increased total sleep time (TST), sleep efficiency index (SEI) and stage 2, and reduced wakefulness. Temazepam increased TST, SEI, stage 2 and slow-wave sleep, and reduced wakefulness. There were no changes in body temperature or performance compared with placebo.


CONCLUSIONS
Melatonin given at 23:30 has no significant clinical effect on nocturnal sleep in healthy individuals. Hypnotic activity of melatonin when given in the early evening (presumably in the absence of endogenous melatonin) is similar to 20 mg temazepam.
Stone
B M
BM
Defence Evaluation and Research Agency, Centre for Human Sciences, Farnborough, Hampshire, UK. bmstone@dera.gov.uk
Turner
C
C
Mills
S L
SL
Nicholson
A N
AN
D000328:Adult; D002940:Circadian Rhythm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography; D004585:Electrooculography; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D011939:Mental Recall / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects*; D013693:Temazepam / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D013693:Temazepam; D008550:Melatonin