A study in rats found that giving delta‑sleep‑inducing peptide (DSIP) or two similar molecules in the evening lowers the activity of an enzyme that makes melatonin during the night. The effect only happens when the peptide is injected at night, not in the morning, and the strongest response was at a dose of about 30 nmol per kilogram. This suggests DSIP can shift the body’s internal clock, but the work was done in animals with IV dosing, so it isn’t ready for direct human use.

Serotonin N-acetyltransferase, an enzyme of the pineal gland, converts serotonin to N-acetylserotonin. The activity of this enzyme is induced by norepinephrine in the evening to reach high levels during the dark phase. Delta-sleep-inducing peptide, a humoral sleep factor, also seems to affect circadian rhythms. Intravenous injection of this peptide or either of two of its analogs in the evening significantly reduced the increase of N-acetyltransferase 4 h later. The dose-response relationship of the peptides showed an inverted U-shaped pattern with the active dose about 30 nmol/kg. The effect appears to be dependent on the time of day of administration, as injections in the morning did not change the enzymatic activity. These findings indicate that delta-sleep-inducing peptide (and two of its analogs) can affect enzymatic activities and that these influences probably vary throughout a time period of 24 h.