DSIP vs Melatonin

DSIP was isolated in the 1970s as a sleep-inducing peptide, but its receptor is unknown and human results are inconsistent. Melatonin is a well-characterised hormone acting on MT1/MT2 receptors with many randomised trials.

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DSIP

A nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) isolated in 1977 from rabbit cerebral venous blood during studies of sleep.

BEST STUDIED FOR

Nootropic & neuro

Read the cited profile →

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Melatonin

The pineal hormone that signals darkness to the body clock — one of the most-trialled sleep and circadian compounds.

BEST STUDIED FOR

Nootropic & neuro

Read the cited profile →

SIDE BY SIDE

	DSIP	Melatonin
The key difference	Delta sleep-inducing nonapeptide	Pineal circadian hormone
Class	Nootropic & neuro	Nootropic & neuro
Mechanism	DSIP was named for enhancing slow-wave (delta) EEG activity after brain infusion in rabbits.	Melatonin acts on MT1/MT2 receptors to shift circadian timing and promote sleep onset; it is also a direct antioxidant and anti-inflammatory molecule in research models.
Status	Studied in the 1980s in small human sleep studies; no approved medicine and little modern research.	Registered medicine in some countries (prolonged-release forms) and a supplement in others; supported by several meta-analyses of randomised trials.
Reported safety signals	Older small studies reported no major issues; data are too limited to characterise safety.	Meta-analyses report a favourable short-term safety profile; dose and timing strongly affect results.
A key study	The isolation paper: a peptide enhancing delta EEG after brain infusion in rabbits, with its amino-acid sequence. (Proc Natl Acad Sci U S A 1977, PMID 265572)	A meta-analysis of randomised trials assessed melatonin’s effect on sleep quality. (J Neurol 2022, PMID 33417003)

WHEN TO RESEARCH WHICH

Melatonin is the evidence-backed circadian compound; DSIP an older, unresolved research peptide. Both are discussed here strictly as research compounds; nothing on this page is medical advice or a dosing guide.

REFERENCES (PUBMED)

[DSIP] Characterization of a delta-electroencephalogram (-sleep)-inducing peptide — Proc Natl Acad Sci U S A 1977. PMID 265572
[DSIP] Delta sleep-inducing peptide (DSIP): a still unresolved riddle — J Neurochem 2006. PMID 16539679
[DSIP] DSIP in sleep disturbances — Eur Neurol 1986. PMID 3758119
[Melatonin] Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials — J Neurol 2022. PMID 33417003
[Melatonin] Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis — J Pineal Res 2024. PMID 38888087
[Melatonin] Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses — Sleep Med Rev 2022. PMID 36179487

FREQUENTLY ASKED

What is the difference between DSIP and Melatonin?

What is the regulatory status of DSIP and Melatonin?

DSIP: Studied in the 1980s in small human sleep studies; no approved medicine and little modern research. Melatonin: Registered medicine in some countries (prolonged-release forms) and a supplement in others; supported by several meta-analyses of randomised trials.

What safety signals have been reported?

DSIP: Older small studies reported no major issues; data are too limited to characterise safety. Melatonin: Meta-analyses report a favourable short-term safety profile; dose and timing strongly affect results.

Which studies is this comparison based on?

For DSIP: “Characterization of a delta-electroencephalogram (-sleep)-inducing peptide” (PMID 265572); “Delta sleep-inducing peptide (DSIP): a still unresolved riddle” (PMID 16539679); “DSIP in sleep disturbances” (PMID 3758119). For Melatonin: “Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials” (PMID 33417003); “Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis” (PMID 38888087); “Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses” (PMID 36179487).