DSIP

Delta sleep-inducing peptide, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, emideltide (INN)

Cognitive & neuro

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Summary

Class: Naturally occurring nonapeptide (9 amino acids) first isolated from the blood of sleeping rabbits; also made synthetically
Mechanism: Unclear. Proposed to modulate the hypothalamic stress axis (lowering ACTH/cortisol, raising LH and GH in some studies), normalise sleep architecture and act as an antioxidant/stress-adaptive peptide — but no receptor has ever been identified
Routes studied: Intravenous (most human trials); intranasal and subcutaneous (human, small); intraperitoneal and intracerebroventricular (animal); subcutaneous and intranasal (community)
Dose range reported: Human trials: 25 nmol/kg IV (roughly 1.5–2 mg for an adult) in sleep and withdrawal studies; some used 0.1–0.5 mg/kg. Community: 100–300 µg subcutaneous before bed, sometimes up to 1 mg. Trial and community figures, not recommendations
Half-life: Very short — around 7–8 minutes in plasma — yet effects are reported to persist for hours or days, which is one of the puzzles about it
Storage: Lyophilised: refrigerate, protect from light. Reconstituted: refrigerate, community practice is use within ~4 weeks; the peptide is relatively unstable in solution
Regulatory status: Not approved anywhere (an INN was assigned but no product was ever licensed). FDA compounding Category 2 (2023)

Doses are as reported in studies or by the community — never recommendations.

1What it is

In 1977 a Swiss group led by Marcel Monnier and Guido Schoenenberger were trying to find a chemical that carried sleep from one animal to another. They induced sleep in rabbits by electrical stimulation of the thalamus, filtered their blood, infused it into other rabbits, and found that it increased slow-wave ("delta") sleep. The active molecule was a nine-amino-acid peptide, which they named for what it appeared to do. DSIP has since been found in human blood, breast milk and brain tissue, so it is a natural human peptide, though its physiological role is still not understood.

Nearly 50 years later DSIP remains one of the most studied and least explained peptides in this field: hundreds of papers, no receptor, no agreed mechanism, and human sleep trials that mostly failed to confirm the name. It is used in the community for sleep, stress and sometimes for opioid or alcohol withdrawal based on older European studies.

2How it's thought to work

Sleep architecture. in early studies it increased slow-wave sleep or shifted sleep–wake patterns in animals; later work suggested a normalising effect — more sleep in the sleep-deprived, no sedation in the rested — rather than a hypnotic one.

Stress axis. reduces basal and stress-induced corticotropin (ACTH) release and cortisol in several studies, and raised luteinising hormone and growth hormone in some; proposed to act as a "stress-limiting" peptide.

Antioxidant and adaptive effects. Russian and Ukrainian groups report reduced oxidative damage and improved tolerance of hypoxia and heat stress in rodents.

Pain and opioid interactions. attenuated opioid and alcohol withdrawal signs in rodents and in small human series; possible interaction with opioid or GABA systems, unproven.

No receptor identified. The short and long effects suggest it may act on the expression of other systems rather than as a classic ligand, or that a metabolite is active. Alternatively, some effects may be artefacts of small studies.

Proposed: delta sleep-inducing peptide was isolated from the blood of sleeping rabbits and named for the slow-wave activity it was associated with. No receptor has been established and the human evidence is weak, so the figure shows an association rather than a mechanism.Schematic — not to scale

3What the research shows

Graded A (inconsistent)

Insomnia and sleep quality

Several small double-blind placebo-controlled trials in the 1980s gave IV DSIP to people with chronic insomnia. Some reported improved sleep efficiency and daytime performance (Schneider-Helmert 1986; Schneider-Helmert & Schoenenberger 1983, Neuropsychobiology), while others found no significant change in objective sleep measures in normal volunteers. The overall picture from the controlled literature is that DSIP is not a reliable sleep inducer in humans. [2][3]

Opioid and alcohol withdrawal

Open and small controlled European studies in the 1980s reported reduced withdrawal symptoms in opioid- and alcohol-dependent patients given IV DSIP, with rapid onset (Dick 1984, Eur Neurol). Small and old; not pursued to approval. [4]

Stress hormones

Studies in healthy volunteers reported lower cortisol and ACTH response to stressors and raised LH after IV DSIP (Schoenenberger 1984 and related). Small.

Chronic pain, migraine

Case series and a small trial in the 1980s–90s reported reduced pain and headache frequency with DSIP courses (Larbig 1984, Eur Neurol). Uncontrolled or very small. [5]

Sleep, stress tolerance and antioxidant effects in animals

Extensive rodent and rabbit literature, including the original transfer experiments, with mixed replication of the sleep effect and more consistent findings on stress and oxidative markers (Khvatova 2003; Mikhaleva 2007 and others, mostly Russian).

Cancer, longevity (Russian studies)

Rodent studies from the Khavinson/Mikhaleva groups report reduced tumour incidence and extended lifespan in mice given DSIP; unreplicated outside those groups.

4Reported side effects and interactions

Literature-reported

Reported as well tolerated in all human trials at IV doses; no serious adverse events attributed. Transient headache, dizziness and nausea noted in some.

Community-reported

headache (the most common), drowsiness or grogginess the next morning, vivid or disturbed dreams, occasional reports of worsened sleep or restlessness, nausea, injection-site redness. Effects described as subtle or absent by many.

Theoretical. effects on LH, GH and cortisol suggest the endocrine system is involved; chronic use could in principle alter the stress axis. The reported lifespan and tumour findings in rodents, if real, imply biological activity whose human relevance is unknown.

Interactions. none established. Additive drowsiness with sedatives, alcohol and GABAergic drugs is plausible given the sleep indication; interaction with opioids suggested by the withdrawal studies.

Markers researchers commonly monitor

Marker	Why it's watched
Cortisol (morning or diurnal) and ACTH	the stress-axis effect is the most reproducible human finding.
Luteinising hormone and, in men, testosterone	LH rise reported in volunteer studies.
IGF-1	a proxy for any GH-releasing effect; expected change small or none.
Sleep measures (actigraphy, sleep diary, or polysomnography where available)	the only efficacy readout; subjective reports alone are unreliable for this compound.
Blood pressure	mild lowering reported in some studies.
General baseline panels (CBC, CMP); no compound-specific safety markers are established

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Typically supplied as powder in 2 mg or 5 mg vials. with , swirl gently, protect from light and keep refrigerated — DSIP is reported to be less stable in solution than many peptides, and community practice is to reconstitute smaller amounts more often.

Open in calculator, pre-loaded →

6Commonly studied alongside

In the literature: nothing systematic. In the community: epitalon (the Khavinson-group link), GH secretagogues (ipamorelin, CJC-1295) in sleep-focused protocols, Selank. No combination data.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Placed in Category 2 of FDA's compounding bulk substances list (2023), restricting compounding
European Union	Not authorised; the INN emideltide was assigned but no product licensed
United Kingdom	Not licensed
Australia	Not approved; prescription-only classification for peptides applies †
South Africa	Not registered
Sport	Not specifically named by WADA; S0 (non-approved substances) applies. Reports that it influences GH release have not led to S2 listing †

8Open questions

What is DSIP's receptor or mechanism? Unknown after nearly 50 years.
Why do effects outlast the molecule by hours or days? Active metabolite, gene expression, or artefact?
Is there any reliable sleep benefit in humans? The controlled trials say "not consistently".
Is intranasal or DSIP bioavailable in a way that matches the IV studies? No data.

9References

1Schoenenberger GA, Monnier M (1977). Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proc Natl Acad Sci U S A. PubMed · DOI
2Schneider-Helmert D, Schoenenberger GA (1983). Effects of DSIP in man: multifunctional psychophysiological properties besides induction of natural sleep. Neuropsychobiology. PubMed · DOI
3Schneider-Helmert D (1986). DSIP in sleep disturbances. Eur Neurol. PubMed · DOI
4Dick P et al. (1984). DSIP in the treatment of withdrawal syndromes from alcohol and opiates. Eur Neurol. PubMed · DOI
5Larbig W et al. (1984). Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes: a clinical pilot study. Eur Neurol. PubMed · DOI
6Kovalzon VM, Strekalova TV (2006). Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem. PubMed · DOI
7Graf MV, Kastin AJ (1986). Delta-sleep-inducing peptide (DSIP): an update. Peptides. PubMed · DOI
8FDA (2023). Bulk drug substances for compounding — DSIP category 2 listing. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

25 Oct 2026Profile published — awaiting medical review

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