DSIP
Also known as: Delta Sleep-Inducing Peptide · Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu
A nonapeptide originally isolated from the cerebral venous blood of sleeping rabbits, studied for sleep modulation, stress resilience, and indirect cognitive effects.
DSIP is a nonapeptide that modulates slow-wave sleep and HPA-axis stress response; used in sleep, opioid-withdrawal, and stress-resilience research protocols.
Evidence tier: B — clinical evidence (trials or approved use in some jurisdictions)
- Category
- Sleep & Recovery
- Half-life
- Short plasma half-life (under 10 min); functional effects persist longer
- Formula
- C₃₅H₄₈N₁₀O₁₅
- Weight
- 848.81 g/mol
- Sequence
- Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu
Section 1
Overview
DSIP (Delta Sleep-Inducing Peptide) is a small endogenous nonapeptide — Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu — first isolated in 1977 from the cerebral venous blood of rabbits during electrically induced delta-wave sleep by Schoenenberger and Monnier's research group. It is one of the earliest 'sleep peptides' to enter the research literature and remains a tool compound for studying the relationship between sleep architecture, stress, and cognition.
Although its name implies a primary role in inducing slow-wave (delta) sleep, the published mechanistic picture is more nuanced: DSIP appears to act more broadly as a stress-resilience and circadian-modulating peptide, with sleep effects that are real but often more subtle and context-dependent than the name suggests.
In research contexts, DSIP is studied alongside cognitive peptides because sleep quality — particularly slow-wave and REM consolidation — is causally upstream of long-term memory formation. Improved sleep architecture is one plausible indirect mechanism for cognitive effects.
Key facts
- DSIP is a nonapeptide — 9 amino acids — with the sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. — This profile's sequence data
- Molecular weight ≈ 848.81 g/mol (C₃₅H₄₈N₁₀O₁₅). — This profile's molecular data
- First isolated in 1977 from the cerebral venous blood of rabbits during electrically induced delta-wave sleep, by Schoenenberger and Monnier's research group. — Discovery & History, this profile
- No marketing authorisation for DSIP was found in the electronic medicines compendium (emc) or on the EMA's list of centrally authorised medicines on 17 October 2026. Regulation 46(1) of the Human Medicines Regulations 2012 prohibits selling or supplying an unauthorised medicinal product. — UK/EU regulatory status, this profile
Section 2
Discovery & History
- Isolated by Schoenenberger and Monnier in 1977 from cerebral venous blood of sleeping rabbits.
- Synthesised and characterised in the following decades by multiple European research groups.
- Studied in human research for sleep onset, sleep architecture, opioid withdrawal, and stress resilience.
- Remains a research peptide; no major clinical authorisations.
Section 3
Mechanism of Action
- 1Modulation of hypothalamic-pituitary-adrenal (HPA) axis activity — reduction of stress-induced corticotropin-releasing hormone release from the paraventricular nucleus and downstream ACTH / cortisol / corticosterone attenuation in research models.
- 2Influence on slow-wave sleep architecture in some — though not all — research conditions, with the effect most consistent in stress-perturbed or sleep-deprived baselines rather than in already-consolidated sleep.
- 3Antioxidant effects in CNS tissue under stress conditions — measurable reductions in lipid peroxidation markers and preserved endogenous antioxidant enzyme activity in stress-injury models.
- 4Modulation of opioid peptide release contributing to the studied role in opioid-withdrawal research, plausibly via enkephalin and endorphin system interactions that overlap with — but are distinct from — the direct-agonist effect at opioid receptors.
- 5Possible direct effects on thalamocortical oscillatory activity, particularly the delta-generating circuit, providing a mechanism for the slow-wave-sleep modulation that separates DSIP from broader stress-axis modulators.
- 6Interaction with the glutamate-GABA balance in the reticular thalamic nucleus, with reports of increased inhibitory tone at the network scale rather than direct receptor binding.
- 7Immunomodulatory effects — measurable normalisation of stress-perturbed cytokine profiles that parallel the pattern seen with Selank, indicating a possible shared upstream stress-response modulation.
Section 4
Researched Benefits
Findings reported in the published preclinical and clinical literature. Effects in research contexts do not constitute claims of therapeutic benefit in humans.
- 1Reduced stress-axis activation in animal stress paradigms — the most-replicated preclinical finding for DSIP and the plausible mechanistic root of many of the downstream effects.
- 2Improvements in subjective sleep quality in early human research, with polysomnographic data showing modest increases in slow-wave sleep duration in some but not all study populations.
- 3Studied utility in opioid withdrawal protocols — Russian addiction-medicine literature reports reductions in withdrawal-symptom severity and improved detoxification tolerability when DSIP is added to the standard regime.
- 4Indirect cognitive effects via improved sleep consolidation — the sleep-cognition link is well-established and DSIP's sleep-architecture effects give it a plausible if indirect nootropic angle.
- 5Generally well-tolerated tolerability profile in published research, with adverse-event rates comparable to placebo across the human studies published to date.
- 6Reported effects on hypertensive stress responses — modest reductions in stress-induced blood-pressure spikes in early cardiovascular research.
- 7Neuroprotective effects in ischaemic and excitotoxic injury models, plausibly downstream of the stress-axis and antioxidant mechanisms.
Section 5
Theoretical Dosing & Protocols
| Route | Dosage | Frequency | Duration | Source |
|---|---|---|---|---|
| Subcutaneous / intranasal (research) | Microgram-range in research protocols | Typically once daily, often pre-sleep | Short courses | None cited |
Note: No standardised human protocol exists in Western clinical practice.
Section 6
Administration Routes
- Subcutaneous — the reference route in the older Russian and European clinical research on DSIP; typically administered as a single evening dose in sleep-relevant protocols.
- Intranasal in some contemporary research protocols, exploiting the nose-to-brain route familiar from the Semax/Selank programme.
- Intramuscular administration is used in some clinical and animal work where injection-volume constraints are relaxed.
- Oral administration is not viable — the nonapeptide is efficiently degraded by gastrointestinal proteases and undergoes complete first-pass metabolism.
Section 7
Safety Profile
Commonly reported
- · Generally well-tolerated in research at studied doses — the tolerability profile is one of DSIP's clearer positive features across the older sleep-research literature.
- · Occasional mild headache or sleep-onset alteration in the initial 1–2 doses; typically transient.
- · Rare reports of transient morning grogginess in intranasal-administered subjects, resolving within 30–60 minutes of waking.
- · Mild injection-site reactions in the subcutaneous route — local redness or transient tenderness that resolves without intervention.
- · Occasional vivid or unusual dreaming, consistent with the modulation of REM architecture reported in the polysomnographic literature.
Rare / theoretical
- · Long-term safety data is limited — most of the published human clinical work is short-course, and chronic-use safety beyond several weeks is not well-characterised.
- · Possible pharmacodynamic interaction with HPA-axis-modulating medications (glucocorticoids, mineralocorticoid antagonists) — theoretical rather than documented.
- · Theoretical interaction with sleep-active pharmaceuticals (Z-drugs, benzodiazepines, orexin antagonists) that share the sleep-architecture endpoint via different mechanisms.
- · Isolated case reports of transient blood-pressure variability during acute administration — the antihypertensive-stress effect can occasionally exceed the intended magnitude.
Contraindications
- · No entry for DSIP was found in the electronic medicines compendium (emc) on 17 October 2026.
- · Pregnancy and lactation — no controlled human data.
- · Concomitant use of sleep-active hypnotics without a specific research rationale — theoretical additive effect on sleep architecture.
- · Acute severe HPA-axis pathology (Addisonian or Cushingoid states) — the HPA-modulating effect is not characterised in these baselines.
Section 8
UK & EU Regulatory Context
United Kingdom
No entry for DSIP was found in the electronic medicines compendium (emc) on 17 October 2026. The emc is not a complete record of UK authorisations, so check the MHRA Products database.
European Union
Not approved by the EMA.
Section 9
Clinical Studies Summary
DSIP and slow-wave sleep architecture
Classic European polysomnographic study reporting modest but statistically significant increases in slow-wave sleep duration and reduced sleep-onset latency in subjects receiving intravenous DSIP versus placebo. The magnitude of the sleep-architecture effect was greater in subjects with disturbed baseline sleep than in normal-sleepers, consistent with the interpretation of DSIP as a modulator rather than an inducer.
DSIP in opioid withdrawal
Russian addiction-medicine trial reporting significant reduction in Objective Opiate Withdrawal Scale severity scores in subjects receiving adjunct intranasal DSIP during opioid detoxification, with the effect most pronounced on autonomic and sleep-quality subscales rather than on craving or acute somatic symptoms.
Read studyDSIP and HPA-axis stress response
Preclinical endocrinology study demonstrating attenuation of stress-induced corticosterone elevations following DSIP administration in rodent restraint-stress and forced-swim paradigms, providing molecular support for the interpretation of DSIP as a stress-axis modulator with sleep-architecture effects downstream of the stress-attenuation.
DSIP polysomnographic characterisation in insomnia
Small-N polysomnographic trial in a chronic-insomnia population reporting reduced wake-after-sleep-onset (WASO) and increased slow-wave sleep proportion following a course of intranasal DSIP; the study is limited by sample size and open-label design.
Section 10
Frequently Asked Questions
Section 10a
Practical Research Guidance
Cycle guidance
Reconstitution & storage
UK sourcing notes
Section 11
Sourcing for Laboratory Research
Sourcing DSIP for laboratory research
Researchers in the United Kingdom and elsewhere typically obtain DSIP from specialist research-chemical suppliers. Purity, third-party testing, and supplier transparency are the principal differentiators worth evaluating before placing an order. The two suppliers below are commonly referenced in UK research contexts.
Reminder: this page is educational. Regulation 46(1) of the Human Medicines Regulations 2012 prohibits selling or supplying an unauthorised medicinal product, and some compounds on this site, such as semaglutide, are authorised prescription-only medicines in the UK.