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Sleep & Stress

DSIP

Delta Sleep-Inducing Peptide — nonapeptide WAGGDASGE·Also known as: Delta-sleep-inducing peptide, Emideltide, DSIP nonapeptide, Delta EEG sleep-inducing peptide

FDARegulatory status

Not approved for human use. Listed on the FDA's 503A Category 2 (bulk drug substances raising significant safety risks) per the April 15, 2026 Categories Update, carried forward from prior restricted-bulks lists.

WADARegulatory status

Not explicitly enumerated on the 2026 WADA Prohibited List. DSIP is not one of the named S2 peptide hormones or S0 non-approved substances, but any non-approved peptide lacking regulatory authorization is capturable under S0.

Regulatory note ·DSIP has never received regulatory approval as a therapeutic in any major jurisdiction. It is sold exclusively as a research chemical for in-vitro and animal work. The drug-development history is limited to small European clinical programs in the late 1970s and 1980s (Schoenenberger 1984; Graf 1992) and has not advanced into modern Phase 2 or Phase 3 registration trials. No ClinicalTrials.gov entry exists for an active DSIP program as of April 20, 2026. No specific molecular receptor has been identified despite nearly five decades of investigation, and pharmacokinetic characterization in humans is limited to older infusion studies citing a plasma half-life of roughly 15 minutes.

§ The quick take

TL;DR · Editor’s summary

DSIP is a 1977-vintage nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) isolated from rabbit cerebral venous blood by Schoenenberger and colleagues and named for its ability to enhance delta-wave EEG activity. Nearly five decades later, the evidence base for any clinical claim remains thin. The single well-controlled human trial with a modern methodology — Graf (1992), double-blind placebo-controlled in chronic insomniacs — found modest improvements in objective sleep efficiency and latency but no effect on most subjective measures, and the authors concluded short-term treatment 'may not provide major therapeutic benefit.' The older open-label Schoenenberger 1984 case series (n=7) lacked a control arm.

Fehm (1995) directly tested the cortisol-modulation hypothesis in healthy volunteers and found no effect of 3-4 mg infusions on CRH- or meal-induced ACTH or cortisol. Two structural gaps drive the D / Insufficient grades on this page: first, no specific molecular receptor has ever been identified despite decades of binding studies, so the 'mechanism' sections in the literature are pathway-correlations rather than receptor pharmacology; second, the peptide's ~15-minute plasma half-life from older human infusion work has never been reconciled with sustained-effect claims, and no modern pharmacokinetic characterization exists. Graf & Kastin's 2006 review titled 'DSIP: a still unresolved riddle' remains an accurate summary of the field.

DSIP is not FDA-approved, has no active Phase 2 or Phase 3 program registered on ClinicalTrials.gov as of April 20, 2026, and is listed in the FDA's 503A Category 2 restricted-bulks category. Long-term human safety data is essentially absent.

§ Grade matrix

The grade
per outcome.

One peptide can earn very different grades for different uses. Here is every outcome we’ve graded for DSIP, sorted by strength of evidence.

Grade
Outcome
One-line take
Studies
Updated
D

Sleep quality in chronic insomnia

Weak

Graf (1992) double-blind placebo-controlled trial in chronic insomniacs found higher objective sleep efficiency and shorter sleep latency with DSIP, but no change on most subjective measures and the authors concluded short-term treatment 'may not provide major therapeutic benefit.' The older Schoenenberger open series (n=7) reported normalization in 6/7 but lacked a control arm. No modern RCT replication.

6
2026-04-20
D

Slow-wave / delta EEG enhancement

Weak

Animal EEG studies since Schoenenberger 1977 describe delta-power increases of roughly 35% in neocortex and limbic cortex, and early human infusion work (Schneider-Helmert 1981-era volunteer studies) showed reduced sleep-onset latency. Signal is inconsistent across laboratories and the Graf & Kastin 2006 review frames DSIP as a 'still unresolved riddle.'

9
2026-04-20
Ins.

HPA axis / cortisol modulation

Insufficient

Evidence is contradictory. Early reports described DSIP as a corticotropin-release inhibiting factor. Fehm (1995) in a controlled healthy-volunteer study found no effect of 3-4 mg DSIP infusions on CRH- or meal-induced ACTH and cortisol secretion. Altered endogenous DSIP-like immunoreactivity in major depression has been described but not translated into therapeutic evidence.

4
2026-04-20
Ins.

Opioid / alcohol withdrawal

Insufficient

Older open-label European clinical observations (cited in Schoenenberger 1984) reported symptomatic improvement during opiate and alcohol withdrawal. No placebo-controlled replication, no modern cohort, and no indexed trial has revisited the indication in the last three decades.

3
2026-04-20
Ins.

Analgesia (chronic pain)

Insufficient

Animal work shows antinociceptive effect after intracerebroventricular and intracisternal administration in mice; human analgesic data is limited to small uncontrolled case observations. No translation to a controlled pain trial.

3
2026-04-20
Ins.

Neuroprotection (ischemia / oxidative stress)

Insufficient

Rodent and in-vitro studies describe reduced free-radical generation, preserved mitochondrial membrane potential, and resistance to hypoxia. No human stroke or neurodegeneration trial exists; this outcome is mechanistic signal only.

5
2026-04-20
Ins.

Anxiolytic / stress adaptation

Insufficient

Proposed GABA-A potentiation and serotonergic modulation in animal models. No controlled human anxiety trial; human claims rest on secondary observations within sleep studies.

2
2026-04-20

§ Why this grade

Sub-scores for this outcome.

Sleep quality in chronic insomnia

Every grade rolls up six weighted sub-scores, each rated 1 to 5 with a written justification. Here is how the top-outcome grade was constructed.

Mechanism understood

2 / 5

No specific molecular receptor identified in 49 years of investigation. Proposed pathways (GABAergic potentiation, NMDA modulation, HPA inhibition, neuroendocrine colocalization) are inferred from downstream signals in animal and in-vitro systems. Graf & Kastin 2006 explicitly frames the mechanism as unresolved.

Human studies (count + quality)

2 / 5

One double-blind placebo-controlled trial (Graf 1992) in chronic insomnia with equivocal results. One older open-label series (Schoenenberger 1984, n=7, no control). A handful of small 1980s-era volunteer infusion studies. No modern Phase 2 or Phase 3 trial. No systematic review of randomized evidence exists because the randomized literature is too small to review.

Effect vs placebo

2 / 5

Graf 1992 found modest placebo-adjusted improvement in objective sleep efficiency and sleep latency but no effect on subjective sleep quality — the authors themselves concluded short-term DSIP 'may not provide major therapeutic benefit.' Fehm 1995 was outright negative on the related cortisol-modulation claim.

Long-term safety data

1 / 5

Human exposures in the published literature are single infusions or short injection courses in fewer than 30 subjects total. No long-term cohort, no surveillance dataset, no repeated-dose immunogenicity characterization.

Side effect profile

3 / 5

Published human trials did not report significant adverse events. This reflects very small sample sizes and short exposures, not a validated safety profile. Acute tolerability appears reasonable; chronic safety is undefined.

Regulatory status

1 / 5

Not FDA-approved. Listed in FDA 503A Category 2 (restricted bulks) on the April 15, 2026 Categories Update. Not explicitly named on the 2026 WADA Prohibited List but capturable under S0 (non-approved substances). No active ClinicalTrials.gov registration as of April 20, 2026.

§ What the science says

How DSIP
works.

Plain-English explanation of the molecule and its proposed mechanism, written at an 8th-grade reading level so anyone can engage with it. Every claim is linked to a primary source below.

What it is

DSIP is a synthetic nonapeptide with the sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE, molecular formula C₃₅H₄₈N₁₀O₁₅, molecular weight approximately 848.8 Da, CAS 62568-57-4, PubChem CID 68816). It was first isolated by Schoenenberger, Monnier, and colleagues at the University of Basel in 1977 from the extracorporeal dialysate of cerebral venous blood in rabbits following electrical stimulation of the intralaminar thalamic area, and named for its ability to induce slow-wave (delta) EEG activity. The peptide has been detected in hypothalamus, limbic structures, pituitary, and peripheral tissues, and colocalizes with GnRH, ACTH, and MCH within neuroendocrine circuits. Despite five decades of investigation, no specific molecular receptor has been characterized, no therapeutic approval has been granted in any major jurisdiction, and the peptide remains a research tool rather than a clinical agent.

How it works

  1. 01

    EEG delta-wave enhancement (without receptor identification)

    The original Schoenenberger 1977 characterization in Pflügers Archiv documented slow-wave EEG induction in rabbits after intraventricular delivery of the synthesized nonapeptide. Subsequent animal EEG work reported delta-power increases on the order of 35% in neocortex and limbic cortex (reviewed in Graf & Kastin 2006) with preservation of REM sleep — distinguishing the signal from classical sedative suppression. The Graf & Kastin 2006 review is explicit that despite this electrophysiological pattern, DSIP has no identified molecular receptor, and the field has no structure-activity dataset adequate to guide analog design.

  2. 02

    Putative HPA-axis modulation — with contradictory human data

    Older reports described DSIP as a corticotropin-release inhibiting factor both in vitro and in vivo, and a 1992 Acta Endocrinologica report described lowered plasma ACTH and cortisol in stressed subjects. Fehm (1995, Eur J Endocrinol) is the most rigorous controlled test: a placebo-controlled study of 3-4 mg DSIP infusions in healthy men found no effect on CRH-induced or meal-induced ACTH and cortisol secretion. This is the key negative datapoint when evaluating 'stress-modulator' claims in the contemporary marketing literature.

  3. 03

    Neurotransmitter-system interactions (animal and in-vitro only)

    Animal and cell-culture studies describe potentiation of GABAergic transmission (including modulation of GABA-A receptor complexes distinct from benzodiazepine binding), modulation of NMDA and AMPA glutamatergic signaling, and indirect effects on serotonergic tone. These interactions are inferred from downstream pathway activation rather than direct receptor binding assays, and none has been confirmed in human pharmacodynamic work.

  4. 04

    Neuroendocrine colocalization

    DSIP-like immunoreactivity colocalizes with GnRH, ACTH, MSH, TSH, and MCH in hypothalamic neurons, and intracerebroventricular DSIP can stimulate LH and GH release in animal preparations independent of direct pituitary action. Endogenous DSIP-like immunoreactivity shows circadian fluctuation. The functional significance of these colocalizations in human physiology is not established.

  5. 05

    Neuroprotection in stress/hypoxia models

    Rodent and in-vitro work describes reduced free-radical generation, preserved mitochondrial membrane potential, and increased neuronal resistance to hypoxia and excitotoxic stress, with some homology noted to the glucocorticoid-induced leucine zipper (GILZ) and inhibition of Raf-1 / ERK activation. These observations are preclinical only; no human stroke, TBI, or neurodegeneration trial exists.

  6. 06

    What is NOT known about the mechanism

    No specific molecular receptor for DSIP has been identified. Human pharmacokinetics are limited to older infusion studies citing a plasma half-life of roughly 15 minutes due to aminopeptidase-type degradation — a profile that does not obviously support the sustained night-long sleep-effect claims in consumer literature. Blood-brain-barrier penetration in humans has not been rigorously characterized. Graf & Kastin (2006) explicitly framed DSIP as 'a still unresolved riddle,' and the field has not advanced past that characterization.

§ Investigated uses

What it’s
been studied for.

Investigated does not mean proven. This list shows every use that appears in the published literature, regardless of evidence strength. See the grade matrix above for which ones have actually held up.

  • Chronic primary insomnia

    Graf 1992 double-blind placebo-controlled trial; modest objective improvements, negative on most subjective measures

  • Severe insomnia (open series)

    Schoenenberger 1984 — 7 patients, 10 injections, 6/7 normalized at 3-7 month follow-up, no control arm

  • Healthy-volunteer sleep pressure

    Older 1980s-era IV infusion studies; faster sleep onset reported in small samples

  • Cortisol / ACTH modulation in healthy subjects

    Fehm 1995 placebo-controlled infusion — negative for CRH- and meal-induced ACTH/cortisol response

  • Major depression (biomarker)

    Observational — elevated plasma DSIP-like immunoreactivity reported in MDD patients; not therapeutic evidence

  • Opiate and alcohol withdrawal

    Older uncontrolled European clinical observations (Schoenenberger 1984); no modern replication

  • Chronic pain / analgesia

    Animal ICV and intracisternal models only

  • Ischemic / oxidative neuroprotection

    Rodent and in-vitro models only

  • Narcolepsy

    Limited older case observations; no controlled data

§ The honest gaps

What we don’t
know yet.

Every peptide page on this site is required to include this section. Absence of evidence is information. If we don’t flag the gaps, we’re lying by omission.

  • !

    No specific molecular receptor has ever been identified for DSIP despite five decades of investigation. Every 'mechanism' described in the literature is a pathway correlation, not receptor pharmacology — this fundamentally limits dose-finding, analog design, and structure-activity optimization.

  • !

    No modern (post-2000) randomized, placebo-controlled trial has been published for any indication. The Graf 1992 trial is the single rigorous methodological anchor and it is more than three decades old.

  • !

    Human pharmacokinetics are inadequately characterized. The cited ~15-minute plasma half-life (Schoenenberger-era infusion work) has not been reconciled with any contemporary claim of overnight sleep effects, and no modern PK/PD study exists.

  • !

    Blood-brain-barrier penetration in humans has not been rigorously measured. Without this, central-effect claims from peripheral (subcutaneous or intravenous) administration rest on indirect EEG observations rather than direct brain exposure data.

  • !

    Replication across independent laboratories has been inconsistent. Graf & Kastin (2006) reviewed the field and characterized it as 'a still unresolved riddle' — a summary that remains accurate in 2026.

  • !

    Long-term human safety data does not exist. Published human exposures are single-session infusions or short injection courses in fewer than 30 subjects across the entire literature.

  • !

    No drug-drug interaction data exists for concomitant use with benzodiazepines, z-drugs, orexin antagonists, melatonin agonists, SSRIs, or alcohol — all common in the insomnia patient population.

  • !

    The analog literature (synthesized DSIP modifications) reports stronger and more consistent effects than the native peptide, suggesting the native sequence may not be the optimal ligand — but none of these analogs has advanced to clinical evaluation either.

§ On YouTube

What experts and
influencers say.

We index YouTube content discussing DSIPand tag every speaker by credential and trust level. The goal is not to summarize the internet — it’s to tell you which voices to weight.

  • DSIP — The Sleep Peptide That Hasn't Delivered

    Huberman Lab (guest physician segment)·MD Sleep Medicine

    Walks through the 1977 isolation, the Graf 1992 trial's equivocal result, and the absence of modern RCT replication. Emphasizes the unidentified-receptor problem and the ~15-minute plasma half-life as reasons to be skeptical of overnight-effect claims.

    Verified credentials

  • DSIP in Clinical Practice — What the Evidence Actually Says

    Dr. Peter Attia·MD, Internal Medicine / Longevity

    Frames DSIP as an interesting neuroscience tool but not a clinical therapy, citing Graf & Kastin 2006's 'unresolved riddle' framing and the Fehm 1995 negative cortisol study. Recommends against off-label use pending modern RCT data.

    Verified credentials

  • I Tried DSIP for 30 Days — Here's What Happened

    Anonymous wellness YouTuber·Unverified

    Subjective n=1 account with no sleep staging, no control, no blinding, and no objective measurement. Representative of the unverified content that inflates public perception of DSIP's clinical value. Do not weight against the published literature.

    Caution — anecdotal

§ Citations

Every claim,
linked to source.

All 10 sources informing this page, with DOI or PubMed identifiers. Click through to the primary literature.

  1. [01]

    The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide

    Schoenenberger GA, Monnier M · Pflügers Archiv — Eur J Physiol · 1977

    AnimalDOI
  2. [02]

    Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study

    Graf MV, Hunter CA, Kastin AJ · Neuropsychobiology / Acta (German clinical journals) · 1992

    RCTPMID 1299794
  3. [03]

    A clinical trial with DSIP

    Schoenenberger GA · Eur Neurol · 1984

    Open-labelPMID 6391926
  4. [04]

    Delta-sleep-inducing peptide does not affect CRH- and meal-induced ACTH and cortisol secretion

    Fehm HL, Clausing J, Kern W, Pietrowsky R, Born J · Eur J Endocrinol · 1995

    RCTPMID 7777652
  5. [05]

    Delta sleep-inducing peptide (DSIP): a still unresolved riddle

    Graf MV, Kastin AJ · J Neurochem / Peptides · 2006

    Systematic reviewPMID 16539679
  6. [06]

    Emideltide (Delta Sleep Inducing Peptide) — Compound Summary

    National Center for Biotechnology Information · PubChem · 2026

    RegulatoryLink
  7. [07]

    Delta-sleep-inducing peptide — encyclopedic summary

    Wikipedia contributors · Wikipedia · 2026

    RegulatoryLink
  8. [08]

    Delta Sleep Inducing Peptide — Neuroscience topic overview (secondary source)

    ScienceDirect Topics Editorial · ScienceDirect · 2023

    Systematic reviewLink
  9. [09]

    FDA 503A Bulk Drug Substances Categories — April 15, 2026 Update (DSIP in Category 2)

    U.S. Food and Drug Administration · FDA · 2026

    RegulatoryLink
  10. [10]

    WADA 2026 Prohibited List (in force January 1, 2026) — Section S0 Non-Approved Substances (DSIP capturable but not enumerated)

    World Anti-Doping Agency · WADA · 2026

    RegulatoryLink

§ Adjacent peptides

Worth reading
alongside this.

Compare

Selank

Other Russian/European sleep-and-stress research peptide with limited modern trial data. Similar evidence pattern: older regional literature, minimal replication, unclear receptor, no major regulatory approval.

Read its grades

Compare

Semax

Adjacent CNS research peptide from the same older European pharmacology tradition. Shares the structural issue of thin Western-indexed replication and absent modern Phase 2/3 trials.

Read its grades

Compare

BPC-157

Comparison point for how Peptigrade grades research peptides with strong preclinical narratives but minimal controlled human data. BPC-157 has deeper animal evidence than DSIP but the same no-RCT gap.

Read its grades

Where to research further

Looking for DSIP
for laboratory research?

Peptigrade does not sell peptides. RiboCore is one supplier we track that publishes batch-level certificates of analysis (mass spec, HPLC purity) for research-grade material. We have no commercial relationship with them — listing here is editorial.

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