What is DSIP?
9-AA peptide (WAGGDASGE), isolated 1970s from sleep-induced rabbit cerebral blood. Also called emideltide. Crosses BBB.[1]
Sleep-associated peptide · research peptide
DSIP (Delta Sleep-Inducing Peptide / Emideltide)
Studied for: sleep architecture (delta-wave), chronic pain modulation (preclinical + small pilot studies)
DSIP is a 9-amino-acid peptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) originally isolated in the 1970s from the cerebral venous blood of rabbits induced into electro-stimulated sleep. Named "delta sleep-inducing" for its early association with slow-wave sleep in animal models, its exact mechanism remains unclear — a 2006 peer-reviewed review explicitly called DSIP "a still unresolved riddle." It is not FDA-approved and was on the April 15, 2026 FDA 503A Category 2 removal list.
- Class
- Sleep-associated nonapeptide
- Sequence
- Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (9 AA)[1]
- Also named
- Emideltide
- Plasma half-life (human)
- ~7–8 minutes[1]
- In-vitro stability
- ~15 minutes (aminopeptidase cleavage)[1]
- BBB permeability
- Yes — freely crosses[1]
- Candidate mechanism
- NMDA receptor modulation · α1 receptor activity (rat)[1][2]
- FDA status
- Not approved · April 15 2026 503A Cat. 2 removal · PCAC 23 Jul 2026[3]
Educational reference only. DSIP has been studied in small pilot trials with reported effects on sleep and pain, but mechanism remains unresolved and there is no FDA-approved clinical use. This page summarizes the published record; it does not recommend doses, protocols, or acquisition channels.
What DSIP is
DSIP — Delta Sleep-Inducing Peptide — is a nonapeptide consisting of nine amino acids: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. It was originally isolated in the mid-1970s by Schoenenberger and Monnier, who identified it in the cerebral venous blood of rabbits that had been induced into electro-stimulated sleep. The peptide is also referred to as emideltide in contemporary research-chemical and regulatory contexts.[1]
Mechanism — an unresolved riddle
A 2006 peer-reviewed review titled "Delta sleep-inducing peptide (DSIP): a still unresolved riddle" explicitly framed DSIP's mechanism as incompletely characterized. What is known from the published record:[1][2]
- NMDA receptor modulation has been reported as a candidate central mechanism.
- α1-adrenergic signaling: one rat study reported DSIP-stimulated acetyltransferase activity through α1 receptors.
- Blood–brain barrier permeability: DSIP freely crosses the BBB. This is notable because most peptides do not.
- Oral absorption: DSIP is reportedly absorbed from the gut without substantial enzymatic denaturation — again, uncommon for small peptides.
- Sleep architecture: early animal work associated DSIP with delta-wave (slow-wave) sleep enhancement, which is the source of the name. Later clinical pilot work has not consistently reproduced a clean sleep-onset effect profile suitable for therapeutic development.
Pharmacokinetics
- Human plasma half-life. Approximately 7–8 minutes.[1]
- In-vitro stability. ~15 minutes, degraded by aminopeptidase-like enzymes in blood.[1]
- Distribution. BBB-permeable; reaches central nervous system targets.
- PD duration. In small pilot clinical work, reported effects on sleep pressure and chronic-pain perception have outlasted plasma exposure — suggestive of downstream signaling persistence rather than sustained drug presence.
Clinical record (small pilot studies only)
- 1981 volunteer study: six volunteers receiving intravenous DSIP reported immediate sleep pressure, increased sleep time, decreased sleep onset, and improved sleep efficiency — without sedative effects.[4]
- Chronic-pain pilot: DSIP significantly reduced pain levels in 6 of 7 chronic-pain patients after IV administration on 5 consecutive days followed by 5 injections every 48–72 hours.[5]
- Current clinical status: no FDA-approved clinical indication; no large-scale Phase 3 program; no adoption into mainstream clinical practice. The peer-reviewed record is dominated by small pilot studies and mechanism-focused papers.
Regulatory status
- FDA approval: None.
- April 15, 2026 503A update. DSIP (emideltide) was listed for removal from Category 2 as one of twelve peptide bulk drug substances affected by the update.[3]
- PCAC review. Scheduled for July 23, 2026, for DSIP-related bulk drug substances (DSIP free base / acetate). Removal from Category 2 does not itself permit compounding; PCAC review and FDA 503A bulks-list inclusion are required.
Storage and handling
- Lyophilized powder. Store sealed per supplier instructions — typically refrigerated at 2–8 °C or frozen at −20 °C.
- After reconstitution. Refrigerate at 2–8 °C. Bacteriostatic water (0.9% benzyl alcohol) for multi-draw use; sterile water for single-draw.
- Handling. Swirl to mix. Avoid freeze–thaw. Discard cloudy or discolored solutions.
Reconstitution math
Math only — no dose recommendation. Concentration after reconstitution determines how many insulin-syringe units equal a given mcg amount.
Example 1 · 5 mg vial + 2 mL bac water
concentration = 5 mg / 2 mL = 2.5 mg/mL = 2500 mcg/mL
1 unit = 0.01 mL = 25 mcg
→ 100 mcg = 4 units
→ 250 mcg = 10 units
→ 500 mcg = 20 units
→ 1 mg = 40 units
1 unit = 0.01 mL = 25 mcg
→ 100 mcg = 4 units
→ 250 mcg = 10 units
→ 500 mcg = 20 units
→ 1 mg = 40 units
Example 2 · 5 mg vial + 1 mL bac water
concentration = 5 mg / 1 mL = 5 mg/mL = 5000 mcg/mL
1 unit = 0.01 mL = 50 mcg
→ 100 mcg = 2 units
→ 500 mcg = 10 units
→ 1 mg = 20 units
→ 5 mg = 100 units (full syringe)
1 unit = 0.01 mL = 50 mcg
→ 100 mcg = 2 units
→ 500 mcg = 10 units
→ 1 mg = 20 units
→ 5 mg = 100 units (full syringe)
Example 3 · 2 mg vial + 2 mL bac water
concentration = 2 mg / 2 mL = 1 mg/mL = 1000 mcg/mL
1 unit = 0.01 mL = 10 mcg
→ 100 mcg = 10 units
→ 500 mcg = 50 units
→ 1 mg = 100 units (full syringe)
1 unit = 0.01 mL = 10 mcg
→ 100 mcg = 10 units
→ 500 mcg = 50 units
→ 1 mg = 100 units (full syringe)
Frequently asked questions
How does it work?
Mechanism incompletely characterized. Candidate pathways: NMDA receptor modulation, α1-adrenergic signaling. Early animal work associates with delta-wave sleep.[1][2]
What's the half-life?
~7–8 min plasma (human). ~15 min in-vitro. Short, but PD effects outlast exposure in pilot studies.[1]
How do I reconstitute a 5 mg vial?
Typical: 5 mg + 2 mL bac water = 2.5 mg/mL → 1 unit = 25 mcg; 500 mcg = 20 units. Using 1 mL doubles concentration.
Is it FDA-approved?
No. April 15, 2026 503A Category 2 removal. PCAC review scheduled July 23, 2026.[3]
What clinical data exists?
1981 small volunteer study on sleep effects; small chronic-pain pilot. No FDA-approved indication; no Phase 3 program.[4][5]
Primary references
- Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem, 2006 (PubMed 16539679). PubMed 16539679
- Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): a review. Peptides, 1984 (PubMed 6145137). PubMed 6145137
- U.S. Food and Drug Administration. 503A Categories Update for April 2026 — DSIP (emideltide) listed for Category 2 removal; PCAC consultation scheduled July 23, 2026. fda.gov/media/94155
- Schneider-Helmert D, Schoenenberger GA. Effects of DSIP in man: multifunctional psychophysiological properties besides induction of natural sleep. Neuropsychobiology, 1983 (PubMed 6895513). PubMed 6895513
- Larbig W, Gerber WD, Kluck M, Schoenenberger GA. Therapeutic effects of DSIP in patients with chronic, pronounced pain episodes. (PubMed 6548970). PubMed 6548970
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