A nine-amino-acid peptide pulled from the blood of sleeping rabbits in 1977, named for an effect that has never been reliably reproduced, encoded by a gene that has never been found, and sold today as a sleep aid on the strength of a name.
Summary
Delta sleep-inducing peptide, DSIP, is the nonapeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, isolated from rabbit cerebral venous blood during electrically induced sleep and reported to induce delta-wave sleep when infused into recipient rabbits.1
No gene encoding it has ever been identified in any species. A 2006 review titled it "a still unresolved riddle" and concluded the hypothesis that it is a sleep factor "is extremely poorly documented and still weak."2
Its half-life in the body is under ten minutes.3
The human sleep studies are from the 1980s, intravenous, and tiny. One group reported improvements; the two independent double-blind trials, in 6 and 16 patients, found effects that were absent or "weak" and "of little clinical significance."45
No study has ever given it by subcutaneous injection or nasal spray, the only routes anyone now uses.3
On 24 July 2026 the FDA's advisory committee voted 7 to 6, with one abstention, against allowing pharmacies to compound it. It was the only one of seven peptides rejected that week.6
A US compounding pharmacy and its owner pleaded guilty to unlawful distribution of compounded drugs including DSIP.3
A targeted PubMed search returns 462 records, the great majority from before 1995.
The Most Common Error About This Compound
Assuming the name is a finding. "Delta sleep-inducing" describes what the Basel group observed in rabbits in 1977. Forty-nine years later, the effect on sleep has not been established in humans, the peptide's natural origin is in doubt, and the researchers who spent careers on it write about it as a puzzle rather than a drug.2 A product called DSIP is named for a hypothesis.
Identity
What Is DSIP?
In 1977 Schoenenberger and Monnier in Basel reported isolating, from the blood draining the brains of rabbits put to sleep by electrical stimulation of the thalamus, a peptide that when infused into other rabbits increased delta-wave activity on the EEG, the signature of deep non-REM sleep. They sequenced it as nine residues and named it for the effect.1 Its international nonproprietary name is emideltide, which is how the FDA refers to it.
What followed was unusual. DSIP-like immunoreactivity was found in hypothalamic nuclei across many species, but no gene, precursor protein or receptor was ever identified. Its sequence resembles no known peptide family. Kovalzon and Strekalova, who worked on it for decades, proposed in 2006 that the immunoreactivity and activity attributed to DSIP belong to some other, still unidentified peptide, and noted that in their own early studies certain synthetic analogues promoted slow-wave sleep in rabbits and rats "but not DSIP itself!"2
How Might It Work?
Through the opioid system, indirectly. In animals, naloxone blocks DSIP's analgesic and sleep-prolonging effects, but DSIP does not itself bind opioid receptors; it appears to trigger release of enkephalins from neurons by a calcium-dependent mechanism.3 It crosses the blood-brain barrier and is destroyed by peptidases in blood and tissue with a half-life under ten minutes.3
The FDA drew an inference from the mechanism that no product page does: "stimulation of the opioid system by emideltide could lead to development of addiction," and no study has examined that liability.3
Evidence Base
What Did the Animal Studies Show?
In rabbits, cats and rats, increased EEG delta power and spindle activity and prolonged sleep, with effects on REM and non-REM sleep that varied by species and route; anticonvulsant and analgesic effects in rodents.3 Graf and Kastin's 1986 review, the most thorough of its era, considered the results preliminary and found "insufficient evidence to show that emideltide reliably induced or maintained sleep."7
What Human Sleep Studies Exist?
Six, all intravenous, all from 1981 to 1992, none larger than 18 people. The FDA tabulated them.3
| Study | Design | n | Reported outcome |
|---|---|---|---|
| Schneider-Helmert 1981 | Randomised, double-blind, placebo-controlled crossover; three nights | 6 | Fewer awakenings, higher sleep efficiency; no effect on sleep onset |
| Schneider-Helmert 1983 | Double-blind; compared with external healthy controls | 6, 4 and 2 | Higher sleep efficiency |
| Schneider-Helmert 19868 | Double-blind; five nights; external controls | 18 | Improved total sleep, efficiency, onset and wake after onset |
| Schneider-Helmert 1987 | Double-blind, "placebo-controlled"; seven nights | 14 | Improvements; "normalised" sleep measures |
| Monti 19874 | Randomised, double-blind, placebo-controlled crossover; four nights, repeated | 6 | No significant difference from baseline or placebo; "of little clinical significance" |
| Bes 19925 | Double-blind, placebo-controlled parallel groups; three nights | 16 | Shorter sleep latency and higher efficiency, but effects "weak and in part could be due to an incidental change in the placebo group"; "not likely to be of major therapeutic benefit" |
The pattern is one investigator reporting benefit, in studies that mostly compared patients with healthy volunteers rather than with placebo, and two independent groups running properly controlled crossover and parallel designs and finding nothing they considered clinically meaningful. The FDA's conclusion: "the results appear inconclusive and at best preliminary," with "no data to support use" by the subcutaneous route at all.3
Withdrawal and Narcolepsy
The other uses the FDA reviewed rest on less. For opioid and alcohol withdrawal, a 1984 open-label study gave intravenous DSIP to 107 people and reported improvement, without blinding, a comparison group or standard scales; a 1998 open-label study of seven people with opioid dependence saw only two complete the schedule, and its authors wrote that "it remains an open question whether DSIP could be an effective alternative."93 For narcolepsy, there is one case report of one man.3
No trial of DSIP is registered on ClinicalTrials.gov, and nothing has been published in people since the 1990s.10
Safety
What Is Known?
Intravenous DSIP in the sleep studies was well tolerated. In the 1984 withdrawal study, 95 of 107 people had no significant adverse events, nine had minor ones such as sweating, headache, nausea and vertigo, and three had serious ones including hypotension on the first injection.3 The FDA's adverse event database holds no reports, which it cautions does not imply safety.
What Is Unknown
Everything about the routes people use. The FDA found "no safety information for emideltide for the proposed SC" route, no nonclinical toxicity studies at all, and no study of the addictive liability its mechanism suggests.3 A peptide with a ten-minute half-life given by intravenous infusion in a sleep laboratory is a different exposure from the same peptide injected under the skin or sprayed into the nose at home, and no one has measured the second.
Regulatory Status
Is It Approved Anywhere?
No. The FDA found emideltide "not registered drugs in any country searched" and absent from the European, Japanese and international pharmacopoeias.3 It is not named on the WADA Prohibited List; as an unapproved substance it may fall under S0, and a tested athlete should ask their anti-doping organisation.
What Happened in July 2026?
In September 2023 the FDA placed emideltide in Category 2 of its interim compounding policy, and as of April 2026 it appears among substances nominated but withdrawn.11
On 24 July 2026 the Pharmacy Compounding Advisory Committee considered it for the 503A bulks list for opioid withdrawal, chronic insomnia and narcolepsy. The FDA proposed against inclusion: neither form was well characterised, safety was insufficiently characterised with an added immunogenicity concern for injection, effectiveness was unsupported for all three uses, and approved therapies exist for each.3 The committee voted 7 to 6, with one abstention, against inclusion, the only rejection among the seven peptides considered that week.6
The FDA's review also recorded that compounding of DSIP "can be traced back to at least 2018," when "a compounding pharmacy and its owner pled guilty and were sentenced for unlawful distribution of compounded prescription drugs, including emideltide," and that integrative neurology clinics, medical spas and online retailers offer it as injectable and intranasal products for sleep, stress, pain, cancer, Alzheimer's, Parkinson's and detoxification.3 No pharmacy in the United States has a lawful basis on which to compound it.
Related ONPEPS Coverage
DSIP sourcing and quality: a ten-minute peptide sold for overnight
DSIP cost and access: the one peptide the committee said no to
Epitalon: the other sleep-marketed peptide reviewed the same day
Selank: a Russian anxiolytic peptide with a different regulatory history
FDA peptide news July 2026: the votes, the dissent and what happens next
What Would Change This Page
Identification of a DSIP gene or receptor, which would settle whether the peptide is a natural signal at all. A modern, adequately sized, placebo-controlled sleep study by any route, which would be the first since 1992. Neither is under way.
References
Schoenenberger GA, Monnier M. Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proc Natl Acad Sci U S A. 1977;74(3):1282-1286. Open access. pubmed.ncbi.nlm.nih.gov/265572
Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem. 2006;97(2):303-309. Open access. pubmed.ncbi.nlm.nih.gov/16539679
US Food and Drug Administration. Emideltide-related bulk drug substances (emideltide (free base) and emideltide acetate): FDA presentation to the Pharmacy Compounding Advisory Committee, 24 July 2026. Docket FDA-2025-N-6895. Primary source for the pharmacology, the tabulated human studies, the safety findings, the 2018 prosecution and the FDA's recommendation. fda.gov
Monti JM, Debellis J, Alterwain P, Pellejero T, Monti D. Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs. Int J Clin Pharmacol Res. 1987;7(2):105-110. Paywalled. pubmed.ncbi.nlm.nih.gov/3583493
Bes F, Hofman W, Schuur J, Van Boxtel C. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study. Neuropsychobiology. 1992;26(4):193-197. Paywalled. pubmed.ncbi.nlm.nih.gov/1299794
ONPEPS. FDA peptide news July 2026: the only source you need. Records the 7 to 6 vote with one abstention against emideltide. onpeps.com
Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update. Peptides. 1986;7(6):1165-1187. Paywalled. pubmed.ncbi.nlm.nih.gov/3550726
Schneider-Helmert D. Efficacy of DSIP to normalize sleep in middle-aged and elderly chronic insomniacs. Eur Neurol. 1986;25(6):448-453. Paywalled. pubmed.ncbi.nlm.nih.gov/3792404
Dick P, Costa C, Fayolle K, Grandjean ME, Khoshbeen A, Tissot R. DSIP in the treatment of withdrawal syndromes from alcohol and opiates. Eur Neurol. 1984;23(5):364-371. Paywalled. pubmed.ncbi.nlm.nih.gov/6548969
ClinicalTrials.gov. Studies listing delta sleep inducing peptide as an intervention. Registry search returning no relevant studies; checked 16 September 2026. clinicaltrials.gov
US Food and Drug Administration. Category 2 of the Bulk Substances Nominated Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act. Entry for emideltide (DSIP). Content current as of 22 April 2026. fda.gov
Not Medical Advice
DSIP is not approved for human use in any jurisdiction, no human dose has been established by any route in use today, and its mechanism raises an addiction question no study has examined. Consult a qualified healthcare provider before acting on anything here.
Evidence counts on the library index retrieved 23 July 2026. Literature and regulatory sources verified 16 September 2026. Re-verify against docket FDA-2025-N-6895 before relying on any regulatory statement here.