DSIP Peptide, the Delta Sleep-Inducing Peptide: What Research Showed and What Is Left of the Name

Few peptides carry a promise in their name as specific as DSIP, the delta sleep-inducing peptide, known internationally as emideltide. It was named in 1977, when a Swiss team isolated it from the blood of rabbits put to sleep by electrical stimulation of the brain. Almost three decades later, a review in the Journal of Neurochemistry called the sleep-factor hypothesis “extremely poorly documented and still weak” (Kovalzon and Strekalova, 2006, PMID 16539679).

This article explains the gap: what studies in animals and humans showed, what almost half a century of research failed to establish and what status DSIP has today. We do not give doses or protocols, and the FAQ section explains why.

In our catalog, the compounds discussed in this article are chemical reagents intended solely for laboratory research (Research Use Only). They are not medicinal products, dietary supplements or foods, and they are not intended for use in humans or animals. What this status means is explained in our material on the legal status of research reagents.

An essential distinction: in Russia, DSIP is the active substance of Deltaran, a registered non-prescription medicine that combines the peptide with glycine. Research material containing DSIP alone is not a substitute for a medicinal product and does not replace medical consultation. Neither the data on Deltaran nor the human sleep studies discussed below apply to research material.

Where DSIP came from

DSIP is a nonapeptide, a chain of nine amino acids: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. Schoenenberger and Monnier’s team in Basel isolated it from dialyzed venous blood leaving the brain of rabbits. In those animals, sleep had been induced by electrical stimulation of the thalamus (Schoenenberger et al., 1978, PMID 568769). Infused into the brain ventricles of other rabbits, the peptide increased delta waves and sleep spindles on EEG, hence the name (Schoenenberger and Monnier, 1977, PMID 265572).

Delta waves are slow, high-amplitude EEG waves typical of deep sleep, also called slow-wave sleep. If wakefulness looks like dense, fine noise on the recording, delta sleep resembles long, rolling swells. A molecule able to produce them on demand would be a ready candidate for a sleeping pill, and that is how DSIP was seen in its early years.

The structure of DSIP does not resemble any known peptide family (PMID 16539679). One detail matters for judging the quality of material: only the form with aspartic acid linked by an α bond proved active, while its β isomer did not (PMID 568769). Both forms have identical mass, yet they act differently. This is one reason why batch identity is confirmed analytically, a subject we cover in our article on how to read a certificate of analysis.

Does DSIP really induce sleep?

This is the core of the matter. If DSIP were a “switch” for deep sleep, its effect should be reproducible across laboratories, and the body should have a receptor and a gene for it. Neither condition has been demonstrated.

Animals: the result depended on species, route and laboratory

The discoverer himself noted that sleep induction was species-specific: in cats, DSIP mainly increased REM sleep rather than delta sleep. The dose-response relationship was also bell-shaped instead of linear (Schoenenberger, 1984, PMID 6548966). Later teams added results that do not add up to a single picture.

In rats, neither intraperitoneal nor intraventricular administration increased sleep or EEG delta power. The authors concluded that DSIP does not qualify as a specific sleep-promoting substance (Tobler and Borbély, 1980, PMID 7405185). In another study, DSIP alone did not increase sleep in rats, whereas its analogs with a D-amino acid at the start of the chain did. The authors suspected that DSIP simply breaks down too fast (Obál et al., 1986, PMID 3754970). This fits the measurements: its plasma half-life averaged 4 minutes in dogs and 2 minutes in rats (Kato et al., 1984, PMID 6379493).

No receptor, no gene

The 2006 review names the main reason the hypothesis stalled: no one has isolated a DSIP gene, a precursor protein or a receptor (PMID 16539679). Five years later, researchers from the Institute of Bioorganic Chemistry in Moscow wrote that the biosynthetic origin of DSIP “remains obscure”. All they could propose was a hypothetical precursor (Mikhaleva et al., 2011, PMID 21262293).

A search for the “DSIP gene” is misleading. In the NCBI Gene database, the term points to TSC22D3, the gene for the GILZ protein, once called the “DSIP immunoreactor”. GILZ is an anti-inflammatory protein induced by glucocorticoids and has nothing to do with making the peptide (NCBI Gene, ID 1831). Likewise, a pig brain protein recognized by anti-DSIP antibodies turned out to have a sequence unrelated to the peptide (Sillard et al., 1993, PMID 8375381). A PubMed search on 24 October 2026 found no paper describing the identification of a DSIP receptor.

What about DSIP made by the body?

If DSIP signaled sleep, its level should rise before deep sleep. In humans, the opposite was seen. In a study of 12 healthy volunteers, DSIP-like immunoreactivity in plasma was measured every 30 minutes around the clock while sleep was recorded. It was clearly lower in REM sleep and slightly lower in slow-wave sleep than in wakefulness, with no rise around deep-sleep episodes (Friedman et al., 1994, PMID 8175965). In another study of seven healthy men, it fell at sleep onset (Seifritz et al., 1995, PMID 8745061).

Human studies: what they showed and why they are hard to reconcile

All studies of the effect of DSIP on human sleep date from 1981–1992 and included between one and a dozen or so people. They fall into two groups that point to different conclusions.

One author’s work: positive results

Most positive results come from a single researcher, Schneider-Helmert, and on several papers a co-discoverer of the peptide was a co-author. In a double-blind crossover trial in six healthy volunteers, median total sleep time over 130 minutes was 59% longer than after placebo (Schneider-Helmert et al., 1981, PMID 6895513). In a placebo-controlled study of 14 middle-aged people with chronic insomnia, the author reported clearly better night sleep within seven nights (Schneider-Helmert, 1987, PMID 3622582).

Independent teams: an effect without clinical significance

Two blinded polysomnography studies from other centers gave a weaker picture. In a crossover trial in people with chronic insomnia, slow-wave sleep and REM sleep did not change, and NREM sleep time already differed from placebo at baseline. The authors judged the improvement to be of little clinical significance (Monti et al., 1987, PMID 3583493). In a parallel-group study of 16 patients, the statistically significant effects were weak and partly reflected a chance change in the placebo group. Subjective sleep quality did not improve, and the authors judged short-term DSIP treatment unlikely to be of much help in chronic insomnia (Bes et al., 1992, PMID 1299794).

The most recent randomized study, from 2009, dealt with a different setting: general anesthesia in 24 women. Given during isoflurane anesthesia, DSIP paradoxically weakened delta rhythm and made anesthesia lighter on the BIS index (Pomfrett et al., 2009, PMID 19142086). No clinical trial of DSIP in sleep disorders has appeared in PubMed since 1993. ClinicalTrials.gov holds no study of this peptide (search on 24 October 2026).

In the 1980s, DSIP was also tested in alcohol and opioid withdrawal, in studies without a described control group (Dick et al., 1983, PMID 6328354). This line of research outlived the sleep hypothesis, as the current status of the peptide shows.

Regulatory status: Russia’s Deltaran and the US view

DSIP is the active substance of the Russian medicine Дельтаран (Deltaran). According to the Russian State Register of Medicines, its current registration certificate dates from 31 July 2026, and an earlier one was issued in 2016. It is a lyophilizate of DSIP with glycine for preparing a nasal solution, dispensed without prescription (GRLS, as of 23 October 2026).

Deltaran is indicated, as part of combination therapy, for stress-induced conditions and for alcohol withdrawal with pathological craving for alcohol. Insomnia is not on that list, and the product information states plainly that the mechanism of action is unknown (Vidal, 2026). The drug’s developers at the Institute of Bioorganic Chemistry titled their 2002 article “Delta sleep peptide: our path from a mythical sleep factor to the effective drug Deltaran”. In it, they admitted that the doubtful hypnotic properties of the peptide had disappointed hopes for a sleeping pill (Mikhaleva et al., 2002).

Data on Deltaran concern a preparation of DSIP with glycine, not the peptide alone, so they do not carry over directly to the reagent. No medicine containing DSIP is approved in the European Union or the United States. None appears in EMA’s Article 57 data (EMA, data as of 9 October 2026), and a Drugs@FDA search on 27 October 2026 returned nothing. FDA lists emideltide among bulk substances for compounding whose nominations were withdrawn. The agency says it lacks sufficient information to know whether emideltide would cause harm if given to humans (FDA, 2026).

FDA later evaluated emideltide on its own initiative for opioid withdrawal, chronic insomnia and narcolepsy. Agency reviewers concluded that the criteria weigh against putting it on the 503A Bulks List, FDA’s list of bulk substances allowed in pharmacy compounding (FDA briefing document, 2026). The agency’s Pharmacy Compounding Advisory Committee reached the same verdict on 24 July 2026: six votes in favor, seven against and one abstention. Of the seven peptides reviewed at that meeting, it was the only one the committee rejected (AJMC, 2026).

Anti-doping note

DSIP is not named on the WADA 2026 Prohibited List or in the 2026 Monitoring Program. Class S0 covers pharmacological substances that no governmental regulatory authority has approved for therapeutic use in humans. DSIP has a current registration in Russia as the active substance of a medicine. By the wording of the List, class S0 therefore does not cover it, and the List assigns it to no other section either. The same List applies to athletes tested by USADA, which has signed the World Anti-Doping Code (USADA, 2026). WADA and national agencies have the final word on interpretation. Our article on how the WADA Prohibited List handles research compounds sets out the classification rules.

Frequently asked questions

Is DSIP a sleep peptide?
The name suggests it, but research has not confirmed it. Animal results depended on species and laboratory; in some studies DSIP did not increase sleep, and in cats given it intraperitoneally it reduced sleep. Two independent, blinded studies in people with chronic insomnia found an effect without clinical significance (PMID 3583493, PMID 1299794).

Why does the article leave out doses?
A research reagent is not meant for use in humans, and neither the EU nor the US has approved any DSIP medicine with established dosing. Russia’s Deltaran has its own product information, but it covers a preparation with glycine and indications other than insomnia. Numbers found online do not come from registration trials in the EU or the US.

Are DSIP and Deltaran the same thing?
No. Deltaran is a Russian medicine containing DSIP and glycine, registered for combination therapy of stress-induced conditions and alcohol withdrawal syndrome. The research reagent is the peptide alone as laboratory material, with no status as a medicine.

Does the body produce DSIP?
DSIP-like immunoreactivity is found in blood, but no gene or protein it could come from has been identified. In humans, its level falls at sleep onset instead of rising (PMID 8745061).

Is DSIP banned in sport?
The 2026 Prohibited List does not mention it, and because of the Russian registration of the medicine, class S0 does not cover it. The final decision belongs to WADA and national agencies, as explained in the anti-doping note above.

Summary

DSIP is a nonapeptide isolated in 1977 from rabbit blood and named after the delta waves it increased on EEG. The name has outlived the hypothesis. Animal results depended on species, route and laboratory, and in rats the peptide alone did not increase sleep. Its gene, precursor and receptor remain unidentified, and its blood level falls at sleep onset. Positive human studies come mainly from one author, while two independent, blinded studies found an effect without clinical significance. Today DSIP survives mainly as the active substance of Russia’s Deltaran, registered for stress-related conditions and alcohol withdrawal, not insomnia. In the US, FDA advisers voted in 2026 against its use in pharmacy compounding.

Product documentation

Reagent pages with batch documentation: DSIP in a vial and DSIP spray. Peptides studied in relation to sleep, stress and recovery are grouped in peptides for well-being. Our overview of nootropic substances provides broader context. Both reagents are intended solely for laboratory research.

Bibliography

1. Schoenenberger GA, Monnier M. Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proc Natl Acad Sci U S A. 1977;74(3):1282-1286. doi:10.1073/pnas.74.3.1282. PMID: 265572
2. Schoenenberger GA, Maier PF, Tobler HJ, et al. The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide. Pflugers Arch. 1978;376(2):119-129. doi:10.1007/BF00581575. PMID: 568769
3. Schoenenberger GA. Characterization, properties and multivariate functions of delta-sleep-inducing peptide (DSIP). Eur Neurol. 1984;23(5):321-345. doi:10.1159/000115711. PMID: 6548966
4. Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem. 2006;97(2):303-309. doi:10.1111/j.1471-4159.2006.03693.x. PMID: 16539679
5. Mikhaleva II, Prudchenko IA, Ivanov VT, et al. JmjC-domain-containing histone demethylases of the JMJD1B type as putative precursors of endogenous DSIP. Peptides. 2011;32(4):826-831. doi:10.1016/j.peptides.2011.01.006. PMID: 21262293
6. Sillard R, Schulz-Knappe P, Vogel P, et al. A novel 77-residue peptide from porcine brain contains a leucine-zipper motif and is recognized by an antiserum to delta-sleep-inducing peptide. Eur J Biochem. 1993;216(2):429-436. doi:10.1111/j.1432-1033.1993.tb18160.x. PMID: 8375381
7. Tobler I, Borbély AA. Effect of delta sleep inducing peptide (DSIP) and arginine vasotocin (AVT) on sleep and motor activity in the rat. Waking Sleeping. 1980;4(2):139-153. PMID: 7405185
8. Obál F Jr, Kovalzon VM, Kalikhevich VN, et al. Structure-activity relationship in the effects of delta-sleep-inducing peptide (DSIP) on rat sleep. Pharmacol Biochem Behav. 1986;24(4):889-894. doi:10.1016/0091-3057(86)90432-6. PMID: 3754970
9. Koval’zon VM. [Hypnogenic properties of DSIP peptide analogs: structural-functional relationship]. Izv Akad Nauk Ser Biol. 2001;(4):467-474. PMID: 11525128
10. Susić V, Masirević G, Totić S. The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat. Brain Res. 1987;414(2):262-270. doi:10.1016/0006-8993(87)90006-0. PMID: 3620931
11. Sommerfelt L. Reduced sleep in cats after intraperitoneal injection of delta-sleep-inducing peptide (DSIP). Neurosci Lett. 1985;58(1):73-77. doi:10.1016/0304-3940(85)90331-3. PMID: 3840239
12. Kato N, Honda Y, Ebihara S, et al. Development of an enzyme immunoassay for delta sleep-inducing peptide (DSIP) and its use in the determination of the metabolic clearance rate of DSIP administered to dogs. Neuroendocrinology. 1984;39(1):39-44. doi:10.1159/000123952. PMID: 6379493
13. Friedman TC, Garcia-Borreguero D, Hardwick D, et al. Diurnal rhythm of plasma delta-sleep-inducing peptide in humans: evidence for positive correlation with body temperature and negative correlation with rapid eye movement and slow wave sleep. J Clin Endocrinol Metab. 1994;78(5):1085-1089. doi:10.1210/jcem.78.5.8175965. PMID: 8175965
14. Seifritz E, Müller MJ, Schönenberger GA, et al. Human plasma DSIP decreases at the initiation of sleep at different circadian times. Peptides. 1995;16(8):1475-1481. doi:10.1016/0196-9781(95)02027-6. PMID: 8745061
15. Schneider-Helmert D, Gnirss F, Monnier M, et al. Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior. Int J Clin Pharmacol Ther Toxicol. 1981;19(8):341-345. PMID: 6895513
16. Schneider-Helmert D. Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia. Eur Neurol. 1987;27(2):120-129. doi:10.1159/000116143. PMID: 3622582
17. Monti JM, Debellis J, Alterwain P, et al. 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. PMID: 3583493
18. Bes F, Hofman W, Schuur J, et al. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study. Neuropsychobiology. 1992;26(4):193-197. doi:10.1159/000118919. PMID: 1299794
19. Pomfrett CJ, Dolling S, Anders NR, et al. Delta sleep-inducing peptide alters bispectral index, the electroencephalogram and heart rate variability when used as an adjunct to isoflurane anaesthesia. Eur J Anaesthesiol. 2009;26(2):128-134. doi:10.1097/EJA.0b013e32831c8644. PMID: 19142086
20. Dick P, Grandjean ME, Tissot R. Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors. Neuropsychobiology. 1983;10(4):205-208. doi:10.1159/000118012. PMID: 6328354
21. Михалева ИИ, Прудченко ИА, Иванов ВТ, Войтенков БО. Пептид дельта-сна: наш путь от мифического фактора сна к эффективному лекарственному препарату Дельтаран [Delta sleep peptide: our path from a mythical sleep factor to the effective drug Deltaran]. Medline.ru. 2002;3:art. 42. medline.ru
22. Ministry of Health of the Russian Federation. State Register of Medicines (GRLS): Deltaran® (Дельтаран®), registration certificate ЛП-№(016126)-(РГ-RU) of 31 July 2026; previous certificate ЛП-003849 of 20 September 2016. Register export as of 23 October 2026. grls.rosminzdrav.ru
23. Vidal (Russia). Deltaran (Дельтаран): product information (updated 4 June 2026). vidal.ru (accessed 24 October 2026)
24. European Medicines Agency. Article 57 product data (data as of 9 October 2026). ema.europa.eu (accessed 27 October 2026)
25. U.S. Food and Drug Administration. Drugs@FDA: FDA-Approved Drugs, search for “emideltide” via the openFDA drugsfda endpoint. accessdata.fda.gov (accessed 27 October 2026)
26. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (content current as of 22 April 2026). fda.gov (accessed 27 October 2026)
27. U.S. Food and Drug Administration. FDA Briefing Document: Emideltide-Related Bulk Drug Substances (Emideltide (free base) and Emideltide acetate). Pharmacy Compounding Advisory Committee meeting, 23–24 July 2026; review dated 11 May 2026. fda.gov (accessed 27 October 2026)
28. Steinzor P. FDA Panel Backs 6 Peptides for Compounding. AJMC. 31 July 2026. ajmc.com (accessed 27 October 2026)
29. National Center for Biotechnology Information. Gene ID 1831, TSC22D3 (TSC22 domain family member 3). ncbi.nlm.nih.gov (accessed 24 October 2026)
30. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026, and 2026 Monitoring Program. wada-ama.org (accessed 24 October 2026)
31. U.S. Anti-Doping Agency. About USADA. usada.org (accessed 27 October 2026)
32. U.S. Anti-Doping Agency. Prohibited List. usada.org (accessed 27 October 2026)