Compound reference
DSIP
Also known as Delta Sleep-Inducing Peptide, Emideltide
DSIP (delta sleep-inducing peptide) is a nonapeptide discovered in 1977 and sold today as a sleep and recovery peptide. Behind it is a large but inconclusive literature — and, half a century on, no identified gene, precursor, or receptor. Experts still call it "a still unresolved riddle."
- CAS
- 62568-57-4
- Formula
- C₃₅H₄₈N₁₀O₁₅
- Molar mass
- ≈848.8 g/mol
- Sequence
- Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE), nonapeptide
Research peptide; not FDA-approved as a drug.
Mode of action
DSIP is a nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) with an unusually clean origin story: in 1977 Schoenenberger and Monnier isolated it from the cerebral venous blood of rabbits placed in an electrically induced sleep state, and showed that infusing it into other rabbits enhanced the delta and spindle EEG activity of slow-wave sleep. It was named for that effect, it crosses the blood-brain barrier, and its plasma levels track the circadian cycle.
What is striking is how little has been pinned down since. After nearly fifty years, no DSIP gene, no precursor protein, and no specific DSIP receptor has ever been identified — the single most important fact about its mechanism, and the reason a leading review titled itself "a still unresolved riddle." The effects attributed to it are correspondingly diffuse: potentiation of GABA and inhibition of NMDA currents, release of Met-enkephalin (its antinociceptive action is blocked by the opioid antagonist naloxone), modulation of the HPA axis, and a characteristic bell-shaped dose-response in which both too little and too much lose the effect. In short, DSIP behaves more like a loosely-defined neuromodulator than a discrete sleep hormone, and its core mechanism remains unsettled.
Main intended effect
To promote or normalize sleep — specifically slow-wave (delta) sleep — with secondary claims around stress resilience, pain relief, and easing of withdrawal.
Areas of interest
Sleep and insomnia are the namesake interest. Beyond that, DSIP has been studied for opioid and alcohol withdrawal, chronic pain and headache, and anti-stress and neuroendocrine effects. In the consumer market it is sold as a sleep and recovery research peptide.
Evidence for intended effects
DSIP is unusual in having a very large literature and very little resolution. The early animal work is real — the 1977 rabbit studies reproducibly induced delta EEG. Small human studies followed: a sleep-laboratory study reported normalized sleep in middle-aged and elderly chronic insomniacs given intravenous DSIP, and an open series reported rapid relief of withdrawal symptoms in alcohol- and opioid-dependent patients. More recent work has engineered DSIP fusion peptides to improve brain delivery in mouse insomnia models.
But the honest reading is the skeptical one. The human studies are small, mostly old, and largely uncontrolled or unblinded. And the field's own reassessment (Kovalzon and Strekalova, 2006) concluded that the hypothesis of DSIP as an endogenous sleep factor is "extremely poorly documented and still weak" — pointing out that the gene, precursor, and receptor were never found, and that much of the activity came from synthetic analogues rather than the natural peptide. There is no modern randomized controlled trial establishing a sleep indication, and no regulatory approval. Decades of interest have not converted into a proven therapy.
| Strand | What exists | Tier |
|---|---|---|
| Delta-EEG / sleep (animal) | Original 1977 rabbit studies; reproducible EEG effect | Foundational preclinical |
| Human sleep | Small, mostly uncontrolled insomnia studies | Weak human |
| Withdrawal / other | Open-label series; diffuse neuroendocrine effects | Preliminary / uncontrolled |
| Mechanism | No gene, precursor, or receptor identified | Unresolved |
Studied amounts (literature dosing context)
Human studies dosed DSIP intravenously at roughly 25–30 nmol/kg — for example 25 nmol/kg in the withdrawal series and repeated 30 nmol/kg doses in the insomnia study. The peptide is rapidly metabolized with a short plasma half-life. These are figures from small investigational studies; there is no approved or established human dose, and this page does not provide dosing guidance.
Safety and regulatory status
In the small human studies DSIP was generally reported as well tolerated, with no major side effects noted — but those studies were small and not designed to characterize safety, so this is reassuring anecdote rather than established data. DSIP is not approved as a drug in any jurisdiction; it is sold as a research peptide for sleep and recovery. As with other gray-market peptides, products labeled "DSIP" are of unverified identity and purity, and the underlying biology remains, by expert consensus, unresolved.
Sources
Characterization of a delta-electroencephalogram (-sleep)-inducing peptide
Foundational study (Schoenenberger and Monnier, Proceedings of the National Academy of Sciences 1977) characterizing delta sleep-inducing peptide. The peptide was isolated from the cerebral venous blood of rabbits placed in an electrically induced sleep state, and when infused intraventricularly into recipient rabbits it specifically enhanced the delta and spindle EEG activity associated with slow-wave sleep. The authors established biological specificity by showing that metabolic fragments, two nonapeptide analogues, and a related tripeptide did not reproduce the effect. This is the original discovery and characterization of DSIP that launched the field.
Characterization, properties and multivariate functions of delta-sleep-inducing peptide (DSIP)
Schoenenberger reviewed roughly two decades of work (isolation, characterization, and synthesis of the nonapeptide from 1970-1977 onward) on delta sleep-inducing peptide (DSIP), an amphiphilic nine-amino-acid peptide. The review synthesizes DSIP's sleep-promoting effects across species, its influence on circadian rhythms and hormonal regulation, structure-activity relationships from amino acid modifications, and biochemical properties including blood-brain barrier penetration, proteolytic metabolism, and carrier-protein binding. It also covers broader interactions involving stress responses and drug effects (morphine, amphetamines, barbiturates). The body of work draws on both animal models and human samples but predates modern controlled-trial standards. DSIP is research-stage; human efficacy and safety are not established.
Efficacy of DSIP to normalize sleep in middle-aged and elderly chronic insomniacs
Schneider-Helmert studied 18 chronic psychophysiological insomniacs in two age groups (middle-aged 29-59 years and elderly 60-83 years) in a sleep-laboratory study using intravenous DSIP at 6 x 30 nmol/kg with polysomnographic monitoring across one week of administration plus a one-week follow-up. In middle-aged insomniacs, sleep improved to normal values by the end of DSIP administration and was maintained through follow-up; in elderly participants the immediate effect was larger but full normalization was reached only by the end of follow-up, with the whole sample showing normal sleep patterns at study end. Effects correlated with baseline sleep-disturbance severity. The sample is very small with no concurrent placebo arm described in the record, limiting strength of inference. DSIP is research-stage; human efficacy and safety are not established.
Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors
Dick, Grandjean, and Tissot administered intravenous DSIP at 25 nmol/kg as the sole treatment to 67 patients with withdrawal symptoms (28 alcohol, 39 opiate), of whom 49 were evaluable. The authors reported beneficial effects in 48 of 49 evaluable patients (22 alcoholics, 26 of 27 opiate-dependent), describing immediate onset with lasting suspension of somatic withdrawal signs while anxiety resolved more gradually over hours, and reported no major side effects. They proposed DSIP as a physiologically based approach to withdrawal syndrome treatment. This is a small, uncontrolled (open-label) early human case series with substantial attrition (27% lost or unsuitable) and no placebo group, so the findings are preliminary. DSIP is research-stage; human efficacy and safety are not established.
Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models
Mu and colleagues engineered DSIP-CBBBP, a fusion of delta sleep-inducing peptide with a blood-brain-barrier-crossing Tat peptide joined by GGGGS linkers and expressed in Pichia pastoris, and tested it in PCPA-induced insomnia in 48 male Kun-Ming mice (PCPA 300 mg/kg intraperitoneally for five days) with the fusion peptide dosed intraperitoneally for five days. Outcomes included locomotor/anxiety behavior (open field, elevated plus maze), depressive-like behavior, sucrose preference, neurotransmitter levels (melatonin, serotonin, dopamine, glutamate), wakefulness time, and hippocampal histology. DSIP-CBBBP outperformed standalone DSIP, restoring neurotransmitter balance, reducing daily wakefulness from 720±45 to 500±32 minutes, and improving hippocampal tissue integrity (P<0.0001). This is a preclinical mouse study of an engineered fusion construct; DSIP is research-stage and human efficacy and safety are not established.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1439536/full
Delta sleep-inducing peptide (DSIP): a still unresolved riddle
Critical review (Kovalzon and Strekalova, Journal of Neurochemistry 2006) reassessing nearly three decades of DSIP research. The authors argue that the central hypothesis — that DSIP is an endogenous sleep factor — is extremely poorly documented and remains weak, because the peptide's natural occurrence and biological activity are still obscure and, crucially, no DSIP gene, precursor protein, or specific receptor has ever been isolated. They note that much of the sleep-promoting activity attributed to DSIP comes from synthetic analogues, and propose that DSIP-like immunoreactivity may reflect other, as-yet-unidentified peptides. This is the most important skeptical appraisal of the field and a corrective to the strong claims in the older and commercial literature.