DSIP
Published research and evidence base
Delta sleep-inducing peptide is a nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) isolated in 1977 from cerebral venous blood of sleep-induced rabbits. Despite five decades of study, no DSIP gene, precursor protein or receptor has been identified, and the peptide's status as an endogenous sleep factor remains contested. Human work is concentrated in the 1980s and early 1990s and includes small double-blind studies in insomnia, chronic pain and opioid withdrawal with inconsistent results; recent research is almost entirely rodent work on stroke, stress and drug-delivery constructs.
- Studies cited
- 17
- Published 2023+
- 1
- Newest paper
- 2024
- Last reviewed
- Aug 2026
Recurring themes in the literature
- slow-wave sleep
- endogenous sleep factor hypothesis
- blood-brain barrier transport
- stress and HPA axis
- opioid withdrawal
- antioxidant and geroprotective effects
- unidentified receptor
Compound identifiers
- CAS
- 62568-57-4
- PubChem
- 68816
Not recommended by an FDA advisory committee.
On 23–24 July 2026 the FDA’s Pharmacy Compounding Advisory Committee considered DSIP, heard under the name emideltide, for the 503A Bulks List and declined to recommend its addition on a reported vote of 6–7 with one abstention. The only one of the seven peptides the committee declined to recommend. It was heard under the name emideltide.
This is not an approval. The committee advises; it does not decide. The recommendation is not binding, the FDA has not completed the rulemaking that would formally change anything, and inclusion on the 503A Bulks List is not equivalent to FDA approval of a drug. The list also governs pharmacy compounding for patients, which is a separate activity from research-use-only supply.
What the July 2026 advisory vote actually did sets out the process, the other compounds heard, and the four things the vote is routinely misreported as meaning.
What DSIP is, chemically.
- Molecular formula
- C35H48N10O15
- Molecular weight
- 848.8 g/mol
- CAS number
- 62568-57-4
- PubChem CID
- 68816
Emideltide
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
17 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Human clinical2009
Delta sleep-inducing peptide alters bispectral index, the electroencephalogram and heart rate variability when used as an adjunct to isoflurane anaesthesia
Pomfrett CJ, et al. · European Journal of Anaesthesiology · randomised controlled trial, 24 female ASA I-II patients; intravenous DSIP 25, 50 or 100 nmol/kg vs saline during isoflurane anaesthesia
DSIP increased heart rate, decreased heart rate variability and, contrary to the hypothesis, reduced delta rhythm and increased bispectral index at 25 nmol/kg. The authors concluded DSIP lightened rather than deepened anaesthetic depth.
- 02Human clinical1998
Opioid detoxification with delta sleep-inducing peptide: results of an open clinical trial
Backmund M, Meyer K, Rothenhaeusler HB, Soyka M · Journal of Clinical Psychopharmacology · open clinical trial in opioid detoxification
This open-label report described use of DSIP during opioid detoxification. It was published as a short communication without a control group.
- 03Human clinical1995
Delta sleep-inducing peptide in normal humans and in patients with sleep apnea and narcolepsy
Vgontzas AN, Friedman TC, Chrousos GP, Bixler EO, Vela-Bueno A, Kales A · Peptides · cross-sectional plasma sampling: 9 sleep apnoea patients, 10 narcolepsy patients, 11 normal controls, plus a second cohort
Morning plasma DSIP-like immunoreactivity did not differ significantly between sleep apnoea patients, narcolepsy patients and controls. The findings did not support single plasma DSIP measures as a disease marker.
- 04Human clinical1994
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
Friedman TC, et al. · The Journal of Clinical Endocrinology and Metabolism · human diurnal sampling with concurrent polysomnography and body temperature
Plasma DSIP correlated positively with body temperature and negatively with REM and slow-wave sleep, a pattern opposite to that expected of a circulating slow-wave-sleep-promoting factor.
- 05Human clinical1992
Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study
Bes F, Hofman W, Schuur J, Van Boxtel C · Neuropsychobiology · double-blind matched-pairs parallel-group trial, n=16 chronic insomnia patients; intravenous DSIP 25 nmol/kg vs glucose placebo on three nights, polysomnography
Polysomnography showed higher sleep efficiency and shorter sleep latency with DSIP, but the effects were weak and partly attributable to change in the placebo group. The authors concluded short-term DSIP treatment of chronic insomnia was unlikely to be of major therapeutic benefit.
- 06Human clinical1984
Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study
Larbig W, Gerber WD, Kluck M, Schoenenberger GA · European Neurology · open pilot study, n=7 patients with migraine, vasomotor headache, chronic tinnitus or psychogenic pain; intravenous DSIP over 5 consecutive days then every 48-72 h
Pain levels fell significantly in 6 of 7 patients relative to baseline, with a concurrent reduction in depressive symptoms. The design was uncontrolled and the sample very small.
- 07Human clinical1983
Effects of DSIP in man. Multifunctional psychophysiological properties besides induction of natural sleep
Schneider-Helmert D, Schoenenberger GA · Neuropsychobiology · five double-blind human studies with single and repeated intravenous DSIP injections, polygraphic recordings and psychophysiological tests
The authors reported a sleep-induction latency of about 1 h with effects lasting up to 20 h, normalisation of disturbed sleep in insomniacs after four consecutive injections, and increased alertness and performance during waking. Tolerability was good provided injection was slow.
- 08Animal in vivo2024
Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models
Mu X, Qu L, et al. · Frontiers in Pharmacology · PCPA-induced insomnia mouse model, recombinant DSIP fusion peptide expressed in Pichia pastoris
A recombinantly produced DSIP fusion peptide crossed the blood-brain barrier and produced measurable effects in a chemically induced insomnia mouse model. This is the most recent primary DSIP study indexed in PubMed.
- 09Animal in vivo2021
Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke
Tukhovskaya EA, et al. · Molecules · Sprague-Dawley rats, focal stroke model
DSIP administration was associated with recovery of motor function after focal stroke in rats.
- 10Animal in vivo2021
DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
Tukhovskaya EA, et al. · Biomedicines · C57Bl/6 mice (cerebral ischaemia) and Sprague-Dawley rats (myocardial ischaemia-reperfusion)
The DSIP-like KND peptide reduced infarct size in both brain and myocardial ischaemia-reperfusion models when given during reperfusion.
- 11Animal in vivo2018
Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude
Roy K, et al. · Life Sciences · rodent model of hypobaric hypoxia / simulated high altitude
Phosphorylated DSIP improved sleep architecture and was associated with restored spatial memory performance and p-CREB expression under simulated high-altitude conditions.
- 12Animal in vivo2016
Effect of Delta Sleep-Inducing Peptide on Functional State of Hepatocytes in Rats During Restraint Stress
Bobyntsev II, et al. · Bulletin of Experimental Biology and Medicine · rat restraint-stress model, hepatocyte morphology and function
DSIP modified stress-induced changes in hepatocyte functional state, consistent with a general anti-stress rather than sleep-specific action.
- 13Animal in vivo2014
Effect of delta sleep-inducing peptide on the expression of antioxidant enzyme genes in the brain and blood of rats during physiological aging
Kutilin DS, Bondarenko TI, et al. · Bulletin of Experimental Biology and Medicine · ageing rats, brain and blood antioxidant enzyme gene expression
DSIP altered expression of antioxidant enzyme genes in brain and blood of ageing rats, forming part of the Russian geroprotection literature on this peptide.
- 14Animal in vivo2012
Effect of delta sleep-inducing peptide on oxidative modification of proteins in rat tissues and blood during physiological aging
Bondarenko TI, et al. · Bulletin of Experimental Biology and Medicine · ageing rats, protein carbonylation markers in tissues and blood
DSIP reduced markers of oxidative protein modification in ageing rats.
- 15Animal in vivo1988
Evidence for a role of delta sleep-inducing peptide in slow-wave sleep and sleep-related growth hormone release in the rat
Iyer KS, McCann SM · Proceedings of the National Academy of Sciences of the United States of America · rat, immunoneutralisation and administration studies of slow-wave sleep and growth hormone release
This landmark study reported evidence linking DSIP to slow-wave sleep and sleep-associated growth hormone release in the rat, and is the most frequently cited mechanistic basis for DSIP's sleep claims.
- 16Review2006
Delta sleep-inducing peptide (DSIP): a still unresolved riddle
Kovalzon VM, Strekalova TV · Journal of Neurochemistry · critical mini-review
The authors concluded that the hypothesis of DSIP as a sleep factor is poorly documented and weak, noting that no DSIP gene, protein precursor or receptor had been isolated and that certain synthetic analogues, but not DSIP itself, promoted slow-wave sleep in rabbits and rats.
- 17Review1984
Delta-sleep-inducing peptide (DSIP): a review
Graf MV, Kastin AJ · Neuroscience and Biobehavioral Reviews · foundational narrative review
This early review consolidated the distribution, pharmacokinetics and reported behavioural actions of DSIP, and established the framing of the peptide as multifunctional rather than sleep-specific.
What this evidence does not establish.
No DSIP receptor, gene or precursor has ever been identified, and the peptide's classification as an endogenous sleep factor is disputed in the primary literature. Human trials are small, mostly pre-1995, used intravenous rather than subcutaneous dosing, and produced inconsistent sleep outcomes; there are no modern randomised controlled trials, no pharmacokinetic characterisation for non-intravenous routes, and no controlled safety data.
Common questions about the research.
- What is DSIP?
DSIP is a nonapeptide originally isolated from rabbit cerebral venous blood during electrically induced slow-wave sleep. It has been studied since the late 1970s and remains one of the more mechanistically unresolved peptides in the neuroscience literature.
- Does the literature explain how DSIP works?
Not conclusively. No receptor has been confirmed and no transduction pathway agreed. Reviewers describe interactions with the hypothalamic-pituitary-adrenal axis and the opioid system, plus reports on thermoregulation and gene expression, but explicitly characterise the overall picture as unresolved.
- Why does recent DSIP research have so little to do with sleep?
Because the sleep findings proved difficult to replicate. Work published since 2010 has largely moved to other endpoints — motor recovery after experimental stroke, antioxidant enzyme expression in ageing animals, and stress-model physiology — which is where the current literature sits.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.