DSIP

DSIP at a Glance

DSIP — delta sleep-inducing peptide — is a nonapeptide isolated in the 1970s from the blood of rabbits in induced sleep, and named for the effect it appeared to produce. Later research largely failed to confirm that sleep effect, which leaves the compound in an unusual position: still named for a property it may not have. It is sold as an injectable research chemical for sleep and stress, is unapproved everywhere, and its endogenous role remains poorly defined.

History & Development

DSIP stands for Delta Sleep-Inducing Peptide, and the name is the problem: the sleep effect it was named for was tested and largely not confirmed.

First described	Not established in the sources consulted for this section
Discovered / synthesised by	Not established in the sources consulted for this section
Institution	Not established in the sources consulted for this section
Origin	Synthetic nonapeptide; no DSIP gene, precursor or receptor has been identified
Key patent	Not established in the sources consulted for this section
Assignee	Not established in the sources consulted for this section
Development status	Never approved anywhere; sold as a research chemical

Discovery

DSIP was isolated on the basis of a functional observation - material associated with delta-wave sleep - and named for that observation before the underlying biology was established.

That biology was never established. There is no identified DSIP gene, no precursor protein and no receptor, which is an extraordinary gap for a molecule that has carried a functional name for decades. Most endogenous peptides can be traced to a gene and a receptor; DSIP cannot, and its status as a genuine endogenous signalling molecule remains unresolved.

Development & ownership

The sleep claim has been tested. The best-controlled human sleep trial ever run on DSIP was negative - this is a compound that was examined properly and not confirmed, rather than one that was never studied.

What replaced it is more interesting and much less marketed. The single most robustly demonstrated human effect of DSIP is suppression of pituitary ACTH secretion, shown in a randomized, double-blind, placebo-controlled crossover in 11 men and independently confirmed. That is a real, replicated endocrine finding - and it is a biomarker, not an indication. Lowering ACTH is not a therapeutic goal in itself, and nothing establishes that it produces a benefit anyone would notice.

How it reached the market

DSIP has never been approved anywhere. It is sold as an injectable sleep aid - for the one effect its best controlled trial failed to confirm, while the effect that is replicated goes unmentioned because it is not something anyone would buy.

What It's Used For

DSIP is a compound whose name is a hypothesis that its own literature never confirmed. In 1977 the Schoenenberger–Monnier group in Basel isolated a nonapeptide — Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu — from the cerebral venous blood of rabbits induced into slow-wave sleep by thalamic stimulation, reported that transferring it induced delta-wave sleep in recipient rabbits, and named it “delta sleep-inducing peptide.” Nearly fifty years later, the field’s own review is blunt about what followed: the link between DSIP and sleep “has never been further characterized,” no DSIP gene, precursor protein, or receptor has ever been isolated, and the hypothesis that DSIP is a sleep factor is “extremely poorly documented and still weak” ^{1Reference 1Kovalzon VM · 2006ReviewDelta sleep-inducing peptide (DSIP): a still unresolved riddle — reviewView study →}.

That same review notes something the marketing never mentions — the significant slow-wave-sleep promotion seen in the authors’ early rabbit and rat work came from artificial structural analogues of DSIP, not from DSIP itself ^{1Reference 1Kovalzon VM · 2006ReviewDelta sleep-inducing peptide (DSIP): a still unresolved riddle — reviewView study →}.

Everything below should be read through three facts. First, the best-controlled human sleep trial ever run on DSIP was negative ^{3Reference 3Bes F et al. · 1992RCTEffects of delta sleep-inducing peptide on sleep of chronic insomniac patientsView study →} — this is a compound that was tested and not confirmed, not one that was never tested. Second, the human evidence is old: a cluster of 1981–1998 European studies, mostly single-dose, mostly small, several with no control group at all, none pre-registered, and none replicated since. Third, route decides everything. Every human study of DSIP delivered it by intravenous infusion under observation — most at 25 nmol/kg, with FDA’s own 2026 tabulation spanning 25–150 nmol/kg across 209 subjects dosed for one to fifteen days. The gray market sells lyophilized powder for subcutaneous injection at bedtime — a route for which, as FDA states plainly, no pharmacokinetic, effectiveness or safety data exist at all. No DSIP-intervention trial is registered on ClinicalTrials.gov.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric. Each application links down to its write-up.

Read this table carefully for this compound. A low score usually means untested. For DSIP, sleep means something different and worse: tested repeatedly in humans, and not confirmed. Sleep sits mid-table not because nobody looked, but because the best-designed study that looked found no meaningful benefit ^{3Reference 3Bes F et al. · 1992RCTEffects of delta sleep-inducing peptide on sleep of chronic insomniac patientsView study →} and the endogenous-peptide data point the wrong way ^{6Reference 6Friedman TC et al. · 1994ObservationalDiurnal 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 — human (observational, n=12)View study →}. Note also what is at the top: the highest-quality human data here is an endocrine biomarker, not a sleep outcome — which is a direct contradiction of how DSIP is marketed.

01Neuroendocrine & HPA-axis suppressionShaky34%The only replicated, properly controlled human effect: randomized double-blind crossover ACTH suppression (n=11) ^{14Reference 14Bjartell A et al. · 1989RCTReduction of immunoreactive ACTH in plasma following intravenous injection of delta sleep-inducing peptide in man — human (randomised double-blind crossover, n=11)View study →} + independent confirmation ^{15Reference 15Chiodera P et al. · 1994RCTDifferent effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men — human (placebo-controlled crossover, n=15; AVP endpoint null)View study →}. A biomarker, not an indication; two related endocrine endpoints were null ^{16,17Reference 16Giusti M et al. · 1993Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women — human (null)View study →Reference 17Späth-Schwalbe E et al. · 1995Delta-sleep-inducing peptide does not affect CRH and meal-induced ACTH and cortisol secretion — human (null)View study →}.

02Alcohol & opioid withdrawalShaky28%The largest human dataset (~175 patients across three reports) but entirely open-label and uncontrolled, from overlapping investigator groups ^{8,9,10Reference 8Dick P et al. · 1983Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors — human (open, uncontrolled, n=67)View study →Reference 9Dick P et al. · 1984DSIP in the treatment of withdrawal syndromes from alcohol and opiates — human (open, uncontrolled, n=107)View study →Reference 10Backmund M et al. · 1998Clinical trialOpioid detoxification with delta sleep-inducing peptide: results of an open clinical trial — human (open clinical trial; abstract not indexed)View study →}.

03Sleep & insomniaShaky22%Tested and not confirmed. One positive n=6 crossover by the discovering group ^{2Reference 2Schneider-Helmert D et al. · 1981RCTAcute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior — human (double-blind crossover, n=6)View study →}; the independent n=16 double-blind trial was negative ^{3Reference 3Bes F et al. · 1992RCTEffects of delta sleep-inducing peptide on sleep of chronic insomniac patientsView study →}; a second independent double-blind crossover (Monti 1987, surfaced by FDA’s 2026 review) was also null; endogenous DSIP anticorrelates with slow-wave and REM sleep ^{6Reference 6Friedman TC et al. · 1994ObservationalDiurnal 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 — human (observational, n=12)View study →}.

04Analgesia & chronic painShaky20%Replicated rodent antinociception with a defined opioid/noradrenergic mechanism ^{12,13Reference 12Nakamura A et al. · 1988AnimalPotent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP) — animal (mouse/rat, central administration)View study →Reference 13Nakamura A et al. · 1989AnimalInvolvement of spinal noradrenergic system in the mechanism of an antinociceptive effect of delta-sleep-inducing peptide — animal (mouse)View study →} + one uncontrolled 7-patient before-and-after human pilot ^{11Reference 11Larbig W et al. · 1984Clinical trialTherapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodesView study →}.

05Antioxidant & geroprotectionShaky15%Rodent only, and mean lifespan was not extended in the flagship mouse study ^{22Reference 22Popovich IG et al. · 2003AnimalEffect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice — animal (mouse); mean lifespan unchangedView study →}. All from one collaborating circle ^{19,20,21,22,23Reference 19Bondarenko TI et al. · 2011AnimalMechanism of delta-sleep inducing peptide geroprotective activity — animal (rat)View study →Reference 20Shustanova TA et al. · 2001AnimalRegulation of free radical processes by delta-sleep inducing peptide in rat tissues under cold stress — animal (rat)View study →Reference 21Kutilin DS et al. · 2014AnimalEffect of delta sleep-inducing peptide on the expression of antioxidant enzyme genes in the brain and blood of rats during physiological aging — animal (rat)View study →Reference 22Popovich IG et al. · 2003AnimalEffect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice — animal (mouse); mean lifespan unchangedView study →Reference 23Voĭtenkov VB et al. · 2009AnimalEffect of delta-sleep inducing peptide preparation Deltaran on longevity, physiological functions, and carcinogenesis in mice — animal (mouse); overlapping authors and model with [22]View study →}.

06Stress adaptation & neuroprotectionShaky13%Single-program rat work on the “Deltaran” preparation ^{18Reference 18Koplik EV et al. · 2008AnimalDelta sleep-inducing peptide and Deltaran: potential approaches to antistress protection — animal (rat); tests the Deltaran preparationView study →}. No human stress or neuroprotection outcome data of any kind.

07Anticonvulsant activityShaky11%One rat seizure model, one laboratory, partly using the analogue DSIP-12 ^{24,25Reference 24Stanojlović OP et al. · 2005AnimalAntiepileptic activity of delta sleep-inducing peptide and its analogue in metaphit-provoked seizures in rats — animal (rat); tests DSIP and the analogue DSIP-12View study →Reference 25Hrnčić D et al. · 2006AnimalDelta-sleep-inducing peptide potentiates anticonvulsive activity of valproate against metaphit-provoked audiogenic seizure — animal (rat)View study →}. No human epilepsy data.

Mechanisms

The last row is the important one. A compound with a demonstrated human endocrine effect but no known receptor, no gene, and no precursor is not a well-characterized drug — it is an unresolved observation. The review that surveys this literature goes further and hypothesizes that DSIP-like immunoreactivity in tissue may come from some other, still unidentified DSIP-like peptide, since it distributes in hypothalamic nuclei that are not particularly relevant to sleep regulation ^{1Reference 1Kovalzon VM · 2006ReviewDelta sleep-inducing peptide (DSIP): a still unresolved riddle — reviewView study →}. On that reading, even DSIP’s status as an endogenous substance is unsettled.

Pharmacokinetics

Route is the practically decisive fact for anyone considering this compound, and there is a direct mismatch between what was studied and what is sold.

What was studied: every controlled human result here — the sleep crossover ^{2Reference 2Schneider-Helmert D et al. · 1981RCTAcute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior — human (double-blind crossover, n=6)View study →}, the negative insomnia trial ^{3Reference 3Bes F et al. · 1992RCTEffects of delta sleep-inducing peptide on sleep of chronic insomniac patientsView study →}, the ACTH suppression ^{14,15Reference 14Bjartell A et al. · 1989RCTReduction of immunoreactive ACTH in plasma following intravenous injection of delta sleep-inducing peptide in man — human (randomised double-blind crossover, n=11)View study →Reference 15Chiodera P et al. · 1994RCTDifferent effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men — human (placebo-controlled crossover, n=15; AVP endpoint null)View study →}, the withdrawal series ^{8,9Reference 8Dick P et al. · 1983Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors — human (open, uncontrolled, n=67)View study →Reference 9Dick P et al. · 1984DSIP in the treatment of withdrawal syndromes from alcohol and opiates — human (open, uncontrolled, n=107)View study →}, the pain pilot ^{11Reference 11Larbig W et al. · 1984Clinical trialTherapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodesView study →} — used slow intravenous infusion, given in a clinic, most often at 25 nmol/kg. FDA’s 2026 tabulation of the human literature puts the full range at 25–150 nmol/kg intravenously in 209 subjects, dosed for one to fifteen days — so the “25 nmol/kg” figure is the commonest dose, not the only one. Rodent work used intraperitoneal, subcutaneous, intracisternal or intracerebroventricular routes; the analgesia data specifically required central administration ^{12,13Reference 12Nakamura A et al. · 1988AnimalPotent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP) — animal (mouse/rat, central administration)View study →Reference 13Nakamura A et al. · 1989AnimalInvolvement of spinal noradrenergic system in the mechanism of an antinociceptive effect of delta-sleep-inducing peptide — animal (mouse)View study →}. One detail worth keeping: infusion rate changed the result — DSIP was reported completely ineffective when infused over one minute and optimal over four to eight minutes, which is not how a bedtime subcutaneous depot behaves.

What is sold: lyophilized powder for subcutaneous injection before bed. No human or animal pharmacokinetic study has characterized subcutaneous DSIP — not absorption, not peak time, not exposure, not CNS entry. FDA states this as a positive finding rather than a gap in its own search: it “did not identify pharmacokinetic or toxicokinetic studies of emideltide (free base) or emideltide acetate delivered via the nominated SC” route. That regimen is an extrapolation from intravenous single-dose data, not an application of it.

Oral is inert. In cultured human intestinal (Caco-2) monolayers, DSIP applied to the apical side was rapidly metabolized — only 8.2% remained after two hours — cleaved primarily to free tryptophan, with Trp-Ala as a minor product. Even with three peptidase inhibitors present raising survival to 95%, no intact DSIP was detected on the far side of the monolayer at all ^{26Reference 26Augustijns PF · 1995In vitroTransport and metabolism of delta sleep-inducing peptide in cultured human intestinal epithelial cell monolayers — in vitro (Caco-2)View study →}. An oral DSIP product delivers amino acids.

Half-life is minutes — and brain entry is better supported than previously credited. FDA’s 2026 review gives DSIP a human plasma half-life of about 8 minutes, with 3–6 minutes in dogs and 2–3 minutes in rats and a monkey after intravenous dosing, and 5–10 minutes in human serum in vitro. The short half-life is due to hydrolysis from the N-terminus by multiple blood peptidases, not to aggregation or protein binding. On blood-brain-barrier penetration, the claim was previously treated as unverified; that was too strict, and the correction matters. The paper it relied on ^{26Reference 26Augustijns PF · 1995In vitroTransport and metabolism of delta sleep-inducing peptide in cultured human intestinal epithelial cell monolayers — in vitro (Caco-2)View study →} concerns the intestinal epithelium, not the BBB, and its finding — that no intact DSIP crosses a Caco-2 monolayer — bears on oral bioavailability rather than CNS entry. FDA cites three separate transport studies for CNS entry: DSIP appeared in dog cerebrospinal fluid after intravenous injection, peaking at 30 minutes; radiolabeled DSIP crossed from blood to CSF by a saturable process in perfused sheep choroid plexus; and brain concentrations rose in rats after high intravenous doses. Systemically-dosed DSIP is also pharmacologically active on animal EEG, which is hard to explain if none of it reaches the brain. Endogenous plasma DSIP-like immunoreactivity follows a clear diurnal rhythm, peaking mid-afternoon and troughing after midnight, tightly coupled to body temperature ^{6Reference 6Friedman TC et al. · 1994ObservationalDiurnal 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 — human (observational, n=12)View study →}.

One concrete interaction mechanism. DSIP is metabolized in part by peptidyl dipeptidase A (ACE) in brain microvessel endothelium, so FDA notes that dipeptidase inhibitors such as captopril could raise its active concentrations. That is a mechanistically specific interaction hypothesis, not a tested one, but it is more than the page could previously say.

Put together: a peptide with an unmeasured half-life expected in minutes, no demonstrated CNS penetration, and no subcutaneous pharmacokinetics at all, injected under the skin at bedtime for an effect meant to last the night. That mismatch is the single most useful fact here for a reader deciding what to do.

Clinical & regulatory status

DSIP has never been approved as a drug or authorized as a dietary supplement in any jurisdiction — no FDA, EMA, MHRA, TGA or PMDA marketing authorization, no approved indication, no pharmacopoeial monograph for human therapeutic use. It is not a scheduled controlled substance in the United States. It reaches consumers exclusively through research-chemical vendors, typically labeled “for research use only / not for human consumption.”

That picture is now backed by a regulator. FDA evaluated DSIP — under its WHO international nonproprietary name, emideltide — for the section 503A compounding bulks list in a briefing document dated 11 May 2026, ahead of a Pharmacy Compounding Advisory Committee meeting on 23–24 July 2026. FDA’s published conclusion is that “a balancing of the criteria weighs against” listing either emideltide free base or emideltide acetate, and it proposes not to add them. The committee has not yet voted, and FDA states it will not issue a final determination until the advisory process concludes. The detail is set out under Sourcing, Route & Legal Status below; the short version is that a regulator ran the systematic search the argument depends on and reached the same verdict on the sleep claim.

The human literature entirely predates trial pre-registration: the sleep, withdrawal, pain and neuroendocrine studies run from 1981 to 1998. A ClinicalTrials.gov search for DSIP and for “delta sleep-inducing peptide” as an intervention returns no DSIP trial — not completed, ongoing, or terminated. EU-CTR and WHO ICTRP were not searched this pass. The plain summary is that after roughly fifty years of scientific interest, there has never been a registered clinical trial of this compound, and the last human study of any kind was published in 1998.

Last checked: 18 July 2026.

Sourcing, Route & Legal Status

Regulatory status. Unapproved everywhere, for everything. There is no country in which DSIP is a licensed medicine, and no regime under which it is a lawful dietary supplement — it fails the definition in the US, EU and UK alike as a synthetic peptide with no history of food use. Unlike semax or thymalin, it does not even hold a national approval in Russia to complicate the picture; the Deltaran preparation used in the Russian rodent literature is not a Western-approved product and its human regulatory status should not be inferred from its appearance in those studies. DSIP is not scheduled or controlled in the US, but “not scheduled” is not “permitted”: marketing it for human use is unlawful in most Western jurisdictions, and it is a prohibited-by-default substance for athletes under the WADA non-approved-substances category (S0), which captures any pharmacological agent with no current approval for human therapeutic use.

A regulator has now assessed this compound — and its verdict is pending, not final. In May 2026 FDA published a briefing document evaluating DSIP for the section 503A list of bulk drug substances that compounding pharmacies may lawfully use. FDA’s name for the molecule is “emideltide” — the WHO international nonproprietary name proposed in 1993 — and the document says so directly: “Emideltide is also referred to as Delta Sleeping Inducing Peptide (DSIP).” If you have been reading about emideltide and DSIP as if they were two substances, they are one. FDA evaluated two distinct bulk substances, emideltide (free base) and emideltide acetate, for subcutaneous injection at 1 mg/mL, in chronic insomnia, narcolepsy and opioid withdrawal. Its conclusion, published ahead of the Pharmacy Compounding Advisory Committee meeting of 23–24 July 2026, is that “a balancing of the criteria weighs against” adding either substance, and it proposes not to add them. The committee has not yet voted, and FDA states expressly that it will not issue a final determination until the advisory-committee process is complete and all reviews finalized. What follows is FDA’s evaluation, not a decision. (FDA briefing document, 23–24 July 2026 PCAC meeting.)

The findings that matter most:

• FDA reaches the same conclusion about the sleep claim, independently. It found “insufficient evidence to make a conclusion on the effectiveness” of intravenous DSIP for chronic insomnia, and that the results “appear inconclusive and at best preliminary.” Its reasoning is the same: the positive insomnia studies come from a single author and mostly have no placebo arm at all, comparing insomniac patients against externally matched healthy controls, while the two independently run placebo-controlled studies — Bes 1992 ^{3Reference 3Bes F et al. · 1992RCTEffects of delta sleep-inducing peptide on sleep of chronic insomniac patientsView study →} and Monti 1987 — “did not reach the same conclusion.” FDA reads Bes 1992 the same way, as a study showing “at best some weak effects.”
• Nothing at all supports the route that is actually sold. FDA states flatly that it “did not identify any data to support the effectiveness of emideltide (free base) or emideltide acetate for the treatment of chronic insomnia, narcolepsy, and opioid withdrawal via the nominated SC” route, that “there are no safety data” for that route, and that it found no pharmacokinetic or toxicokinetic study by that route either. Every human datum FDA located was intravenous.
• The nominations were withdrawn; FDA carried on anyway. Two compounding businesses nominated the substance (Wells Pharmacy Network; LDT Health Solutions); both nominations were later withdrawn, and FDA elected to evaluate the substances “at its discretion.” A fourth proposed use, “paradoxical sleep disorder,” was not evaluated because the nominations gave FDA too little to work with.
• The nominators could not say what molecule they were nominating. One nomination named “emideltide” but attached a certificate of analysis for the acetate; the other attached a CoA whose stated molecular formula (C35H57N13O14S24S2) “does not correspond to any emideltide structure” — DSIP contains no sulfur. Free base and acetate are legally and chemically distinct substances with the same CAS number circulating between them, and the acetate has no UNII code and no CAS number of its own. FDA judged both forms “not well-characterized” physically and chemically. This is the same failure documented for KPV on the sibling KPV page — a buyer cannot establish which of two different substances is in the vial.
• The 1 mg/mL product may not be physically possible. Free-base DSIP dissolves in water at only ~0.5 mg/mL, and FDA says it is “unclear how it would be possible to formulate the proposed injectable dosage form with the concentration of 1 mg/mL” without a co-solvent. The acetate salt (~10 mg/mL) does not have this problem — which means free base and acetate are not interchangeable in practice, and no vendor label distinguishes them.
• The toxicology file is close to empty. No repeat-dose toxicity study, no genotoxicity study, no developmental or reproductive toxicity study, and no 2-year carcinogenicity study of DSIP in any species. The single acute-toxicity report FDA located is a 1988 rat study finding bradycardia and a shift in circadian body temperature. The Deltaran mouse work cannot fill the gap because Deltaran is nine parts glycine to one part peptide (see Antioxidant & geroprotection).
• Zero adverse-event reports — which is not reassurance. FDA’s search of the FAERS database for emideltide through 3 March 2024 retrieved zero reports, and it found no relevant case reports in the literature. No outsourcing facility has ever reported compounding a DSIP product to FDA. An empty file for a substance sold almost entirely outside any reporting system is a measure of surveillance, not of safety.
• A safety hypothesis not previously noted: abuse potential. FDA’s pharmacologists note that DSIP does not bind opioid receptors directly but is reported to trigger calcium-dependent endorphin and enkephalin release — and that stimulating endorphin release in reward circuitry is one of the proposed mechanisms of reinforcement for addictive drugs. FDA found no study of the abuse liability of DSIP at all. For a compound marketed to people managing sleep and withdrawal, that is a conspicuous unknown.
• Immunogenicity is unassessed. FDA holds that a nine-residue peptide injected subcutaneously “may pose a significant risk for immunogenicity,” amplified by aggregation and synthesis impurities, and that neither nominator provided — nor could FDA find — anything showing DSIP does not carry that risk. Subcutaneous dosing carries more immunogenic risk than intravenous.
• No monograph, no approval, anywhere. DSIP appears in no USP/NF, European, Japanese or International Pharmacopoeia, and FDA found it registered as a drug in no country. Compounding history is thin but real: FDA cites a US Attorney’s press release showing a Kentucky pharmacy compounded and distributed DSIP products between 25 October 2018 and 1 April 2020, and the resulting prosecution was for unlawful distribution.
• FDA also documents the marketing. Integrative neurology clinics, medical concierge services, medical spas and online retailers sell DSIP injection and nasal-spray products in the US for sleep, stress, pain, cancer, Alzheimer’s, Parkinson’s and detox — one as a “ready to use” kit with syringes and a “complementary telemed consult.” FDA notes that none of these sites states whether the product is the free base or a salt.

How it’s supplied & administered. Vendors sell DSIP as a lyophilized powder in 2–5 mg vials for reconstitution with bacteriostatic water and subcutaneous injection, usually promoted for use shortly before bed. Two things about that are worth stating flatly. First, the route has no supporting pharmacokinetic or efficacy data of any kind (see Pharmacokinetics) — the human studies were intravenous. Second, oral and sublingual DSIP products cannot work: the peptide is cleaved to tryptophan in the gut epithelium and no intact peptide crosses it ^{26Reference 26Augustijns PF · 1995In vitroTransport and metabolism of delta sleep-inducing peptide in cultured human intestinal epithelial cell monolayers — in vitro (Caco-2)View study →}. Reconstituted peptide is chemically unstable, generally requires refrigeration, and has no established shelf-life or stability standard in consumer material.

Sourcing reality (this is a safety issue, not a footnote). DSIP reaches buyers through unregulated research-chemical suppliers with no manufacturing oversight, no compendial identity or purity requirement, and no regulatory accountability. The documented risks of that supply chain are concrete: wrong, absent, or mis-stated active ingredient; synthesis impurities including truncated and scrambled sequences, which for a nine-residue peptide can be difficult to separate from the target; bacterial endotoxin and microbial contamination in a product intended for injection; and user reconstitution and sterility error. A genuine third-party Certificate of Analysis — mass-spec identity, HPLC purity, and a bacterial endotoxin result — is the minimum any buyer should demand, and COAs in this market are themselves frequently supplier-generated or falsified. No COA makes an unapproved injectable of unproven efficacy a sensible thing to inject. No vendors are recommended or linked here.

Safety

DSIP has never shown dramatic toxicity, but it has also never been studied well enough for that to mean much — the entire human safety record is single intravenous doses given four decades ago, and there is none at all for the subcutaneous route people actually use.

Safety at a Glance

❔ Toxicity unknownDrug interactionsCardiac risk

• Three serious adverse events in the only sizeable series. Two hypotensive episodes at the start of a first injection, and one case of progressive hypotension after a second.
• It suppresses pituitary ACTH secretion in humans. Nobody has studied what repeated dosing does to that axis — every human study was a single dose.
• Never assessed in pregnancy or breastfeeding. No human data and no reproductive-toxicity study in any species — see the box below.
• Zero adverse-event reports is not a safety signal. Almost nobody injecting DSIP is inside a system that would generate one, so the empty file measures missing surveillance.
• No dose ceiling is established. No tolerability or dose-escalation study has ever been performed at any dose, by any route.
• Dipeptidase inhibitors such as captopril. Expected to slow DSIP’s breakdown and raise active concentrations.

Full Safety & Interactions Detail

Overall posture. DSIP has never shown dramatic toxicity, and it has also never been studied well enough for that to carry much weight. The entire human safety record is single intravenous doses given to a few hundred people, four decades ago, with no systematic adverse-event collection and no follow-up. The 1981 crossover reported the compound “well-tolerated” with no psychological, physiological or biochemical side effects observed in six subjects ^{2Reference 2Schneider-Helmert D et al. · 1981RCTAcute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior — human (double-blind crossover, n=6)View study →}; the 107-patient withdrawal series reported good tolerance apart from headaches in a few patients ^{9Reference 9Dick P et al. · 1984DSIP in the treatment of withdrawal syndromes from alcohol and opiates — human (open, uncontrolled, n=107)View study →}. FDA’s 2026 review reads that series more closely and finds more than the abstract implies: nine of the 107 had minor transient effects (perspiration, headache, nausea, vertigo) and three had serious ones — two hypotensive episodes at the start of a first injection, and one patient with “progressive hypotension” after a second. FDA also notes that in the withdrawal setting adverse effects cannot be separated from withdrawal itself. That is the whole of the human safety record. FDA’s own conclusion is that “safety for emideltide-related products is insufficiently characterized,” particularly for chronic intermittent use. No repeat-dose safety study, no dose-ranging study, no long-term exposure data, and no safety data at all for the subcutaneous route people actually use.

Zero reported adverse events, and that is not a safety signal. FDA’s search of FAERS through 3 March 2024 returned no reports for this substance, and no case reports exist in the medical literature. Almost nobody who injects DSIP is inside a system that would generate a FAERS report, so the empty file measures the absence of surveillance rather than the absence of harm.

Dose-limiting effect. Not established. No tolerability or dose-escalation study has ever been performed, so there is no known ceiling dose and no characterized toxicity at any dose.

Mechanism-plausible concerns (hypotheses, not findings). DSIP demonstrably suppresses pituitary ACTH secretion in humans ^{14,15Reference 14Bjartell A et al. · 1989RCTReduction of immunoreactive ACTH in plasma following intravenous injection of delta sleep-inducing peptide in man — human (randomised double-blind crossover, n=11)View study →Reference 15Chiodera P et al. · 1994RCTDifferent effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men — human (placebo-controlled crossover, n=15; AVP endpoint null)View study →}. Repeated suppression of an endocrine axis is not a trivial thing to do casually, and nobody has ever studied what repeated dosing does to that axis — the human studies were single doses, and cortisol was unaffected acutely ^{14Reference 14Bjartell A et al. · 1989RCTReduction of immunoreactive ACTH in plasma following intravenous injection of delta sleep-inducing peptide in man — human (randomised double-blind crossover, n=11)View study →}, which tells you nothing about chronic use. Separately, the rodent antinociceptive effect is naloxone-reversible ^{12Reference 12Nakamura A et al. · 1988AnimalPotent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP) — animal (mouse/rat, central administration)View study →}, and DSIP was hypothesized to have opiate-receptor agonist activity ^{8,9Reference 8Dick P et al. · 1983Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors — human (open, uncontrolled, n=67)View study →Reference 9Dick P et al. · 1984DSIP in the treatment of withdrawal syndromes from alcohol and opiates — human (open, uncontrolled, n=107)View study →}; if that hypothesis has any truth in humans, opioid-related caution follows. Both of these are class-level inferences and neither has been tested.

Abuse liability — raised by FDA, and unstudied. FDA’s 2026 pharmacology review notes that DSIP is reported to trigger calcium-dependent endorphin and enkephalin release in reward-relevant brain regions, and that this is one of the proposed mechanisms by which stimulants become reinforcing. It then records that no nonclinical study of DSIP’s abuse potential exists. This is a hypothesis, not a finding — but it is a regulator’s hypothesis about a compound sold for nightly use, and nobody has tested it.

Interactions. Not assessed — with one specific mechanistic exception. No controlled human drug-interaction study of DSIP exists. FDA identifies one concrete candidate: DSIP is degraded by peptidyl dipeptidase A, so dipeptidase inhibitors such as captopril would be expected to slow its breakdown and raise active concentrations. Beyond that, mechanism-level cautions only, and they are speculative: opioids and opioid-dependence pharmacotherapy (the animal opioid link), corticosteroids and other agents acting on the HPA axis (the ACTH effect), and sedative-hypnotics (on the marketed indication, though DSIP notably did not produce classic pharmacologic sedation in the one study that looked ^{2Reference 2Schneider-Helmert D et al. · 1981RCTAcute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior — human (double-blind crossover, n=6)View study →}).

Injection-specific risks. Because the sold route is self-administered subcutaneous injection of self-reconstituted, unregulated powder, the dominant practical risks are not the peptide’s pharmacology at all: injection-site reactions, infection from non-sterile technique, systemic reaction to bacterial endotoxin in untested material, and dosing error from home reconstitution of a milligram-scale vial.

Who should avoid it. Anyone pregnant, breastfeeding, or trying to conceive; anyone with an endocrine disorder, adrenal insufficiency, or on corticosteroid therapy, given the demonstrated ACTH effect; anyone on opioid therapy or in opioid-dependence treatment; anyone subject to anti-doping testing; and anyone who cannot verify the identity, purity and sterility of what is in the vial — which, in this market, is effectively everyone. As an unapproved injectable whose defining claim its own best trial failed to support, it is not appropriate for self-administration by anyone.

Scope disclosure (honesty, not a claim):

• Human data? Yes, unusually much for a gray-market peptide — and that is the point. A dozen-odd small studies between 1981 and 1998, all intravenous, totalling 209 dosed subjects on FDA’s count, several uncontrolled. Both independently run controlled trials of the marketed indication were negative ^{3Reference 3Bes F et al. · 1992RCTEffects of delta sleep-inducing peptide on sleep of chronic insomniac patientsView study →} (and Monti 1987). Nothing since 1998.
• Interactions assessed? No. Mechanism-level speculation only (opioid, HPA axis, sedatives).
• Pregnancy/lactation assessed? No — no human data and no animal reproductive-toxicity studies located.
• Long-term safety established? No. The longest documented human exposure is a short series of injections over days. No repeat-dose or chronic safety data exist for any route, and none at all for the subcutaneous route sold to consumers.

Never imply safety from silence. Where DSIP has not been studied — subcutaneous pharmacokinetics, repeat dosing, interactions, pregnancy, long-term use, gray-market purity — the correct statement is “not assessed,” not “safe.”

Pregnancy & Lactation

? Not established in pregnancy? Not established in lactation

Not assessed / not established. No human pregnancy or lactation data exist, and no reproductive or developmental toxicity study of DSIP was located in any species — a gap FDA independently confirms, stating that it identified no nonclinical developmental or reproductive study of either emideltide form. There is no label, no monograph, and no regulator’s assessment to fall back on. Treat as contraindicated by default.

Dosage

There is no established human dose for DSIP, and none is recommended here. It is not an approved drug or supplement in any country, its defining indication is not supported by its own best-controlled trial, and every figure below is reported as data, not as a protocol.

The commonest dose in the controlled human literature is 25 nmol/kg by slow intravenous infusion in a clinical setting — the sleep crossover ^{2Reference 2Schneider-Helmert D et al. · 1981RCTAcute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior — human (double-blind crossover, n=6)View study →}, the negative insomnia trial ^{3Reference 3Bes F et al. · 1992RCTEffects of delta sleep-inducing peptide on sleep of chronic insomniac patientsView study →}, the ACTH studies ^{14,15Reference 14Bjartell A et al. · 1989RCTReduction of immunoreactive ACTH in plasma following intravenous injection of delta sleep-inducing peptide in man — human (randomised double-blind crossover, n=11)View study →Reference 15Chiodera P et al. · 1994RCTDifferent effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men — human (placebo-controlled crossover, n=15; AVP endpoint null)View study →}, and the withdrawal series ^{8,9Reference 8Dick P et al. · 1983Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors — human (open, uncontrolled, n=67)View study →Reference 9Dick P et al. · 1984DSIP in the treatment of withdrawal syndromes from alcohol and opiates — human (open, uncontrolled, n=107)View study →} all used it, because they descend from the same original Basel protocol. It is not the only one: FDA’s 2026 tabulation of every human study it could find puts the range at 25–150 nmol/kg intravenously across 209 subjects, dosed for one to fifteen days, and the reports FDA surfaces include 30 nmol/kg nightly for a week and 35 nmol/kg up to six times a day. For a 70 kg adult, 25 nmol/kg is roughly 1.5 mg of a peptide of about 850 Da. Some of the withdrawal and pain work repeated that dose over consecutive days or every 48–72 hours ^{9,11Reference 9Dick P et al. · 1984DSIP in the treatment of withdrawal syndromes from alcohol and opiates — human (open, uncontrolled, n=107)View study →Reference 11Larbig W et al. · 1984Clinical trialTherapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodesView study →}.

The subcutaneous bedtime regimen sold by vendors — commonly quoted in the range of 100–300 µg — has no controlled dose-finding study, no human pharmacokinetic data, no human efficacy data, and no human safety data by that route. It is a number that circulated in community protocols until it acquired the appearance of a standard. There is no dose known to reliably improve sleep in humans, so there is no dose to report for the use this compound is sold for. This entry is informational only.

References

1. Kovalzon VM, Strekalova TV (2006). Delta sleep-inducing peptide (DSIP): a still unresolved riddle — review. Journal of Neurochemistry. https://pubmed.ncbi.nlm.nih.gov/16539679/
2. Schneider-Helmert D, Gnirss F, Monnier M, Schenker J, Schoenenberger GA (1981). Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior — human (double-blind crossover, n=6). International Journal of Clinical Pharmacology, Therapy and Toxicology. https://pubmed.ncbi.nlm.nih.gov/6895513/
3. Bes F, Hofman W, Schuur J, Van Boxtel C (1992). Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study — human (double-blind matched-pairs trial, n=16; negative). Neuropsychobiology. https://pubmed.ncbi.nlm.nih.gov/1299794/
4. Schneider-Helmert D (1984). DSIP in insomnia — narrative summary of the author’s earlier human investigations (not primary data). European Neurology. https://pubmed.ncbi.nlm.nih.gov/6391925/
5. Kaeser HE (1984). A clinical trial with DSIP — human (open, uncontrolled series, n=7). European Neurology. https://pubmed.ncbi.nlm.nih.gov/6391926/
6. Friedman TC, Garcia-Borreguero D, Hardwick D, et al. (1994). 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 — human (observational, n=12). Journal of Clinical Endocrinology and Metabolism. https://pubmed.ncbi.nlm.nih.gov/8175965/
7. Mu X, Qu L, Yin L, Wang L, Liu X, Liu D (2024). Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models — animal (mouse); tests the DSIP-CBBBP fusion peptide, not DSIP. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/39444618/
8. Dick P, Grandjean ME, Tissot R (1983). Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors — human (open, uncontrolled, n=67). Neuropsychobiology. https://pubmed.ncbi.nlm.nih.gov/6328354/
9. Dick P, Costa C, Fayolle K, Grandjean ME, Khoshbeen A, Tissot R (1984). DSIP in the treatment of withdrawal syndromes from alcohol and opiates — human (open, uncontrolled, n=107). European Neurology. https://pubmed.ncbi.nlm.nih.gov/6548969/
10. Backmund M, Meyer K, Rothenhaeusler HB, Soyka M (1998). Opioid detoxification with delta sleep-inducing peptide: results of an open clinical trial — human (open clinical trial; abstract not indexed). Journal of Clinical Psychopharmacology. https://pubmed.ncbi.nlm.nih.gov/9617990/
11. Larbig W, Gerber WD, Kluck M, Schoenenberger GA (1984). Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study — human (uncontrolled before-and-after pilot, n=7). European Neurology. https://pubmed.ncbi.nlm.nih.gov/6548970/
12. Nakamura A, Nakashima M, Sugao T, Kanemoto H, Fukumura Y, Shiomi H (1988). Potent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP) — animal (mouse/rat, central administration). European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/2853064/
13. Nakamura A, et al. (1989). Involvement of spinal noradrenergic system in the mechanism of an antinociceptive effect of delta-sleep-inducing peptide — animal (mouse). Brain Research. https://pubmed.ncbi.nlm.nih.gov/2713670/
14. Bjartell A, Ekman R, Bergquist S, Widerlöv E (1989). Reduction of immunoreactive ACTH in plasma following intravenous injection of delta sleep-inducing peptide in man — human (randomised double-blind crossover, n=11). Psychoneuroendocrinology. https://pubmed.ncbi.nlm.nih.gov/2554357/
15. Chiodera P, Volpi R, Capretti L, et al. (1994). Different effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men — human (placebo-controlled crossover, n=15; AVP endpoint null). Hormone Research. https://pubmed.ncbi.nlm.nih.gov/7698722/
16. Giusti M, et al. (1993). Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women — human (null). Psychoneuroendocrinology. https://pubmed.ncbi.nlm.nih.gov/8475226/
17. Späth-Schwalbe E, et al. (1995). Delta-sleep-inducing peptide does not affect CRH and meal-induced ACTH and cortisol secretion — human (null). Psychoneuroendocrinology. https://pubmed.ncbi.nlm.nih.gov/7777652/
18. Koplik EV, et al. (2008). Delta sleep-inducing peptide and Deltaran: potential approaches to antistress protection — animal (rat); tests the Deltaran preparation. Neuroscience and Behavioral Physiology. https://pubmed.ncbi.nlm.nih.gov/18975104/
19. Bondarenko TI, Maĭboroda EA, Mikhaleva II, Prudchenko IA (2011). Mechanism of delta-sleep inducing peptide geroprotective activity — animal (rat). Advances in Gerontology. https://pubmed.ncbi.nlm.nih.gov/21809625/
20. Shustanova TA, Bondarenko TI, Milyutina NP, Mikhaleva II (2001). Regulation of free radical processes by delta-sleep inducing peptide in rat tissues under cold stress — animal (rat). Biochemistry (Moscow). https://pubmed.ncbi.nlm.nih.gov/11421812/
21. Kutilin DS, Bondarenko TI, Kornienko IV, Mikhaleva II (2014). Effect of delta sleep-inducing peptide on the expression of antioxidant enzyme genes in the brain and blood of rats during physiological aging — animal (rat). Bulletin of Experimental Biology and Medicine. https://pubmed.ncbi.nlm.nih.gov/25257425/
22. Popovich IG, Voitenkov BO, Anisimov VN, et al. (2003). Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice — animal (mouse); mean lifespan unchanged. Mechanisms of Ageing and Development. https://pubmed.ncbi.nlm.nih.gov/12782416/
23. Voĭtenkov VB, Popovich IG, Zabezhinskiĭ MA, Iurova MA, Piskunova TA, Mikhaleva II (2009). Effect of delta-sleep inducing peptide preparation Deltaran on longevity, physiological functions, and carcinogenesis in mice — animal (mouse); overlapping authors and model with [22]. Advances in Gerontology. https://pubmed.ncbi.nlm.nih.gov/20405733/
24. Stanojlović OP, Zivanović DP, Mirković SD, Mikhaleva II (2005). Antiepileptic activity of delta sleep-inducing peptide and its analogue in metaphit-provoked seizures in rats — animal (rat); tests DSIP and the analogue DSIP-12. Seizure. https://pubmed.ncbi.nlm.nih.gov/15911358/
25. Hrnčić D, et al. (2006). Delta-sleep-inducing peptide potentiates anticonvulsive activity of valproate against metaphit-provoked audiogenic seizure — animal (rat). Pharmacology. https://pubmed.ncbi.nlm.nih.gov/16645330/
26. Augustijns PF, Borchardt RT (1995). Transport and metabolism of delta sleep-inducing peptide in cultured human intestinal epithelial cell monolayers — in vitro (Caco-2). Drug Metabolism and Disposition. https://pubmed.ncbi.nlm.nih.gov/8689946/

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