{"site":"DSIP Peptide","url":"https://dsippeptiderx.com","format":"evidence-manifest/v1","claim_count":58,"claims":[{"id":"clm-001","text":"DSIP is the nonapeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE), molecular formula C35H48N10O15, molecular weight 848.8 g/mol, CAS 62568-57-4, UNII YN28Z5YZ73, PubChem CID 68816. Its INN (international nonproprietary name) is emideltide.","source_url":"https://pubchem.ncbi.nlm.nih.gov/compound/68816","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://dsippeptiderx.com/entity","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data"]},{"id":"clm-002","text":"The name emideltide, the INN under which FDA evaluated this substance in 2026, appears in the title or abstract of exactly one record in the entire indexed literature, and that record is a 2020 chemistry methods paper about protein cross-linkers that merely uses the peptide as a test molecule. The clinical literature, such as it is, exists entirely under the names DSIP and delta sleep-inducing peptide.","source_url":"https://europepmc.org/search?query=TITLE_ABS%3A%22delta%20sleep-inducing%20peptide%22%20OR%20TITLE_ABS%3A%22emideltide%22","grade":"analytical","grade_label":"Analytical study","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-003","text":"Delta Sleep-Inducing Peptide is a Medical Subject Headings (MeSH) descriptor, D003701, in the National Library of Medicine vocabulary.","source_url":"https://meshb.nlm.nih.gov/record/ui?ui=D003701","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://dsippeptiderx.com/entity","https://dsippeptiderx.com/monograph"]},{"id":"clm-004","text":"DSIP was isolated in 1977 from the cerebral venous blood of rabbits whose thalamus was electrically stimulated, and named for what the synthetic peptide did to rabbit EEG after infusion into the brain ventricles: it enhanced delta-wave and spindle activity. The 1977 characterization tested nine synthetic peptides in 58 rabbits under double-blind conditions and only DSIP showed the delta-enhancing effect.","source_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC430668/","grade":"animal","grade_label":"Animal","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com","https://dsippeptiderx.com/faq"]},{"id":"clm-005","text":"The name DSIP was coined because treatment of animals with the peptide increased the power of EEG delta waves and spindles, hallmarks of deep non-REM sleep. FDA's 2026 review states this naming history explicitly.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq","https://dsippeptiderx.com"]},{"id":"clm-010","text":"No FDA-approved drug product contains emideltide in any form. Drugs@FDA queries for emideltide and for delta sleep-inducing peptide as active ingredients return no matches, and FDA's 2026 evaluation states that neither emideltide (free base) nor emideltide acetate is a component of an FDA-approved drug and that no USP or NF monograph applies.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/entity","https://dsippeptiderx.com/warning_box","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/comparisons"]},{"id":"clm-011","text":"FDA lists Emideltide (DSIP) on its page of bulk drug substances that may present significant safety risks in compounding. The entry reads, verbatim: Compounded drugs containing emideltide may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. FDA has not identified safety-related information regarding emideltide for the proposed route of administration. Therefore, the agency lacks sufficient information to know whether the drug would cause harm if administered to humans.","source_url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/warning_box","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/pk","https://dsippeptiderx.com/faq"]},{"id":"clm-012","text":"In the FDA briefing document for the July 23 to 24, 2026 Pharmacy Compounding Advisory Committee meeting, FDA proposed that emideltide not be added to the 503A Bulks List. The document states, verbatim, as points 9 and 10 under the July 24, 2026, morning session: FDA is proposing that Emideltide (free base) NOT be included on the 503A Bulks List. FDA is proposing that Emideltide acetate NOT be included on the 503A Bulks List.","source_url":"https://www.fda.gov/media/193342/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/warning_box","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/comparisons"]},{"id":"clm-013","text":"Both nominations of emideltide to the 503A list (LDT Health Solutions, Inc. on behalf of the International Peptide Society, and Wells Pharmacy Network) had been withdrawn by the nominators before the meeting, and FDA elected to proceed with the presentation of emideltide to the committee anyway.","source_url":"https://www.fda.gov/media/193342/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-014","text":"The uses FDA evaluated for emideltide were opioid withdrawal, chronic insomnia, and narcolepsy, and the evaluated dosage form was subcutaneous injection at a concentration of 1000 mcg/mL (1 mg/mL). The FDA meeting page's uses-evaluated chart lists Opioid withdrawal, chronic insomnia, and narcolepsy for Emideltide (free base) and Emideltide acetate.","source_url":"https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-015","text":"FDA's overall conclusion on emideltide, verbatim from the evaluation: These substances are not well characterized from a physical and chemical characterization perspective, and endotoxin testing for injectable ROA is lacking. And: Accordingly, we propose not adding emideltide (free base) or emideltide acetate to the 503A Bulks List.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/warning_box","https://dsippeptiderx.com","https://dsippeptiderx.com/faq"]},{"id":"clm-016","text":"Trade press reported that the advisory committee voted against recommending emideltide, the only one of the seven peptides reviewed at the July 2026 meeting to be rejected. Regulatory Focus (RAPS) reported, verbatim: The committee voted against recommending emideltide for inclusion on the 503A Bulks List in a narrow 6-7 vote with one abstention. The same article reports the committee voted in favor of BPC-157, KPV, TB-500, MOTS-c, epitalon and semax. This is press reporting: vote tallies were not posted on FDA's meeting page as of this build and were not verified against an FDA source.","source_url":"https://www.raps.org/resource/fda-advisory-committee-backs-two-more-peptides-rejects-one-for-compounding-list.html","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/comparisons"]},{"id":"clm-017","text":"A PCAC recommendation is advisory and inclusion on the 503A Bulks List would not make a substance an approved drug in any case: the list governs what compounders may use within the section 503A exemptions, and FDA states it will not issue a final determination until the advisory process and all reviews are complete. The rulemaking is pending as of this build.","source_url":"https://www.fda.gov/media/193342/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-018","text":"FDA's verdict on the insomnia evidence, verbatim: There is insufficient evidence to make a conclusion on the effectiveness of IV emideltide for chronic insomnia. Although some studies showed that short-term IV emideltide appeared to exert an effect on disturbed sleep, the results appear inconclusive and at best preliminary. FDA also states that the Schneider-Helmert studies reporting improvement and the two double-blind placebo-controlled studies by Bes et al. 1992 and Monti et al. 1987, which were similarly designed, did not reach the same conclusions.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/comparisons"]},{"id":"clm-019","text":"FDA identified no effectiveness data at all for the route in which emideltide products are actually sold and was nominated (subcutaneous injection): every clinical study FDA found used intravenous administration. Verbatim: FDA 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 ROA.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data"]},{"id":"clm-020","text":"FDA's nonclinical review credits emideltide with sleep-inducing properties that are conserved across species and mediated via opioid-dependent mechanisms (stimulating calcium-dependent endorphin release without direct opioid-receptor binding), and raises the concern that stimulation of the opioid system could lead to development of addiction, noting FDA did not identify nonclinical studies of the addictive potential.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-021","text":"A search of FDA's adverse event reporting system (FAERS) for emideltide through March 3, 2024 retrieved zero reports. This is a fact about reporting, not about safety: no approved product exists, and FDA separately states it lacks sufficient information to know whether the drug would cause harm.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com/faq"]},{"id":"clm-022","text":"Across the clinical studies FDA identified, intravenous emideltide doses of 25 to 150 nmol/kg were administered to a total of 209 subjects for 1 to 15 days. FDA identified no clinical studies of the subcutaneous route.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-023","text":"FDA's historical-use finding: emideltide has been studied in humans since at least 1981 and there is evidence it has been used in compounding since at least 2018; emideltide injection and intranasal products are available in the US through integrative neurology clinics, medical concierge services, medical spas, wellness clinics, and online retailers, though it is unclear whether these products are compounded.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-024","text":"FDA found the certificate of analysis offered to establish the identity, purity and impurity profile of emideltide lacked specific tests for impurities, aggregates, and endotoxins, and found no such characterization data in the public literature. For the free base, no bioburden/endotoxin test and no residual solvent testing appeared in the nomination.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/comparisons"]},{"id":"clm-025","text":"Emideltide free base is soluble in water at only about 0.5 mg/mL, and FDA states it is unclear how the proposed 1 mg/mL injectable could be formulated without a co-solvent. Verbatim: based on their limited solubility in water, it is unclear how it would be possible to formulate the proposed injectable dosage form with concentration of 1,000 mcg/ml without co-solvent used.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-026","text":"Even the pharmaceutical-grade vials used in the 1984 Geneva withdrawal study had problems: the study authors attributed some side effects to solubility difficulties of some of the vials, which were obtained from Hoffman-La Roche. FDA notes it is not clear what the authors meant and that solubility difficulties were not reported in other publications.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-027","text":"As a nine-amino-acid peptide given by injection, emideltide has the potential to be immunogenic, a risk FDA says may be amplified by aggregation and peptide-related impurities; the SC route is associated with increased immunogenicity compared to IV. Nobody has provided FDA information suggesting these substances do not present these risks.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/pk"]},{"id":"clm-030","text":"The indexed literature on DSIP comprises 419 records matching the full name (delta sleep-inducing peptide, any hyphenation, or emideltide) in title or abstract in Europe PMC, archived record by record on 2026-08-14. An acronym-only search (DSIP without the full name) adds 63 further records, a set that mixes genuine peptide papers with false positives from other fields and is disclosed rather than silently included or excluded.","source_url":"https://europepmc.org/search?query=TITLE_ABS%3A%22delta%20sleep-inducing%20peptide%22%20OR%20TITLE_ABS%3A%22emideltide%22","grade":"analytical","grade_label":"Analytical study","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/site_counts"]},{"id":"clm-031","text":"The DSIP literature is old and thinning: the median publication year of the 419 records is 1992; 272 of 419 (64.9 percent) were published before 1996; 7 records have appeared since 2016 and 4 in the 2020s. The most-published decade was the 1980s (152 records).","source_url":"https://europepmc.org/search?query=TITLE_ABS%3A%22delta%20sleep-inducing%20peptide%22%20OR%20TITLE_ABS%3A%22emideltide%22","grade":"analytical","grade_label":"Analytical study","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/site_counts","https://dsippeptiderx.com/faq"]},{"id":"clm-032","text":"Exactly 5 of the 419 records carry the Randomized Controlled Trial publication tag, and the five together enrolled 72 people. Only two are insomnia trials: the 1981 crossover in 6 insomniacs and the 1992 parallel-group study in 16. The other three are an anesthesia study (n=24) and two endocrine-mechanism studies (n=11 and n=15). The corpus contains zero meta-analyses and zero records tagged systematic review.","source_url":"https://europepmc.org/search?query=TITLE_ABS%3A%22delta%20sleep-inducing%20peptide%22%20OR%20TITLE_ABS%3A%22emideltide%22","grade":"analytical","grade_label":"Analytical study","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/site_counts","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/faq"]},{"id":"clm-033","text":"ClinicalTrials.gov lists zero registered clinical trials that administer DSIP under any of its names. Intervention searches for delta sleep-inducing peptide, emideltide, and DSIP return totals of 1, 0, and 0; the single full-name hit is a false positive (an L-carnitine and circadian-cycle study, NCT05251207, whose interventions do not include DSIP) and is disclosed rather than counted.","source_url":"https://clinicaltrials.gov/search?intr=delta%20sleep-inducing%20peptide","grade":"analytical","grade_label":"Analytical study","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/site_counts"]},{"id":"clm-034","text":"No published analysis of what commercial DSIP products actually contain exists in the indexed literature: a census of the 419-record corpus for product-analysis vocabulary (counterfeit, purity of, quality control of, sold online, research chemical, gray market, internet, dietary supplement) returns zero records. The only vial-content datapoints in the entire record are the 1984 note that even Hoffman-La Roche trial vials had solubility difficulties and FDA's 2026 finding that the offered certificate of analysis lacked impurity, aggregate and endotoxin tests.","source_url":"https://europepmc.org/search?query=TITLE_ABS%3A%22delta%20sleep-inducing%20peptide%22%20OR%20TITLE_ABS%3A%22emideltide%22","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com/faq"]},{"id":"clm-035","text":"No human pharmacokinetic study of DSIP has been published: the corpus contains no study reporting a human half-life, bioavailability, Cmax or exposure curve for any route. The pharmacokinetic work that exists is in dogs (IV half-life 4.0 +/- 0.7 minutes), monkeys, rats and in vitro plasma, and FDA's evaluation likewise identified no clinical data for the marketed subcutaneous route.","source_url":"https://europepmc.org/search?query=TITLE_ABS%3A%22delta%20sleep-inducing%20peptide%22%20OR%20TITLE_ABS%3A%22emideltide%22","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://dsippeptiderx.com/pk","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com/faq"]},{"id":"clm-040","text":"Schneider-Helmert and Schoenenberger 1981 (Experientia): randomized, double-blind, intra-subject placebo-controlled crossover in 6 middle-aged chronic insomniacs, IV emideltide 25 nmol/kg before bedtime over three test nights. Sleep-promoting effects appeared in the second hour after injection and persisted up to 6 hours; sleep-onset latency and final waking times were not influenced; the authors reported tendencies toward fewer awakenings and higher sleep efficiency. FDA found the results insufficient to interpret, reported partly as p values and percentages without numerical data for placebo.","source_url":"https://europepmc.org/abstract/MED/6112579","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data"]},{"id":"clm-041","text":"Schneider-Helmert, Gnirss, Monnier, Schenker and Schoenenberger 1981: first-in-human randomized double-blind placebo-controlled crossover in 6 healthy volunteers given IV emideltide 25 nmol/kg in the morning. Median total sleep time in the 130 minutes after infusion increased 59 percent versus placebo without classic sedation; delayed effects on the following night (13 to 22 hours after dosing) included shorter sleep onset and better sleep efficiency; the compound was reported well tolerated.","source_url":"https://europepmc.org/abstract/MED/6895513","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data"]},{"id":"clm-042","text":"Schneider-Helmert and Schoenenberger 1983 reported five small double-blind investigational series (healthy volunteers and chronic insomniacs; series III: 6 severe insomniacs, randomized crossover; series IV: 4 insomniacs dosed on 4 consecutive evenings; series V: 2 sleep-disturbed inpatients dosed on 6 mornings). The paper states a sleep-induction latency of about 1 hour and effect duration up to 20 hours, and claims complete normalization of disturbed sleep after four consecutive injections. FDA found insufficient detail on study design to interpret the series.","source_url":"https://europepmc.org/abstract/MED/6689058","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data"]},{"id":"clm-043","text":"The infusion-rate fragility: in the 1983 healthy-volunteer series, the same 25 nmol/kg dose of emideltide increased total sleep time by 30 minutes when infused over 2.5 minutes, by 1 hour when infused over 7.5 minutes, and was completely ineffective when infused over 1 minute. The 1984 Graf and Kastin review likewise describes a U-shaped activity curve for both dose and infusion time.","source_url":"https://www.fda.gov/media/193344/download","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-044","text":"Schneider-Helmert 1984: a single 35-year-old man with narcolepsy received a week each of evening and morning IV emideltide 25 nmol/kg. The report describes fewer sleep attacks (6 per week at baseline to 3) and more daytime alertness. It is a one-patient case report; FDA states this design cannot support an effectiveness conclusion, citing insufficient methodological rigor, potential recall bias, researcher subjectivity, and issues of reliability and external validity. It is the entire narcolepsy literature for this compound.","source_url":"https://europepmc.org/abstract/MED/6548968","grade":"human-obs","grade_label":"Human observational","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-045","text":"Schneider-Helmert 1986: 18 chronic insomniacs (9 middle-aged, 9 elderly) received IV emideltide 30 nmol/kg on five consecutive evenings after placebo baseline nights, with outcomes compared to baseline and to externally matched healthy controls. The author reported sleep improved to normal values. FDA found the small sample and the lack of an adequate control group (comparison to an external group of healthy people rather than a placebo arm) limit any effectiveness interpretation.","source_url":"https://europepmc.org/abstract/MED/3792404","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data"]},{"id":"clm-046","text":"Schneider-Helmert 1987: 14 middle-aged chronic insomniacs received 7 successive nightly IV injections of emideltide 30 nmol/kg. Reported changes were large: mean sleep-onset latency fell from 58.4 to 27.6 minutes, wake after sleep onset from 120.8 to 65.6 minutes, and total sleep time rose from 313 to 385 minutes. But FDA notes the study had no placebo arm despite being described as placebo-controlled: results were compared with an externally matched group of healthy subjects, a design FDA calls challenging to interpret due to inherent limitations.","source_url":"https://europepmc.org/abstract/MED/3622582","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data"]},{"id":"clm-047","text":"Monti et al. 1987: randomized, double-blind, placebo-controlled crossover in 6 patients with severe chronic insomnia, IV emideltide 25 nmol/kg. No significant differences versus baseline or placebo were found on awakenings, sleep latency or total sleep time, and the authors concluded that sleep improvement under DSIP treatment is of little clinical significance.","source_url":"https://europepmc.org/abstract/MED/3583493","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-048","text":"Bes et al. 1992, the only double-blind parallel-group placebo-controlled trial of DSIP for insomnia ever published (16 chronic insomniac patients, matched pairs, IV 25 nmol/kg on three afternoons): the DSIP group showed higher sleep efficiency and shorter sleep latency, but the authors state the statistically significant effects were weak and in part could be due to an incidental change in the placebo group, and concluded, verbatim: short-term treatment of chronic insomnia with DSIP is not likely to be of major therapeutic benefit.","source_url":"https://europepmc.org/abstract/MED/1299794","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-049","text":"Kaeser 1984: an open, uncontrolled series in which 7 patients with severe insomnia received 10 DSIP injections; the report claims sleep was normalized in all but one case for follow-up periods of 3 to 7 months. There was no control group, no blinding and no randomization; on FDA's criteria such a design cannot establish effectiveness.","source_url":"https://europepmc.org/abstract/MED/6391926","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data"]},{"id":"clm-050","text":"The 1986 Graf and Kastin update, reviewing the clinical data then available, found the results preliminary and the evidence insufficient to show that emideltide reliably induced or maintained sleep, per FDA's account of the review. This was the state of the field at its peak, from the laboratory that did much of the foundational work.","source_url":"https://europepmc.org/abstract/MED/3550726","grade":"review","grade_label":"Review or guideline","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-051","text":"The most recent human study of DSIP, a 2009 randomized controlled anesthesia study in 24 patients, found the opposite of what the name promises: IV DSIP at 25 nmol/kg during isoflurane anaesthesia paradoxically and significantly REDUCED delta rhythm, while increasing heart rate, decreasing heart rate variability and increasing (lightening) the measured depth of anaesthesia. The authors had hypothesized it would deepen anaesthesia as a natural hypnotic.","source_url":"https://europepmc.org/abstract/MED/19142086","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/faq","https://dsippeptiderx.com/tool-data"]},{"id":"clm-052","text":"Two small randomized double-blind human studies examined endocrine mechanisms: in 11 healthy men, IV DSIP 25 nmol/kg reduced plasma ACTH-like immunoreactivity for at least 3 hours without changing cortisol (1989); in 15 normal men, DSIP did not change circulating vasopressin (1994). A 1995 study in 20 men found DSIP did not affect CRH- or meal-induced ACTH and cortisol secretion, failing to support the proposed corticotropin-release-inhibiting role.","source_url":"https://europepmc.org/abstract/MED/2554357","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph"]},{"id":"clm-053","text":"Measured DSIP-like immunoreactivity in blood does not track the diseases the peptide is marketed for: a 1995 study found no significant differences in plasma DSIP-LI between narcolepsy patients, sleep apnea patients and normal controls, and concluded the findings do not support a biological marker role.","source_url":"https://europepmc.org/abstract/MED/8532601","grade":"human-obs","grade_label":"Human observational","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph"]},{"id":"clm-055","text":"Dick, Grandjean and Tissot 1983: open-label uncontrolled series in 67 inpatients with alcohol (28) or opiate (39) withdrawal symptoms given IV DSIP 25 nmol/kg as sole treatment. 27 percent were lost or unsuitable for evaluation; of the 49 evaluable patients the authors report benefit in 48, with rapid onset. There was no control group and no blinding.","source_url":"https://europepmc.org/abstract/MED/6328354","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data"]},{"id":"clm-056","text":"Dick et al. 1984: the larger open uncontrolled Geneva series, 107 inpatients (60 opioid, 47 alcohol) treated with IV DSIP 25 nmol/kg, up to 6 injections daily for up to six days. The authors claim marked rapid improvement in 97 percent of opiate and 87 percent of alcohol patients, but also that nothing allows any conclusion about maintenance treatment; many successfully treated patients relapsed into anxiety with marked insomnia within 24 to 72 hours of stopping. FDA's safety read of the same study: 9 subjects had transient side effects (perspiration, headaches, nausea, vertigo) and three had serious adverse effects, including hypotension at first injection and one case of progressive hypotension after a second injection.","source_url":"https://europepmc.org/abstract/MED/6548969","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-057","text":"Backmund et al. 1998: open trial of IV DSIP 35 nmol/kg on a fixed multi-day schedule in 7 opioid-dependent subjects. Mean withdrawal scores (SOWS) fell from 34.4 to 17.8 after the first injection, but only 2 of 7 subjects received all scheduled injections and successfully detoxified, both needing doxepin for insomnia by day 3, and recurrence of withdrawal symptoms was not suppressed after the second and following injections except in one subject. The authors called effectiveness an open question requiring placebo-controlled studies.","source_url":"https://europepmc.org/abstract/MED/9617990","grade":"human-trial","grade_label":"Human trial","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data"]},{"id":"clm-058","text":"FDA's conclusion on the withdrawal literature: there is insufficient evidence to make a conclusion on the effectiveness of IV emideltide for opioid withdrawal; the positive reports should be interpreted cautiously due to the small number of studies, small samples, differing regimens, and nonrandomized, uncontrolled designs. The 2026 evaluation was the last of it: the withdrawal literature consists of the two Geneva reports and the 1998 Munich trial.","source_url":"https://www.fda.gov/media/193344/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-060","text":"The 2006 Journal of Neurochemistry review by Kovalzon and Strekalova states, verbatim: the link between DSIP and sleep has never been further characterized, in part because of the lack of isolation of the DSIP gene, protein and possible related receptor. Thus the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak. The review adds that DSIP's natural occurrence and biological activity still remains obscure, that its structure differs from every known peptide family, and hypothesizes that unidentified DSIP-like peptides may account for the immunoreactivity attributed to DSIP.","source_url":"https://europepmc.org/abstract/MED/16539679","grade":"review","grade_label":"Review or guideline","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com","https://dsippeptiderx.com/comparisons","https://dsippeptiderx.com/faq"]},{"id":"clm-061","text":"DSIP is unstable in blood: incubation in human or rat blood leads to rapid degradation (release of tryptophan-like fragments), and iodinated analogs formed non-specific aggregates. The authors investigated this precisely because rates of inactivation might contribute to the peptide's variable effects in vivo.","source_url":"https://europepmc.org/abstract/MED/3628078","grade":"in-vitro","grade_label":"In vitro","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/pk","https://dsippeptiderx.com/monograph"]},{"id":"clm-065","text":"Kafi, Monnier and Gallard 1979 reported that DSIP increased the duration of sleep in rats (Neuroscience Letters; title claim; abstract not indexed).","source_url":"https://europepmc.org/abstract/MED/530466","grade":"animal","grade_label":"Animal","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph"]},{"id":"clm-066","text":"In cats the animal literature contradicts itself: intraperitoneal DSIP 30 nmol/kg REDUCED sleep (less light slow-wave and REM sleep, longer REM latency; Sommerfelt 1985), while an intracerebroventricular study in paradoxical-sleep-deprived cats found no change in slow-wave sleep, paradoxical sleep or total sleep time, only a shift from light to deep slow-wave sleep (Susic and Masirevic 1985).","source_url":"https://europepmc.org/abstract/MED/3840239","grade":"animal","grade_label":"Animal","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/comparisons"]},{"id":"clm-067","text":"The strongest mechanistic animal result is indirect: in rats, microinjection of a specific antiserum against DSIP into the third ventricle blocked the increases in slow-wave sleep and plasma growth hormone that normally follow sleep deprivation, suggesting endogenous DSIP-like material participates in those responses (Iyer et al. 1988, PNAS). This is a rat antibody-blockade experiment; no human study has measured growth hormone as an outcome of DSIP administration in the indexed corpus.","source_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC280272/","grade":"animal","grade_label":"Animal","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-068","text":"A DSIP-containing preparation called Deltaran (emideltide free base plus glycine, per FDA's description) appears in seven records of the corpus, mostly Russian-language, studied in mice for stress-protection and aging endpoints; in female SHR mice it reduced spontaneous tumor incidence, a finding FDA declined to interpret as reassurance about emideltide because glycine itself has reported antimutagenic and anticarcinogenic properties. This site could not verify any marketing authorization for Deltaran and asserts none.","source_url":"https://europepmc.org/abstract/MED/12782416","grade":"animal","grade_label":"Animal","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/faq"]},{"id":"clm-069","text":"Dog pharmacokinetics: after IV injection of 1 to 2 mg DSIP in 4 anesthetized dogs, the peptide disappeared with a mean half-life of 4.0 +/- 0.7 minutes and a mean metabolic clearance rate of 30.7 +/- 2.5 mL/kg per minute (enzyme immunoassay, 1984). Additional measurements were made in a monkey and 3 rats.","source_url":"https://europepmc.org/abstract/MED/6379493","grade":"animal","grade_label":"Animal","used_on":["https://dsippeptiderx.com/studies","https://dsippeptiderx.com/pk","https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data"]},{"id":"clm-070","text":"The 1977 Experientia paper compared the original isolated peptide and the synthetic nonapeptide and found comparable delta-sleep-inducing properties in rabbits (title claim; abstract not indexed). Together with the PNAS characterization it is the founding document of the field.","source_url":"https://europepmc.org/abstract/MED/862769","grade":"animal","grade_label":"Animal","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies"]},{"id":"clm-080","text":"No dedicated human safety or toxicity study of DSIP exists; there is no long-term human data at any dose, no study of the marketed subcutaneous route, and no nonclinical toxicology program: FDA states that neither the nominator submitted nor FDA identified nonclinical toxicity studies to inform safety considerations.","source_url":"https://www.fda.gov/media/193344/download","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/studies","https://dsippeptiderx.com/faq"]},{"id":"clm-081","text":"There is no established human dose of DSIP. The trial regimens were intravenous (25 to 150 nmol/kg, most commonly 25 nmol/kg, about 21 micrograms per kilogram), the effect depended on infusion rate in the only dose-response work, and the products sold today use routes (subcutaneous injection, intranasal) for which no clinical data exist at all.","source_url":"https://www.fda.gov/media/193344/download","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://dsippeptiderx.com/monograph","https://dsippeptiderx.com/tool-data","https://dsippeptiderx.com/faq"]},{"id":"clm-082","text":"This site's own study table contains 28 rows (16 human, 6 animal, 1 in vitro, 5 documented absences), drawn from 42 fetch-verified citations of which 41 (97.6 percent) are peer-reviewed journals or government sources; the single press citation is used only for the attributed committee-vote report.","source_url":"https://europepmc.org/search?query=TITLE_ABS%3A%22delta%20sleep-inducing%20peptide%22%20OR%20TITLE_ABS%3A%22emideltide%22","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://dsippeptiderx.com","https://dsippeptiderx.com/site_counts","https://dsippeptiderx.com/monograph"]}]}