FDA's advisers turned down DSIP. Its sleep trials did not replicate outside one lab.

Why this note exists

DSIP is one of the most widely stocked compounds in pepmg's index. In the index generated on September 8, 2026, 88 of 108 vendors carried it, across 120 listings; ten compounds were carried by more vendors, and it tied with PT-141 for the next place.[22] The common vial sizes were 5 mg, on 47 listings, and 10 mg, on 42. None of the 120 listing names uses the word emideltide.[22] pepmg covered the July meeting in its note on the committee's votes, where DSIP got one paragraph as the lone negative result. This note reads FDA's review of it, and the trials that review is built on.

A note on what kind of evidence this is: most of what follows is human data, and each study carries its design and size in the same sentence. The human studies are small, and nearly all were published between 1981 and 1998. Where a finding comes from rabbits, rats, cats, dogs or mice, the paragraph is labeled as animal data.

The vote

What the committee was asked, and what FDA staff had proposed

Two nominators, Wells Pharmacy Network and LDT Health Solutions, had asked for emideltide to be added to the 503A Bulks List and then withdrew; FDA evaluated emideltide free base and emideltide acetate anyway, "at its discretion."[1] It considered three uses, opioid withdrawal, chronic insomnia and narcolepsy, for a subcutaneous injection at 1 mg/mL.[1][2]

FDA's review, dated May 11, 2026, concluded that "a balancing of the criteria weighs against" both forms being placed on the list, and ended: "we propose not adding emideltide (free base) or emideltide acetate to the 503A Bulks List."[1] The committee agreed, narrowly. A law-firm summary of the meeting records the vote as 6 in favor and 7 against, with one abstention; STAT reported the same 6 to 7 split.[4][3]

A committee vote is advice. FDA's briefing package says the agency "will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized."[1] When checked on September 13, 2026, the meeting page had posted no summary minutes, and FDA's 503A bulk substances page, content current as of May 14, 2026, did not mention emideltide.[2][6] FDA's safety-risk page, current as of April 22, 2026, carries this entry: "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."[5]

The molecule

A sleep factor whose own biology is still unresolved

Animal data, labeled as such: DSIP was first found in the cerebral venous blood of rabbits and isolated by a Basel group in 1977. It is a nine-amino-acid peptide, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu.[1][20] Its name comes from animal experiments in which it increased the EEG delta waves of deep sleep, in rabbits, rats and cats. FDA notes that the animal findings are inconsistent, that one group failed to detect any increase in delta power in rats, and that "[t]he reasons underlying the discrepant findings have not been discussed or elucidated."[1] In rats, the opioid blocker naloxone prevented its sleep effect, although in laboratory binding studies it does not attach to opioid receptors directly.[1]

A 2006 review in the Journal of Neurochemistry put the basic problem plainly: 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," and "the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak."[20]

FDA also judged both forms "not well-characterized." The nominations were inconsistent about which substance they meant; one certificate of analysis listed a molecular formula that FDA says "does not correspond to any emideltide structure," and the certificates carried no tests for impurities, aggregates or bacterial endotoxin.[1] FDA added that because of the free base's limited water solubility, "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."[1]

The trials

Six insomnia studies, one case report, two open withdrawal studies

Counts and designs as described in FDA's May 11, 2026 evaluation; the 1981 study in six healthy volunteers is counted there as pharmacology, not as an insomnia study.[1]

The first human study, published in 1981, gave six healthy volunteers an intravenous infusion of 25 nmol/kg or placebo in a double-blind crossover; the authors reported a 59% increase in median sleep time over the following 130 minutes.[7] The same year, the group reported a randomized crossover in six middle-aged people with chronic insomnia.[8] FDA's reading of that second study: emideltide "did not influence" sleep latency or final waking time compared with placebo, some outcomes were reported "without reporting results for placebo," and it is "unclear" whether the tendencies the authors saw were clinically meaningful.[1]

The strongest-looking result is a 1987 study of 14 people with chronic insomnia given seven nightly intravenous injections. It reported mean sleep latency falling from 58.4 minutes at baseline to 27.6 minutes after the last injection, and total sleep time rising from 313 to 385 minutes; its abstract describes the design as placebo-controlled.[10][1] FDA disagreed with that description: "Even though the authors described the study as 'placebo-controlled', there was no placebo arm in the study." The comparison was each patient's own baseline night plus an outside group of healthy sleepers, a design FDA calls "challenging to interpret."[1] A 1986 study in 18 people, nine middle-aged and nine elderly, had the same problem in FDA's reading: no adequate control group.[1]

Two other research groups ran placebo-controlled studies of the same intravenous dose, and neither found much.[1] Monti and colleagues gave six people with severe chronic insomnia 25 nmol/kg or placebo in a randomized double-blind crossover; the differences were not significant against baseline or placebo nights, and the authors concluded "that sleep improvement under DSIP treatment is of little clinical significance."[11][1] At the University of Amsterdam, Bes and colleagues assigned 16 people with chronic insomnia, in matched pairs, to 25 nmol/kg or a glucose placebo for three nights. The statistically significant effects "were weak and in part could be due to an incidental change in the placebo group," subjective sleep quality did not change, and the authors concluded that short-term treatment "is not likely to be of major therapeutic benefit."[12]

FDA's summary of the whole insomnia record is "inconclusive and at best preliminary," and it says the positive studies "had poor study methodologies (i.e., lack of or poor selection of control groups)."[1] A 1986 review by Graf and Kastin had reached a similar place; in FDA's summary, it found the results preliminary and the evidence insufficient to show that emideltide reliably induced or maintained sleep.[13][1]

For narcolepsy, "[t]he nominator did not provide any clinical references." FDA found one: a 1984 case report of a single 35-year-old man with a ten-year history of narcolepsy, whose sleep attacks fell from six in a baseline week to three during weeks of injections.[1][14] A single-subject report cannot establish effectiveness, and FDA concluded the evidence was insufficient.[1]

For opioid withdrawal, the evidence is two open studies with no comparison group. In a 1984 Geneva study, 107 inpatients in alcohol or opiate withdrawal received intravenous DSIP; the authors reported that symptoms disappeared or improved markedly in 97% of evaluable opiate patients and 87% of alcohol patients, judged by doctors and nursing staff rather than standard withdrawal scales.[15][1] The authors also wrote that "nothing allows [sic] to draw any conclusion as to a potential usefulness of a maintenance treatment with DSIP."[1] In a 1998 study of seven people, only two completed the scheduled injections and detoxified, and both needed doxepin for insomnia on day three; its authors wrote that "it remains an open question whether DSIP could be an effective alternative detoxification approach" and called for placebo-controlled studies.[1][16] A ClinicalTrials.gov search on September 13, 2026 returned no registered study of DSIP for any use.[21]

The route

Every human dose FDA found was intravenous, and the infusion speed mattered

FDA was asked to evaluate a subcutaneous injection. It found no human study of that route: no effectiveness data, no pharmacokinetics and no safety data.[1] Every human dose it found was intravenous, between 25 and 150 nmol/kg, given to 209 people for 1 to 15 days.[1]

The intravenous details matter because the peptide barely lasts in the blood. FDA gives a plasma half-life of 8 minutes in humans, and 5 to 10 minutes when it is incubated with human serum in the laboratory.[1] In the originating group's own studies in healthy volunteers, the speed of the infusion changed the result: total sleep time rose by about 30 minutes with a 2.5-minute infusion and about an hour with a 7.5-minute infusion, and emideltide "was completely ineffective if infused over 1 minute."[1] The authors' own summary: "Slow injection proved essential."[9] None of that says anything about a subcutaneous dose, and pepmg does not translate an infusion protocol into one.

What the few later human studies found

The later human work does not tidy the picture. In a 2009 randomized study of 24 women having surgery, 12 received saline and 12 received DSIP at one of three intravenous doses. During isoflurane anaesthesia, the 25 nmol/kg dose "paradoxically, significantly reduced delta rhythm" and raised the bispectral index, and the authors concluded that DSIP "probably reduced parasympathetic tone and decreased (lightened) the depth of anaesthesia."[17] That is one small study in anaesthetized patients, not a sleep trial, and it is the most recent randomized human study pepmg found; its result runs opposite to the peptide's name.

Even DSIP's hormonal effects in people have not replicated. A 1989 double-blind crossover in 11 healthy men reported lower ACTH-like immunoreactivity for at least 3 hours after an intravenous dose, with cortisol unaffected.[18] A 1995 study found that DSIP infusions did not change ACTH or cortisol responses to CRH or to a meal, and its authors wrote that their data "do not support an inhibitory role of DSIP on ACTH and cortisol secretion in man."[19]

Safety

Tolerated in small intravenous studies. Almost everything else is unstudied.

In the small intravenous insomnia studies, FDA found the peptide "well tolerated and not associated with significant AEs."[1] The 1984 withdrawal study is where problems were recorded: of 107 patients, nine had minor transient effects such as sweating, headache, nausea and vertigo, and three had serious ones, two of them hypotension at the start of the first injection. One of the three, given a second injection, developed what FDA quotes as "progressive hypotension."[1] FDA notes that these events are hard to separate from withdrawal itself.[1]

FDA's search of its adverse event reporting system through March 3, 2024 retrieved zero reports, and it found no relevant case reports in the medical literature.[1] For a substance that is not an approved drug, an empty database is not a safety finding.

Animal and laboratory data, labeled as such: FDA found no repeat-dose toxicity study, no developmental or reproductive toxicity study, no genotoxicity study of either form and no two-year carcinogenicity study.[1] The one long-term mouse study submitted, of a Russian product called Deltaran that combines the peptide with glycine, reported fewer tumors in treated mice. FDA said it could not be read as evidence of no cancer risk, partly because glycine itself has reported anti-tumor properties, and partly because the study was not designed to assess carcinogenicity; the mice received the product for at most about 4.5 months.[1]

FDA also raised two questions nobody has studied. Because the peptide appears in animal work to act by releasing the body's own opioid peptides, FDA wrote that it "could have reinforcing properties," and it identified no study of abuse potential. And as a nine-amino-acid peptide injected under the skin, it "may pose a significant risk for immunogenicity," with no data offered to the contrary.[1]

The market

Widely sold, almost never under its drug name

FDA's review found injection and nasal spray products marketed in the US through integrative neurology clinics, medical concierge services, medical spas, wellness clinics and online retailers, for uses ranging from sleep and stress to pain, cancer, neurodegenerative disease and detoxification. None of the websites it searched said whether the product was the free base or a salt.[1] It cites a federal prosecutors' press release describing a pharmacy that compounded and distributed products containing emideltide between October 2018 and April 2020, and it notes that no outsourcing facility has reported compounding it.[1]

In pepmg's index, it is sold under the research name: 5 mg or 10 mg on 89 of 120 listings, three listing names describing a nasal or spray product, and none using the name emideltide.[22] pepmg makes no claim about the contents of any vendor's product.

Three things this note is not saying

First, it is not saying DSIP does nothing. The originating group's studies reported effects on sleep, and some animal experiments found real changes in EEG delta activity.[7][10][1] FDA's word for the human evidence is inconclusive, not negative.[1]

Second, it is not saying the vote settled DSIP's legal status. The committee advises FDA, FDA has not issued a final determination, and FDA's own position is that it "lacks sufficient information to know whether the drug would cause harm if administered to humans."[1][5]

Third, it is not saying the favorable studies were wrong. They may have found something real in a small number of people. What is missing is a trial large enough, controlled well enough and long enough to tell, and none is registered.[21]

What it is saying is narrower: DSIP has placebo-controlled human trials, and the ones run by groups outside the originating laboratory found little or no benefit. Every dose FDA found was intravenous, and the committee FDA asked declined to recommend it for compounding.[1][11][12][4]

Questions people are asking