DSIP

What it is

Delta sleep-inducing peptide (DSIP), also called emideltide, is a nine-amino-acid peptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) described in 1977 by Schoenenberger and Monnier's group in Basel, who isolated it from rabbits and named it for the slow-wave (delta) EEG activity it produced after infusion into the brain. A synthetic version was made the same year, and small clinical studies in insomnia and drug withdrawal followed in the 1980s and early 1990s.

Mechanism of action

How DSIP works, and whether it is a natural sleep factor at all, is unresolved. In the original rabbit experiments, Schoenenberger and Monnier (1977) reported that synthetic DSIP infused into the brain ventricles enhanced delta and spindle EEG patterns, while related fragments and analogs did not. No gene, precursor protein or dedicated receptor for DSIP has been identified, which has made the peptide hard to place in known signaling pathways. In a 2006 review, Kovalzon and Strekalova described the evidence for DSIP as a sleep factor as extremely poorly documented and still weak, raised the possibility that the original isolation picked up the wrong molecule, and suggested that an undiscovered DSIP-like peptide might account for the reported effects. The same review discusses other proposed roles, including stress protection, pain modulation, neuroendocrine effects and neuroprotection. The 1984 withdrawal study based its rationale on earlier animal experiments.

What it’s most studied for

DSIP research has focused on sleep. The discovery work measured slow-wave EEG activity in rabbits, and clinical groups then gave intravenous DSIP to adults with chronic insomnia and recorded sleep in the laboratory. A second line of work, also from the 1980s, examined DSIP in inpatients going through alcohol or opiate withdrawal, and a small pilot study in the same period looked at chronic pain. Later reviews have also discussed stress protection and neuroendocrine effects, largely on the basis of animal studies. Interest in DSIP as a sleep aid persists outside research settings, but the most recent controlled human sleep study identified for this summary was published in 1992.

Notable findings

Each finding carries the species or population it was observed in and the dose that study used. Doses are reported as research context, exactly as published. They are not guidance.

Study quality

Human evidence on DSIP is small, old and inconsistent. The largest placebo-controlled sleep study cited here enrolled 16 adults with chronic insomnia (Bes et al., 1992), and its authors described the effects as weak and possibly influenced by a change in the placebo group. Earlier positive reports came largely from Schneider-Helmert, who published with Schoenenberger, one of the peptide's discoverers, and the withdrawal series of 107 inpatients had no control group and relied on clinician observation. No controlled human study published after 1992 was identified for this summary. The animal foundation is the 1977 intraventricular work in rabbits; rodent studies followed, but a 2006 review still judged the sleep-factor hypothesis poorly documented. The abstracts cited here do not report systematic adverse-event data, so the safety of DSIP in humans has not been characterized in modern trials. The FDA advisory committee voted against it in July 2026.

References

1. 1
   Schoenenberger GA, Monnier M (1977). Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proceedings of the National Academy of Sciences of the United States of America. PMID 265572
2. 2
   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. Neuropsychobiology. PMID 1299794
3. 3
   Schneider-Helmert D (1984). DSIP in insomnia. European Neurology. DOI 10.1159/000115714
4. 4
   Dick P, Costa C, Fayolle K, et al. (1984). DSIP in the treatment of withdrawal syndromes from alcohol and opiates. European Neurology. PMID 6548969
5. 5
   Kovalzon VM, Strekalova TV (2006). Delta sleep-inducing peptide (DSIP): a still unresolved riddle. Journal of Neurochemistry. PMID 16539679
6. 6
   US Food and Drug Administration, Pharmacy Compounding Advisory Committee (2026). July 23-24, 2026 Meeting of the Pharmacy Compounding Advisory Committee: votes on nominated bulk drug substances for the 503A list. U.S. Food and Drug Administration.