DSIP

DSIP (delta sleep-inducing peptide) is an endogenous amphiphilic nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, ~850 Da) first isolated in 1974 by Monnier and Schoenenberger from the cerebral venous blood of rabbits in an induced sleep state. Despite decades of study, no specific high-affinity receptor, gene, or precursor protein has been definitively identified, so its mechanism remains poorly characterized and it is generally described as a neuromodulator rather than a classical receptor agonist. Proposed actions reported in the literature include modulation of glutamatergic (NMDA) and GABAergic signaling, interaction with the MAPK cascade, homology to glucocorticoid-induced leucine zipper (GILZ), and neuroendocrine stress-limiting effects.

Human evidence

Sparse, mixed human data from small, mostly decades-old trials; no modern well-powered Phase III trials.

Regulatory status

Not FDA-approved for any indication. The FDA designation is "Emideltide." On April 15, 2026 the FDA's updated 503A bulk drug substances list removed Emideltide/DSIP from Category 2 (substances raising significant safety concerns) and scheduled it for Pharmacy Compounding Advisory Committee (PCAC) review on July 24, 2026 (part of the July 23-24, 2026 PCAC meeting); as of June 2026 its compounding status is unresolved pending that review. Outside any such pathway it is handled as a research chemical, not a licensed medicine.

• —Studied as a modulator of slow-wave (delta) sleep and in small trials of insomnia, though results across studies have been contradictory.
• —Investigated as a stress-limiting factor and for neuroendocrine effects (e.g., modulation of corticotropin and other hormones).
• —Examined in early research for alleviation of opioid and alcohol withdrawal symptoms.
• —Explored in preclinical work for antinociceptive (pain-modulating) and antioxidant/mitochondrial effects.

• ⚠No long-term human safety data exists; published clinical exposure is largely from short-duration (days-to-weeks) studies, and chronic use is essentially unstudied.
• ⚠DSIP has a very short plasma half-life (animal estimates of minutes, in vitro estimates around 15 minutes via an aminopeptidase-like enzyme) and is unstable in plasma, which complicates both research and any dosing interpretation.
• ⚠Small early human trials reported few overt side effects, but these studies were small and not designed to detect uncommon or delayed harms; effects noted in secondary/user literature (e.g., drowsiness, headache, injection-site reactions) are not regulator-verified.
• ⚠Research-grade material is not manufactured to pharmaceutical quality standards, so purity, sterility, and content can vary between sources.