Research in plain language

DSIP

What it is

DSIP (Delta Sleep-Inducing Peptide) is a nonapeptide first isolated in 1977 from the blood of sleeping rabbits, which gave it its name. Despite that name, no DSIP gene and no single confirmed receptor have ever been found, so its molecular mechanism remains unresolved (review PMID 16539679). It is studied as a neuromodulatory peptide in three overlapping areas: sleep regulation, the stress axis (it appears to dampen the HPA axis, lowering stress-induced ACTH and cortisol), and antioxidant/geroprotective effects (it activates antioxidant enzymes in rodents). Sold strictly for in-vitro and laboratory research, not for human or animal use; no therapeutic efficacy is claimed.

How studies used it

Model: Human, six adults with chronic insomnia (disturbed sleep)
Studied for: Disturbed sleep / insomnia: whether a single intravenous dose of DSIP improves objective and subjective sleep parameters
Dose: 25 nmol/kg (about 21 mcg/kg). Reported per kilogram in the paper, so no body-weight conversion was needed
Dosing: Single intravenous dose given before sleep
Route: Intravenous injection
Duration: Acute, one night, with the effect tracked for up to 6 hours

Effects measured: Sleep was longer, of better subjective quality, and had fewer interruptions, with slightly more REM sleep relative to baseline

Side effects: No adverse events were reported in this study; there was no daytime sedation, only a mild arousing effect during the first hour

Sources: Schneider-Helmert & Schoenenberger, 1981

Model: Rat, model of emotional stress and HPA-axis activation
Studied for: Emotional stress and the HPA axis: whether DSIP given before a stressor changes hypothalamic substance P and the adrenal/thymic stress response
Dose: 60 and 120 nmol/kg (two dose levels tested). Reported per kilogram in the paper, so no body-weight conversion was needed
Dosing: Single dose given before the stressor
Route: Intraperitoneal injection
Duration: Single pre-stress dose

Effects measured: DSIP raised hypothalamic substance P and increased stress resistance; the lower 60 nmol/kg dose cut stress-induced adrenal hypertrophy and thymus involution, with the strongest effect at the lower dose

Side effects: No adverse events were reported in this study; the effect was strongest at the lower of the two doses

Sources: Salieva et al., 1992

Model: Rat, model of cold-induced oxidative stress
Studied for: Oxidative stress: whether DSIP pre-treatment changes endogenous antioxidant enzyme activity under cold stress
Dose: 12 mcg per 100 g body weight. Reported per 100 g of body weight in the paper, so no further body-weight conversion was made
Dosing: Single pre-treatment dose
Route: Intraperitoneal injection
Duration: Acute pre-treatment

Effects measured: DSIP raised the activity of superoxide dismutase, catalase and glutathione peroxidase/glutathione reductase, and increased reduced glutathione

Side effects: No adverse events were reported in this study

Sources: Shustanova et al., 2001

Model: Rat aged 2 to 24 months, ageing/geroprotection model
Studied for: Geroprotection and ageing: whether intermittent DSIP across the lifespan affects markers of oxidative damage and antioxidant defence
Dose: 10 mcg per 100 g body weight. Reported per 100 g of body weight in the paper, so no further body-weight conversion was made
Dosing: Five consecutive days per month
Route: Subcutaneous injection
Duration: Repeated monthly courses across the 2 to 24 month age span

Effects measured: DSIP suppressed lipid peroxidation and raised superoxide dismutase, catalase and ceruloplasmin

Side effects: No adverse events were reported in this study

Sources: Bondarenko et al., 2011

Model: Dog, monkey and rat, pharmacokinetic study
Studied for: Pharmacokinetics: how quickly DSIP is cleared from plasma across three species after intravenous dosing
Dose: 1 to 2 mg intravenous (absolute dose as published, not per kilogram)
Dosing: Single intravenous dose
Route: Intravenous injection
Duration: Acute pharmacokinetic sampling

Effects measured: Plasma half-life was very short: 4.0 minutes in dog, 2.9 minutes in monkey and 2.0 minutes in rat, with a clearance of 30.7 ml/kg/min

Side effects: No adverse events were reported in this study

Sources: Kato et al., 1984

How solid the evidence is

Honest assessment: the evidence base for DSIP is small, old and mechanistically unresolved. The human data amount to early, small studies (the sleep work was done in only six chronic insomniacs and measured acute effects over a single night), and the rest is rodent and multi-species animal work from the 1980s to early 2010s. Most importantly, after nearly fifty years no DSIP gene and no single confirmed DSIP receptor have ever been identified, and the foundational hypothesis of DSIP as a circulating sleep factor is only weakly documented in the literature (review PMID 16539679). The functional signals that do exist are real and measured: a faster clearance with intravenous half-lives of 2 to 4 minutes across three species, dampening of the HPA stress response with raised hypothalamic substance P in rats, and activation of antioxidant enzymes in rodents. But these are short-term, mostly preclinical readouts, not clinical efficacy. Doses are reported as published in each species (human as nmol/kg, rat as nmol/kg or mcg per 100 g, the cross-species PK study as an absolute 1 to 2 mg intravenous), with no animal-to-human conversion. On the regulatory side, DSIP (as Emideltide) was on the FDA 503A Category 2 list (significant safety concerns); the updated 503A document published 15 April 2026 removed Emideltide/DSIP from Category 2 effective 22 April 2026, but removal from Category 2 is not by itself a compounding clearance, and a PCAC review is scheduled for 24 July 2026. Bottom line: a genuine but thin and ageing research signal around sleep, stress and antioxidant biology, with the core mechanism still open, and no basis for any health claim.

Sources

Study data, research use only. No established human dosing protocol.