DSIP Results

What DSIP is and where the name comes from

DSIP, or delta sleep-inducing peptide, is a nine-amino-acid peptide with the sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. Researchers isolated it in the 1970s from the cerebral venous blood of rabbits. In rabbit experiments with 61 animals, including controls, EEG delta activity in the neocortex and limbic cortex rose by a mean of 35% after synthetic DSIP compared with controls. Eight related fragments and analogues did not produce this pattern, and only the alpha-aspartyl form was highly active.Animal study · PMID 568769Animal study · PMID 265572

DSIP-like material has also been measured in tissue from people. In gut samples taken from people, DSIP-like immunoreactivity appeared in several endocrine cell types, at higher concentrations than in pig or rat gut. In an observational study of 15 drug-free men with schizophrenia, DSIP-like immunoreactivity in cerebrospinal fluid correlated with stage 3 and delta sleep on the night before sampling. The authors called this a first report that still had to be tested in other groups.Human observational · PMID 2664725Human observational · PMID 1475566

Early human sleep studies reported large changes

The first human study was a double-blind crossover trial in 6 healthy volunteers who were given DSIP in the morning. Median total sleep time rose 59% over placebo within a 130-minute window. On the following night, sleep onset came sooner, the share of stage 1 sleep fell, and sleep efficiency rose. EEG and behavioral tests showed no classic sedation, and no psychological, physiological or biochemical side effects were recorded.Human RCT · PMID 6895513

In a small study of 6 middle-aged chronic insomniacs, a single exposure was followed by longer sleep with fewer interruptions and slightly more REM sleep. The change appeared only in the second hour. In the first hour, the authors noted a slight arousing effect. No daytime sedation was reported.Human trial · PMID 7028502

In a placebo-controlled, double-blind study of 14 middle-aged chronic insomniacs given DSIP for 7 consecutive nights, night-sleep efficiency and daytime rest reached the levels of normal controls. Daytime alertness and performance rose, and the changes held through the first placebo night afterward. An open study of 7 people with severe insomnia, each given 10 sessions, reported normalized sleep in 6 of 7 over follow-up periods of 3 to 7 months. That study had no control group.Human RCT · PMID 3622582Human trial · PMID 6391926

A 1983 summary of five human studies from the same research group reported that sleep began about 1 hour after exposure and that effects lasted up to 20 hours. The authors described tolerability as good.Review · PMID 6689058Review · PMID 6391925

Later controlled trials found weak or no differences

In a 1992 double-blind, matched-pairs trial, 16 chronic insomniacs spent 5 consecutive nights in a sleep laboratory. Half were given DSIP and half a glucose placebo before nights 3 to 5. Compared with placebo, the DSIP group showed higher sleep efficiency and shorter sleep latency. The authors judged these effects weak and said they might partly reflect a chance shift in the placebo group. Subjective sleep quality and the other measures did not change.Human RCT · PMID 1299794

In a double-blind crossover study of chronic insomniacs over four nights, total sleep time and non-REM sleep rose, almost entirely because of more stage 2 sleep. Slow-wave sleep and REM sleep did not change. The gaps between DSIP and placebo nights were already present at baseline, and the authors rated the changes as of little clinical significance.Human RCT · PMID 3583493

Taken together, the human sleep record is inconsistent. The most positive reports came early, mostly from one group, with 6 to 14 participants. The two later controlled trials did not reproduce the large changes.Human RCT · PMID 6895513Human RCT · PMID 1299794Human RCT · PMID 3583493

Hormone and brain-activity results in people

In a randomized, double-blind crossover study of 11 healthy men, plasma ACTH-like immunoreactivity fell for at least 3 hours after DSIP compared with saline. Plasma cortisol did not differ and followed its normal daily decline. In a placebo-controlled study of 8 healthy men aged 23 to 34, ACTH also fell after DSIP, while vasopressin did not change, even under osmotic or orthostatic stimulation.Human RCT · PMID 2554357Human RCT · PMID 7698722

Not every hormone study agrees. In 1995 experiments with 20 healthy young men, DSIP did not change ACTH or cortisol responses to corticotropin-releasing hormone or to a midday meal. The authors wrote that their data did not support an inhibitory role for DSIP on ACTH in people.Human trial · PMID 7777652

In a randomized trial of 24 women under isoflurane anesthesia, 12 received saline and 12 received DSIP at one of three exposure levels. Heart rate rose and heart rate variability fell. Contrary to the researchers' hypothesis, delta rhythm fell and the bispectral index rose in the lowest-exposure group, which suggests anesthesia became lighter rather than deeper.Human RCT · PMID 19142086

In a Russian study of 30 people with insulin-dependent diabetes, a DSIP-based preparation was given for two months. In the retinopathy subgroup, the time for visual evoked potentials to return to baseline after photostress fell from 137.2 seconds to 95.1 seconds. Healthy controls measured 73.5 seconds.Human trial · PMID 25739189

Animal and cell results

In rats given DSIP into the brain's ventricles, plasma growth hormone rose within 30 minutes, and levels stayed up for the full 120 minutes measured. A dopamine blocker stopped the rise. In cultured rat pituitary cells, growth hormone release rose about 50% above baseline at the most active concentration.Animal study · PMID 3575154

In ovariectomized rats, LH rose within 30 minutes of DSIP exposure and stayed up for 2 hours, while FSH did not change. Cultured pituitary cells did not respond, but hypothalamic tissue released more LHRH. A separate rat study found that LH rose only in animals primed with ovarian steroids.Animal study · PMID 3121137Animal study · PMID 3550343

In rats with chemically provoked audiogenic seizures, DSIP and its analogue DSIP-12 lowered seizure incidence, mean grade and duration, and DSIP-12 had the larger effect. In another rat study, DSIP alone did not change seizure latency, but when it was combined with valproate, latency was longer for 6 hours. In rats with focal stroke, 8 days of DSIP exposure was followed by higher rotarod motor scores. Infarct size was smaller than in controls, but the difference was not significant.Animal study · PMID 15911358Animal study · PMID 16645330Animal study · PMID 34500605

In stressed rats that later had cerebral ischemia, all animals given Deltaran, a DSIP-glycine formulation, survived, while 38% of animals without it died. In mice, a DSIP fusion protein shortened sleep latency and lengthened pentobarbital-induced sleep. In neonatal rat pups, a DSIP analogue crossed from the gut into the blood and brain.Animal study · PMID 18975104Animal study · PMID 28462721Animal study · PMID 6688848

What the DSIP evidence adds up to

The human DSIP results rest on small, short laboratory studies, mostly from the 1980s and early 1990s. The evidence pack contains no large modern randomized trial. Sleep results range from a 59% rise in total sleep time to differences the authors judged of little clinical significance. The ACTH results also conflict. Animal studies point to links with growth hormone, LH, seizures and stroke models, but none of these has been tested in people.Human RCT · PMID 6895513Human RCT · PMID 1299794Human RCT · PMID 3583493Human trial · PMID 7777652

Even the earliest work found that only the pure alpha-aspartyl form of DSIP was highly active, and any compound's research value depends on what is actually in the vial, which is why batch testing matters.Animal study · PMID 568769

The studies at a glance

Selected DSIP studies and their measured results

Frequently asked questions