Delta-sleep-inducing peptide (DSIP) is an endogenous neuropeptide that was first isolated from rabbits by Monnier and associates in 1964. It helps to induce delta EEG sleep. It has a diverse influence on the central nervous system, regulates circadian rhythm, sleeping patterns, regulates the endocrine system, and alleviates hypothermia. DSIP further protects against oxidative stress and reduces the body’s response to acute stress.
Research suggests substance P, beta-endorphin, and cortisol levels in the hypothalamus and blood plasma show alterations. DSIP induces changes in other peptides which mediate the acute and long-term stress coping effect.
The peptide further regulates the opioid-peptidergic systems along with morphine. It thus helps in dealing with opioid withdrawal in cases of chronic pain.

What have Research Studies Shown?

Scientific research has revealed the following functions of DSIP.
-Regulation of sleep
-Betterment of REM sleep
-Suppression of paradoxical sleep
-Overcome daytime sedation
-Modification of thermogenesis, heart rate, blood pressure, pain threshold
-Alteration of substance P, beta-endorphin, and cortisol levels
-Regulation of diurnal and circadian rhythmicity
-Increase in LH secretion
-Reduction of Chronic Pain

DSIP for Sleep and Circadian Rhythm

The peptide exists in both free and bound forms in the hypothalamus, limbic system, and pituitary gland. It triggers hypothalamic neural circuitry, increasing LH during sleep, and can thus help in chronic insomnia.
A study of 14 chronic insomniacs was done to determine the intermediate effect of the peptide on sleep and daytime performance. DSIP was administered under placebo-controlled, double-blind conditions for seven successive nights.
Polysomnograms were captured for placebo baseline, beginning and end of DSIP treatment, and one placebo post-treatment night. The daytime psychological state and mental performance were extensively analyzed before and after 6 DSIP injections. They were each given IV DSIP 25 nmol/kg, and each subject reported improved sleep quality. The treatment substantially enhanced night sleep with the first and additionally with repeated doses. These effects were maintained for the first post-treatment (placebo) night. The efficiency of night sleep and daytime rest became equivalent to the levels of normal controls. Alertness and performance in the daytime also increased tremendously.
The work demonstrates the efficacy of DSIP for the improvement of impaired sleep and daytime functions as well. DSIP also helps in narcolepsy by reducing the number of sleep attacks during the day and enhancing REM sleep. The peptide was repeatedly administered to a 35-year-old male narcoleptic. Efficacy was evaluated by self-report, performance tests, multiple sleep latency tests, and all-night polysomnography. DSIP decreased the frequency of sleep attacks and improved activity, alertness, and performance during the daytime. DSIP reduced the sleep period with the enhancement of REM sleep. The findings prove the peptide to accentuate circadian and ultradian rhythms of DSIP.

Dsip and Opioid Withdrawal

DISP helps in dealing with opioid withdrawal due to its agonistic activity at opioid receptors. Several animal studies conducted by Tissot regarding DISP have shown that morphine, alcohol, pentobarbital, and DSIP, when injected directly into the bulbo-mesencephalon-thalamic recruiting system, triggers slow-wave sleep with numerous spindles reversed by naloxone. The peptide was introduced intravenously to 107 in patients with symptoms of alcohol (n = 47) and opiate (n = 60) withdrawal. Both physicians and nursing staff clinically evaluated the effect of DISP, and 97% of patients, after two weeks, showed significant disappearance of clinical symptoms and signs associated with withdrawal. It took longer to control the anxiety. Patients reported good tolerance to the DSIP treatment aside from a few cases of headaches.

DSIP for Chronic Pain and Depression

DSIP is also evaluated for use in chronic pain and/or depression. DSIP has been shown to significantly reduce pain levels and depressive states when administered. Due to the findings of DISP modulating endogenous opioid-peptidergic systems and significant effects on circadian rhythms and cortisol levels, a study was conducted to determine if there was any potential for alleviating chronic pronounced pain episodes.
The study is investigating the therapeutic effect on seven patients with migraine episodes and vasomotor headaches, chronic tinnitus, psychogenic panic attacks, and depressive states. The baseline anamnestic values were statistically compared with the katamnestic control period. DSIP remarkably lowered the pain levels of 6 out of 7 patients after intravenous administration on five consecutive days followed by five injections every 48-72 hours. A significant decrease in depressive states was also observed.

Other Indications

-Acts as a stress limiting factor
-Normalizes blood pressure and myocardial contraction
-Enhances the efficiency of oxidative phosphorylation in rat mitochondria in vitro
-Mediates antioxidant effects


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