What is Delta Sleep Inducing Peptide (DSIP)


Delta-sleep-inducing peptide (DSIP) was first isolated from rabbits by Monnier and associates in 1964. It is an endogenous neuropeptide that has been shown to induce natural delta EEG sleep. It has a wide range of modulatory effects in the central nervous system and its mechanism of action has not been fully determined. Aside from its sleep inducing effects, it acts on circadian rhythms by interacting with serotonin and melatonin. It has also been shown to have a regulatory effect on the endocrine system by interacting with temperature regulation and having a direct or indirect effect on alleviating hypothermia. Further studies have shown that it has significant effects on the protection against oxidative damage.

DSIP has the ability to enhance the efficiency of oxidative phosphorylation and contributes to pronounced stress protective and antioxidant action. DSIP also has been shown to reduce the body’s natural response to acute stress. Laboratory studies suggest marked changes in substance P, beta-endorphin, and cortisol levels in hypothalamus and blood plasma. This suggests that the acute and long-term stress-coping effect of DSIP depends on considerable changes in the level of other oligopeptides and hormones induced by DSIP. It seems DSIP triggers a cascade of complex interrelated molecular reactions in response to emotional stress.

Lastly, DSIP has been shown to aid with opioid withdrawal and chronic pain. A study was done and showed significant reductions of pain episodes in patients suffering from chronic pain problems along with depressive states. It seems to modulate endogenous opioid-peptidergic systems along with exogenously administered morphine.

What have Research Studies Shown?

Scientific research has revealed that DSIP can do the following:

-Regulate sleep

-Improve REM sleep

-Suppress paradoxical sleep

-No daytime sedation

-Modify thermogenesis, heart rate, blood pressure, pain threshold

-Modify substance P, beta endorphin and cortisol levels

-Help regulate diurnal and circadian rhythmicity

-Increase LH secretion

-Reduce Chronic Pain

Sleep and Circadian Rhythm

Although the mechanism of action for DSIP and the gene that encodes it remain unknown, the peptide has been found in both free and bound forms in the hypothalamus, limbic system, and pituitary. It has also been shown to increase LH suggesting that DSIP may activate the hypothalamic neural circuitry responsible for stimulation of LH release reported to occur during sleep. One of the primary indications for its use is aiding sleep in chronic insomniacs.

A study of 14 chronic insomniacs was done to determine the effects of intermediate-term delta-sleep inducing peptide administration on sleep and daytime performance. DSIP was administered under placebo-controlled, double-blind conditions for 7 successive nights.

Polysomnograms were obtained for placebo baseline, beginning and end of DSIP treatment, and one placebo post treatment night. daytime psychological state and mental performance were extensively tested before and after 6 DSIP injections. They were each given IV DSIP 25 moles/kg and each reported improved sleep quality. The treatment substantially improved night sleep with the first and additionally with repeated doses. These effects were maintained for the first posttreatment (placebo) night. Efficiency of night sleep and daytime rest reached the levels of normal controls. Alertness and performance at daytime increased significantly.

The study demonstrates the efficacy of DSIP for the treatment of impaired sleep and daytime functions as well. DSIP has also been shown to be effective in the treatment of narcolepsy by reducing the amount of sleep attacks throughout the day while also enhancing REM sleep. Repeated injections of DSIP were given to a 35-year-old male narcoleptic. Effects of wakefulness and sleep were evaluated by self-reports, performance tests, multiple sleep latency tests and all-night polysomnography. DSIP reduced the frequency of sleep attacks and increased activity, alertness, and performance during day-time. The sleep period was compressed by DSIP with enhancement of REM sleep. The results suggest that the effects are due to an accentuation of circadian and ultradian rhythms of DSIP.

Opioid Withdrawal

DISP has also been indicated in the treatment of opioid withdrawal due to its agonistic activity at opioid receptors. Due to the several animal studies conducted by Tissot in regard to DISP showing that morphine, alcohol, pentobarbital as well as DSIP, when injected directly into the bulbo-mesencefalo-thalamic recruiting system, induced slow-wave sleep with numerous spindles reversed by naloxone, a study was done to determine the efficacy of DSIP in opioid withdrawal. DISP was administered intravenously to 107 inpatients presenting with symptoms of alcohol (n = 47) and opiate (n = 60) withdrawal. The assessment of the effect of DISP was based on clinical evaluation of both physicians and nursing staff, and a reported 97% of patients, after two weeks, showed marked disappearance of clinical symptoms and signs associated with withdrawal. Anxiety, however, took a little bit longer to decrease. Tolerance to the DSIP treatment was good, aside from headaches reported by a few patients.

Chronic Pain and Depression

Another important clinical indication for DSIP is its use in the treatment and care for patients suffering from chronic pain and/or depression. DSIP has been shown to significantly lower pain levels and depressive states when administered. Due to the findings of DISP modulating endogenous opioid-peptidergic systems along with pronounced effects on circadian rhythms and cortisol levels, a study was done to determine if there was any potential for alleviating chronic pronounced pain episodes.

An investigation of the therapeutic effect was done on 7 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 significantly lowered the pain levels of 6 out of 7 patients after intravenous administration on 5 consecutive days followed by 5 injections every 48-72 hours. A significant reduction in depressive states was also observed.

Other Indications

-Act as a stress limiting factor

-Normalize blood pressure and myocardial contraction

-Enhance the efficiency of oxidative phosphorylation in rat mitochondria in vitro

-Possible antioxidant effects


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Ouichou; et al. Delta-sleep-inducing peptide stimulates melatonin, 5-methoxytryptophol and serotonin secretion from perifused rat pineal glands. Biol Signals. 1992 Mar-Apr;1(2):65-77.

Bjartell; et al. Delta sleep-inducing peptide (DSIP)-like immunoreactivity in gut: coexistence with known peptide hormones. Peptides. 1989 Jan-Feb;10(1):163-70.

Khvatova, EM; et al. Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia. Peptides. 2003 Feb;24(2):307-11.

Dick; et al. DSIP in the treatment of withdrawal syndromes from alcohol and opiates. Eur Neurol. 1984;23(5):364-71.

Larbig; et al. Therapeutic Effects of Delta-Sleep-Inducing Peptide (DSIP) in Patients with Chronic, Pronounced Pain Episodes. Eur Neurol 1984;23:372–385. Sahu A, et al. Life Sci. 1987 Mar 23;40(12):1201-6. Schneider-Helmert, D. & Schoenenberger, G.A. Experientia (1981) 37: 913

Schneider-Helmert, D. Effects of DSIP on narcolepsy. Eur Neurol. 1984;23(5):353-7. Sudakov et al. 1983; Graf et al. 1984, 1986; Schoenenberger 1984; Kovalzon 1986, 1994; Inouéet al. 1988, 1990; Yehuda et al. 1988; Inoué 1989; Bjartell 1990; Prudchenko et al. 1994; Lysenko et al. 1995; Strekalova 1998; Gershtein and Dovedova 1999; Pollard and Pomfrett 2001 Schoenenberger 1984; Yehuda et al. 1988; Inoué 1989; Prudchenko et al. 1994; Strekalova 1998

Mikhaleva; et al. Antioxidative and detoxifying effects of analogues of delta-sleep inducing peptide (DSIP). Bioorg Khim. 2014 Jan-Feb;40(1):3-11.

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