What is DSIP?

Delta sleep-inducing peptide (DSIP) is a multifunctional regulatory peptide. It was first isolated from cerebral venous blood of rabbits in an induced state of sleep in 1974 by the Swiss Schoenenberger-Monnier group. Although usually used for sleep, another important clinical indication for DSIP is its use in the treatment and care for patients suffering from chronic pain and/or depression.

For years after its discovery, the functions of the DSIP peptide were actively investigated. The effect of DSIP on the induction of slow-wave sleep and sleep-related growth hormone release was shown consequently in the work of Iyer et al. (1988). Not shortly thereafter, another study showed that the absence of the effect of DSIP in the formation of sleep was shown when injected into the nucleus raphe dorsalis of rats.

A wide range of studies conducted to identify the biological activities of DSIP showed that endogenous DSIP or DSIP-like peptides have regulatory activity and play an important role in endocrine regulation. Thus, it has been shown that DSIP reduces the basal level of corticotropin and stimulates the secretion of luteinizing hormone and the release of somatoliberin and somatotropin.

All of this being said, DSIP has a wide range of physiological activities, some of which are not related to each other which is why it makes such a great, versatile peptide product.

What is DSIP and How Does It Work?

“Delta sleep-inducing peptide (DSIP) is a naturally occurring substance, which was originally isolated from rabbit brain in 1977. This curious substance is a nonapeptide that is normally synthesized in the hypothalamus and targets multiple sites including some within the brainstem. As its name suggests DSIP promotes sleep, and this has been demonstrated in rabbits, mice, rats, cats and human beings. In fact, DSIP promotes a particular type of sleep which is characterized by an increase in the delta rhythm of the EEG.”

“DSIP is normally present in minute amounts in the blood. Brain and plasma DSIP concentrations exhibit a marked diurnal variation and there has been shown to be a correlation between DSIP plasma concentrations and circadian rhythm in human beings. Concentrations are low in the mornings and higher in the afternoons. An elevation of endogenous DSIP concentration has been shown to be associated with suppression of both slow-wave sleep and rapid-eye-movement sleep and interestingly also with body temperature.”

“Plasma concentrations of DSIP are influenced by the initiation of sleep. Patients with Cushing’s syndrome suffer from a lack of slow-wave sleep but the diurnal variation in slow-wave and rapid-eye-movement sleep in those patients appears to be similar to that in normal patients.”

“When compared with most other peptides, DSIP is unusual in that it can freely cross the blood–brain barrier and is readily absorbed from the gut without being denatured by enzymes. DSIP is present in relatively high concentrations in human milk (10–30 ng mL^–1). Any mother who has breast-fed her babies will attest to the ability of a feed to induce sleep. However, a feed of artificial milk may have a similar effect, and it is not known whether DSIP concentrations are related to the sleep–wake cycle in human neonates.”

Based on literature, DSIP has been shown to:

• Help induce better sleep

• Relieve emotional and psychological responses to stress

• More energy

• Enhance mood

• Reduce chronic pain

Research Example 1:

Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study.

Experimental results suggested a modulation or ‘programming’ interaction of delta sleep-inducing peptide (DSIP) with endogenous opioid-peptidergic systems and exogenous intracerebrally or systemically administered morphine and amphetamine. The induction of cerebral MAO-A activity, a pronounced influence on the circadian rhythms of locomotion and intracerebral neurotransmitter as well as plasma protein and cortisol concentrations has been reported. DSIP was also shown to counteract experimentally induced stress situations in animals. An improvement of the psychomotor performance and the concentration capacity in humans beside sleep normalization and pronounced effects on withdrawal symptoms including pain states in alcoholics and opiate addicts was discovered. This encouraged a pilot study for a possible action of the peptide in humans suffering from chronic pronounced pain episodes. We investigated the therapeutic effect in 7 patients with migraine episodes and vasomotor headaches, chronic tinnitus, and psychogenic pain attacks. The anamnestic (baseline) 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 h. Remarkably, a simultaneous significant reduction of the concomitantly occurring depressive states was observed.

Research Example 2:

Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs

The effects of delta sleep-inducing peptide (DSIP), on the sleep cycle of insomniac patients were assessed by means of polysomnographic recordings. DSIP in a dose of 25 nmol/kg or a placebo was administered i.v. for four nights using a double-blind crossover design. The number of nocturnal awakenings, non-rapid-eye-movement (NREM) sleep latency, total waking time and waking time after sleep onset were decreased under DSIP treatment, but no significant differences were found in comparison to baseline or to double-blind placebo nights. Total sleep time and NREM sleep time were increased by the peptide. Their increase was related to increases in stage 2, while stage 1, slow wave sleep (stages 3 and 4) and rapid-eye-movement sleep were not modified. For NREM sleep time and stage 2 sleep differences between DSIP and a placebo were significant, but the same differences existed already for the baseline values. It can be concluded that sleep improvement under DSIP treatment is of little clinical significance.

Research Example 3:

Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study

The influence of delta sleep-inducing peptide (DSIP) on sleep was studied in 16 chronic insomniac patients according to a double-blind matched-pairs parallel-groups design. Subjects slept for 5 consecutive nights in the laboratory. Night 1 was used for adaptation, night 2 for baseline measurements. In the afternoon before the 3rd, 4th and 5th night, half of the patients received intravenously 25 nmol/kg body weight DSIP, and half of the patients a glucose solution (placebo). Measures for sleep structure, objective (polysomnography) and subjective sleep quality and for subjective tiredness were assessed. The results for objective sleep quality indicated higher sleep efficiency and shorter sleep latency with DSIP as compared to placebo. One measure of subjectively estimated tiredness decreased within the DSIP group. Data analysis suggested, however, that the statistically significant effects were weak and in part could be due to an incidental change in the placebo group. As none of the other measures, including subjective sleep quality, showed any change, it was concluded that short-term treatment of chronic insomnia with DSIP is not likely to be of major therapeutic benefit.

Research Example 4:

The influence of the delta-sleep-inducing peptide on convulsive activity

Data are presented in this paper on the influence of the delta-sleep-inducing peptide (DSIP) on various forms of convulsive activity. The capacity of this peptide to suppress convulsive activity in foci created in the cerebral cortex by the application of strychnine has been demonstrated in experiments on cats. It has been established in experiments on rats that DSIP determines the later development of the convulsive kindling syndrome and prevents the development of convulsions in mice induced by bicuculline, picrotoxin, and Corozal, but is devoid of such action in relation to thiosemicarbazone and strychnine. It was demonstrated that the anticonvulsant action of DSIP is associated with its influence on the reticular portion of the substantia nigra. The lowest level of this peptide itself has been discovered, in the reticular portion of the substantia nigra at the late stages of pharmacological kindling. It is inferred that DSIP may represent one of the factors of the endogenous control of the excitability of the brain.

Summary/Takeaway

DSIP is a well-known neuromodulator and natural sleep-promoting nonapeptide with many other physiologic functions. It has been heavily studied in research to aid in better sleep, increase energy levels, enhance your mood, reduce chronic pain, and much more.