DSIP Dosing Protocol: Sleep Enhancement Guide

Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2-6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process.

Limitations: Animal study only — human translation uncertain.

ACTH (4-10) analogue injection inhibited stress-induced Fos expression in the pPVN and the medial septum, but only in predisposed rats. The experiments indicate that DSIP and ACTH (4-10) analogue reduce pPVN and limbic neurone responses to emotional stress in the rats predisposed to emotional stress; the effects on Fos expression may play a role in the biological activities of these peptides.

Limitations: Animal study only — human translation uncertain.

This assumption is based on: (i) a highly specific distribution of DSIP-like immunoreactivity in the neurosecretory hypothalamic nuclei of various vertebrate species that are not particularly relevant for sleep regulation, as revealed by the histochemical studies of the Geneva group (Charnay et al.); (ii) a large spectrum of DSIP biological activity revealed by biochemical and physiological studies in vitro; (iii) significant slow-wave sleep (SWS) promoting activity of certain artificial DSIP structural analogues (but not DSIP itself!) in rabbits and rats revealed by our early studies; and (iv) significant SWS-promoting activity of a naturally occurring dermorphin-decapeptide that is structurally similar to DSIP (in five of the nine positions) and the sleep-suppressing effect of its optical isomer, as revealed in rabbits. Potential future studies are outlined, including natural synthesis and release of this DSIP-like peptide and its role in neuroendocrine regulation.

Limitations: No placebo control reported. Review article — no new primary data.

Delta sleep-inducing peptide. (European journal of anaesthesiology, 2001)

Limitations: No placebo control reported. Review article — no new primary data.

CSF DSIP-LI was significantly correlated with polysomnography the night before the LP: with stage 3 sleep (p = 0.05), stage 3 and delta (stages 3 + 4) sleep during the first nonrapid eye movement NREM period (p = 0.02 and p = 0.05, respectively) and the ratio of the first and second NREM period (p < 0.05), and negatively with stage 2% sleep (p < 0.05). Whether this first report of a potential relationship between CSF DSIP-LI and slow-wave sleep in man might be generalized to sleep in nonpsychiatric subjects awaits further study.

Limitations: No placebo control reported.

These results suggest that DSIP produces an antinociceptive effect by acting at the supraspinal level and that this effect is mediated via the opioid receptor, either directly or indirectly. DSIP may play an important role in pain regulation in the central nervous system.

Limitations: Animal study only — human translation uncertain.

In all three species, high-performance liquid chromatography revealed a single peak of DSIP-like material with approximately the same retention time as DSIP 3-9. Taken together, the present results provide evidence for the presence of DSIP-LI in gut endocrine cells in man, pig and rat; the human gut seems to be the richest source of DSIP-like peptides.

Limitations: No placebo control reported.

Significant decreases of DSIP-LI compared with age-matched controls (C1) were observed for S2, S3, MD, PD, VD and H. In contrast, no significant differences corresponding to pathology were found for P-DSIP-LI.

Limitations: Standard limitations apply. Check original paper for full discussion.

The clearance of DSIP from the ventricles during ventriculo-cisternal perfusion in the rabbit indicated no significant flux of the intact peptide out of the CSF. The results suggest that DSIP crosses the blood-CSF barrier, while the system lacks the specific mechanisms for removal from the CSF found with most, if not all, amino acids and several peptides.

Limitations: Animal study only — human translation uncertain.

A sleep-related increase in LH release is seen during puberty in man. It is possible that DSIP released within the hypothalamus may play a physiological role in sleep-related LH release.

Limitations: Animal study only — human translation uncertain.

Immunohistochemical as well as radioimmunochemical studies provided further insights into the natural occurrence of the nonpeptide and the distribution of DSIP-like material in the body, suggesting possible relations of the peptide to certain diseases. Various physiological functions of DSIP and a possible mechanism of action involving the modulation of adrenergic transmission remain to be established.

Limitations: No placebo control reported. Review article — no new primary data.

The increase in S2 was caused by a prolongation of S2 episodes and not by their more frequent occurrence. The results obtained suggest a sleep-facilitating property of DSIP.

Limitations: Animal study only — human translation uncertain.

However, DSIP (10(-8) or 10(-6)M) had no effect on either basal or luteinizing hormone-releasing hormone-induced in vitro LH release from the hemipituitaries of ovarian steroid-primed rats. These findings are in accord with the hypothesis that DSIP or DSIP-like peptide(s) may activate the hypothalamic neural circuitry responsible for stimulation of LH release reported to occur during sleep.

Limitations: Animal study only — human translation uncertain.

It was concluded that the rapid disappearance of injected DSIP in blood was due to degradation, whereas complex formation together with slower degradation resulted in longer persistence of apparently intact analogs. Whether this could explain the sometimes stronger and more consistent effects of DSIP-analogs remains to be examined.

Limitations: No placebo control reported.

There was no change in the amount of REM sleep. These findings support the belief that DSIP can increase sleep wave activity when administered by peripheral route.

Limitations: Animal study only — human translation uncertain.

DSIP-like material was found by RIA and immunohistochemistry in brain and by RIA in peripheral organs of the rat as well as in plasma of several mammals. In addition to sleep, the peptide also has been observed to affect electrophysiological activity, neurotransmitter levels in the brain, circadian and locomotor patterns, hormonal levels, psychological performance, and the activity of neuropharmacological drugs including their withdrawal.

Limitations: No placebo control reported. Review article — no new primary data.

Digestion with trypsin, however, produced small immunoreactive peptides with only a minimal reduction in total immunoreactivity. Thus, DSIP-like material is widespread in peripheral tissues and appears to exist mainly in a large form, probably bound to protein, that can be reduced in size by tryptic digestion and can be dissociated at lower concentrations of tissue to yield small immunoreactive peptides.

Limitations: Animal study only — human translation uncertain.

The results cannot be explained by either regurgitation of intestinal contents, or by stimulation of endogenous peptide. They show that a DSIP peptide administered orally can be absorbed through the GI tract into the systemic circulation.

Limitations: Animal study only — human translation uncertain.

Results of 6-day consecutive intravenous administration (50 microgram/kg) indicate that there is no obvious sign of adaptation to DSIP. Results suggest that the physiological function of endogenous sleep-inducing peptide is different from that of general sleeping draught.

Limitations: Animal study only — human translation uncertain.

Sleep-promoting effects occurred only in the second hour after injection, in the first hour a slight arousing effect was indicated. The study corroborates the findings of previous investigations in healthy subjects and shows that DSIP has a normalizing influence on human sleep regulation.

Limitations: No placebo control reported.