DSIP Nasal Spray

DSIP, delta-sleep-inducing peptide, is an endogenous nonapeptide with the sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. The Basel group around Schoenenberger and Monnier isolated it in 1977 from the cerebral venous blood of sleeping rabbits and named it after what it did in animals: more delta waves in the EEG, meaning more deep sleep. Since then DSIP has been one of the longest-studied and at the same time least understood sleep peptides.

This variant is the finished nasal spray: 10mg of DSIP dissolved in 5ml of saline (NaCl) plus 0.4ml of bacteriostatic water, 5.4ml in total, which gives 1.85mg per ml. The pump delivers 0.1ml per spray, so about 185mcg of DSIP (0.185mg). On paper the bottle holds 54 sprays, after priming the pump roughly 50 remain. No mixing, no syringe, no maths: the spray is made fresh after you order and ships as an express item. If you prefer the vial and syringe, the DSIP vial entry has the calculator.

The spray is not a scene shortcut either, it has a footing in the literature: two small human studies gave DSIP intranasally, one with a measurable EEG effect, one at 0.3mg per day for two months. Thin data, but nasal data. Few of the peptides offered as sprays can say that.

This information is for research and educational purposes only. No medical advice.

This is where DSIP gets unusual: to this day no receptor and no gene are known for it. Kovalzon and Strekalova summed this up soberly in the Journal of Neurochemistry in 2006 and suspect that a DSIP-like peptide nobody has cleanly isolated sits behind the observed effects. What does exist are observations: in animals DSIP promotes deep sleep, but species-dependently and with a parabolic dose-response curve that has an optimum beyond which more substance delivers less. The discovering group around Schoenenberger described that themselves (European Neurology 1984).

The second solid trail is the stress axis. In eleven healthy men an intravenous dose (25 nmol per kg) lowered blood ACTH for at least three hours while cortisol stayed unchanged (Psychoneuroendocrinology 1989). In animal models DSIP blunts CRF-induced corticosterone release. A Lübeck group, however, found no effect of 3 to 4mg DSIP infusions on CRH- or meal-induced ACTH and cortisol release in 1995 (Psychoneuroendocrinology 1995), so even this trail is not free of contradiction. Add to that Met-enkephalin release from nerve endings in rat brain (Journal of Neurochemistry 1991), interactions with stress and with drugs such as morphine, amphetamine and barbiturates as well as effects on the day-night rhythm of locomotion, brain messengers and cortisol. DSIP therefore behaves more like a signal that resets programmes than like a sleeping pill that sedates.

That the body makes it says nothing about the direction: in twelve healthy volunteers circulating DSIP peaked in the afternoon and bottomed out at one in the morning, it was lower during REM and deep sleep than while awake and tracked the curve of body temperature (Journal of Clinical Endocrinology and Metabolism 1994). A simple sleep hormone it is not. Pharmacokinetically DSIP is a sprinter: aminopeptidases in blood, cerebrospinal fluid and epithelial cells clip the tryptophan off the start of the chain. In dogs the half-life after i.v. dosing was about 4 minutes (Kato and colleagues, Neuroendocrinology 1984). Yet the human studies describe sleep induction with a latency of about an hour and a duration of up to 20 hours. What acts is the impulse, not the level.

The nasal mucosa is thin, richly perfused and in principle passable for a small, water-soluble peptide of 849 daltons. Part of the dose crosses into the blood there, part is broken down by mucosal peptidases, part runs down the throat with the secretions and is digested. For DSIP the direct route into the brain along the olfactory and trigeminal nerves, which is discussed for other peptides, has not been measured in humans. What is shown is that DSIP given into the blood crosses the blood-brain barrier: Banks, Kastin and Coy demonstrated rising cerebrospinal fluid levels in dogs in 1982.

That nasal DSIP nevertheless moves something in the human brain is shown by two small studies. Hruz and colleagues from the Basel group reported in a 2001 letter to the Journal of Clinical Psychopharmacology that intranasal DSIP increased the P300 wave, an EEG measure of attention and stimulus processing; dose and design are only in the full text of the letter, there is no abstract. A group from Odessa gave diabetics with retinal damage 0.3mg of DSIP per day intranasally for two months, after which visual evoked potentials recovered faster from photostress (Eksperimental'naia i Klinicheskaia Farmakologiia 2014). Both are pilot findings without replication, but they frame the range: tenths of a milligram nasally are enough for a measurable effect, milligrams are not needed.

In practice: before first use, pump 2 to 3 times into the air until a fine mist appears. Gently clear your nose first, keep your head upright, point the nozzle slightly outward towards the nasal wall rather than at the septum, breathe in calmly and do not sniff hard. Avoid blowing your nose for 10 to 15 minutes afterwards. Each spray delivers 0.1ml; two sprays in quick succession into the same nostril tend to run down the back rather than work twice as hard. With two sprays, use one per nostril.

The human data on DSIP come mostly from Basel and are old. Schneider-Helmert and Schoenenberger (Neuropsychobiology 1983) summarised five double-blind studies with single and repeated intravenous dosing: DSIP was well tolerated, slow injection proved essential, sleep set in with a latency of about an hour and the effect lasted up to 20 hours. In insomnia patients disturbed sleep normalised after four consecutive injections. During the day participants reported more alertness and better performance rather than tiredness. The authors saw a peptide that resets day-night programming, not a sedative.

The damper came from the Netherlands. Bes and colleagues (Neuropsychobiology 1992) gave 16 chronic insomnia patients 25 nmol per kg of DSIP or placebo intravenously on three afternoons under double-blind conditions and measured in the sleep lab. Sleep efficiency was higher and sleep latency shorter, but the effects were weak, partly explainable by an incidental shift in the placebo group. Subjective sleep quality did not change. The authors' conclusion: a major benefit of short-term treatment is unlikely. Kovalzon and Strekalova (Journal of Neurochemistry 2006) went further and called DSIP's role as a sleep factor poorly documented; in their own experiments artificial analogues promoted deep sleep, DSIP itself did not.

On nasal use there are the two pilot studies from the section above: the P300 increase after intranasal DSIP (Basel 2001) and the 0.3mg per day for two months in diabetics (2014). Beyond that DSIP was tried in an open study of opioid withdrawal (Journal of Clinical Psychopharmacology 1998) and tested as an adjunct to anaesthesia, where it paradoxically lightened anaesthetic depth and raised heart rate (European Journal of Anaesthesiology 2009). Bottom line: in humans DSIP measurably does something to the EEG, to stress hormones and to sleep structure, but the direction is not always the expected one and the effects are moderate. None of the studies has been repeated at scale. Anyone using the spray is testing a hypothesis, not following a proven protocol.

• Tolerability: in the intravenous human studies DSIP was consistently described as well tolerated, even at doses far above what reaches the blood nasally. None of the studies we reviewed describes serious adverse effects.
• Circulation: in the 2009 anaesthesia study intravenous DSIP raised heart rate and lowered heart rate variability, probably by dampening parasympathetic tone. Unlikely nasally, but palpitations or restlessness in the evening are a signal to stay at one spray or pause.
• Alertness instead of sleep: DSIP does not sedate; in the Basel series it made people more alert during the day. Under anaesthesia it reduced anaesthetic depth. Some users therefore report rumination or falling asleep late instead of deeper sleep. The answer is an earlier evening slot or stopping, not a higher dose.
• Next day: grogginess, prolonged drowsiness or a dull head in the morning are possible, because the described duration of action reaches up to 20 hours. Occasionally headache or dizziness.
• Nose: burning, sneezing, a runny nose or a dry feeling in the lining. Pause if irritation persists or the nose bleeds. Saline itself is mild, the nozzle and the peptide can still irritate.
• Hormone axis: in two studies DSIP lowered ACTH secretion in humans for several hours while cortisol stayed stable, a third study found no effect; growth hormone, prolactin and vasopressin did not change in further work. Anyone with adrenal problems or on corticosteroids should clear this with a doctor first.
• Long-term data: the longest nasal use in the literature lasted two months. There are no data for continuous use, pregnancy, breastfeeding or children. The mechanism is unknown, which by itself is a reason for restraint.

The spray belongs in the fridge (2 to 8 degrees), not in the freezer and not in the door compartment where the temperature swings every time it opens. Protect it from light by leaving the bottle in its outer packaging or box. Store it upright so the dip tube stays in the solution. A few hours at room temperature, in the post or in a bag, do the solution no harm, but it should not sit warm for long.

Once opened, the solution keeps for several months in the fridge. DSIP is a small peptide without cysteine or methionine, the two building blocks that are most fragile in solution. Saline is a stable medium. The 0.4ml of bacteriostatic water also adds a little benzyl alcohol as a preservative. The tryptophan at the start of the chain is light-sensitive, hence the box. Beyond that the solution's weak spots are enzymes and germs, so cleanliness counts for more than cold alone. At 1 to 2 sprays an evening the bottle is empty after 3 to 7 weeks anyway.

Wipe the nozzle with a clean tissue after each use and put the cap back on so nothing dries in and no germs migrate into the bottle. A bottle is personal, do not share it. If the solution turns gel-like, lumpy or smells different, stop using it. Slight cloudiness on its own is not a reason.