DSIP
DSIP has one of the more misleading names in the peptide catalog. Schoenenberger and Monnier isolated it from the cerebral venous blood of rabbits and published its characterization in PNAS in 1977: a nine amino acid sequence, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, about 849 Da. In that original work they infused synthetic DSIP and eight related peptides directly into the rabbit brain ventricles under double-blind conditions across 58 animals, and only the full nonapeptide produced significant enhancement of delta and spindle EEG patterns. The name records what happened in that specific experiment, which was intraventricular delivery into a rabbit brain, not what happens when a peptide is injected under human skin.
- class
- linear nonapeptide, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, molecular weight about 849 Da
- origin
- isolated from rabbit cerebral venous blood by Schoenenberger and Monnier, published in PNAS in 1977
- route
- subcutaneous in self-directed use; every published human trial used intravenous administration
- typical dose
- 100–300 mcg subcutaneously before bed in self-directed protocols; human trials used 25–30 nmol/kg IV, which is roughly 1.7–2.0 mg for an 80 kg adult
- half-life
- 4.0 ± 0.7 minutes in dogs, 2.9 minutes in monkey, 2.0 ± 0.5 minutes in rats (Kato 1984); no human PK study exists
- storage
- lyophilized refrigerated 2–8°C, protected from light; reconstituted with BAC water, 2–8°C, 28-day max
- regulatory
- research chemical, not approved for human use in any country, no identified gene, protein precursor, or receptor
DSIP Reconstitution & Dosage Protocol
weekly dose · reduces side effects| Phase | Window | Weekly dose | Draw (U-100, 5mL BAC) | Note |
|---|---|---|---|---|
| Reconstitution + baseline | Day 0 | 0.00 mg | 0 units· 0.00 mL | Reconstitute 5 mg in 5 mL bacteriostatic water for 1000 mcg/mL. At that concentration 100 mcg is 0.1 mL (10 units on a U-100 syringe) and 200 mcg is 0.2 mL (20 units). If the vial is too small to hold 5 mL, use 2.5 mL for 2000 mcg/mL, which puts 200 mcg at 10 units and costs you some measurement precision at the low end. Add the water slowly down the inside wall and swirl; do not shake. Before the first dose, log two weeks of baseline sleep data (bedtime, sleep latency, wake count, morning alertness) from a tracker or a paper log, because sleep perception is unusually susceptible to expectancy and you cannot judge this compound without a comparison |
| Opening block | Days 1–14 | 0.10 mg | 10 units· 0.10 mL | 100 mcg subcutaneously, 30 to 60 minutes before bed (10 units at 1000 mcg/mL). The pre-bed timing is a convention borrowed from the compound name rather than from pharmacology: measured plasma half-life is 2 to 4 minutes across three species, so the peptide is cleared long before the sleep architecture it is supposed to alter. Keep every other sleep variable fixed during this block (bedtime, caffeine cutoff, alcohol, screen exposure) or the log will be uninterpretable |
| Standard block | Days 15–28 | 0.20 mg | 20 units· 0.20 mL | 200 mcg on the same pre-bed schedule (20 units at 1000 mcg/mL). This is the upper end of ordinary self-directed dosing. Worth keeping in perspective: the 25 nmol/kg intravenous dose used by Bes and colleagues in 1992 works out to about 1.7 mg for an 80 kg adult, roughly 8 times this dose and delivered by a route with complete bioavailability, and that trial still concluded the effect was weak. Escalating past 300 mcg does not close that gap and has no supporting data |
| Washout | Days 29–56 | 0.00 mg | 0 units· 0.00 mL | Four weeks off. No tolerance or receptor downregulation data exists for DSIP, for the straightforward reason that no DSIP receptor has ever been identified, so this interval reflects general convention rather than a measured rebound. The washout is the actually informative part of the protocol: compare washout sleep logs against both the on-cycle block and the Day 0 baseline |
| Reassess | After week 8 | 0.00 mg | 0 units· 0.00 mL | Judge from the logged data, not from recall. If washout sleep matches on-cycle sleep, the honest conclusion is that nothing happened. Kovalzon and Strekalova reviewed the field in the Journal of Neurochemistry in 2006 and concluded the hypothesis linking DSIP to sleep is poorly documented and weak, and nothing published since has changed that. Anyone taking prescribed sedatives, benzodiazepines, or opioids should not add DSIP without physician oversight, since the interaction literature is nonexistent |
What is DSIP?
DSIP has one of the more misleading names in the peptide catalog. Schoenenberger and Monnier isolated it from the cerebral venous blood of rabbits and published its characterization in PNAS in 1977: a nine amino acid sequence, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, about 849 Da. In that original work they infused synthetic DSIP and eight related peptides directly into the rabbit brain ventricles under double-blind conditions across 58 animals, and only the full nonapeptide produced significant enhancement of delta and spindle EEG patterns. The name records what happened in that specific experiment, which was intraventricular delivery into a rabbit brain, not what happens when a peptide is injected under human skin.
Almost fifty years later the basic biology is still missing. Kovalzon and Strekalova laid this out plainly in a 2006 minireview in the Journal of Neurochemistry titled, accurately, a still unresolved riddle: no DSIP gene has been isolated, no protein precursor identified, and no receptor found. Their proposal was that the DSIP-like immunoreactivity measured in tissue may come from some other, still unidentified peptide, partly because that immunoreactivity concentrates in hypothalamic neurosecretory nuclei that have little to do with sleep regulation. They also noted something awkward for the sleep hypothesis: certain synthetic DSIP analogues promote slow-wave sleep in rabbits and rats, while DSIP itself does not.
The pharmacokinetics are the single most important practical fact and the one least often mentioned by vendors. Kato and colleagues developed an enzyme immunoassay for DSIP and used it to measure clearance directly (Neuroendocrinology, 1984). After intravenous injection they found a mean half-life of 4.0 ± 0.7 minutes in dogs, 2.9 minutes in a monkey, and 2.0 ± 0.5 minutes in rats, with a metabolic clearance rate around 30.7 mL/kg/min. Graf and colleagues showed why in Peptides in 1987: incubated in human or rat blood, DSIP degrades rapidly, releasing tryptophan-equivalent fragments. A peptide that is gone in single-digit minutes is a difficult fit for a compound taken to change the structure of an entire night of sleep.
The human trial record is small, old, and inconsistent, and it is worth reading in the right order. Schneider-Helmert ran the positive studies: 6 × 30 nmol/kg IV in chronic insomniacs normalized sleep in both middle-aged and elderly groups (Eur Neurol, 1986), and a placebo-controlled crossover in 14 severe chronic insomniacs reported improved night sleep plus better daytime alertness and performance (Eur Neurol, 1987). Then Bes and colleagues ran a double-blind matched-pairs study in 16 chronic insomniacs with 25 nmol/kg IV on three nights (Neuropsychobiology, 1992). Sleep efficiency and latency did improve against placebo, but the authors judged the effects weak, noted that part of the difference may have come from an incidental change in the placebo group, and concluded that short-term DSIP treatment is not likely to be of major therapeutic benefit. Note the doses: 25 to 30 nmol/kg is roughly 1.7 to 2.0 mg for an 80 kg adult given intravenously, which is close to an order of magnitude above what people inject subcutaneously today.
The non-sleep findings are, oddly, better supported than the sleep ones. Bjartell and colleagues gave 11 healthy men 25 nmol/kg IV in a randomized double-blind crossover and measured a significant reduction in plasma ACTH-like immunoreactivity lasting at least three hours, with cortisol itself unchanged (Psychoneuroendocrinology, 1989). Iyer and colleagues reported that DSIP stimulates growth hormone release in the rat through both hypothalamic and pituitary actions (Peptides, 1987). Backmund and colleagues published an open trial of DSIP in opioid detoxification (J Clin Psychopharmacol, 1998), following an earlier report in the American Journal of Psychiatry in 1997. Meanwhile Seifritz and colleagues found that plasma DSIP-like immunoreactivity actually falls at the transition from wakefulness to sleep in healthy men (Peptides, 1995), which is the opposite of what an endogenous sleep-promoting factor should do. Taken together: DSIP appears to do something to the neuroendocrine axis, and the case that what it does is generate sleep remains unproven.