Key papers ✓ 3✗ 3~ 1? 2

• ✗ Negative human RCTNeuropsychobiology · 1992

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

  Humans16 peopleRandomizedPlacebo-controlledDouble-blind5 consecutive nights (DSIP before nights 3 to 5)

  Double-blind matched-pairs parallel-groups study

  Double-blind parallel trial in 16 chronic insomniacs: DSIP gave slightly better sleep efficiency and latency, but effects were weak and subjective sleep quality did not change; judged not of major therapeutic benefit.

  Study details

  Studied

  Chronic insomniac patients sleeping in the laboratory

  Compared with

  Glucose solution (placebo)

  Main outcome

  Sleep structure, objective (polysomnography) and subjective sleep quality, tiredness

  Sample

  16 chronic insomniac patients

  Authors' conclusion

  Objective sleep efficiency was higher and latency shorter with DSIP, but effects were weak and partly due to a change in the placebo group; short-term DSIP treatment is not likely to be of major therapeutic benefit.

  Limitations

  Small sample; effects weak; short-term treatment.

  DOI 10.1159/000118919PubMed 1299794
• ✗ Negative human trialInt J Clin Pharmacol Res · 1987

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

  Humanssize not reportedPlacebo-controlledDouble-blindFour nights

  Double-blind crossover with polysomnography

  Double-blind crossover trial in insomniacs over 4 nights: changes vs placebo were explained by baseline differences; improvement judged of little clinical significance.

  Study details

  Studied

  Chronic insomniac patients

  Compared with

  Placebo

  Main outcome

  Polysomnographic sleep parameters

  Authors' conclusion

  Sleep improvement under DSIP 25 nmol/kg i.v. is of little clinical significance; NREM and stage 2 differences vs placebo already existed at baseline.

  Limitations

  Sample size not stated in abstract; short-term.

  PubMed 3583493
• ✗ Negative human RCTEur J Anaesthesiol · 2009

  Delta sleep-inducing peptide alters bispectral index, the electroencephalogram and heart rate variability when used as an adjunct to isoflurane anaesthesia.

  Humanssize not reportedRandomized

  Randomized controlled study with saline controls

  24 surgical patients randomized to DSIP or saline during isoflurane anaesthesia: DSIP raised heart rate, reduced heart-rate variability and paradoxically lightened anaesthetic depth.

  Key resultDSIP at 25 nmol/kg significantly increased heart rate, decreased HRV, reduced delta rhythm and increased BIS during isoflurane anaesthesia

  Study details

  Studied

  Female ASA I or II patients under propofol/isoflurane anaesthesia

  Compared with

  Saline

  Main outcome

  Bispectral index, EEG and heart rate variability

  Sample

  Twenty-four female patients (12 saline, 12 DSIP), written in words

  Authors' conclusion

  DSIP probably reduced parasympathetic tone and lightened the depth of anaesthesia, contrary to the hypothesis that it would increase anaesthetic depth.

  Limitations

  Small groups of 12 patients; anaesthesia setting, not sleep.

  DOI 10.1097/EJA.0b013e32831c8644PubMed 19142086
• ✓ Positive human trialEur Neurol · 1987

  Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia.

  Humans14 peoplePlacebo-controlledDouble-blind7 successive nights

  Placebo-controlled double-blind administration with polysomnography

  Placebo-controlled, double-blind 7-night study in 14 severe chronic insomniacs: improved night sleep and daytime alertness and performance.

  Study details

  Studied

  Middle-aged severe chronic insomniacs

  Compared with

  Placebo baseline and posttreatment nights

  Main outcome

  Night sleep and daytime alertness and performance

  Sample

  14 middle-aged chronic insomniacs

  Authors' conclusion

  DSIP substantially improved night sleep and daytime alertness and performance in chronic insomniacs, with efficiency reaching normal-control levels.

  Limitations

  Small sample of 14.

  DOI 10.1159/000116143PubMed 3622582
• ✓ Positive human trialExperientia · 1981

  The influence of synthetic DSIP (delta-sleep-inducing-peptide) on disturbed human sleep.

  Humans6 peopleNo control groupSingle administration; effects up to 6 h of night sleep

  Acute intravenous administration study

  6 chronic insomniacs given intravenous DSIP: longer and less interrupted sleep, with a slight arousing effect in the first hour.

  Study details

  Studied

  Middle-aged chronic insomniacs

  Main outcome

  Sleep duration and quality

  Sample

  6 middle-aged chronic insomniacs

  Authors' conclusion

  DSIP 25 nmoles/kg gave longer sleep duration and higher sleep quality with fewer interruptions, with a normalizing influence on human sleep regulation.

  Limitations

  Only 6 patients; no placebo comparison described.

  DOI 10.1007/BF01971753PubMed 7028502
• ? Inconclusive human trialEur Neurol · 1984

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

  Humans7 people5 consecutive days then 5 injections every 48-72 h

  Clinical pilot study comparing baseline with control period

  Uncontrolled pilot in 7 patients with chronic pain episodes (migraine, tinnitus, psychogenic pain): pain levels fell in 6 of 7 after DSIP courses.

  Key resultDSIP lowered pain levels significantly in 6 out of 7 patients

  Study details

  Studied

  Patients with migraine, vasomotor headaches, chronic tinnitus and psychogenic pain attacks

  Compared with

  Baseline (anamnestic) values

  Main outcome

  Pain levels and depressive states

  Sample

  7 patients

  Authors' conclusion

  Pilot study suggests DSIP lowered pain and concomitant depressive states significantly after intravenous administration.

  Limitations

  Pilot with 7 patients; no placebo control.

  DOI 10.1159/000115716PubMed 6548970
• ? Inconclusive reviewJ Neurochem · 2006

  Delta sleep-inducing peptide (DSIP): a still unresolved riddle.

  No new data

  Mini-review

  Review concluding the link between DSIP and sleep is poorly documented and weak, with no identified gene, precursor protein or receptor.

  Study details

  Authors' conclusion

  The hypothesis that DSIP is a sleep factor is poorly documented; the authors hypothesize a DSIP-like peptide responsible for DSIP-like immunoreactivity and activity.

  Limitations

  Narrative mini-review presenting a hypothesis; no original data reported.

  DOI 10.1111/j.1471-4159.2006.03693.xPubMed 16539679
• ~ Mixed animalMolecules · 2021

  Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke.

  Animalssize not reportedSham/vehicle control8 days of treatment, 21 days follow-up

  Vehicle-controlled animal study with sham group; behavioural tests days 1-21

  Rats with induced focal stroke (MCAO) given intranasal DSIP before and for 7 days after: infarct volume was smaller but not significantly so, while rotarod motor performance recovered significantly faster than with vehicle.

  Study details

  Studied

  Sprague-Dawley rats with middle cerebral artery occlusion (MCAO)

  Compared with

  Vehicle (and sham-operated rats)

  Main outcome

  Infarct volume and motor tests (rotarod, bilateral asymmetry)

  Authors' conclusion

  Intranasal DSIP over 8 days accelerated recovery of motor function, although the reduction in infarct size was not significant.

  Limitations

  Rat stroke model; infarct-size difference not significant; no human data.

  DOI 10.3390/molecules26175173PubMed 34500605Free full text
  Figure 1
• ✓ Positive animalLife Sci · 2018

  Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude.

  Animalssize not reported

  Controlled animal study with telemetric sleep recording

  Rats exposed to simulated high altitude (hypobaric hypoxia): daily phosphorylated DSIP increased non-REM and REM sleep and improved water-maze memory; naloxone reduced the memory benefit.

  Study details

  Studied

  Rats trained in the Morris water maze and exposed to chronic hypobaric hypoxia (7620 m)

  Compared with

  Untreated hypoxia-exposed rats (naloxone arm also tested)

  Main outcome

  Sleep architecture, water-maze memory, hippocampal CREB/p-CREB

  Authors' conclusion

  The authors conclude that improving sleep quality with p-DSIP restored spatial memory via CREB phosphorylation during simulated high-altitude hypoxia.

  Limitations

  Rat study of the phosphorylated analogue; no human data.

  DOI 10.1016/j.lfs.2018.08.026PubMed 30107169

Reported side effects

• reportedIncreased heart rate and reduced heart-rate variability (during anaesthesia) [ref]
• reportedTransient mild arousal in the first hour after injection [ref]

Human data are limited to small, mostly older trials; one insomnia study reported no daytime sedation or other side effects.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.