OVERVIEW

Delta Sleep-Inducing Peptide (DSIP) is a naturally occurring neuropeptide, first discovered in 1977, that plays a role in sleep regulation, stress response, and metabolic function. Although initially studied for its sleep-promoting effects, research suggests that DSIP has a wide range of physiological and endocrine functions beyond sleep.

Studies indicate that DSIP may:

• Reduce oxidative stress and support mitochondrial function.
• Improve heart function by normalizing myocardial contractility.
• Regulate stress response and lower cortisol levels.
• Modulate pain perception and opioid receptor activity.
• Influence blood pressure and metabolic processes.
• Show potential in treating major depressive disorder (MDD).

While DSIP was originally thought to induce sleep, research has produced mixed results, with some studies confirming sleep benefits and others suggesting it plays a regulatory role rather than directly causing sedation.

RESEARCH

DSIP and Sleep Regulation

• DSIP was named for its ability to induce sleep in rabbits.
• Human studies have shown inconsistent results—some report improved sleep quality, while others found no direct sedative effect.
• DSIP may help regulate sleep cycles rather than act as a traditional sedative.
• EEG studies have shown both increased slow-wave sleep and no effect, indicating complex sleep interactions.
• DSIP is being researched for its potential in managing chronic insomnia.

DSIP and Pain Modulation

• Animal studies show that DSIP reduces pain sensitivity.
• Acts on central opioid receptors, providing analgesic effects without opioid dependence.
• Human trials suggest DSIP may help reduce chronic pain perception and ease opioid withdrawal symptoms.
• DSIP appears to influence serotonin and dopamine activity, which are critical for pain regulation.

DSIP and Stress Reduction

• DSIP has been shown to lower cortisol levels, helping to modulate the body’s stress response.
• Research suggests DSIP inhibits somatostatin, a peptide involved in stress and hormone regulation.
• Animal models of chronic stress indicate DSIP helps normalize metabolic disruptions.
• Potential applications in PTSD and anxiety disorders are under investigation.

DSIP and Metabolic Regulation

• DSIP may support mitochondrial function, protecting against oxidative stress and metabolic dysfunction.
• Research suggests DSIP helps prevent metabolic damage during stroke and heart attacks by maintaining cellular energy production.

DSIP and Depression Treatment

• Low DSIP levels have been observed in individuals with major depressive disorder (MDD).
• DSIP influences monoamine oxidase type A (MAO-A) and serotonin, both key targets for depression treatment.
• Early studies suggest DSIP may help stabilize mood and reduce suicidal tendencies.

DSIP and Withdrawal Management

• DSIP has been studied for its potential to ease withdrawal symptoms in alcohol and opioid detoxification.
• Study in 107 patients found:
  • 97% of alcohol-dependent patients showed significant improvement.
  • 87% of opioid-dependent patients experienced substantial symptom relief.
• More frequent dosing was required for opioid withdrawal, but overall results were promising.

DSIP and Cancer Prevention

• Animal studies suggest a 2.6-fold reduction in tumor development with DSIP treatment.
• DSIP-treated mice exhibited a 22.6% reduction in chromosomal abnormalities, suggesting potential anti-cancer properties.
• Further research is needed to determine whether DSIP directly prevents cancer or if its benefits are due to overall stress reduction and metabolic regulation.

STRUCTURE

• Molecular Formula: C₃₅H₄₈N₁₀O₁₅
• Molecular Weight: 848.824 g/mol
• Amino Acid Sequence: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu
• CAS Registry Number: 62568-57-4
• PubChem Identifier: 68816
• Synonyms: Emideltide, DSIP nonapeptide, Deltaran

CITATIONS

1. Graf M., Christen H., Schoenenberger G. DSIP/DSIP-P and circadian motor activity of rats under continuous light. Peptides (1982).
2. Yehuda S., Kastin A. J., Coy D. H. Thermoregulatory and locomotor effects of DSIP: Paradoxical interaction with d-amphetamine. Pharmacology Biochemistry and Behavior (1980).
3. Sinyukhin A. B. et al. Delta sleep-inducing peptide analogue corrects CNS functional state in children treated with chemotherapy. Eur. Neuropsychopharmacol. (2009).
4. Koplik E. V. et al. Delta sleep-inducing peptide and Deltaran: Potential approaches to antistress protection.Neurosci. Behav. Physiol. (2008).
5. Feller L., Khammissa R. A. G., Lemmer J. Basal cell carcinoma, squamous cell carcinoma, and melanoma of the head and face. Head & Face Medicine (2016).
6. McMillan T. R. et al. Melanotan II, a melanocortin agonist, partially rescues the impaired thermogenic capacity of pituitary adenylate cyclase-activating polypeptide deficient mice. Exp. Physiol. (2021).
7. Jetté L. et al. Effect of DSIP-containing preparation Deltaran on biomarkers of aging, lifespan, and spontaneous tumor incidence in mice. PubMed (2005).
8. Wessells H., Levine L. A. Evaluation of the efficacy of DSIP in psychogenic erectile dysfunction. J. Sex Med. (2012).
9. Fowkes M. M. et al. Peptidomimetic DSIP derivatives for PET imaging. Eur. J. Med. Chem. (2018).