DSIP molecular structure
DSIP molecular structure
Experimental
🛌Sleep & Recovery

DSIP

Also known as: Delta Sleep-Inducing Peptide, Factor Delta, DSIP Peptide

MW

848.82 Da

Formula

C35H48N10O15

CAS

62568-57-4

Routes

3 routes

Delta Sleep-Inducing Peptide (DSIP) is a naturally occurring nonapeptide first isolated from the cerebral venous blood of rabbits during electrically induced sleep in 1977 by the Swiss Schoenenberger-Monnier group. Named for its ability to induce delta (slow-wave) sleep in rabbits, DSIP has since been found to have far broader physiological effects extending beyond sleep modulation to include stress response regulation, pain modulation, endocrine function, and antioxidant activity. DSIP is present in human blood plasma, cerebrospinal fluid, and breast milk, with concentrations showing circadian variation — peaking during nighttime hours. Despite extensive research over four decades, its precise receptor and primary signaling mechanism remain incompletely characterized, making DSIP one of the more enigmatic bioactive peptides in neuroscience. Beyond sleep promotion, DSIP research has revealed stress-protective (adaptogenic) properties, normalization of disturbed circadian rhythms, reduction of drug and alcohol withdrawal symptoms, and modulation of pituitary hormone secretion. It is used clinically in some countries for insomnia and sleep disorders.

Research Use OnlyFor educational and research purposes only

Research Applications

Insomnia and Sleep Disorders

DSIP's primary research application is for sleep disorders, particularly those involving reduced slow-wave sleep. Clinical studies demonstrate improvements in sleep onset latency, total sleep time, sleep efficiency, and subjective sleep quality. It is particularly effective for normalizing disrupted sleep architecture.

Chronic Stress and Burnout

DSIP's adaptogenic properties make it researched for chronic stress conditions. Studies show normalization of cortisol rhythms, improved stress resilience, and reduced anxiety scores in chronically stressed subjects.

Withdrawal Syndromes

Clinical studies demonstrate DSIP reduces withdrawal symptoms from opioids and alcohol, including anxiety, insomnia, autonomic dysfunction, and craving. The mechanism involves normalization of endogenous opioid and GABAergic systems disrupted by substance dependence.

Chronic Pain

DSIP's opioid-modulating and direct analgesic properties have been studied for chronic pain conditions, including headache/migraine, fibromyalgia, and neuropathic pain.

Circadian Rhythm Disorders

DSIP research addresses jet lag, shift work disorder, and age-related circadian disruption. Its chronobiotic properties help re-synchronize disrupted sleep-wake rhythms.

Neurodegeneration Research

DSIP's antioxidant and neuroprotective properties are researched in the context of neurodegenerative diseases, where oxidative stress and sleep disruption are prominent features.

Mechanism of Action

Delta Wave Sleep Promotion

DSIP promotes slow-wave (delta) sleep by modulating neuronal activity in sleep-regulating brain regions. It enhances GABAergic signaling in the ventrolateral preoptic area (VLPO) — the primary sleep-active nucleus — while suppressing wake-promoting orexin/hypocretin neurons in the lateral hypothalamus. The net effect is a shift in sleep architecture toward increased stage 3/4 deep sleep.

Stress Response Modulation (Adaptogenic)

DSIP acts as a stress-protective (adaptogenic) peptide. It normalizes the HPA axis response to stress — reducing excessive cortisol and ACTH release during chronic stress while preserving appropriate acute stress responses. This bidirectional modulation is characteristic of adaptogens rather than simple stress suppressors.

Endocrine Normalization

DSIP modulates pituitary hormone secretion in a normalizing manner. It stimulates LH and GH release, suppresses excess somatostatin, and normalizes cortisol rhythms. These effects are context-dependent — DSIP tends to correct deviations from homeostasis rather than forcing hormonal changes in a single direction.

Opioid System Interaction

DSIP modulates endogenous opioid signaling — enhancing met-enkephalin levels in brain tissue and modulating opioid receptor sensitivity. This contributes to its analgesic properties and its ability to reduce withdrawal symptoms from opioids and alcohol.

Antioxidant Activity

DSIP exhibits direct and indirect antioxidant properties, scavenging reactive oxygen species and enhancing endogenous antioxidant enzyme expression (SOD, catalase). This may contribute to its neuroprotective and stress-protective effects.

Biological Pathways

GABAergic Sleep Circuitry

DSIP enhances GABA-A receptor-mediated inhibition in the VLPO and median preoptic nucleus, promoting sleep-active neuron firing. Simultaneously, it inhibits wake-promoting circuits in the tuberomammillary nucleus (histamine) and locus coeruleus (norepinephrine).

HPA Axis Modulation

DSIP acts at the hypothalamic level to normalize CRH release. In stressed conditions, it reduces excessive CRH/ACTH/cortisol output. In unstressed conditions, it preserves normal circadian cortisol patterns. This homeostatic regulation involves modulation of glucocorticoid receptor sensitivity.

Enkephalin/Opioid Pathway

DSIP increases met-enkephalin concentrations in the brain, enhancing δ-opioid receptor signaling. This pathway mediates analgesic effects and contributes to anxiolysis and stress resilience.

Circadian Clock Regulation

DSIP influences core clock gene expression and melatonin synthesis, helping to synchronize circadian rhythms. This chronobiotic action may underlie its ability to normalize disturbed sleep-wake patterns.

Dosage Information

Typical dosage ranges for research applications. Always verify with current literature.
Typical Dose
150 mcg
Dose Range
100 - 250 mcg
Frequency
Once nightly, 30-60 min before bed
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Calculation Results

Concentration
2.5 mg/ml
Dose Volume
0.1 ml0.100 ml
Insulin Syringe
10 units
Doses per Vial
2020 doses @ 250 mcg

Syringe Fill Level (100u syringe)

05010010.0uunits
0u10.0 / 100 units (10%)100u

Protocols

DSIP Sleep Enhancement Protocol
Beginner
🏃Sport & Performance
8-12 weeks

Delta sleep-inducing peptide for improved sleep quality, recovery, and stress reduction.

Dosage
100-300mcg subcutaneous
Frequency
Once nightly, 30-60 minutes before bed
Cycle
Weeks 1-4: 100-250mcg, Washout weeks 5-8, Resume weeks 9-12. Full benefits may require 8+ weeks.
Stacking Notes
Works best with good sleep hygiene. Can combine with magnesium glycinate (400mg). Effects improve over time.

Warning: May cause morning grogginess initially. Start with 100mcg.

Stability & Storage

DSIP is supplied as a lyophilized white powder. Store at -20°C for long-term stability (12-18 months) or 2-8°C for up to 3 months. DSIP is relatively fragile compared to many peptides due to its linear structure and susceptibility to aminopeptidase degradation.

Reconstitute with bacteriostatic water. Store reconstituted solution at 2-8°C and use within 14-21 days. DSIP has a short in-vivo half-life (approximately 7-8 minutes), which has been a challenge for clinical development. Various strategies to enhance stability have been explored, including phosphorylated derivatives and encapsulation.

The tryptophan residue at position 1 is susceptible to photooxidation — protect from light during storage and handling. Acidic pH (below 4) may cause aspartate isomerization, so maintain neutral pH in formulations.

Side Effects & Precautions

Generally Well-Tolerated

Clinical studies report a favorable safety profile with minimal adverse effects at therapeutic doses.

Drowsiness

Expected and generally desired, drowsiness can persist into the following morning if doses are taken too close to wake time. Recommended administration 30-60 minutes before desired sleep onset.

Mild Headache

Occasional headache during initial use, typically resolving with continued administration.

Injection Site Reactions

Mild redness or discomfort at subcutaneous injection sites.

Short Duration of Action

The short half-life (~7-8 minutes) limits the duration of effect. Sleep-maintaining effects may not persist through the full night, leading some to awaken earlier than desired.

Limited Long-Term Safety Data

Comprehensive long-term safety studies are not available. Most clinical data comes from short-term use (weeks to months).

Possible Tolerance

Some reports suggest diminishing effects with prolonged daily use, though this is not consistently documented in clinical literature.

Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.

Regulatory Status

Experimental

DSIP is not approved by the FDA or major Western regulatory agencies. It has been used clinically in some European countries (particularly Switzerland and Germany) and Russia for insomnia and sleep disorders, but does not have formal drug approval status in most jurisdictions.

The peptide is classified as an investigational research compound in the United States and most Western countries. It is available from research peptide suppliers for laboratory use.

DSIP is not on the WADA prohibited list and is not a controlled substance. Its short half-life and challenging pharmacokinetics have limited pharmaceutical development despite decades of research interest.

Research Studies

Delta Sleep-Inducing Peptide (DSIP): An Update

Kovalzon VM, Strekalova TV.

Neuroscience and Behavioral Physiology
2006
View Source

Isolation of DSIP from Rabbit Brain During Induced Sleep

Schoenenberger GA, Monnier M.

Proceedings of the National Academy of Sciences
1977
View Source

DSIP in Insomnia: A Clinical Study

Schneider-Helmert D, Schoenenberger GA.

European Neurology
1983
View Source

Stress-Protective Effects of DSIP

Khvatova EM, Samartzev VN, Zagoskin PP, et al.

Regulatory Peptides
2003
View Source
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