DSIP is a nonapeptide (9 amino acids) discovered by Monnier et al. in 1977. It modulates delta EEG activity — the slow brainwaves hallmarking deep N3 sleep. It acts on multiple receptor types and is believed to regulate CRH and ACTH release, helping quiet the HPA axis at night. It also exhibits antioxidant and neuroprotective properties, and may influence melatonin circadian rhythm.
💤 Deep / SWS⚡ Cortisol / HPA Axis🕐 Circadian Rhythm
Isolated from rabbit cerebral venous blood (1977)
Small clinical trials; no Phase III data available
Key Research Highlights
›Reduced sleep-onset latency by ~22 minutes in chronic insomnia patients (controlled studies)
›Normalized disrupted sleep patterns in open-label clinical trial of 7 severe insomnia patients
›Endogenous DSIP peaks in the body coincide with onset of slow-wave sleep
›May lower nighttime cortisol, helping suppress the HPA stress axis during sleep
›Shows promising results in fibromyalgia and neuropathic-pain-related insomnia
›Appears to have low toxicity and no reported dependence or withdrawal
Known Side Effects
Possible mild fatigueRare headachePoorly characterized safety profile in humans
Often Researched With
+ Epithalon+ Selank
Research context only. This compound is NOT FDA-approved for sleep or insomnia treatment. It should not be used outside of licensed clinical research settings.
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Epithalon
Epitalon — Tetrapeptide Ala-Glu-Asp-Gly
Research Only
Pineal Gland / Circadian Peptide
Epithalon (Ala-Glu-Asp-Gly) mimics the bioactive tetrapeptide derived from bovine pineal gland extract (epithalamin). It stimulates synthesis and secretion of melatonin by the pineal gland, and regulates BMAL1/CLOCK gene expression — the master circadian clock genes. In aging individuals with declining pineal function, Epithalon may ‘reset’ circadian rhythm disruption and restore normal night-time melatonin peaks. Also shows telomere elongation activity (telomerase activation).
🕐 Circadian Rhythm🌙 REM Sleep💤 Deep / SWS
Synthetic analog of pineal gland extract (epithalamin)
Multiple Russian clinical trials; limited Western replication
Key Research Highlights
›Stimulates melatonin synthesis, particularly in aging individuals with low pineal output
›In elderly patients, restored normal circadian melatonin secretion patterns
›May maintain REM sleep architecture through circadian normalization
›Long-term study (Khavinson et al.) showed improved longevity metrics in treated patients
›Reported ‘circadian reset’ effects lasting several months per treatment cycle
Known Side Effects
Generally well tolerated in reported studiesLong-term human safety data limited
Often Researched With
+ DSIP+ CJC-1295/Ipamorelin
Research context only. This compound is NOT FDA-approved for sleep or insomnia treatment. It should not be used outside of licensed clinical research settings.
☮️
Selank
Tuftsin analog (TP-7) — anxiolytic neuropeptide
Clinical Trials
Anxiolytic Neuropeptide
Selank is a synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) derived from the immunopeptide Tuftsin. It exerts anxiolytic effects via modulation of GABA-A receptors, and upregulation of BDNF (brain-derived neurotrophic factor). Unlike benzodiazepines, it doesn’t cause sedation or impair cognition. By reducing baseline anxiety and hyperarousal, it allows the nervous system to enter the parasympathetic state required for sleep onset. It also modulates serotonin and dopamine systems without causing tolerance or dependence.
☮️ Anxiolytic⚡ Cortisol / HPA Axis💤 Deep / SWS
Synthetic analog of the immunopeptide Tuftsin
Phase III approved in Russia; Phase II data available
Key Research Highlights
›Approved in Russia for anxiety and neurasthenia; used clinically in post-Soviet medical systems
›Reduced anxiety scores by ~40% in clinical trials vs. benzodiazepines without cognitive blunting
›Modulates GABA-A receptors for anxiolytic effects without sedation or tolerance
›Upregulates BDNF — promotes neuroplasticity and healthy brain-sleep interaction
›Corrects sleep architecture in anxiety-driven insomnia by reducing hyperarousal
›Shows anti-inflammatory cytokine activity (reduces IL-6 and TNF-α) which can disrupt sleep
Known Side Effects
Mild post-injection fatigueRare nasal irritation (if intranasal route)Mild drowsiness in some users
Often Researched With
+ DSIP+ BPC-157
Research context only. This compound is NOT FDA-approved for sleep or insomnia treatment. It should not be used outside of licensed clinical research settings.
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CJC-1295 + Ipamorelin
GHRH + GHRP Sleep Stack
Research Only
GH Secretagogue Stack
CJC-1295 is a GHRH (Growth Hormone Releasing Hormone) analogue. Ipamorelin is a ghrelin-mimicking GHRP (Growth Hormone Releasing Peptide). Together, they produce a synergistic GH pulse that amplifies the natural night-time GH surge occurring during N3 deep sleep. The brain’s ‘GH clock’ releases ~70% of daily GH during the first slow-wave sleep cycle. Enhancing this pulse can deepen N3 sleep duration and quality. Unlike earlier GHRPs, ipamorelin does not elevate cortisol or prolactin — making it uniquely suitable for sleep applications.
💤 Deep / SWS📈 GH Pulse
Preclinical + observational clinical data; no RCTs for sleep indication
Key Research Highlights
›70% of daily GH is released during N3 slow-wave sleep — this stack amplifies that pulse
›Ipamorelin selectively stimulates GH without raising cortisol (which would impair sleep quality)
›Observational data: users commonly report faster onset of deep sleep and more vivid dreams
›GH promotes cellular repair during sleep — tissues repaired overnight include muscle, bone, and gut
›UC Berkeley 2025 research identified the precise neural circuit linking sleep-dependent GH release
›CJC-1295 half-life ~7 days (with DAC); allows stable GH elevation without daily injections
Known Side Effects
Water retentionTingling/numbness (carpal tunnel-like at high doses)Rare hypoglycemiaInjection site reactions
Often Researched With
+ Sermorelin+ BPC-157+ Epithalon
Research context only. This compound is NOT FDA-approved for sleep or insomnia treatment. It should not be used outside of licensed clinical research settings.
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Sermorelin
GHRH (1-29) — FDA-Approved GHRH Analogue
FDA Approved
GHRH Analogue (FDA Approved)
Sermorelin directly mimics GHRH at the anterior pituitary, triggering natural GH pulses. Because it stimulates the pituitary through the body’s own feedback loop (not bypassing it), it’s considered physiologically safer than exogenous GH. GHRH administration is one of the best-documented sleep promoters in human research: multiple controlled trials show it increases N3 slow-wave sleep, reduces sleep latency, and suppresses nocturnal cortisol release — the cortisol suppression being particularly important for uninterrupted sleep.
💤 Deep / SWS📈 GH Pulse
Synthetic replica of first 29 amino acids of natural GHRH
FDA-approved (pediatric GH deficiency); extensive adult off-label literature
Key Research Highlights
›Direct GHRH mechanism — most well-studied sleep-promoting peptide with human trial data
›Anti-aging benefit: restores the age-related decline in GH secretion that disrupts sleep architecture after 40
Known Side Effects
Injection site rednessFlushingHeadacheRare hypoglycemiaPotential water retention
Often Researched With
+ Ipamorelin+ DSIP
🛡️
BPC-157
Body Protection Compound 157
Research Only
Gut-Brain Peptide
BPC-157 modulates both the gut-brain axis (vagus nerve) and central dopamine/serotonin neurotransmitter systems. Chronically elevated cortisol and dysregulated neurotransmitters are among the most common drivers of insomnia and poor sleep quality. BPC-157 appears to attenuate HPA axis hyperactivation, normalize dopamine and serotonin signaling, and reduce neuroinflammation — collectively lowering the ‘arousal floor’ required for natural sleep onset. In animal studies, it reverses corticosterone-induced sleep disruption and drug-induced HPA dysfunction.
⚡ Cortisol / HPA Axis🧠 Neuropeptide☮️ Anxiolytic
Isolated from human gastric juice
Preclinical (animal studies); Phase II IND cleared by FDA
Key Research Highlights
›Normalizes HPA axis hyperactivation — the chronic stress pattern that suppresses sleep
›Modulates dopamine and serotonin systems without receptor binding (indirect mechanism)
›Reverses corticosterone-induced anxiety and associated sleep disruption in animal models
›Gut-brain axis activity: restores serotonin synthesis in enterochromaffin cells (~95% of body’s serotonin)
›Anti-inflammatory: reduces neuroinflammation (a growing recognized driver of poor sleep quality)
›Supports melatonin’s action indirectly by normalizing the serotonin → melatonin precursor pathway
Known Side Effects
Generally well tolerated in animal studiesNausea (oral route)Human safety data limited
Often Researched With
+ Selank+ CJC-1295/Ipamorelin
Research context only. This compound is NOT FDA-approved for sleep or insomnia treatment. It should not be used outside of licensed clinical research settings.
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GHRH (Native)
Growth Hormone Releasing Hormone
FDA Approved
Endogenous Hypothalamic Peptide
GHRH is the body’s endogenous signal for GH release and has a well-documented bidirectional relationship with sleep. It’s a designated ‘sleep regulatory substance’ (SRS) — endogenous GHRH levels peak at sleep onset and drive N3 deep sleep. GHRH neurons in the hypothalamus both promote sleep and are activated by sleep. Reduced GHRH signaling in aging (which begins around age 35) is a mechanistic driver of the progressive loss of slow-wave sleep seen across the human lifespan. Both Sermorelin and CJC-1295 work by activating GHRH receptors.
💤 Deep / SWS📈 GH Pulse🧠 Neuropeptide
Secreted by hypothalamic arcuate nucleus neurons
Extensive human RCT data for sleep promotion specifically
Key Research Highlights
›Classified as a ‘Sleep Regulatory Substance’ by sleep neuroscientists — one of the most evidence-based
›Controls studies: pulsatile GHRH increased SWS by significant margins in young adults
›Age-related GHRH decline is a primary mechanism behind age-related SWS loss
›2025 UC Berkeley study (Cell journal) identified the precise neural circuit: GHRH neurons → locus coeruleus feedback
›GHRH-GH axis forms a ‘sleep-growth’ axis: adequate sleep → more GH → better cellular repair → better next-day sleep
Known Side Effects
Research context only; studied via analogues (Sermorelin, CJC-1295)No standalone therapeutic form available outside trials
Often Researched With
+ Sermorelin+ CJC-1295+ Ipamorelin
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VIP
Vasoactive Intestinal Peptide
Research Only
Circadian / REM Regulating Neuropeptide
VIP is produced by a subset of neurons in the suprachiasmatic nucleus (SCN) — the brain’s master circadian clock. VIP neurons act as pacemakers that synchronize the circadian system across the body, and are specifically required for the normal light-dark entrainment of the sleep-wake cycle. VIP also promotes REM sleep: mouse models lacking VIP show severely reduced REM sleep, disrupted circadian amplitude, and fragmented sleep architecture. VIP is not a therapeutic candidate itself, but understanding its role illuminates why circadian-resetting peptides like Epithalon work.
›VIP neurons in SCN are essential for generating normal circadian amplitude — confirmed in 2020 Nature Communications
›VIP knockout mice show 40–60% reduction in REM sleep and severely disrupted circadian rhythms
›VIP signaling synchronizes peripheral clocks throughout the body via hormonal relay
›VIP neurons receive light input and translate it into circadian phase adjustments
›VIP stimulates melatonin production pathways — mechanistically linking light, VIP, and sleep onset
›VIP receptor agonists are being investigated as novel circadian sleep therapeutics
Known Side Effects
Not applicable — no therapeutic form; mechanistic research only
Often Researched With
+ Epithalon
Research context only. This compound is NOT FDA-approved for sleep or insomnia treatment. It should not be used outside of licensed clinical research settings.
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Orexin (Hypocretin)
Wake-Promoting Neuropeptide System
FDA Approved
Wakefulness Neuropeptide (Antagonist Target)
Orexin-A and Orexin-B are wake-promoting neuropeptides produced by ~70,000 neurons in the lateral hypothalamus. They stabilize wakefulness by activating arousal centers (locus coeruleus, raphe nucleus, tuberomammillary nucleus). Loss of orexin neurons causes narcolepsy (inability to maintain wakefulness). Crucially for insomnia, blocking orexin receptors is now the dominant pharmacological sleep strategy: Lemborexant (Dayvigo) and Suvorexant (Belsomra) are FDA-approved dual orexin receptor antagonists (DORAs), replacing older benzodiazepine approaches with better-tolerated, mechanism-targeted therapy.
💤 Deep / SWS🌙 REM Sleep🕐 Circadian Rhythm
Secreted by lateral hypothalamus neurons (~70,000 cells in humans)