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Peptide Atlas
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Peptides studied for deeper sleep and the systems that govern it

Deep, restorative sleep depends on the brain's sleep architecture, the calming signals that quiet it at night, and the hormones that either disrupt or support that process. The six compounds here act on different parts of that system: some are studied directly for sleep depth, others for the melatonin, cortisol, growth-hormone or calming (GABA) signals that shape it. The evidence ranges from human clinical trials to community reports, and the strength varies sharply from one compound to the next.

The biology of this goal

Sleep is not one single state. It moves through stages, and the deepest of these — called slow-wave or delta sleep — is when the body does much of its physical repair. Waking up feeling restored depends on getting enough of this deep sleep and on the sleep being efficient, meaning you spend most of your time in bed actually asleep rather than lying awake. Several signals in the body push you toward deep sleep at night: melatonin, a hormone made by a small gland in the brain that tracks the day-night cycle; GABA, the brain's main calming chemical that quiets nerve activity; and growth hormone, which is released in a large burst during deep sleep. When these signals are weak or disrupted — as often happens with age or stress — sleep becomes lighter and less restful.

What the research supports

6 of 6 compounds considered

DSIP

Tier 2 · Preclinical

Human trials report that DSIP increases total sleep, improves sleep efficiency, and correlates with deep (stage 3/delta) sleep.

DSIP (delta sleep-inducing peptide) is a tiny nine-amino-acid peptide first found in the blood of sleeping rabbits and named for its ability to boost deep, slow-wave sleep. Unlike a sleeping pill, it appears to support natural sleep rather than force sedation. It is the one compound here studied directly in humans for sleep depth and efficiency.

  • In a double-blind cross-over study in six volunteers, slow intravenous DSIP (25 nmol/kg) increased sleep by 59% (median total sleep time) within a 130-minute window versus placebo, and subjects immediately reported a feeling of sleep pressure.1

  • DSIP produced delayed effects on the following night, including shorter sleep onset, reduced stage 1 sleep, and improved sleep efficiency, without classic pharmacologic sedation.1

  • Cerebrospinal-fluid DSIP-like immunoreactivity was significantly correlated with stage 3 sleep (p = 0.05) and with delta (stages 3+4) sleep in the first NREM period, and negatively correlated with stage 2% sleep.2

  • Intravenous DSIP at 25 µg/kg produced measurable increases in delta-wave sleep on EEG that persisted across multiple nights, beyond its plasma clearance.3

What this doesn't establish

The controlled human trial was small (six volunteers) and used intravenous dosing; effects are described as strongest in disrupted sleepers and modest in healthy ones, and no established human half-life or receptor is confirmed.

Epithalon

Tier 3 · Reported use

Human data report normalization of circadian clock-gene expression and restored melatonin output, with weaker (tier 2 and tier 3) support for melatonin and cortisol effects; there are no large randomized controlled trials.

Epithalon is a synthetic four-amino-acid peptide based on a natural pineal-gland extract. It is studied as a regulator of the body clock, reportedly helping restore normal nighttime melatonin production and circadian rhythm. It is relevant to sleep through timing and stress-hormone regulation rather than through sleep depth directly.

  • In middle-aged people with reduced melatonin-producing pineal function, AEDG peptide normalized hyper-expression of the circadian Clock and Csnk1e genes (1.9–2.1×) and increased hypo-expressed Cry2 (2×), and raised urinary 6-sulfatoxymelatonin excretion 1.7×.4

  • AEDG peptide is described as restoring pineal melatonin-producing function through regulation of human circadian gene expression.4

  • In elderly humans (n=14) Epithalon was reported to restore the nighttime melatonin peak and to normalize the circadian cortisol pattern, with the pineal gland as its primary target.5

  • Preclinical reports describe antioxidant activity in the brain and increased melatonin in elderly adults with pineal dysfunction and in aged animals, though effects varied by species.6

What this doesn't establish

The evidence does not establish that Epithalon improves subjective sleep depth or sleep architecture in humans; most work comes from a single laboratory group and small samples, and melatonin/cortisol findings sit at lower evidence tiers.

Cortexin

Tier 1 · Human trials

Animal and laboratory studies suggest Cortexin acts through glutamatergic and GABAergic receptor binding; the sleep-relevant claims are mechanistic, not sleep outcomes.

Cortexin is a mixture of small polypeptides extracted from the brain cortex of cattle and pigs, used clinically in Russia as an injectable neuroprotectant. Its link to sleep here is indirect: it is reported to act on GABA, the brain's calming chemical. There is no direct human sleep study for it.

  • In rat brain-ischemia models, Cortexin's in vivo effects were attributed to glutamatergic and GABAergic actions, with in vitro binding to GABA-A1 (44.0%) and multiple glutamate receptors.7

  • Manufacturer literature describes Cortexin's mechanism as optimizing the balance of excitatory and inhibitory amino acids plus a GABAergic effect.8

What this doesn't establish

No study here measures sleep depth, sleep architecture, or any sleep outcome for Cortexin; its GABAergic link is inferred from receptor binding and manufacturer commentary, and independent reviewers judge its human evidence weak.

MK-677

Tier 1 · Human trials

Human trials (via a review of GH secretagogues) report that these compounds improve sleep, while the specific magnitude claims for REM and deep sleep come from community and practitioner sources.

MK-677 (ibutamoren) is an orally active molecule that mimics the hunger hormone ghrelin, prompting the body to release more of its own growth hormone. Because the biggest natural growth-hormone burst happens during deep sleep, it has been studied and reported for effects on sleep architecture.

  • A review of growth hormone secretagogues in human subjects reported that GHSs improve sleep, alongside effects on lean mass and appetite, with some concern for reduced insulin sensitivity.10

  • Community and practitioner sources describe hypothalamic GHS-R1a activation modulating sleep architecture, with reports of increased REM and Stage 4 deep sleep by up to 50%, and note MK-677 completed Phase 2 trials that included sleep.9

  • GHS-R1a activation is described as modulating sleep architecture, insulin sensitivity, and cellular repair pathways.11

What this doesn't establish

The strong human claim is a general statement that GH secretagogues improve sleep, not a dedicated MK-677 sleep-architecture trial; the specific 50% deep-sleep figure rests on lower-tier community sources, and MK-677 can raise appetite and reduce insulin sensitivity.

Sermorelin

Tier 1 · Human trials

Community reports and practitioner commentary describe enhanced slow-wave sleep with sermorelin; there are no large randomized controlled trials supporting sleep benefit.

Sermorelin is a lab-made copy of the active part of the body's own growth hormone-releasing hormone. It signals the pituitary to release growth hormone in natural bursts. Because the body's largest growth-hormone pulse occurs during deep sleep, it is discussed for supporting slow-wave sleep.

  • Practitioner sources describe sermorelin enhancing deep (slow-wave) sleep architecture and increasing slow-wave sleep duration.13,14

  • Most protocols call for nightly dosing because the largest natural GH pulse occurs during slow-wave sleep, roughly one to two hours after falling asleep.12

  • The compounded sermorelin used for adult wellness is not FDA-approved, and the sleep and related goals it is discussed for are not supported by large randomized controlled trials.12

What this doesn't establish

The sleep claims are practitioner and vendor commentary, not clinical trial outcomes; compounded sermorelin is not FDA-approved for any indication and its wellness goals including sleep are explicitly noted as unsupported by large RCTs.

Selank

Tier 2 · Preclinical

Human trials report Selank reduced benzodiazepine side effects, and animal and laboratory studies suggest it modulates the GABAergic system.

Selank is a synthetic seven-amino-acid peptide with calming (anti-anxiety) effects. Its relevance to sleep is indirect: it fine-tunes the brain's main calming GABA system and, notably, was studied for its ability to reduce the unwanted sedation and sleep-related side effects of a benzodiazepine tranquilizer rather than to induce sleep itself.

  • In patients with anxiety disorders, adding Selank to phenazepam decreased that tranquilizer's undesirable side effects — including sedation, increased sleep duration, and attention/memory impairment — during treatment and after withdrawal.15

  • Laboratory work indicates Selank's mechanism may involve the GABAergic system, though it produced no direct change in GABAergic-system gene mRNA in neuroblastoma IMR-32 cells.16

  • Selank and GABA together affect the expression of genes involved in GABAergic neurotransmission.17,16

What this doesn't establish

None of the evidence here shows Selank deepens sleep or improves sleep architecture; the human data concern anxiety disorders and reducing another drug's side effects, and one such side effect it lessened was increased sleep duration.

How they work together

Check this stack

DSIP sits at the center of this set for sleep. It pairs with Epithalon on the same downstream goal — both converge on restoring melatonin secretion and circadian rhythm, by different upstream routes — and with Sermorelin and MK-677, which deepen sleep through the growth-hormone axis while DSIP works through GABA and enkephalin pathways; these are complementary angles on sleep architecture. Because MK-677 also raises appetite and can cause vivid dreams or morning grogginess, its combined effect on sleep is worth watching. DSIP also overlaps with Selank and Cortexin, both of which raise GABAergic tone; these are plausible calming pairings but their additive sedation should be monitored. Sermorelin and MK-677 share a downstream endpoint — both raise pulsatile GH/IGF-1 and are reported to deepen slow-wave sleep — from different upstream triggers. Cortexin and Selank complement each other on the neuroprotective and anxiolytic sides. Several combinations here have no documented interaction in our data, which is an absence of evidence rather than a clearance.

  • Cortexin + DSIP

    Worth caution — see why below

    Both enhance GABAergic tone and dampen glutamate/NMDA excitatory signaling, giving overlapping anti-excitotoxic and calming effects — DSIP primarily to deepen slow-wave sleep, Cortexin to protect neurons. Their converging effects on the excitation/inhibition balance make them a reasonable complementary pairing, though additive sedation should be monitored.

    Not fully established

    Both peptides' mechanisms clearly support GABAergic signaling as a shared dimension. Cortexin targets GABA-A receptor and produces GABAergic/neurotransmitter-balancing effects with neuroprotection against excitotoxicity. DSIP functionally enhances GABA-A receptor current (though without direct binding) and increases GABAergic tone in the ventrolateral preoptic nucleus. Both also modulate glutamatergic transmission (Cortexin via AMPA/kainate/mGluR; DSIP via NMDA blockade and negative allosteric modulation). The proposed complementary relationship is justified: they converge on excitation/inhibition balance through overlapping GABAergic and anti-glutamatergic mechanisms, with distinct primary endpoints (neuroprotection vs. sleep architecture). The explanation accurately reflects the mechanism material provided.

  • DSIP + Selank

    Worth caution — see why below

    Both peptides calm the nervous system through overlapping routes: DSIP enhances GABA-A currents and releases enkephalins, while Selank is an anxiolytic that positively modulates GABA-A signaling and boosts enkephalins by inhibiting enkephalinase (neprilysin). Their shared GABA and enkephalin actions make this a plausible anxiolytic/sleep-support pairing, though the combined sedative/calming effect should be monitored.

    Not fully established

    Both peptides' mechanisms clearly establish GABA_signaling as a shared dimension. DSIP is described as enhancing GABA-A receptor functional currents (without direct binding) and increasing GABAergic tone in the ventrolateral preoptic nucleus. Selank is explicitly described as producing allosteric modulation of GABA-A receptors (positive modulation). Both also converge on enkephalin system enhancement—DSIP via direct Met-enkephalin release, Selank via enkephalinase inhibition. The proposed 'complementary' relationship type is justified: the mechanisms show overlapping anxiolytic and GABAergic pathways that would plausibly combine without direct antagonism. The explanation accurately reflects the provided mechanism material.

  • Cortexin + Selank

    May be complementary

    Both influence GABAergic tone and neurotransmitter balance and support BDNF signaling, but by different routes — Cortexin protects against glutamate excitotoxicity and Selank adds anxiolytic GABA-A/serotonergic modulation plus enkephalinase inhibition. Together they cover both the neuroprotective and the calm/anxiolytic side of brain function.

    Not fully established

    The mechanisms clearly establish the four shared dimensions: (1) GABA_signaling—both target GABA-A receptor (Cortexin: direct modulation via multiple glutamate receptors and GABAergic effects; Selank: allosteric modulation); (2) BDNF_signaling—both explicitly list BDNF-like/NGF-like neurotrophic signaling and BDNF signaling in their pathways; (3) dopaminergic_system—both include dopaminergic neurotransmitter balance/modulation in their mechanisms; (4) anti_inflammatory—both have anti-inflammatory effects listed. The complementary relationship is justified: Cortexin acts primarily through glutamate receptor modulation, caspase inhibition, and antioxidant/neuroprotective mechanisms, while Selank acts through serotonergic (5-HT1A/2A) and enkephalinergic pathways with allosteric GABA-A modulation. The explanation accurately reflects that they converge on shared neurotransmitter systems (GABA, dopamine, BDNF) but via distinct mechanistic routes—one emphasizing excitotoxicity protection and the other anxiolytic/serotonergic modulation—making them genuinely complementary rather than redundant.

  • DSIP + Sermorelin

    May be complementary

    Sermorelin stimulates the pituitary's own GH pulse, which independently increases slow-wave (deep) sleep duration, while DSIP promotes delta sleep through GABAergic and enkephalin/opioid mechanisms. Because the upstream mechanisms are entirely different but both converge on deeper sleep, they can complement each other for sleep-focused protocols.

    Not fully established

    Both peptides' mechanisms clearly establish independent pathways to increased slow-wave/delta sleep: DSIP via GABAergic tone enhancement, NMDA blockade, and enkephalin release; Sermorelin via GH/IGF-1 axis stimulation. The mechanisms are mechanistically distinct (opioid/GABA/glutamate modulation vs. somatotroph GH secretion), both explicitly produce the shared dimension of sleep_architecture (slow-wave sleep increase), and convergence on a common endpoint (deeper sleep) from different upstream mechanisms is the definition of complementarity. The explanation accurately reflects the provided mechanism material without contradiction.

  • DSIP + MK-677

    May be complementary

    Both are used to improve sleep quality but through completely different routes: DSIP deepens slow-wave (delta) sleep via GABA-A enhancement and opioid/enkephalin signaling, while MK-677 raises GH/IGF-1 and has been reported to increase REM and deep sleep. Stacking them targets sleep architecture from two angles, which can be additive. Note that MK-677 also raises appetite and can cause vivid dreams or morning grogginess in some users, so evaluate how the combination affects your own sleep.

    Not fully established

    Both peptides' mechanisms explicitly target sleep architecture through distinct pathways. DSIP increases slow-wave (delta) sleep via GABAergic tone, NMDA inhibition, and enkephalin release. MK-677 modulates sleep architecture through GH/IGF-1 axis elevation and hypothalamic signaling. The mechanisms confirm they operate on different neurobiological systems affecting sleep, supporting the 'complementary' relationship claim with 'sleep_architecture' as a shared dimension. The explanation accurately reflects the distinct routes (GABA/opioid vs. GH/IGF-1) described in both mechanism profiles.

  • DSIP + Epithalon

    May be complementary

    Both peptides converge on restoring normal melatonin secretion and circadian rhythm, but by different upstream mechanisms: DSIP influences pineal melatonin synthesis and delta sleep, while Epithalon reportedly upregulates the pineal melatonin (AANAT) axis and circadian clock genes. Used together they could reinforce circadian normalization and sleep timing.

    Not fully established

    Both peptides' mechanisms explicitly converge on the melatonin pathway and circadian rhythm restoration via distinct upstream mechanisms. DSIP's mechanism includes 'Circadian/melatonin (pineal NAT, melatonin, serotonin, 5-methoxytryptophol)' and effects on sleep architecture. Epithalon's mechanism explicitly includes 'Melatonin biosynthesis (AANAT / pineal axis)' and 'Circadian gene regulation (Clock, Csnk1e, Cry2)' with restoration of melatonin secretion and circadian rhythms as documented effects. Both are tagged with 'melatonin_pathway'. The proposed relationship correctly identifies that they target the same downstream outcome (melatonin/circadian restoration) through different upstream pathways (DSIP via GABAergic/sleep-promoting mechanisms; Epithalon via telomerase/epigenetic mechanisms), which is precisely what 'same_downstream' describes.

  • Sermorelin + MK-677

    May be complementary

    Sermorelin is a GHRH-receptor agonist, a different upstream trigger from MK-677's ghrelin-receptor action, yet both raise pulsatile GH and IGF-1 and both are reported to deepen slow-wave sleep. Using a GHRH signal plus a ghrelin-mimetic can enhance the GH pulse more than either alone, and their overlapping sleep benefits reinforce each other.

    Not fully established

    Both peptides' mechanisms clearly converge on the same downstream GH/IGF-1 axis despite different upstream triggers. MK-677 activates GHS-R1a (ghrelin receptor) via Gq/11-phospholipase C cascade; Sermorelin activates GHRH receptor via Gs/adenylyl cyclase/cAMP. Both mechanisms result in pulsatile GH secretion from pituitary somatotrophs and subsequent IGF-1 elevation. Both approved tags explicitly include GH_axis, IGF1_signaling, protein_synthesis, and sleep_architecture. The mechanism descriptions confirm both increase pulsatile GH release, elevate IGF-1, improve body composition through protein synthesis/lean mass gains, and increase slow-wave/deep sleep. The proposed explanation that they use different upstream pathways (ghrelin vs GHRH) but converge on common downstream GH release and sleep effects is directly supported by the provided mechanisms. This is a classic example of convergent pathway activation producing overlapping phenotypes.

  • Cortexin + Sermorelin

    No documented interaction in our data — that is not a safety clearance.

  • Cortexin + MK-677

    No documented interaction in our data — that is not a safety clearance.

  • Cortexin + Epithalon

    No documented interaction in our data — that is not a safety clearance.

  • Sermorelin + Selank

    No documented interaction in our data — that is not a safety clearance.

  • Sermorelin + Epithalon

    No documented interaction in our data — that is not a safety clearance.

  • MK-677 + Selank

    No documented interaction in our data — that is not a safety clearance.

  • MK-677 + Epithalon

    No documented interaction in our data — that is not a safety clearance.

  • Selank + Epithalon

    No documented interaction in our data — that is not a safety clearance.

Sources

Ordered as cited above.

  1. Acute and delayed effects of DSIP (delta sleep-inducing peptide) on ...(opens in a new tab)
    Tier 1Web · pubmed.ncbi.nlm.nih.gov
  2. Delta sleep-inducing-peptide-like immunoreactivity (DSIP-LI) and delta sleep in schizophrenic volunteers.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov
  3. DSIP Half-Life: ~30–40 Min IV — Pharmacokinetics & Sleep Data | Halflife Labs(opens in a new tab)
    Tier 1Web · halflife-labs.com
  4. [AEDG peptide regulates human circadian rhythms genes expression during pineal gland accelerated aging.].(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov
  5. Epithalon and Telomere Research: What Science Knows So Far - Peptides FYI(opens in a new tab)
    Tier 2Web · peptides.fyi
  6. Epithalamin/Epithalon(opens in a new tab)
    Tier 3Web · alzdiscovery.org
  7. Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov
  8. Cortexin®(opens in a new tab)
    Tier 3Web · russianmeds.com
  9. MK-677: 42 Studies Reviewed (2026) | PepCodex(opens in a new tab)
    Tier 3Web · pepcodex.com
  10. The Safety and Efficacy of Growth Hormone Secretagogues.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov
  11. MK-677 Ibutamoren: Mechanism & GH Secretagogue Research(opens in a new tab)
    Tier 3Web · newtropin.com
  12. Sermorelin: How It Works, Safety, and Access(opens in a new tab)
    Tier 3Web · testing.com
  13. Sermorelin: GHRH Analog for Natural Growth Hormone | Peptidepedia(opens in a new tab)
    Tier 3Web · peptidepedia.org
  14. Sermorelin Peptide: Evidence, Dosing & Real Clinical Data | FormBlends(opens in a new tab)
    Tier 3Web · formblends.com
  15. [Optimization of the treatment of anxiety disorders with selank].(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov
  16. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov
  17. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission(opens in a new tab)
    Tier 2Web · pmc.ncbi.nlm.nih.gov

This brief reports what published research says about these compounds. It is information, not medical advice, and not a recommendation to use anything described here. Evidence quality varies by compound and is labelled throughout. Talk to a qualified clinician before acting on any of it.