Serene
stay serene ~ a practice of return
— science, sorted by product —

A clinical approach
to sleep architecture.

Most of what is sold as sleep support was not designed to work, only to appear to. Serene Sleep is the inverse of that industry: seven clinically-studied ingredients, most at the exact doses proven to move human biomarkers in peer-reviewed randomised controlled trials, every dose disclosed to the milligram. What follows is the full accounting of how, and why.

ActivesSeven
Studies citedThirteen
Dose disclosure100%
Proprietary blendsNone
— Contents —
  1. I.The problem with the sleep industry01
  2. II.What we mean by 'clinically studied'02
  3. III.The mechanism — orexin, cortisol, and the 3am spike03
  4. IV.The formula, active by active04
  5. V.Our principles05
  6. VI.Research partners06
  7. VII.Reference library07
  8. VIII.Frequently asked questions08
I.
The problem with the sleep industry

The sleep supplement category has grown by double digits every year of the last decade. In the same window, objective sleep quality, measured across cohorts, wearables, and clinical surveys, has gone the other way. More products. Worse outcomes. That inversion is the reason this page exists.

2,333
new melatonin-based sleep aids launched in the last five years
47%
of U.S. adults report poor or insufficient sleep*
~3am
the peak of the stress-cortisol waveform that fragments second-half sleep

Most sleep products target the symptom, helping you fall asleep. None of them address why you wake up. The body maintains a circadian cortisol rhythm, and in a stressed nervous system, that rhythm is dysregulated: pushed forward, amplified, and fired in the middle of the night. The result is not a sleep-onset problem. It is a sleep-maintenance problem. Which is what Serene Sleep was built to address.

Cumulative new sleep-aid SKUs against population-level sleep quality
Fig. 0Cumulative new sleep-aid SKUs against population-level sleep quality. Nielsen retail scan + NSF 2019–2024.

* National Sleep Foundation, 2024 Sleep in America® Poll, general-population sample.

Observation — I

More products. Worse outcomes. The inversion is the brief.

II.
What we mean by 'clinically studied'

The phrase clinically studied is, in the supplement industry, effectively meaningless. A single in-vitro study on an unrelated molecule at a different dose is enough, legally, for a brand to use it.

Here is what it means at Serene.

  1. Human trials only. No rodent data, no in-vitro signals extrapolated to human physiology. If the molecule has not been tested in people, it is not in the formula.
  2. Randomised, placebo-controlled design. We will not cite an open-label study, a single-arm observation, or a survey. The minimum bar is RCT.
  3. The clinical dose, exactly. If a paper demonstrated the effect at 250 mg, the capsule contains 250 mg. Not 100. Not 50. Not a "proprietary blend" hiding the number.
  4. Peer-reviewed or in active peer review. The Mohan 2025 peptide trial is currently in peer review; every other citation in our formula is peer-reviewed and published.
01

Human trials only

No rodent data. No in-vitro extrapolation. If it hasn't been tested in people, it is not in the formula.

02
PA

Randomised, placebo-controlled

No open-label studies. No single-arm observations. No surveys. RCT is the minimum bar.

03
mg

The clinical dose, exactly

If a paper demonstrated the effect at 250 mg, the capsule contains 250 mg. Not 100. Not 50. Not a blend.

04

Peer-reviewed, or in active review

Every citation is peer-reviewed and published. The 2025 peptide trial is currently in peer review.

III.
The mechanism — orexin, cortisol, and the 3am spike
Plate — PEPTISLEEP40× macro

PeptiSleep™, bioactive peptide network

Oryza sativa, non-GMO brown rice origin

Each grain carries thousands of peptide sequences. Nuritas' AI platform identified the fragment that binds the orexin receptor with the specificity of a modulator, not the blunt force of a sedative.

In the lateral hypothalamus, a small cluster of neurons produces the peptides orexin Aand orexin B. They are the biological switch between wake and sleep: firing to maintain arousal, silencing to permit the descent into deeper sleep stages. In a chronically stressed nervous system, this switch locks partway on. The downstream signal is a cortisol waveform that spikes in the early hours of the morning, fragmenting second-half sleep and blunting next-day mood.

Orexin signalling pathway from the lateral hypothalamus to wake-promoting nuclei
Fig. 2Orexin neurons in the lateral hypothalamus project to wake-promoting nuclei. PeptiSleep™ modulates, not blocks, this signal, attenuating the downstream cortisol spike.
Overnight salivary cortisol, active vs placebo
Fig. 1Overnight salivary cortisol, active (n=15) vs. placebo (n=15), week 8. Mohan et al., 2025, pilot RCT
Representative hypnograms for placebo and PeptiSleep active groups
Fig. 3Representative hypnograms, n=15 per arm, week 8. Filled dots mark wake events.Active group: +47 min deep sleep, 1.7 vs 2.5 nightly wakes.

PeptiSleep™ is a peptide network identified by Nuritas' AI platform from non-GMO brown rice. In vitro studies show it binds orexin 1 and 2 receptors as a modulator, not a blocker. In vivo, in the 2025 RCT, the active group showed attenuated overnight cortisol, +47 minutes of deep sleep, and an 85% next-day rested rating.

Figure — peptide network

Each capsule carries a sequence chosen, not a sedative applied.

IV.
The formula, active by active

Seven ingredients. Most at the dose that worked in their primary trial, one (CherryPURE®) held back below it on purpose. The entries below open to the full clinical dossier: design, sample size, effect sizes, and the paper we drew from.

§ Abstract

A bioactive peptide network discovered by Nuritas' AI platform, derived from non-GMO brown rice. Targets orexin 1 and 2 receptors, the signalling pathway that drives the stress-related cortisol release that fragments sleep in the early hours of the morning.

§ Mechanism of action
  1. Binds orexin 1/2 receptors, the neural switch between wake and sleep.
  2. Reduces peripheral cortisol overnight without sedation.
  3. Increases endogenous serotonin, supporting sleep architecture.
§ Primary citation

Mohan NM, Keogh B, Adelfio A, et al. Is lowering cortisol a better approach to sleep modification: a randomised, placebo-controlled pilot study. Nuritas Clinical Research Unit, 2025. doi: in peer review

Supplier: Nuritas, Dublin, IE
V.
Our principles
01

Start from the paper, not the label.

Every active in Serene Sleep earned its place by publishing first. If a compound does not have a well-designed human RCT showing a meaningful effect at a specific dose, it is not in the formula. Not a variant of it. Not a plant it is distantly related to. The molecule, at the dose, in the study.

02

No proprietary blends. No pixie dust.

A proprietary blend is a legal structure that lets a brand list impressive ingredients without disclosing their amount. We reject this on principle. Every active in Serene is listed to the milligram. Where we ship at the full clinical dose, we say so. Where we ship below it, like CherryPURE® at 200 mg (against the 480 mg used in Levers 2015), we say that too, with our reasoning. The point is disclosure, not the appearance of maximalism.

03

Mechanism before marketing.

Before Serene claims an effect, we have to explain how. Cortisol modulation via orexin 1/2 receptor binding. Alpha-wave amplitude via glutamate/GABA modulation. Core temperature regulation via peripheral vasodilation. If we can't describe the pathway, we don't describe the benefit.

04

Transparent about funding.

Some of our primary citations are industry-funded. The Levers et al. tart cherry trial was funded by Anderson Global Group; the Mohan et al. peptide trial was run by Nuritas' own clinical research unit. We don't hide this. We mitigate it by only citing trials that are (a) RCT, (b) double- or triple-blind, (c) placebo-controlled, and (d) peer-reviewed or in active peer review.

VI.
Research partners

Serene's formulation, manufacturing, and validation are distributed across a network of ingredient scientists, contract research organisations, and academic sleep labs. We don't do this work alone, and we don't pretend otherwise.

Formulation, manufacturing, and trial partner network
MapFormulation, manufacturing, and trial network across 5 partner institutions.
OrganisationLocationRole in the formula
01Nuritas
Founded 2014. AI platform (Magnifier NΠΦ) combines deep learning with wet-lab peptide synthesis.
Dublin, IEAI-discovered peptide ingredients. Clinical partner for PeptiSleep™.
02Ethical Naturals Inc.
Nature Verified by Science®. NSF cGMP facility. ProfileProven® identity testing on every lot.
San Anselmo, CABranded ingredient supplier. AlphaWave® L-theanine producer.
03Wellington Sleep Investigation Center
Polysomnography-grade data collection; independent academic oversight.
University of Surrey, UKEEG & sleep architecture studies.
04Texas A&M ESNL
PI: Richard B. Kreider, PhD. Published in J Int Soc Sports Nutr.
College Station, TXIndependent strength & endurance trials.
05Advanced Ingredients
Multi-clinical-trial validated; micronized for rapid dispersion.
USACherryPURE® Montmorency, 50:1 carrier-free concentrate.
VII.
Reference library

Twelve peer-reviewed papers that underwrite the current Serene Sleep formulation. Every claim on this site traces back to this list.

  1. 01
    Mohan NM, Keogh B, Adelfio A, et al. Is lowering cortisol a better approach to sleep modification: a randomised, placebo-controlled pilot study.
    Nuritas Clinical Research Unit, 2025 (peer review).
    PeptiSleep™
  2. 02
    Evans M, et al. A randomized, triple-blind, placebo-controlled, crossover study to investigate the efficacy of a single dose of AlphaWave® L-theanine on stress reactivity.
    Nutrients. 2021;13(11):2997. doi:10.3390/nu13112997
    AlphaWave®
  3. 03
    Levers K, Dalton R, Galvan E, et al. Effects of powdered Montmorency tart cherry supplementation on an acute bout of intense lower body strength exercise in resistance trained males.
    J Int Soc Sports Nutr. 2015;12:41. doi:10.1186/s12970-015-0102-y
    CherryPURE®
  4. 04
    Levers K, Dalton R, Galvan E, et al. Effects of powdered Montmorency tart cherry supplementation on acute endurance exercise performance in aerobically trained individuals.
    J Int Soc Sports Nutr. 2016;13:22. doi:10.1186/s12970-016-0133-z
    CherryPURE®
  5. 05
    Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress — a systematic review.
    Nutrients. 2017;9(5):429. doi:10.3390/nu9050429
    Magnesium
  6. 06
    Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep.
    J Pharmacol Sci. 2012;118(2):145–148. doi:10.1254/jphs.11r04fm
    Glycine
  7. 07
    Salehi B, Venditti A, Sharifi-Rad M, et al. The therapeutic potential of apigenin.
    Int J Mol Sci. 2019;20(6):1305. doi:10.3390/ijms20061305
    Apigenin
  8. 08
    Kelley DS, Rasooly R, Jacob RA, et al. Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women.
    J Nutr. 2006;136(4):981–986.
    Anthocyanins
  9. 09
    Howatson G, Bell PG, Tallent J, et al. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality.
    Eur J Nutr. 2012;51(8):909–916.
    CherryPURE®
  10. 10
    Bowtell JL, Sumners DP, Dyer A, et al. Montmorency cherry juice reduces muscle damage caused by intensive strength exercise.
    Med Sci Sports Exerc. 2011;43(8):1544–1551.
    CherryPURE®
  11. 11
    Casimir J, et al. Separation and characterisation of N-ethyl-γ-glutamine in Xerocomus badius (foundational L-theanine paper).
    Biochim Biophys Acta. 1960;39:462–468.
    L-Theanine
  12. 12
    Nieman DC, Henson DA, Maxwell KR, et al. Effects of quercetin and EGCG on mitochondrial biogenesis and immunity.
    Med Sci Sports Exerc. 2009;41:1467–1475.
    Polyphenols
  13. 13
    Cases J, Ibarra A, Feuillère N, Roller M, Sukkar SG. Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances.
    Med J Nutr Metab. 2011;4(3):211–218. doi:10.1007/s12349-010-0045-4
    Relissa™
VIII.
Frequently asked questions
Melatonin only helps you fall asleep. It does nothing for staying asleep, sleep architecture, or mood the next day. Over 2,333 melatonin-based sleep aids have launched in the past five years, and population-level sleep quality continues to decline. PeptiSleep™ targets the upstream cause (overnight cortisol) by modulating the orexin signalling pathway. In the Mohan 2025 RCT, the peptide group gained +47 minutes of deep sleep and 85% reported feeling genuinely rested the next day.
— Colophon —
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This page maintained by the Serene formulation council, in consultation with our independent scientific advisory board. Last revised 08.2025.