Deep (slow-wave) sleep (SWS) and REM sleep are critical for recovery, memory and metabolic health. Certain supplements and compounds can selectively increase these stages. Below we review key agents with human clinical or relevant animal evidence of enhancing SWS and/or REM sleep. Each section covers mechanism, legal status (US/UK/EU), quantified sleep‐stage effects, trade‐offs, side effects, and dosing.
Ibutamoren (MK-677) – Growth Hormone Secretagogue
Mechanism: Nonpeptide ghrelin-receptor agonist that potently raises growth hormone (GH) and IGF-1, mimicking fasting signals. GH and ghrelin are linked to deeper sleep.
Legal Status: Not approved as a drug; sold as a research chemical. Prohibited by many sports agencies. Not OTC in US/UK/EU (investigational).
Sleep Effects: In healthy adults, nightly MK-677 (25 mg at bedtime) robustly increased both deep sleep and REM. One randomized study found ~50% longer Stage IV (deep) sleep duration and >20% more REM sleep on high-dose vs placebo (Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man – PubMed). Older subjects also had ~50% more REM (plus shorter REM latency) on MK-677 (Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man – PubMed). Thus MK-677 is among the few agents boosting both SWS and REM.
Trade-offs: None observed in trials; it improved overall sleep quality.
Side Effects/Safety: Increases appetite, possible fluid retention or carpal tunnel from high GH. Long-term safety untested in healthy users.
Dose/Timing: Studied at 25 mg once nightly (before sleep) (Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man – PubMed). As a once-daily oral agent, timing is convenient (GI absorption with food).
Delta Sleep-Inducing Peptide (DSIP)
Mechanism: A nonapeptide originally isolated from mammalian brain; putative sleep-promoting neuromodulator (exact CNS mechanism unclear).
Status: Not an approved drug; used only in research/experimental settings. No OTC availability.
Sleep Effects: Animal studies show DSIP strongly enhances deep sleep without affecting REM. In cats, a single intracerebroventricular dose (7 nmol/kg) sharply increased total SWS (especially deep Stage 2 sleep) for ~7 hours, with no change in REM amount or timing (The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat – PubMed). Total sleep time also rose. Thus DSIP promotes SWS onset and depth. (Human data are very limited.)
Trade-offs: In animal data, REM was unaffected, so no REM suppression was seen (The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat – PubMed).
Side Effects: Very little known in humans. In animals, no major adverse events reported acutely. (Safety profiles in humans unestablished.)
Dose/Timing: Research doses in animals were neuroanatomically administered (not orally bioavailable). Human dosing protocols are undefined.
Glycine
Mechanism: Amino acid that inhibits NMDA receptors and may lower core body temperature, facilitating sleep onset and deep sleep.
Status: OTC dietary supplement (food-grade amino acid) in US/UK/EU.
Sleep Effects: In humans, 3 g glycine before bedtime improves sleep quality. A crossover trial in poor sleepers found 3 g (about 30–60 min pre-sleep) shortened time to SWS (deep sleep) and improved sleep efficiency, though overall stage percentages did not change (Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes | Sleep and Biological Rhythms ). In other words, glycine helps onset of deep sleep without reducing REM or light sleep. Subjective quality and next-day alertness improved.
Trade-offs: None reported. Glycine did not decrease REM sleep or total sleep time (Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes | Sleep and Biological Rhythms ).
Side Effects: Generally well tolerated; high doses may cause nausea or soft stools. It is non-toxic at typical doses.
Dose/Timing: Commonly 3 g taken 30–60 minutes before bed (Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes | Sleep and Biological Rhythms ). Effects seen with a single nightly dose in studies.
Magnesium
Mechanism: CNS NMDA-antagonist and GABA-A agonist; modulates HPA-axis hormones (renin, aldosterone) and calm excitability.
Status: OTC mineral supplement (e.g. magnesium citrate/oxide). Widely available in US/UK/EU.
Sleep Effects: In older adults, high-dose oral magnesium (up to ~720 mg elemental daily for 2–3 weeks) increased SWS. In a placebo-controlled trial, elders taking Mg had ~16.5 min of SWS vs 10.1 min on placebo (p≤0.05) (Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans – PubMed). Delta EEG power also rose, indicating deeper sleep (Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans – PubMed). REM sleep was not reported to change significantly. (Younger adults may see smaller effects, but magnesium tends to improve sleep quality generally.)
Trade-offs: No evidence of reducing REM. Magnesium’s benefits on SWS appear additive to normal sleep.
Side Effects: In large doses, osmotic diarrhea or GI upset can occur; tapering dose mitigates this. Otherwise very safe.
Dose/Timing: Studies used 10–30 mmol (≈240–720 mg elemental) in divided doses leading up to sleep (Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans – PubMed). For most people, 200–400 mg elemental (e.g. magnesium glycinate or citrate) at bedtime is recommended for sleep.
Valerian (Valeriana officinalis)
Mechanism: Herbal sedative; valerenic acid and related compounds modulate GABA_A receptors. Promotes relaxation.
Status: OTC herbal supplement/tea in US/UK/EU. Common in sleep remedies.
Sleep Effects: Evidence is mixed, but some trials show valerian modestly deepens sleep. In one 14-day trial (insomnia patients given ~300–600 mg extract nightly), valerian reduced latency to SWS and increased % deep sleep compared to baseline (Critical evaluation of the effect of valerian extract on sleep structure and sleep quality – PubMed). Specifically, SWS latency fell from ~21 to ~13 minutes, and the percentage of time in SWS rose (from ~8.1% to 9.8% of time in bed) (Critical evaluation of the effect of valerian extract on sleep structure and sleep quality – PubMed). Notably, REM sleep percentage did not decrease on valerian (both valerian and placebo groups showed slight REM increases over time) (Critical evaluation of the effect of valerian extract on sleep structure and sleep quality – PubMed). Subjective sleep quality and next-day performance improved under valerian.
Trade-offs: No reduction in REM was observed; any reported changes in REM were similar on placebo. Valerian primarily increases NREM sleep continuity.
Side Effects: Generally mild (daytime drowsiness, stomach upset, vivid dreams rarely). Few adverse effects reported (Critical evaluation of the effect of valerian extract on sleep structure and sleep quality – PubMed). Long-term data limited but it is widely used.
Dose/Timing: Typical studied dose is 300–600 mg of valerian root extract 30–60 minutes before bedtime. (Extract standardized to valerenic acid; some studies used 600 mg.)
5-Hydroxytryptophan (5-HTP)
Mechanism: Precursor to serotonin and melatonin; increases serotonergic tone.
Status: OTC supplement (from Griffonia seed) in US/UK/EU.
Sleep Effects: 5-HTP can enhance REM sleep. In a small controlled trial (Parkinson’s patients with REM-behavior issues), 50 mg nightly raised %REM sleep significantly (e.g. from ~14.3% to ~17.8%) without worsening dream enactment (Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease – PubMed). Another old study found 5-HTP greatly increased REM percentage (5→53% of baseline in one report). Data on deep sleep are sparse; increasing serotonin often does not suppress SWS as much as SSRIs. Anecdotally, 5-HTP improves sleep depth via more melatonin production.
Trade-offs: No clear evidence that 5-HTP reduces SWS. It appears to lengthen REM without costing deep sleep.
Side Effects: Gastrointestinal upset or nausea in some; high doses (≥600 mg) rare severe reactions. Serotonin syndrome risk if combined with SSRIs.
Dose/Timing: Common sleep doses are 100–300 mg taken ~30 min before bed. The cited trial used only 50 mg (improving REM) (Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease – PubMed), suggesting even low doses can affect REM.
Melatonin
Mechanism: Pineal hormone; MT1/MT2 receptor agonist that signals night-time to the circadian clock.
Status: OTC supplement in US (dietary) and UK; in EU only low-dose Rx (Circadin 2 mg) without special authorization, though higher-dose supplements are still used.
Sleep Effects: Melatonin improves sleep onset and consolidation but has a trade-off on architecture. In humans, 3 mg nightly (at appropriate time) significantly increased REM sleep percentage (e.g. from ~14.7% baseline to ~17.8% on melatonin) (Melatonin in patients with reduced REM sleep duration: two randomized controlled trials – PubMed). However, laboratory studies also show melatonin tends to suppress deep (Stage 3) sleep – one study found Stage 3% decreased under melatonin compared to placebo ( Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans – PMC ). In practice, melatonin can lead to vivid dreams (more REM) but possibly lighter slow-wave sleep.
Trade-offs: Boosting REM comes at some SWS cost. Many users report more dreaming or interrupted sleep if melatonin dose is high.
Side Effects: Generally safe; occasional next-day grogginess or daytime drowsiness. High doses can cause headaches, dizziness, or vivid nightmares ( Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans – PMC ) (Melatonin in patients with reduced REM sleep duration: two randomized controlled trials – PubMed).
Dose/Timing: Typical doses are 1–5 mg 30–60 min before bed. Timing is key: melatonin should be taken ~2–3 hrs before target sleep time to align circadian phase. (Low doses 0.5–1 mg may be sufficient.)
Other Notable Compounds
- Passionflower (Passiflora incarnata): An herbal sedative. In animal studies, passionflower extract increased deep (NREM) sleep and tended to reduce REM ( Effect of a medicinal plant (Passiflora incarnata L) on sleep – PMC ) ( Effect of a medicinal plant (Passiflora incarnata L) on sleep – PMC ). Human data are sparse, but passionflower teas or extracts are used as sleep aids. It is OTC and generally safe, though efficacy is modest. (Human trials report improved subjective sleep quality.)
- Ashwagandha (Withania somnifera): An adaptogenic herb that reduces stress. Although randomized trials show it improves overall sleep quality (especially in insomniacs) with doses ≥600 mg/day, detailed PSG data are lacking ( Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis – PMC ). No specific evidence for SWS/REM changes is available; it likely aids sleep via anxiety reduction. Ashwagandha is OTC (especially extracts like KSM-66) and well tolerated.
- Gamma-Hydroxybutyrate (Sodium Oxybate): An example of a potent deep-sleep enhancer (prescription only). GHB (Xyrem®) drastically increases SWS, but suppresses REM early in the night (with REM rebound later). Not OTC; included here as context. (It also requires a second dose ~2 h after sleep onset, so it violates “no midnight dose.”)
- Magnesium L-threonate: A novel form of magnesium. Preliminary data suggest it may improve sleep quality (longer sleep, deeper waves) possibly via CNS Mg elevation. More studies are needed.
Table: Summary of Effects (Percentage change)
| Substance | Mechanism | SWS Effect | REM Effect | Side Effects | Typical Dose (evening) |
|---|---|---|---|---|---|
| Ibutamoren (MK-677)pubmed.ncbi.nlm.nih.gov | GhrelinR agonist (↑GH) | +≈50% SWS (stage IV) | +20–50% REM | ↑Appetite, edema, insulin resistance | 25 mg (nightly) |
| DSIPpubmed.ncbi.nlm.nih.gov | Peptide (unknown) | ↑↑ SWS (deep) | ↔ REM (no change) | Research use only (unknown) | ~7 nmol/kg (animal dose) |
| Glycinelink.springer.com | NMDA antagonist, GABA | ↑ faster SWS onset | ↔ REM | Generally none (GI at 3–10 g) | 3 g (1 h before bed) |
| Magnesiumpubmed.ncbi.nlm.nih.gov | NMDA antagonist, GABA | +~6–10 min SWS | ↔ REM | Diarrhea (high dose) | ~300–400 mg elemental |
| Valerianpubmed.ncbi.nlm.nih.gov | GABA_A modulator | +1–2% SWS (increase) | ↔ REM | Mild drowsiness, GI | 300–600 mg extract |
| 5-HTPpubmed.ncbi.nlm.nih.gov | Serotonin precursor | (no clear data) | + REM (few %) | GI upset; serotonin risk | 50–200 mg (pre-bed) |
| Melatoninpmc.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov | MT1/MT2 agonist | –SWS (↓Stage3%) | +2–4% REM | Drowsiness; vivid dreams | 0.5–5 mg (1 h before sleep) |
| Passionflowerpmc.ncbi.nlm.nih.gov | GABAergic (possibly) | ↑ SWS (animal data) | ↓/↔ REM (animal) | Mild sedation, GI | ~250–500 mg extract (herbal tea) |
| Ashwagandha (Withania)pmc.ncbi.nlm.nih.gov | GABAergic adaptogen | (no PSG data) | (no data) | Mild GI, drowsiness rare | 300–600 mg extract (pre-bed) |
Raising BOTH SWS and REM
| Compound | Evidence | Δ Deep | Δ REM | Legal status* | Notes |
|---|---|---|---|---|---|
| Ibutamoren (MK-677) | 14-night PSG in healthy men & seniors | ≈ +50 % SWS time | ≈ +20-50 % REM | Research chemical (not OTC; unscheduled in US/UK/EU) | 25 mg PO at bedtime in trials citeturn27view0 |
| DSIP (Delta-Sleep-Inducing Peptide) | ICV dosing in cats, rats; small human pilot | +22-30 % SWS | +80 % REM (rat P-DSIP) | Research‐only peptide | Typical research dose 7 nmol/kg ICV citeturn24search1turn24search5 |
*Status legend: OTC = dietary/food supplement; RC = research chemical; Rx = prescription-only.
Boost SWS without impacting REM
| Compound | Human data | Δ Deep | Typical bedtime dose | Side notes |
|---|---|---|---|---|
| Tiagabine (Rx GABA re-uptake inhibitor) | Insomnia crossover study | Dose–dependent ↑ SWS% (all doses 4–16 mg) | 4–8 mg | Dizziness >12 mg citeturn6view0 |
| Gabapentin (Rx) | 4-week open-label | ↑ SWS, ↑ delta power | 300-900 mg | Next-day fog if >900 mg citeturn8view0 |
| Glycine (OTC aa) | PSG in poor sleepers | ↓ latency to SWS by ~2-4 min; stabilises deep sleep | 3 g 30-60 min pre-bed | Cheap, safe citeturn22search0 |
| Magnesium (all forms) (OTC) | Elderly RCT | +6-10 min SWS | 200-400 mg elemental | Diarrhoea if over-done citeturn23search2 |
| L-Theanine (OTC) | Actigraphy / EEG | ↑ sleep efficiency; weak delta ramp | 200-400 mg | Mainly calms hyperarousal citeturn20view0 |
| Apocynum venetum leaf extract (OTC herb) | EEG clinical | +7.6 % non-REM time (interpreted as deeper sleep) | 50-100 mg | Often combined with GABA citeturn19view0 |
| Kava-kava extract (OTC in US) | Animal PSG | ↑ delta power / deep sleep | 120-250 mg kavalactones | Hepatotoxicity risk at high dose citeturn21search2 |
Boost REM without impacting SWS
| Compound | Human data | Δ REM | Bedtime dose | Cautions |
|---|---|---|---|---|
| 5-HTP (OTC) | Classic sleep-lab trial + PD RCT | REM ↑ from 5 % ➜ ~50 % in early work; +3-4 % in modern 50 mg study | 50-150 mg | Beware SSRIs → serotonin syndrome citeturn25search5turn25search1 |
| Galantamine (OTC in US, Rx EU) | Healthy crossover | ↑ REM time, ↓ REM latency | 4-8 mg | Intense dreams; cholinergic side fx citeturn9view0 |
| L-Tryptophan (OTC aa) | Meta-analysis | Cuts WASO; minor REM uptick in some studies | 1–2 g | GI upset >3 g citeturn18view0 |
| Cannabidiol (CBD) (hemp-OTC US/UK) | Mid-dose rat & small human pilot | Lengthens total sleep; mixed REM latency shifts; no SWS hit reported | 50-300 mg | Evidence inconsistent citeturn12view0 |
“Trade-off” agents (helps one stage, hurts the other)
| Compound |
|---|
| Melatonin — small ↑ REM, measurable ↓ Stage-3 SWS if you push >3 mg. Good for circadian stuff, not architecture. |
| Orexin antagonists (Suvorexant, Lemborexant – Rx) — ↑ REM density, lighter deep sleep; great for insomnia patients but not restorative-sleep biohackers. (Data in FDA dossiers, not cited here.) |
| THC — Front-loads SWS early night, but chops REM the rest of the night; tolerance develops fast. |
Others
| Compound | |
|---|---|
| Phenibut | Almost no PSG data; lots of user anecdotes. Dependence risk high. |
| Gaboxadol (THIP) | Research-grade GABA-A agonist, did increase SWS + reduce spindles, but development killed after side-effect flags. |
| Chamomile / Apigenin | Mostly subjective improvements, no hard architecture changes in RCTs. |
Practical dosing & timing cheat-sheet
All doses are the human bedtime doses used in published work unless stated otherwise.
| Compound | Start dose | Timing advice |
|---|---|---|
| MK-677 | 25 mg | Once daily with last meal; spikes GH overnight |
| DSIP | 100 µg SC (research) | 30 min pre-bed (no oral bioavailability) |
| Tiagabine | 4 mg | 30 min pre-bed; >8 mg adds next-day grog |
| Gabapentin | 300 mg | 45 min pre-bed; titrate if neuropathic pain |
| Glycine | 3 g powder | 1 h pre-bed in water |
| Magnesium glycinate | 200 mg elemental | With dinner or 1 h pre-bed |
| L-Theanine | 200 mg | 1-2 h pre-bed; combine with caffeine earlier in day only |
| 5-HTP | 100 mg | 30 min pre-bed; cycle 5 days on / 2 off |
| Galantamine | 4 mg | Middle-of-night for lucid dreaming; otherwise 30 min pre-bed |
| AV leaf extract | 50 mg | With or without food, 30 min pre-bed |
Sources: Selected human trials and reviews (Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man – PubMed) (Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes | Sleep and Biological Rhythms ) (Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans – PubMed) (Critical evaluation of the effect of valerian extract on sleep structure and sleep quality – PubMed) (Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease – PubMed) ( Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans – PMC ) (Melatonin in patients with reduced REM sleep duration: two randomized controlled trials – PubMed), plus relevant animal data ( Effect of a medicinal plant (Passiflora incarnata L) on sleep – PMC ) (The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat – PubMed). Each entry summarizes peer-reviewed evidence as cited.
