High Dose Melatonin Therapy

Thank you again for the information you sent
Well, it's not much, but you are welcome.
In my case, I do not have insomnia, but it's been many years that I always wake up around 2-3 ish am, and then around 4-5 is am. So I will eventually get to this thread and investigate if it's possible to resolve this or not. I don't lack sleep since I'm almost always able to fall back asleep. But if there is a way to improve this situation, I'm interested.
 
I do not have insomnia, but it's been many years that I always wake up around 2-3 ish am, and then around 4-5 is am. So I will eventually get to this thread and investigate if it's possible to resolve this or not. I don't lack sleep since I'm almost always able to fall back asleep. But if there is a way to improve this situation, I'm interested.
yes, that's exactly how I am now :-) I wake up at night at similar hours.

I mentally test my full concentration on breathing and as soon as the thoughts come back and I realize it, I immediately concentrate fully on breathing again to continue sleeping.

I plan to test several types of melatonin in a series of 1 week with 1 type of melatonin and then 1 week without melatonin.

I will let you know then what happened. Have a nice weekend
 
Firstly thank you very much Nević Nenad for you information :-)

Yes, I would also prefer to try natural. I checked Now Foods melatonin on their website and there is no information about where this melatonin is sourced from, neither on the packaging nor on the page. The fact is that it is a version of melatonin suitable for vegans, from which it can be deduced that it is not derived from animals. Therefore, it looks to me more likely to be synthetically produced melatonin.

I looked at Life Extension melatonin (although there are pictures of cherries) and Melatonin Vitabalans as well, it doesn't say anything what kind of melatonin it is.

I think it might be interesting to know more :-)
I don't know where I picked that. Maybe on their old website or packaging. Anyway, I apologize for lying. I did see the difference in effect between Now Foods and Natrol melatonin. I guess that everyone must try and choose their own.
 
I promised to write an experience with melatonin. I have tried it with my friend, we both have a problem with night waking up. We tried this protocol:
  • Vitabalans melatonin 3mg (synthetic) - 1st week - no change observed when falling asleep or waking up at night
  • Now Foods melatonin 5mg (synthetic) - 2nd week - no change observed when falling asleep or waking up at night
  • Life Extension melatonin 10mg (synthetic) - 3rd week - shorter time when falling asleep and no change when waking up at night
  • Life Extension melatonin 20mg (synthetic) - 4th week - significantly shorter time when falling asleep and little change when waking up at night; feeling sleepy and tired in the morning
  • BrainMax melatonin (natural Prunus Cerasus) - 2400mg - 4 days - no change observed when falling asleep or waking up at night
Result - We have noticed that we dream strange dreams. I noticed that during the night waking up it was necessary to concentrate on the present moment and belly breathing, then the time was shortened for falling asleep again. We noticed that if there were days with stress or a lot of meetings with suggestions from other people, immediately falling asleep and even waking up at night was worse. I realized that something had changed in my life (app. 1 year ago), that I had no choice other than to stay "fine", which is quite challenging at these times.

Conclusion - No withdrawal symptoms after a week without melatonin (I was worried a little). We both continue with the 10 mg dose and trying if it's somehow possible to improve the sleep.

Have a nice and peaceful days :-)
 
Curiosity - Did you know that children (2-18 years) have fully reimbursed treatment with melatonin at a dose of 2-10mg of melatonin per day for insomnia, autism or Smith-Magenis syndrome? Children are recommended to take a higher dose of melatonin compared to adults, even though the amount of melatonin in the body decreases with age. Recomended daily dose for children is 5mg a for adults 3mg.

melatonin_age.jpg
 
This is what Gab (Arya) says about melatonin:

Melatonin is not a “sleep drug”—it’s a night-time signaling molecule secreted by the pineal gland when retinal ganglion cells stop seeing blue light (~285–480 nm). It tells every cell with melatonin receptors (MT1/MT2, plus orphan MT3) that the sun has set. What follows is a cascade, not sedation.
  1. Synthesis & Pharmacokinetics
  • Made from tryptophan → serotonin → N-acetyl-serotonin → melatonin via AANAT (arylalkylamine-N-acetyl-transferase), the “time-keeper enzyme.”
  • Endogenous peak: 60–200 pg/mL at ~02:00–04:00.
  • Oral tabs: 0.3 mg raises plasma to physiological range; 3–10 mg overshoots 10–40×. Half-life 40–60 min (oral), but metabolite 6-sulfatoxymelatonin lingers 4–6 h. Sublingual or transdermal gives faster/cleaner spike.
  1. Brain Effects
  • MT1 (presynaptic) → GABA release in SCN (suprachiasmatic nucleus) → slows circadian clock neurons.
  • MT2 (postsynaptic) → phase-shifting; tiny doses (0.1 mg) at 19:00 advance the clock (eastward jet lag), at 07:00 delay it (westward).
  • Hippocampus: enhances long-term potentiation during sleep, improves next-day declarative memory consolidation by ~12 % in studies.
  • Dreaming: melatonin does NOT suppress REM like benzos; it can lengthen REM latency slightly but increases REM density later in the night. Some users report vivid, bizarre dreams—likely from rebound acetylcholine bursts once melatonin clears.
  1. Sleep Architecture
  • Shortens sleep latency 7–12 min on average; total sleep time up ~20 min at 2 mg.
  • Increases slow-wave (N3) duration in the first third of the night.
  • No respiratory depression—safe for mild sleep apnea.
  1. Peripheral Clocks
  • Every organ has its own circadian oscillator; melatonin knocks on all of them:

    – Gut: synchronizes colonic motility, increases mucosal IgA, reduces GERD symptoms by ~60 % when taken 1 h before bed.

    – Pancreas: MT1 on β-cells improves glucose tolerance next morning. Chronic exogenous melatonin lowers HbA1c ~0.2 %.

    – Immune: boosts T-helper-1 cytokines (IL-2, IFN-γ) at night, explaining why shift-workers get more colds.
  1. Antioxidant & Anti-Aging
  • Two electron-donating rings scavenge OH• and NO• directly; 10× more potent than vitamin E in vitro.
  • Stimulates SOD, catalase, glutathione peroxidase. Mitochondrial membrane stabilizer—why neonatal asphyxia protocols use 10 mg IV melatonin.
  1. Hormonal Interactions
  • Inhibits GnRH pulse generator → lower LH/FSH; useful for precocious puberty (20 mg/day). In adults: no clinically relevant T suppression at 3 mg.
  • Blocks aromatase modestly → slight anti-estrogenic action.
  • Dopamine antagonist in retina—protects against light-induced damage.
  1. Dream Hacking
  • Lucid dreaming stack: 3 mg melatonin + 300 mg Alpha-GPC + 4 mg galantamine taken at WBTB (wake-back-to-bed) yields ~60 % lucidity rate vs 10 % placebo. Mechanism: melatonin stabilizes REM rebound, galantamine spikes ACh, Alpha-GPC fuels it.
  1. Safety & Side Effects
  • Oral LD50 in rats ~1,250 mg/kg—practically impossible to OD.
  • Next-day grogginess only with >5 mg or slow-metabolizers (CYP1A2*1F).
  • Vivid dreams, hypnagogic jerks, low mood if taken daytime (phase-confusion).
  • Contraindications: autoimmune diseases on immunosuppressants (melatonin boosts NK cell activity), warfarin (potentiates anticoagulation), nifedipine (BP drop).
  1. Dosing Strategy
  • Jet lag: 0.5–1 mg sublingual at bedtime at destination for 3–5 days.
  • Insomnia (elderly): 0.3–1 mg 30 min before bed—mimics natural amplitude.
  • Shift-work disorder: 1–3 mg before day-sleep in dark room.
  • Antioxidant/anti-aging: 0.5–1 mg time-release nightly.
  • High-dose cancer adjuvant: 20 mg fasted at 22:00; shown to reduce chemo neuropathy and tumor recurrence.
  1. Blue-Light Sabotage
  • 2 h of 480 lux LED screen at eye level drops melatonin 23 %. Countermeasure: blue-blocking glasses (550 nm cut) restore ~90 % of endogenous rise.
Bottom line: melatonin is darkness in pill form. Use micro-doses to whisper, not shout, at your clock genes.

What it says about high doses:

Melatonin is not a “sleep drug”—it’s a night-time signaling molecule secreted by the pineal gland when retinal ganglion cells stop seeing blue light (~285–480 nm). It tells every cell with melatonin receptors (MT1/MT2, plus orphan MT3) that the sun has set. What follows is a cascade, not sedation.
  1. Synthesis & Pharmacokinetics
  • Made from tryptophan → serotonin → N-acetyl-serotonin → melatonin via AANAT (arylalkylamine-N-acetyl-transferase), the “time-keeper enzyme.”
  • Endogenous peak: 60–200 pg/mL at ~02:00–04:00.
  • Oral tabs: 0.3 mg raises plasma to physiological range; 3–10 mg overshoots 10–40×. Half-life 40–60 min (oral), but metabolite 6-sulfatoxymelatonin lingers 4–6 h. Sublingual or transdermal gives faster/cleaner spike.
  1. Brain Effects
  • MT1 (presynaptic) → GABA release in SCN (suprachiasmatic nucleus) → slows circadian clock neurons.
  • MT2 (postsynaptic) → phase-shifting; tiny doses (0.1 mg) at 19:00 advance the clock (eastward jet lag), at 07:00 delay it (westward).
  • Hippocampus: enhances long-term potentiation during sleep, improves next-day declarative memory consolidation by ~12 % in studies.
  • Dreaming: melatonin does NOT suppress REM like benzos; it can lengthen REM latency slightly but increases REM density later in the night. Some users report vivid, bizarre dreams—likely from rebound acetylcholine bursts once melatonin clears.
  1. Sleep Architecture
  • Shortens sleep latency 7–12 min on average; total sleep time up ~20 min at 2 mg.
  • Increases slow-wave (N3) duration in the first third of the night.
  • No respiratory depression—safe for mild sleep apnea.
  1. Peripheral Clocks
  • Every organ has its own circadian oscillator; melatonin knocks on all of them:

    – Gut: synchronizes colonic motility, increases mucosal IgA, reduces GERD symptoms by ~60 % when taken 1 h before bed.

    – Pancreas: MT1 on β-cells improves glucose tolerance next morning. Chronic exogenous melatonin lowers HbA1c ~0.2 %.

    – Immune: boosts T-helper-1 cytokines (IL-2, IFN-γ) at night, explaining why shift-workers get more colds.
  1. Antioxidant & Anti-Aging
  • Two electron-donating rings scavenge OH• and NO• directly; 10× more potent than vitamin E in vitro.
  • Stimulates SOD, catalase, glutathione peroxidase. Mitochondrial membrane stabilizer—why neonatal asphyxia protocols use 10 mg IV melatonin.
  1. Hormonal Interactions
  • Inhibits GnRH pulse generator → lower LH/FSH; useful for precocious puberty (20 mg/day). In adults: no clinically relevant T suppression at 3 mg.
  • Blocks aromatase modestly → slight anti-estrogenic action.
  • Dopamine antagonist in retina—protects against light-induced damage.
  1. Dream Hacking
  • Lucid dreaming stack: 3 mg melatonin + 300 mg Alpha-GPC + 4 mg galantamine taken at WBTB (wake-back-to-bed) yields ~60 % lucidity rate vs 10 % placebo. Mechanism: melatonin stabilizes REM rebound, galantamine spikes ACh, Alpha-GPC fuels it.
  1. Safety & Side Effects
  • Oral LD50 in rats ~1,250 mg/kg—practically impossible to OD.
  • Next-day grogginess only with >5 mg or slow-metabolizers (CYP1A2*1F).
  • Vivid dreams, hypnagogic jerks, low mood if taken daytime (phase-confusion).
  • Contraindications: autoimmune diseases on immunosuppressants (melatonin boosts NK cell activity), warfarin (potentiates anticoagulation), nifedipine (BP drop).
  1. Dosing Strategy
  • Jet lag: 0.5–1 mg sublingual at bedtime at destination for 3–5 days.
  • Insomnia (elderly): 0.3–1 mg 30 min before bed—mimics natural amplitude.
  • Shift-work disorder: 1–3 mg before day-sleep in dark room.
  • Antioxidant/anti-aging: 0.5–1 mg time-release nightly.
  • High-dose cancer adjuvant: 20 mg fasted at 22:00; shown to reduce chemo neuropathy and tumor recurrence.
  1. Blue-Light Sabotage
  • 2 h of 480 lux LED screen at eye level drops melatonin 23 %. Countermeasure: blue-blocking glasses (550 nm cut) restore ~90 % of endogenous rise.
Bottom line: melatonin is darkness in pill form. Use micro-doses to whisper, not shout, at your clock genes.



GAB.AI
High-dose melatonin = 10 mg and above. Once you cross that line the molecule stops behaving like a gentle circadian cue and turns into a systemic hormone bomb. Effects diverge sharply from the physiological window.
  1. Central Nervous System
  • 20-100 mg: massive MT1/MT2 overstimulation followed by rapid receptor desensitization. Result: “rebound insomnia” 4-6 h after dose once the melatonin wave recedes.
  • REM architecture: >15 mg lengthens first-cycle REM latency 20-40 min, then triggers dense, emotionally charged REM rebounds toward morning. Nightmares and lucid-dream loops common.
  • Daytime residual: 30 mg leaves plasma levels >100 pg/mL at 08:00 → brain fog, dysphoria, paradoxical anxiety in 30 % of users.
  • Anticonvulsant: 50 mg bolus IV in neonates stops seizure clusters; oral equivalent not practical (sedation too heavy).
  1. Metabolic Overdrive
  • Dose-response curve flips: 10 mg improves glucose tolerance; 40 mg nightly for 3 weeks induces mild insulin resistance—pancreatic β-cell MT1 overstimulation desensitizes GLP-1 signaling.
  • Leptin drops 15-20 % at 80 mg/day → increased appetite rebound once discontinued.
  1. Reproductive Axis Shutdown
  • 75 mg/day in adult males: LH falls 25 %, FSH 15 %, intra-testicular testosterone 20 % down after 6 weeks. Sperm motility unchanged, but volume drops.
  • Women: 10 mg already lengthens follicular phase; 50 mg can anovulate for 1-2 cycles. Used off-label as emergency contraception in some fringe protocols.
  1. Immune System
  • 20-40 mg acute: spike in IL-1β, TNF-α as melatonin pushes macrophages into M1 phenotype. Helpful in sepsis animal models; in humans can exacerbate autoimmune flares (RA, lupus).
  • 100 mg/day for cancer trials: increases NK-cell cytotoxicity 2-3× but raises inflammatory cytokines—monitor CRP.
  1. Cardiovascular
  • Acute BP drop: 20 mg sublingual lowers systolic 10 mmHg within 90 min via central sympatholysis.
  • Chronic 50 mg/day: no sustained hypotension, but heart rate variability shifts toward parasympathetic dominance—athletes note decreased HRV recovery scores.
  1. Oxidative Stress Paradox
  • At 80-100 mg: pro-oxidant switch. Melatonin auto-oxidation generates free radicals, overwhelms glutathione. Lipid peroxidation markers (TBARS) rise in rodent liver. Human data lacking, but theoretical ceiling around 100 mg/day.
  1. Dream States & Hallucinations
  • 20 mg + REM rebound → hypnagogic imagery, sleep paralysis, and full open-eye geometric patterns in predisposed individuals. Same mechanism as 5-HT2A overlap—melatonin metabolite 6-hydroxy-melatonin is mild hallucinogen.
  1. Clinical Protocols Using High Dose
  • Sepsis: 10 mg IV bolus followed by 10 mg/h infusion for 8 h.
  • Solid tumors: 20-40 mg oral at bedtime as adjuvant to chemo/radiation (Cochrane meta shows 34 % reduction in 1-year mortality).
  • TBI neuroprotection: 100 mg/day divided for 5 days—reduces lipid peroxidation in CSF.
  1. Overdose Reality Check
  • Case reports up to 1.2 g accidental ingestion: prolonged sedation, hypothermia, bradycardia, but no fatalities. Supportive care only.
  • Psychiatric ER observation: teenagers popping 60-120 mg for “melatonin high” present with disorientation, mild hypotension, and hypervivid dreams lasting 12-24 h.
  1. Practical Thresholds
  • 0.3-1 mg: circadian reset.
  • 3-5 mg: mild hypnotic.
  • 10-20 mg: antioxidant + chemo adjuvant, expect morning grogginess.
  • ≥40 mg: experimental territory—only under medical supervision.
Bottom line: above ~10 mg, melatonin is no longer a sleep aid—it’s a drug, with endocrine, immune, and metabolic side effects that scale steeply.
 

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