10 replies to this topic

[purerealm]

3 mg used to knock me out everytime, but now not even 9 will have as strong effects, even though I haven't taken melatonin in a long time. Am I ever going to get the same effects from 3 mg?

[sentinel]

In the absence of any more learned responses I would volunteer that the weight of opinion favours that one does not build a tolerance to melatonin and that 3 is generally the magic number and you should not need to go over this.

Based on my personal experience 3mg was always fine, then I bought from another (reputable) manufacturer and didn't get anything like the same effect ie more drowsy than "knocked out" and a tendency to wake up and be wide awake after c 4 hours which isn't ideal.

Taking a step back I tried a friends brand one evening and it worked as before so, given that you haven't tried it for a while it could be something as mundane as just not being as good a product/manufacturer.

Not terribly exciting but a possible explanation.

Sentinel

[jackinbox]

After 1 year on melatonin, I don't see any sign of tolerance. I use 3 mg almost every night. I use instant release if I want to wake up early in the morning and timed-release for a longer sleep. I used valerian too for the past year but I switched to L-Theanine recently. It's too hard to wake up in the morning when I take Valerian.

[xanadu]

I noticed a sort of tollerance to it. 3mg has almost no effect on me now.

[jackinbox]

Try to mix it with something else (valerian, bacopa, theanine, rhodiola, etc). Melatonin work better when you feel tired or at least relaxed. That's why it's soo good for jet lag. It doesn't relax your body. It just tell it "time to sleep now". I take my theanine or valerian about 1 hour before going to bed and my melatonin just before closing my eyes.

[purerealm]

I forgot where I read it but I've read that for most people 3 mg melatonin is more than necessary. With all that extra melatonin the body shuts off melatonin production or shuts off receptors or something like that. Of course I've also read that very large amounts of melatonin are good for the body, but I'm not sure what to think. I don't seem to get a very big effect from theanine and I've had to resort to GABA which actually does seem to help my sleep despite having read reports of low brain barrier absorption.

[nutrovitasub]

Melatonin is a neurohormone produced in humans by the pineal gland. A favorite of travelers, it governs the body's circadian rhythms. Melatonin is also a potent antioxidant.
Melatonin is a hormone secreted by the pineal gland that aidsbiorhythm regulation. Biorhythm is disturbed by stress, crossingtime zones and changing work shifts. Melatonin production also declines with age. Vitamin B6 aids melatonin metabolism.
Melatonin supports healthy sleep patterns. The body naturally releases Melatonin in response to changes in light, with melatonin levels rising at night. It is in this way that melatonin helps promote sleep.

For Melatonin Produts
Melatonin

For More Information Nutrovita

[Florian Xavier]

any more infos on melatonin tolerance ? thanks

[jadamgo]

3 is a lot more than you need, though I personally didn't have any tolerance issues with that.

Still, maybe our bodies work differently. Try sublingual melatonin, 0.5mg or 1mg right at bedtime. If that doesn't work, try time-release melatonin, 0.3mg, 0.7mg, or 1mg a few hours before bedtime. If that still doesn't work, you probably have primary sleep-onset insomnia, not a circadian rhythm disorder.

[Epigenesis]

I have 300mcg tablets and they work pretty well for me when I need them. In an MIT study, it was shown 300mcg worked better than 3mg for treating insomnia. Although one caveat of the study was it was done on people over the age of 50, not sure what difference age makes. A lower dosage should result in less tolerance as well. I don't think I have enough posts to post links I think, but there is a long thread on reddit about it, if you google the title "I want to stress the importance of trying low dose(.25mg~) melatonin compared to high dose(3mg+)" it should show up.

[medicineman]

Can someone find out how much valproate the mice were bathed in?

Novel targets for valproic acid: up-regulation of melatonin receptors and neurotrophic factors in C6 glioma cells.

AuthorsCastro LM, et al. Show all Journal
J Neurochem. 2005 Dec;95(5):1227-36.

Affiliation
Abstract
Valproic acid (VPA) is a potent anti-epileptic and effective mood stabilizer. It is known that VPA enhances central GABAergic activity and activates the mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) pathway. It can also inhibit various isoforms of the enzyme, histone deacetylase (HDAC), which is associated with modulation of gene transcription. Recent in vivo studies indicate a neuroprotective role for VPA, which has been found to up-regulate the exp<b></b>ression of brain-derived neurotrophic factor (BDNF) in the rat brain. Given the interaction between the pineal hormone, melatonin, and GABAergic systems in the central nervous system, the effects of VPA on the exp<b></b>ression of the mammalian melatonin receptor subtypes, MT1 and MT2, were examined in rat C6 glioma cells. The effects of VPA on the exp<b></b>ression of glial cell line-derived neurotrophic factor (GDNF) and BDNF were also examined. RT-PCR studies revealed a significant induction of melatonin MT1 receptor mRNA in C6 cells following treatment with 3 or 5 mm VPA for 24 h or 5 mm VPA for 48 h. Western analysis and immunocytochemical detection confirmed that the VPA-induced increase in MT1 mRNA results in up-regulation of MT1 protein exp<b></b>ression. Blockade of the MAPK-ERK pathway by PD98059 enhanced the effect of VPA on MT1 exp<b></b>ression, suggesting a negative role for this pathway in MT1 receptor regulation. In addition, significant increases in BDNF, GDNF and HDAC mRNA exp<b></b>ression were observed after treatment with VPA for 24 or 48 h. Taken together, the present findings suggest that the neuroprotective properties of VPA involve modulation of neurotrophic factors and receptors for melatonin, which is also thought to play a role in neuroprotection. Moreover, the foregoing suggests that combinations of VPA and melatonin could provide novel therapeutic strategies in neurological and psychiatric disorders.

PMID 16313512 [PubMed - indexed for MEDLINE]
Full text: Blackwell Publishing

I'm planning to give valproate a trial @100mg daily, with two days off per week.

Edited by medicineman, 19 February 2014 - 02:52 PM.