N&PD Moderators: Skorpio
NMDA antagonists for tolerance (part 2)
http://www.bluelight.ru/vb/threads/...lection-of-the-evidence-and-anecdotal-reports
http://www.bluelight.ru/vb/threads/648050-memantine-don-t-work-for-drug-tolerance
lol thats because D4 receptors dont downregulate, D4 agonism causes the therapeutic effects for ADHD.
JackiesBabyy
Bluelighter
Not always. Many people with ADHD still develop tolerance to their meds overtime and require much higher doses.
cannibalsnail
Bluelighter
I doubt it. The "high" and the stimulant properties of the medication wane, but the increase in focus is constant. I've been taking ritalin at 50mg a day (roughly) for 8 months now and I still get an identical increase in focus. However the stimulant properties are essentially absent. If anything it exhibits sedative properties due to its calming effect on my restless leg syndrome. Most days I can sleep inbetween lectures without an issue.
JackiesBabyy
Bluelighter
I'm just going by what people on ADDforums say in addition to being told many times that tolerance to the therapeutic ADHD effects develops much more slowly than it to the stimulating effects but it still develops.
D1 also (but much less) plays a role in the prefrontal cortes and ADHD effects, this one does downregulate wich explains that.
Day2 of using mdpv and desoxy feel really tired tough was sleep deprived so most likely rapid tolerance, i just tried a low intranasal dose of MXE and see wheter it makes them active again, doubtfull but ill report back.
Seems like it does help.. interesting
preventive concurrent low doses would have been better tough but since mxe has tolerance issues on its own it can only be used half a week to reverse tolerance.
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Someone posted anecdotal info that d aspartic acid completely reversed he's ketamine tolerance and tolerance to all stims too, so will try daily low mxe doses combined that with that see wheter i can replicate he's anecdotals
Ill have to try it as everyone dismisses those anecdotals as bullshit and if i replicate it its placebo, good i managed to get a shitload of anecdotes for my nmda antagonist ppl thread on tolerance for ppl to try or the same would have happened haha.
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Still dont have daa yet tough, atm doing little mxe dosises every 3 hours togheter with my stims and benzo's (and phenibut). Will just see how that goes for now.
MXE has been reported to be very dramatic in reversing withdrawals and tolerance but unlike mem and dxm ppl report tolerance to that effect.
tenshu2k
Bluelighter
At higher doses, it seems like memantine diminishes the effects of Amphetamine a bit for me - While also making the anxiety coming down worse. I'm still experimenting with it, but I feel like a lot of people are overstating the efficacy of memantine.
http://www.ncbi.nlm.nih.gov/pubmed?term=ketamine memantine addiction
If you take a NMDA antagonist to cure tolerance but you're more prone to take drugs impulsively, the benefice isn't really here!
jambabomba
Bluelighter
Brief report of my own experiences with DXM. I've written more from it to OD.
I used DXM extensively during my last benzo withdrawal. It was the most succesful withdrawal in my life. I reduced my clonazepam rapidly in under two weeks from 1,5mg to 0,25mg. Before DXM I was sleeping about 2-4 hours before I woke up in withdrawals. After I added DXM I was soon sleeping over 10 hours a night with only 0,5mg of clonazepam.
So at least I've felt DXM not only kept tolerance low but it actually lowered it. As tolerance set a new lower level very quickly after taper wich has never happened before.
jambabomba
Bluelighter
I'm not so sure I'm an lucky expection. Infact, I believe I'm very sensitive person compared to many others I've met. Allmost hypersensitive. What kind of stimulative effect do you mean? Physical adrenergic stimulation or something mental?
When I first started DXM in benzo withdrawals it did cause me massive panic attacks I suppose because of that noradrenalin. I pushed them through and after few days my panic attacks, fears and depression started to subside. Allso it might have been that my adrenergic receptors were allready downregulated because of previous clenbuterol course.
Edit: Forgot to mention I have also Lyrica and phenibut... wich might help or might not because I have withdrawals from them also.
jambabomba
Bluelighter
So DAA for reversing tolerance to simulants and ketamine only or..? I tried it little amount sometime ago during my benzowithdrawal. Didn't affect positively but seemed to made a little tight feeling.
I think that anecdote only referred to those drugs yes.
Been taking my stim combo daily lately but noticed tolerance mostly to desoxy, it still makes mdpv work alot better tough (dont like mdpv on its own) so daily mxe doses dont really prevent tolerance when taking stims daily (in my case) but most needed a one or 2 day break a week with memantine too when using it for stim tolerance, i suppose i really need regular small breaks. For opiates and benzo's nmda antagonists seem more powerfull (even able to reverse tolerance while using the drug).
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This may be but the old thread clearly indicated that the benefits far outweigh the risks, as people are able to keep their doses lower and keep tolerance (wich is one of the biggest problems with addiction) under control.
Also people reported withdrawing easier and faster.
Resveratrol Preserves Response to Morphine
Emma Hitt, PhD
Resveratrol, a polyphenol found in red wine, also may have an ability to preserve the pain-relieving effect of morphine in rats that are morphine tolerant, a study suggests.
Their work "provides new evidence that resveratrol has potential as an analgesic adjuvant in clinical pain management, particularly for patients who need long-term morphine administration and for morphine-tolerant patients who require better pain relief," the researchers, led by Chih-Shung Wong, MD, and colleagues from Cathay General Hospital, Taipei, Taiwan, conclude.
The results were published in the October issue of Anesthesia & Analgesia, the official journal of the International Anesthesia Research Society (IARS).
Antioxidant and Antiinflammatory
According to the researchers, morphine tolerance includes opioid receptor uncoupling and endocytosis/desensitization, increased binding of β-arrestin to the opioid receptor, glutamatergic receptor activation, and neuroinflammation.
Resveratrol is found in many plant-based foods, including the skin of grapes, and is thought, on the basis of the findings of many studies, to have antioxidant and antiinflammatory effects as well as protective effects on the nervous system.
Dr. Wong and colleagues induced morphine tolerance in rats and then tested whether resveratrol significantly enhanced the effects of morphine.
They found that the pain-relieving response to morphine was only about 20% of normal in the morphine-tolerant rats, whereas in similar rats receiving resveratrol, morphine responses were restored to about 60% of normal.
A potential mechanism of action for resveratrol for improving the morphine response is that long-term morphine infusion upregulated expression of protein subunits of the N-methyl-D-aspartate receptor (NMDAR), Dr. Wong and colleagues speculate.
"Emerging evidence suggests that NMDAR activation has a crucial role in morphine tolerance, and blockade of NMDAR function effectively attenuates morphine tolerance," they note. Resveratrol also blocked the expression of cytokines, potentially decreasing the neuro-inflammatory response in rats with morphine tolerance.
The study was supported by a grant from the National Science Council and the Cathay General Hospital, Taipei, Taiwan. The authors have disclosed no relevant financial relationships .
Anesth Analg. 2012;115:944-952. Abstract
Medscape Medical News © 2012 WebMD, LLC
Send comments and news tips to [email protected].
Cite this article: Resveratrol Preserves Response to Morphine. Medscape. Nov 20, 2012.
sekio
Bluelight Crew
The problem with flavonoids is that they are poorly absorbed (polyphenols) and quite easily destroyed (like by stomach acid or enzymes). I don't think blood levels of e.g. quercertin are achievable at a level like what people use for treating lab rats.
Another problem is lack of selectivity, many flavones are MAO inhibitors too.
