Agreed. But, I thought I'd post the study above because it just came out, and definitely adds to the theoretical library of combatting tolerance with more tried and true NMDA antagonists like memantine & dxm in humans.
-
N&PD Moderators: Skorpio
NMDA antagonists for tolerance (part 2)
- Thread starter MeDieViL
- Start date
Agreed. But, I thought I'd post the study above because it just came out, and definitely adds to the theoretical library of combatting tolerance with more tried and true NMDA antagonists like memantine & dxm in humans. 
lenses
Bluelighter
Curcumin is a pretty noticable MAO inhibitor for me, but its the speedy side of MAO...
I think the reason people have problems with curcumin is bioavailability issues. I have taken many brands and done much research on curcumin dosage forms and theres a brand called bcm-95 that is superior to any curcumin out there (look for the softgels-curamed!) .
from : http://journals.lww.com/neuroreport...min_blocks_chronic_morphine_analgesic.12.aspx
Theres a lot of info about curcumin and its effect on NMDAr and its modulatory and protective effects on NMDA toxicity! Would be pretty helpful to do a course of curcumin after kicking BUPE for me,i imagine...
-lensesThis thread is about people using a combo of quercetin for its PDE4 inhibiting effects and a cAMP increaser like forskolin for the induction of LTP (long term potentiation) anecdote after anecdote report that quercetin actively works in normal doses, low bioavailability means shit if in the end its still enough to provide positive effects.
http://www.longecity.org/forum/topic/51732-chemically-induced-ltp/King Kong
Bluelighter
Many traditional medicinal plants have a large content of flavonoids. I don’t prove that flavonoids are the active ingredients, but it’s a good point for this hypothesis. Which could mean that flavonoids possess an activity in spite of their poor bioavailability.jambabomba
Bluelighter
That's true but some companies are making products that has good bioavailability. If I remember correctly ex. Life Extension do its own research on this area and has patented some products with enchanced bioavailability. I'm not sure if ubiqinol was their patent..
About curcumin I have Now product (Bio-curcumin phytosome) and it definately absorps because it made a short lived mild serotonin syndrome to me. Not serious but enough that I noticed I got too much of it (shivering, excessive sweating, nausea, panic and confusion). It wasn't that alone but I used amitriptyline and tramadol together and took curcumin with tramadol at morning. Tramadol and amitriptyline together are ok, good serotonin boost but they haven't cause any problems ever to me.
On a side note, when I took that curcumin I didn't even knew then it was MAO inhibitor. So hard to believe it was placebo
sekio
Bluelight Crew
because some of these compounds are only active in the ~1 gram IV level (rosiridin for instance). mix that with low bioavailibility and you have a recipe for a bad time, because you have to take 50 gm of compound to produce an effect
and besides at that dose level the compound *must* be very selective, because if it has any other actions they will surely have an effect at large dose levels. in addition poro biaoavailibility could mean that many side metabvolites are made, or most of the drug has effects on perhiphery
and do you really want to be eating 1/4 pounds of tumeric daily? its liable to get expensive
Epsilon Alpha
Bluelighter
Doubt it, outside the brain the stuff doesn't stick around in the body too long. Curcumin has a lot of promise, but it is quite possibly the dirtiest "drug" I have ever worked with. I really wanted to probe epigenetic mechanisms of tolerance and it was the main well researched, easily available tool we had access to. But, handle it incorrectly and you will be yellow as can be
sekio
Bluelight Crew
I wonder if you could see epigentic changes resulting from a dietary changeover to heavily spiced curries 3 meals a day?
Some of them yes, but the discussed ones have enough anecdotes that show they are either bioavailable enough or the taste of curcumin induces a massive placebo effect compared to bad tasting flavonoids.Anecdotal evidence, but...I take 150mg of DXM every day and have for many years. One of the side effects is being completely immune to nicotine addiction. I smoke when I want to, which is rarely, not when I don't, which is normally. I also don't seem to develop a tolerance to opiates, but I skip my DXM dose when I take narcotics. Yes, it lowers the effective dose, but it also kills some of the euphoria (while enhancing pain relief). I've used DXM to come off morphine and methadone, after a many month binge, and all I did was trip balls. Take about 250mg when the WD sets in and wait for gods to come.
blueberries
Bluelighter
I agree with cannibalsnail, I've been taking amphetamines for a few months now and no longer feel any sort of high but I know it's working and still get a great deal of focus from it. If I want the high back I'll take 3-FA instead but my tolerance to speed's stimulant properties is so high it's just wasteful to use it for that.True, but I don't think the mood effect totally goes away. That's what I've been told by an expert with thirty years of experience, and in my own experience after about three months.Back on DXM for tolerance, flavonoids are cool but seems like for me only nmda antagonists are truly effective.
When you stop dxm for example tolerance will go up like if you never used dxm.
Ive allways retained the rewarding effects of stims completely.I have some question about Tramadol addiction and NMDA antagonists use for tolerance reduction.
I know like everybody that DXM and tramadol shouldn't be mixed at recreative dose. But how to deal with tramadol addiction with NMDA antagonists? It is possible to take 60mg DXM 2 time a day with tramadol? I did the combo once (with just 60mg DXM) and didn't feel any bad reaction. Maybe the serotoninergic effect of DXM at 60mg is too low to interact with tramadol?
Or is it to dangerous to combine DXM at 60mg and tramadol, and do I have to prefer memantine?
Moreover, tramdol withdrawal is like an opiate and a SNRI combined. I think NMDA antagonist deal with great success with the opiate part of the physical dependence, but what about the SNRI part? Is DXM or memantine have a great impact on this action too?
That's because if you truly suffer from ADD/ADHD your brain is hard-wired to perform inadequately -- resulting in things such as depression/anxiety from outright exhaustion. If you fix these underlying issues with enhanced focus, then yes, the mood effect will remain. But, don't expect it to be as a result of anything but enhanced clarity with extended use.It shares a common mechanism with a plethora of antidepressants, notwithstanding adrenergic/dopaminergic activity, see the tolerance prevention thread. Its a good one.None of those effects last. Anyone who has taken therapeutic doses of amphetamine long-term can attest to this. Other than better transmission in the prefrontal cortex, you're not going to get energetic, euphoric, or in many cases motivated as you keep going.Trust me, they do. One can't tell the effects on the brain just from a feeling. I've read up on this. Unless someone like EA or Sekio says I'm wrong. I'm not talking about euphoria, I'm talking,ring about a neurological mechanism against depression. If you abuse it, like alcohol, its detrimental in many ways.
