15 replies to this topic

[coldlampin]

can anyone explain to me how Acetylcholinesterase inhibition, by the means of supplementing Huperzine A, might be detrimental to my (male, 20, healthy) long term brain "health". The main concern i have read about is down regulation, possibly permanent. but have not found a solid reasoning behind this concern.

there seems to be no studies on huprezines effect on healthy individuals, which makes me think that an answer to my question will be hard to find but hopefully someone can help.

also if anyone has supplemented Huprezine for extended periods of time, please tell me your experience.

i am starting school again soon and am interested in Huprezines memory enhancing properties.

if i do begin supplementation i would plan on taking huprezine 5 times a week for the entirety of my fall and spring semesters. and discontinue for the one month i have in between them.

thanks in advance for your contributions.

[kismet]

i am starting school again soon and am interested in Huprezines memory enhancing properties.

What memory enhancing effects do you refer to?

there seems to be no studies on huprezines effect on healthy individuals, which makes me think that an answer to my question will be hard to find but hopefully someone can help.

[coldlampin]

i am starting school again soon and am interested in Huprezines memory enhancing properties.

What memory enhancing effects do you refer to?

there seems to be no studies on huprezines effect on healthy individuals, which makes me think that an answer to my question will be hard to find but hopefully someone can help.

from reading many experiences/reviews online about huperzine, it seems to be a consistently Short/long term memory enhancer.

but for me im hoping it would help me retain all the new information i will be learning over the semester. i do not have much difficulty with short term memory but long term "ideas/facts learned days/weeks ago" seems to be a problem of mine. which is a big problem because in class everything builds off what you just learned previously.

hopefully this supplement will help but i am hesitant about trying it.

and i have been fine tuning my study habits this summer which has helped, but am looking for the extra help

[chrono]

There's a good collection of abstracts posted here which raises some important questions about the wisdom of using AChEIs, especially on a regular basis. Basically, inhibiting the enzyme which breaks down ACh will effectively raise levels of that neurotransmitter, but also might interfere with the brain's ability to regulate it, or even cause some long-term neural problems.

I bought a bottle of Hup A recently. In light of these concerns, I used it more than I should have for a few weeks. A few times, I noticed some very rewarding increases in quality and fluidity of thinking. But I can't say I felt any significant improvement in memory (but my memory is pretty sharp to begin with). Will probably be using this once a week, at most.

Unfortunately, I think memory is one of the hardest targets to improve directly via pharmaceutical means. I'd focus more on effective study practices, like meaningful organization of notes and a review schedule of key points, to better move information into long-term memory. Training working memory via dual-n-back might translate to improvement in long-term memory (among other things). And finally, a lot of 'safer' nootropics are available which might help you focus better; concentration and engagement are key requisites for retaining information.

[Curiouser]

Another important issue, outside of long-term AChEI effects:

HupA has NMDA antagonism activity. Try looking up the effects of PCP (also NMDA antagonist) and you'll see the worst-case scenario of how bad this can theoretically be. Now HupA's NMDA antagonistic effects aren't nearly as strong as those in PCP, but if you have any personal or family hx of mental illness, you'd be crazy to try this-- no pun intended. And even if you don't have such a hx, there are still better ways.

If you ultimately decide that you do want to try an AChEI, why not give galantamine a shot? It's the same AChEI mechanism, but that "bonus" nAChH agonism activity is likely to be much more beneficial to you than NMDA antagonism ever could be.

Edited by Curiouser, 30 July 2010 - 11:19 AM.

[KimberCT]

Another important issue, outside of long-term AChEI effects:

HupA has NMDA antagonism activity. Try looking up the effects of PCP (also NMDA antagonist) and you'll see the worst-case scenario of how bad this can theoretically be. Now HupA's NMDA antagonistic effects aren't nearly as strong as those in PCP, but if you have any personal or family hx of mental illness, you'd be crazy to try this-- no pun intended. And even if you don't have such a hx, there are still better ways.

If you ultimately decide that you do want to try an AChEI, why not give galantamine a shot? It's the same AChEI mechanism, but that "bonus" nAChH agonism activity is likely to be much more beneficial to you than NMDA antagonism ever could be.

I really hate this comparison but it keeps popping up.  Recreational doses of PCP are 100-200X greater than that of your common 50mcg HupA dose.  Such tiny doses of PCP, like HupA, are also neuroprotective.

[kassem23]

Unfortunately, I think memory is one of the hardest targets to improve directly via pharmaceutical means. I'd focus more on effective study practices, like meaningful organization of notes and a review schedule of key points, to better move information into long-term memory. Training working memory via dual-n-back might translate to improvement in long-term memory (among other things). And finally, a lot of 'safer' nootropics are available which might help you focus better; concentration and engagement are key requisites for retaining information.

I second that. Don't try go looking for some amazing memory improvement pharmaceutical, despite what the anecdotals tell you. Practice memory techniques for long-term memory improvement.. Spaced repetition schemes comes to mind. Look up ANKI on Google for learning terms, ideas, words or whatever.

[nito]

Cool i didn't know iherb had Alpha GPC, i thought you had to get it through smartpowders etc. I tried CDP with not much success, Alpha i've heard is meant to be better than CDP so I'll probably give it a shot. They have the jarrow forumula. http://www.iherb.com...e-Caps/176?at=0

[chrono]

HupA has NMDA antagonism activity. Try looking up the effects of PCP (also NMDA antagonist) and you'll see the worst-case scenario of how bad this can theoretically be. Now HupA's NMDA antagonistic effects aren't nearly as strong as those in PCP, but if you have any personal or family hx of mental illness, you'd be crazy to try this-- no pun intended. And even if you don't have such a hx, there are still better ways.

I really hate this comparison but it keeps popping up.  Recreational doses of PCP are 100-200X greater than that of your common 50mcg HupA dose.  Such tiny doses of PCP, like HupA, are also neuroprotective.

I agree; comparing pretty much any of the NMDA antagonists that we discuss here to recreational PCP is like comparing a glass of wine to drinking a large bottle of Jägermeister; same general mechanisms, but an ocean apart in practicality.

[coldlampin]

chrono, thank you for the link. pretty clear to me now that Acetylcholinesterase inhibition is just not something to be messing around with.

[zm3thod]

chrono, thank you for the link. pretty clear to me now that Acetylcholinesterase inhibition is just not something to be messing around with.

I tried different nootropics for the last 2-3 years in college and didn't find a stack that definitely worked for me until my final semester. I hated huperzine when I tried it

The combination that worked was alternating Jarrow CDP Choline and Alpha GPC when studying or taking a test, occasional low dose 1fast400 piracetam when studying (too erratic for me to risk on tests), and 500mg Doctor's Best ALCAR on waking during the weekdays.

http://www.imminst.o...showtopic=37123

[NR2(x)]

With your acetylcholine easterase inhibitors you need to be careful of not inhibiting the B---?acetylcholine easterase which is exclusive to perpherial nerves, heard of Iraq war syndrome? Some of them do, some dont

[chrono]

With your acetylcholine easterase inhibitors you need to be careful of not inhibiting the B---?acetylcholine easterase which is exclusive to perpherial nerves, heard of Iraq war syndrome? Some of them do, some dont

Yeah, steer clear of organophosphate and carbamate AChEIs. But I don't think those are readily available to us.

The paper Acetylcholinesterase inhibitors and Gulf War illnesses didn't identify a definite mechanism that was particularly responsible (not sure what "B---?acetylcholine easterase" refers to), and mentioned that clinical AChEIs may or may not share this danger. It seems unlikely, as nothing like GWS has been reported, but coadministration of nerve gas might be something to avoid if you're taking hup A.

[NR2(x)]

lol

butyrylcholinesterase or acylcholine ----

The above and regular inhibitors act act on acetylcholine but butyrylcholinesterase is a ligand that selectively binds to serum acetylcholine easterase. I know that you dont want to inhibit serum or body acetylcholine but cannot think of the mechanism, its unlikely to be singular. And the effects of gulf war syndrome could in part be mediated by ligands that block this peptide.

I know some of the acetylcholine esterase inhibitors do block butyrylcholinesterase but not sure of the specifics, so dont not
galantamine is a acetylcholine agonist rather than a acetylcholine esterase so should be alright

[Ben]

Galantamine might be worth looking into.

[chrono]

galantamine is a acetylcholine agonist rather than a acetylcholine esterase so should be alright

Not quite sure what you're trying to say, here; galantamine is a positive allosteric modulator of nAChR, but is also an AChE inhibitor. I don't think it's a direct agonist.

BuChE doesn't bind to AChE, but performs much the same hydrolytic cleavage of ACh. It's also present in the brain, though I think its function and activity are somewhat unclear.


Galantamine is selective for AChE (with an negligible affinity for BuChE). A 10mg dose only inhibits 36-55% of AChE, doesn't accumulate in the body even after months of treatment, and nearly all AChE inhibition disappears by 30h after the last dose [1] [2]. It sounds like it obviates some of the concerns about Hup A's over-inhibition in the thread I linked above.

Edited by chrono, 03 August 2010 - 07:28 PM.