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Thread: (L)-Huperzine-A

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    Senior Member Darksanity's Avatar
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    Quote Originally Posted by PubMed
    Second generation cholinesterase inhibitors: effect of (L)-huperzine-A on cortical biogenic amines.

    Zhu XD, Giacobini E.



    Department of Pharmacology #1222, Southern Illinois University School of Medicine, Springfield 62794-9230, USA.



    L-Huperzine-A (Hup-A), a natural cholinesterase inhibitor (ChEI) derived from the Chinese herb Huperzia serrata, was administered systemically (i.p.) or locally through the microdialysis probe into the rat cortex. Systemic Hup-A significantly increased acetylcholine (ACh) levels above baseline at doses of 0.1, 0.3, and 0.5 mg/kg; the increases were 54%, 129%, and 220%, respectively. Norepinephrine (NE) and dopamine (DA) levels were also increased 121% and 129% above baseline at 0.3 mg/kg, and 143% and 153% at 0.5 mg/kg. Peak cholinesterase (ChE) inhibition was 23% at 60 min with the 0.3 mg/kg dose. Huperzine-A, perfused through the microdialysis probe, produced a maximal increase of ACh levels of 3090% and 7790% at concentrations of 5 and 50 microM. The ACh increase seen at both concentrations lasted at least 6 hr. At the 5-microM dose, NE and DA were increased by 214% and 386%; at the 50-microM dose, NE and DA were increased by 216% and 1141%. There were no changes of 5-HT levels. With local administration (via the probe), both doses produced facial-forelimb seizures that lasted throughout the perfusion. Our results show that Hup-A is a potent inhibitor of ChE which penetrates into the brain and produces a dose-dependent increase of ACh, NE, and DA in rat cortex. This effect is seen with both systemic and local intracerebral administration, suggesting cortical as well as subcortical effects of the drug.
    http://www.ncbi.nlm.nih.gov/sites/entrez?c...pt=AbstractPlus



    Sounds interesting...

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    Definitely sounds interesting, but I read on these forums that HupA downregulates something, I forget what it was. Anyone know?

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    Senior Member Benson's Avatar
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    Quote Originally Posted by Concentrate' post='414638' date='Jul 28 2007, 05:38 AM
    Definitely sounds interesting, but I read on these forums that HupA downregulates something, I forget what it was. Anyone know?


    Acetylcholinerase.
    Remember, believe none of what you hear and half of what you see...





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    Senior Member ziddy's Avatar
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    Downregulation of ACE in what brain regions? Is bradykinesia/dystonia/tremors/impairment of fine motor skills/etc. a common effect of prolonged use?
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    Senior Member Benson's Avatar
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    Well its not wasp spray but overuse often leads to neck/shoulder tension. I suppose if you kept at it, dystonia or some of the other consequences of AChE inhibition would manifest.
    Remember, believe none of what you hear and half of what you see...





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    Quote Originally Posted by Benson' post='414665' date='Jul 28 2007, 07:30 AM
    Acetylcholinerase.




    Correct me if Im wrong, but isnt that a good thing? Obviously we dont want to destroy the ability to produce acetylcholinerase, but a little down regulation wouldn't be so bad. I mean thats the whole point of HupA in the first place, isnt it?

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    Quote Originally Posted by Concentrate' post='414700' date='Jul 28 2007, 05:35 PM
    Correct me if Im wrong, but isnt that a good thing? Obviously we dont want to destroy the ability to produce acetylcholinerase, but a little down regulation wouldn't be so bad. I mean thats the whole point of HupA in the first place, isnt it?


    Sure. Like most thing, moderation is the key.
    Remember, believe none of what you hear and half of what you see...





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    Quote Originally Posted by uniquenutrition' post='414675' date='Jul 28 2007, 12:24 PM
    It's something you probably should be taking everyday even cycle it (mon-fri or every other day) to protect against brain aging. Thats not to say you can't take massive doses and have a reaction or simply be sensitive to it.


    Everyone should take Huperzine A? It's a plant derived drug, not a vitamin.



    AChE inhibitors should be taken with caution and preferably under the guidance of a physician, like other drugs with a similar mechanism of action (donepezil, tacrine, etc). The suggestion that everyone, of every age group and demographic, should take HupA because of "anti-aging" benefits is simply irresponsible and entirely unfounded (not to mention shameful as a marketing technique).



    WRT the original thread topic, HupA has been shown, in rodents, to increase the release of DA and NE in certain brain regions associated with downstream cholingeric stimulation. However, increased release of these neurotransmitters does not equate necessarily to a stimulant-type effect characteristic of other catecholamine releasing agents. Excess cholinergic stimulation can also be a contributing factor to the various dimensions of clinical depression. HupA does have clinical benefits, but without a specific goal in mind (other than "anti-aging") it is probably not worth the cost or potential risk.
    "When men are most sure and arrogant they are commonly most mistaken, giving views to passion without that proper deliberation which alone can secure them from the grossest absurdities." - David Hume

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    Quote Originally Posted by uniquenutrition' post='414675 View Post
    Everyone should take Huperzine A? ..........The suggestion that everyone, of every age group and demographic, should take HupA because of "anti-aging" benefits is simply irresponsible and entirely unfounded (not to mention shameful as a marketing technique)....


    Dopamine, considering your avatar (chomsky) contribution to linguistics, you yourself might at least pay sufficient attention to the use of written language, so as not to so easily go about misquoting a person, then using that misquote to attack a person.



    "It's something you 'probably' should" DOES NOT DIRECTLY EQUAL "Everyone should"



    Furthermore, Steve has clearly given the warning : "Thats not to say you can't take massive doses and have a reaction or simply be sensitive to it."



    I would think Steve's message is therefore quite clear, and indeed responsible i.e. HupA is probably beneficial, but be careful.





    My .02 cents.



    Hypno.





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    Quote Originally Posted by Hypnoracetam' post='417626' date='Aug 13 2007, 12:56 AM
    Dopamine, considering your avatar (chomsky) contribution to linguistics, you yourself might at least pay sufficient attention to the use of written language, so as not to so easily go about misquoting a person, then using that misquote to attack a person.



    "It's something you 'probably' should" DOES NOT DIRECTLY EQUAL "Everyone should"



    Furthermore, Steve has clearly given the warning : "Thats not to say you can't take massive doses and have a reaction or simply be sensitive to it."



    I would think Steve's message is therefore quite clear, and indeed responsible i.e. HupA is probably beneficial, but be careful.





    My .02 cents.



    Hypno.

    >


    "It's probably something you should be taking everyday" - this is a blanket statement insinuating the HupA has universal application, which is unsupported by the research literature. There have been one or two studies on healthy humans (short term use) so it is not responsible to suggest use of a plant derived drug as if it were an essential ingredient to healthy living. If "should" meant "not everyone" by implication, then it should have been made much more sufficiently clear that there are people who should not take HupA for specific and generalized reasons.



    People don't need a doctor telling them what to take and what not to take in every regard. Unless you're an idiot. It's a plant compound no different than a compound found in food and is safe when taken as directed.



    L-Huperzine A is highly neuroprotective and since everyone brain's damage as they age you can either let it happen or take something it block it. If you want your brain to rot be my guest.


    What food is Huperzine A found in again? Have you ever eaten Chinese club moss? There are a lot of powerful, plant-derived alkaloids that are commonly considered drugs, and HupA is no exception. Of course people can put what they want in to their body, but the general guideline for taking drugs for certain purposes is in the guidance of a physician. "Everyone's brain" is not damaged to the point of necessitating pharmacological intervention. Do you recommend that your customers take plant derived drugs that you sell without first consulting with a physician?
    "When men are most sure and arrogant they are commonly most mistaken, giving views to passion without that proper deliberation which alone can secure them from the grossest absurdities." - David Hume

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    The basic principle is that it is safer to take APPROPRIATE pecursors e.g. CDP choline, etc and let the body make what it needs, then to monkey with Acetyl cholinesterase. Not that Huperzine taken in responsible doses is likely to be dangerous, for most people because it's not. But when you take precursors the body has much more leeway to prevent you from doing anything stupid. Inhibit Acetyl cholinesterase and the body has less recourse if there is a problem. The point is for healthy people if precursors will get you what you need why bother with huperzine?
    <span style="color:#FF0000"><span style="font-family:Arial Black">THEORY=/REAL WORLD</span></span>

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    Quote Originally Posted by Dopamine' post='417641 View Post
    it should have been made much more sufficiently clear that there are people who should not take HupA for specific and generalized reasons.


    Again, IMHO, I think Steve did this when he gave the caution "Thats not to say you can't take massive doses and have a reaction or simply be sensitive to it."



    i.e.



    'take massive doses and have a reaction' seems like a fairly specific kind of a warning.



    AND



    'simply be sensitive to it' seems like quite a generalized kind of a warning.



    Those are my interpretation(s), anyway, FWIW.



    Your own interpretation(s) of course may differ. Indeed it seems that they do. And it also seems to me that you cannot really begin to know many other people's interpretations unless you do a survey, or something.



    Is it worth your time & effort to start a large-scale linguistic study, Mr. Chomsky? ;-)



    At the end of the day, (language interpretations notwithstanding), HupA is completely legal, and therefore, whatever your own personal opinions/interpretations/conclusions, I imagine it shall continue to be 'business as usual'.



    A finely-spun word dabbler you may certainly be, Mr Chomsky, but still....... 'Supply & Demand' is an even older game than that, doncha think?













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    You may have interpreted it that way, Dopamine, but others, including myself, may not.



    IMHO..... 'probably' DOES NOT EQUAL 'definitely'



    'probably' seems to me a word that carries more personal choice than 'definitely'.


    My interpretation seems to be verified by Steve's own words, i.e. everyone's brain ages, HupA protects against such aging, therefore everyone should ("probably") take HupA. Again, "probably" was not qualified by any specification or exempted category, i.e. those who should not take the supplement/drug.



    Again, IMHO, I think Steve did this when he gave the caution "Thats not to say you can't take massive doses and have a reaction or simply be sensitive to it."



    i.e.



    'take massive doses and have a reaction' seems like a fairly specific kind of a warning.



    AND



    'simply be sensitive to it' seems like quite a generalized kind of a warning.


    Being sensitive to a compound is very different from contraindication. There are segments of the population who should not take HupA or any AChEi because of pre-existing conditions. What Steve said was not a warning at all, but rather the elementary observation that some people may be sensitive to the effects of HupA, as is the case with any drug.



    The fact is that those who publicly suggest that everyone ought to take a particular substance, elementary precautions aside (i.e. individual sensitivity, and overdose), carry a heavy burden of evidence. Being familiar with the literature on HupA, it seemed to me to be completely unsubstantiated to say that HupA "should probably" be taken by everyone, as if it were a vitamin or nutrient essential to life itself. The fact that he doesn't even recommend consultation with a physician prior to self-administering plant-derived drugs demonstrates to an even greater extent the irresponsibility of such a recommendation.



    Of course Steve can say whatever he wants to sell his products. However, I won't stand by idly without calling out such pseudoscientific postulations.



    Your own interpretation(s) of course may differ. Indeed it seems that they do. And it also seems to me that you cannot really begin to know many other people's interpretations unless you do a survey, or something.



    Is it worth your time & effort to start a large-scale linguistic study, Mr. Chomsky? ;-)



    At the end of the day, (language interpretations notwithstanding), HupA is completely legal, and therefore, whatever your own personal opinions/interpretations/conclusions, I imagine it shall continue to be 'business as usual'.



    A finely-spun word dabbler you may certainly be, Mr Chomsky, but still....... 'Supply & Demand' is an even older game than that, doncha think?


    The demand for and selling of nootropics and related substances is not the issue. Rather, it is those who propagate the idea that everyone should take certain "elixers of youth" because they are universally beneficial. If people want to believe it, lack of evidence not withstanding, that is their choice. However, such BS shouldn't go unscrutinized in a forum that calls itself scientific.
    "When men are most sure and arrogant they are commonly most mistaken, giving views to passion without that proper deliberation which alone can secure them from the grossest absurdities." - David Hume

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    I agree with Dopamine on this one, Steve's claim that "everyone should probably take L-Huperzine A" is irresponsible and unsubstantiated empirically. There's no research that taking this stuff in the long-term is safe in normal, healthy adults.



    Furthermore, there's actual research that shows that humans need Acetylcholine levels to be low during sleep in order to consolidate memories. When you take Acetylcholinesterase inhibitors like L-Huperzine-A anywhere near bedtime, it actually significantly impairs your ability to remember memories from the day before. A random student or employee taking this stuff to improve studying or concentrate at work, without knowing this literature or side effects, would be making things worse for themselves, even though they're trying to get "nootropic" effects.
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    Senior Member Hypnoracetam's Avatar
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    Quote Originally Posted by Dopamine' post='417702 View Post
    .....There are segments of the population who should not take HupA.......Being familiar with the literature on HupA...


    I must admit that I myself do not have that familiarity/background, (and it would be foolish of me to pretend otherwise)



    Quote Originally Posted by Dopamine' post='417702 View Post
    it seemed to me to be completely unsubstantiated to say that HupA "should probably" be taken by everyone, as if it were a vitamin or nutrient essential to life itself. The fact that he doesn't even recommend consultation with a physician prior to self-administering plant-derived drugs demonstrates to an even greater extent the irresponsibility of such a recommendation.


    I'm sure at some time or another I've heard/seen coffee ads that say something like "Everyone enjoys a nice cup of coffee. It's the natural way to start your day!"



    Well, fine, such is the world of advertising on planet earth, I suppose.



    Myself, I'm happy to appreciate Steve's follow-on warning (re HupA) : "Thats not to say you can't take massive doses and have a reaction or simply be sensitive to it."



    Furthermore, a peek at the page on Unique Nutrition web-site that sells HupA, carries (at bottom of page) the disclaimer "These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease." There is also mention of research done into HupA, and names of researchers, which could, presumably, be looked into by any potential consumer of HupA, should they so wish.



    This is A LOT more than a 'caffeine-seller' gives on label of a jar of coffee!



    It seems to me, in this context, that it could in fact be said that Steve has been even more responsible than the giant "Nestle". (Yeah, I know, caffeine & HupA are different substances, but still...... one could argue they both have nootropic effect, are both quite potent, and are both freely available as legal substances)



    Quote Originally Posted by Dopamine' post='417702 View Post
    The demand for and selling of nootropics and related substances is not the issue.


    I hear what you are saying.



    But still..... HupA, coffee, whatever...... life goes on.



    Quote Originally Posted by Dopamine' post='417702' date='Aug 13 2007, 06:42 PM
    Rather, it is those who propagate the idea that everyone should take certain "elixers of youth" because they are universally beneficial. If people want to believe it, lack of evidence not withstanding, that is their choice.


    It most certainly is their choice.



    And my choice, right now, although hitherto completely un-warned to possible dangers by the conglomerate caffeine peddlers, is to go get myself another cup of coffee.



    Mmmmmmm, nice.



    Cheers!







    Hypno.





    >

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    Quote Originally Posted by SoulSeeker' post='417731 View Post
    Furthermore, there's actual research that shows that humans need Acetylcholine levels to be low during sleep in order to consolidate memories. When you take Acetylcholinesterase inhibitors like L-Huperzine-A anywhere near bedtime, it actually significantly impairs your ability to remember memories from the day before.


    That's interesting.



    If correct, then no HupA with the bedtime vodka, I mean cocoa.



    I'm curious to know, in your opinion, are there are other substances that specifically taken near bedtime would impair ability to consolidate memory?



    Also, what substances (if any) taken near bedtime would encourage consolidation of memory?



    I ask these questions, as I am spending some time each day learning some new stuff, and (extra) memory consolidation whilst sleeping may be of value to me.



    Thanks.



    Hypno.







    >

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    An advertising label is entirely different than the owner of a company representing his products on a scientifically based forum. Further, as you noted, caffeine in coffee and concentrated alkaloid extracts in pills is an apples to oranges comparison. The basic fact is that you can't equate one drug's safety with another simply by virtue of the fact that they are both "drugs." We could go into the painstaking details of why caffeine isn't on a comparative level with HupA, but I hope the objection has been addressed.



    Furthermore, a peek at the page on Unique Nutrition web-site that sells HupA, carries (at bottom of page) the disclaimer "These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease." There is also mention of research done into HupA, and names of researchers, which could, presumably, be looked into by any potential consumer of HupA, should they so wish.


    It is, in most instances, a legal requirement to at least print on the label (and other extraneous material) that the claims have not been supported by the FDA. UN's page could simply list the precautions and adverse reactions that, for example, are listed in the PDR -



    "PRECAUTIONS

    Huperzine A should be avoided by children, pregnant women and nursing mothers.



    Because of possible adverse effects in those with seizure disorders, cardiac arrhythmias and asthma, those with these disorders should avoid huperzine A. Those with irritable bowel disease, inflammatory bowel disease and malabsorption syndromes should avoid huperzine A.



    ADVERSE REACTIONS



    Adverse effects reported with huperzine A include gastrointestinal effects, such as nausea and diarrhea, sweating, blurred vision, fasciculations and dizziness. Possible adverse effects include vomiting, cramping, bronchospasm, bradycardia, arrhythmias, seizures, urinary incontinence, increased urination and hypersalivation."


    I sincerely trust that you will be devoting as much of your energy to the giant Nestle as to Unique-Nutrition. ;-)



    Furthermore, I would humbly suggest that IF it is your ultimate intent to bring down Unique Nutrition, then this intent may not concur with those of us in the Avant/M&M community who enjoy the responsible use of nootropics, as supplied by Unique Nutrition (& others).


    It is not my intent to bring anyone "down" or anything of the sort. I am glad there are companies bringing new products to the market, and I hope UN continues to do very well.



    Correct me if I'm wrong, but are you suggesting that because I do not endorse UN that I do not then have a place in discussion? I sincerely hope other members would disagree. If your going to question my intent, and other related ad-hominem attacks, then I suggest you present it within the proper venue (i.e. the lounge).
    "When men are most sure and arrogant they are commonly most mistaken, giving views to passion without that proper deliberation which alone can secure them from the grossest absurdities." - David Hume

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    Quote Originally Posted by Dopamine' post='417758 View Post
    Further, as you noted, caffeine in coffee and concentrated alkaloid extracts in pills is an apples to oranges comparison. The basic fact is that you can't equate one drug's safety with another simply by virtue of the fact that they are both "drugs." We could go into the painstaking details of why caffeine isn't on a comparative level with HupA, but I hope the objection has been addressed.


    I realise that an absoultely 100% direct comparison would be ludicrous, but nevertheless I'm inclined to think SOME comparison is not unfair. IMHO.



    Quote Originally Posted by Dopamine' post='417758 View Post
    It is not my intent to bring anyone "down" or anything of the sort. I am glad there are companies bringing new products to the market, and I hope UN continues to do very well.


    Good to know this.



    Quote Originally Posted by Dopamine' post='417758 View Post
    I sincerely hope other members would disagree. If your going to question my intent, and other related ad-hominem attacks, then I suggest you present it within the proper venue (i.e. the lounge).


    No man, no offense intended, you just seem quite often 'on the attack', and I've sometimes wondered why.



    No biggie.



    On a more general note, I was thinking earlier, that, yes, there ARE risks with nootrpoics, but we are all adults, and must have a level of self-responsibility. It behooves us all to do at least SOME research, before consuming these products. We can't expect nootropic (etc) suppliers to hold our hands every step of the way, and print endless precautions, etc.



    Again, (if you'll forgive the less-than-100%-accurate comparison) I can walk into just about any pub (& many other places) in the U.K., and purchase that severely mind-altering substance called 'alcohol', which carries very little in the way of precautions re adverse reactions, etc. Surprising, really, considering the resultant road carnage caused by alcohol fuelled drivers.



    It's time for revolution. All pubs must make way for noop-bars. The past is dark, the future is smart. Let the evolution begin!

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    (We can dream, eh?)











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    That's my point exactly, you were taking this stuff without being aware of the side effects it has on memory. L-Huperzine is a VERY powerful Acetylchholinesteraste inhibitor, prelimary research shows that its stronger than most prescription Alzheimers drugs on the market. People should NOT be taking powerful Alzheimers drugswithout knowing what they're doing. This is not like taking a choline or lechithin supplement, you could never get this effect from food like eggs or soy. This is a powerful drug that should not be toyed around with, and its irresponsible to say "everyone should probably take it" and that no medical supervision is neccessary. Maybe for simple supplements, but not with this stuff. Citation:



    ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

    PNAS - Proceedings of the National Academy of Sciences

    Published online before print February 6, 2004, 10.1073/pnas.0305404101



    Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation



    Steffen Gais *, and Jan Born



    Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany



    The neurotransmitter acetylcholine is considered essential for proper functioning of the hippocampus-dependent declarative memory system, and it represents a major neuropharmacological target for the treatment of memory deficits, such as those in Alzheimer's disease. During slow-wave sleep (SWS), however, declarative memory consolidation is particularly strong, while acetylcholine levels in the hippocampus drop to a minimum. Observations in rats led to the hypothesis that the low cholinergic tone during SWS is necessary for the replay of new memories in the hippocampus and their long-term storage in neocortical networks. However, this low tone should not affect nondeclarative memory systems. In this study, increasing central nervous cholinergic activation during SWS-rich sleep by posttrial infusion of 0.75 mg of the cholinesterase inhibitor physostigmine completely blocked SWS-related consolidation of declarative memories for word pairs in human subjects. The treatment did not interfere with consolidation of a nondeclarative mirror tracing task. Also, physostigmine did not alter memory consolidation during waking, when the endogenous central nervous cholinergic tone is maximal. These findings are in line with predictions that a low cholinergic tone during SWS is essential for declarative memory consolidation.

    --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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    Quote Originally Posted by Hypnoracetam' post='417782' date='Aug 13 2007, 10:24 PM
    On a more general note, I was thinking earlier, that, yes, there ARE risks with nootrpoics, but we are all adults, and must have a level of self-responsibility. It behooves us all to do at least SOME research, before consuming these products. We can't expect nootropic (etc) suppliers to hold our hands every step of the way, and print endless precautions, etc.



    Again, (if you'll forgive the less-than-100%-accurate comparison) I can walk into just about any pub (& many other places) in the U.K., and purchase that severely mind-altering substance called 'alcohol', which carries very little in the way of precautions re adverse reactions, etc. Surprising, really, considering the resultant road carnage caused by alcohol fuelled drivers.



    It's time for revolution. All pubs must make way for noop-bars. The past is dark, the future is smart. Let the evolution begin!


    It is not as much the danger of the substance but rather the context in which those precautions ought to be presented. Within a scientific discussion, certain statements and assumptions can be questioned and examined in determining the tenacity of various types of claims.



    I agree that companies should not "hold our hands" with constant warning. However, this is quite distinct from the actual assertion made: that HupA should (probably) be taken by everyone (elementary precautions aside). If someone had suggested this, Steve would not be obligated to warn against it, however, he carries the burden when he makes the actual claim. This is precisely why the comparison to alcohol or coffee is simply not apt. Further, as a member posting in the Neuroscience section, he is held to the same standard as everyone else. There is no exception to being called out on BS simply because one sells the substance being promoted.
    "When men are most sure and arrogant they are commonly most mistaken, giving views to passion without that proper deliberation which alone can secure them from the grossest absurdities." - David Hume

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