Although I've been using this since december, myself (christmas day, actually), I would say that [IMHO] the 'racetams and many other nootropics are not as "safe" to use in long-term (which I would say falls into the 3-month+ range) high dosages as a lot of people think
under certain circumstances. I say this mostly in response to a only
some of piracetam's effects; particularly the cerebral blood flow enhancement (CBE).
Simply put:
ALL of the nootropics that i've had the chance to research extensively (save for the 3 mentioned in the end) (the list is exhausting) which improve memory/concentration via increasing cerebral glucose utilization typically act as vasodilators. The effect of this, in "bro-theory" (a.k.a. "unsubstantiated" theory that probably has a supporting study somewhere which I'm too lazy ATM to look up), comes from the CBE effect. Additionally, all of the said kinds of nootropics typically inhibit platelet aggregation, thus thinning the blood and synergizing its own action (most notably seen with Vinpocetine, an underrated nootropic which receives more skepticism than it should, especially when research exists that contradicts the skeptical reservations kept by many). Finally, to top off the benefits of CBEs, a nice little "side effect" is the increased oxygen delivery to the brain.
Here's where you run into the roadblocks of chronic use, and even moreso in those of us who use more than one nootropic agent (of which, I would say 4/5 ImmInst'ers do who openly admit to using nootropics):
homeostasis. FunkOddessy once wrote a little one liner in a thread here (I can't recall which) where he said "Ahh, homeostasis strikes again," to which, i laughed uncontrollably in the middle of my school's computer lab. See, the problem that most nootropic users face is homeostasis. We have almost uncountable receptors in our body to detect the slightest physiological change in about... anything. Your body, simply put, LOVES to stay just as it is.
On to the safety concerns:
1 - Vasodilation: While using a vasodilator, your body increases it's vascular (particularly, capillary) permeability, allowing for better blood flow and, therefore, better nutrient (or drug) delivery. Unless you have some kind of chronic vascular disease, homeostatic resistance is going to eventually step in and downregulate some of your body's mechanisms that already perform similar actions so it can bring it back to "normal." A homeostatic response to chronic vasodilation might be something along the lines of an upregulation of muscle tension that surround the cardiovascular system.
2 - Metabolic Glucose Enhancement: There's actually a few safety concerns to worry about with this. The first would be an assumed homeostatic response that would probably occur if you're NOT regularly exercising, which would simply be a decrease in metabolism. The other two concerns I have are more "bro-theory" (again, me addressing my lack of research) concerns which include me wondering the kind of effect that chronic use might entail for those who simply don't have lots of carbohydrates in their diet, and a possible insulin-related homeostatic response!
3 - Platelet Aggregation Inhibition: The homeostatic response to this should be a no brainer....
4 - Increased Oxygen Uptake: Here's where it could get ugly, your body might compensate for the increased oxygen intake by downregulating the efficiency of your oxygen utilization.
Now, don't let the safety concerns worry you TOO much. Your biggest concern would probably be high-dose chronic use, followed by a sudden and immediate STOP in use. A sudden halt to your administration cold be rather detrimental to your health (vessel constriction, blood sugar problems, hypoxia...) if you've been using high dosages for quite a while. To minimize risk, you're left with two options, of which, neither is really all that bad. 1) When you're deciding to take a break, just ease off the dose rather than stop. 2) Cycle everything.
However, there is some hope among the most popular nootropics:
Out of all of them, there are THREE I am aware that increase glucose metabolism WITHOUT the common mechanism of action of typical CBEs. Of the 3, 2 display no great similarity in MOA, and 1 is among the "true nootropics" (in the sense that there has been SOME research done that displayed cognitive enhancement in
fully healthy people)! They are:
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Hydergine - DOES inhibit platelet aggregation and enhance glucose metabolism, BUT act's as a vasoconstrictor, and not a dilator.
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Sulbutiamine - The synthetic allithiamine which rapidly crosses the BBB, and increases cellular glucose metabolism by the vastly increased amounts ThTP. Additionally, since it partially inhibits dopamine release, your body compensates by an upregulation of dopamine-receptor density (good for me and ADHD)!
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Pyrithioxine - Enhances cerebral blood flow, yet among all the research available to it, it neither acts as a vasodilator, nor does it inhibit platelet aggregation! It's also one of the "true nootropics" because there is research that exists which shows enhancement in fully healthy people! Some people take really high doses of this for an effect, but seeing as it so closely resembles pyridoxine (it's literally just 2 pyridoxine molecules that have been bonded together) I would be rather hesitant to use anything more than 200mg a day, but probably more like 100mg seeing as I already take a B-complex.
Edited by Pike, 20 May 2009 - 05:07 PM.