From: 71450.1773@compuserve.com ("Steven B. Harris") Subject: Nootropic Introduction Date: Wed, 05 Apr 1995 newsgroups: sci.life-extension From Steve Harris, M.D. Kevin (kgpl@uno.edu) in article 2958 wants to see some information about nootropics, and wants to see info about them improving IQ scores in young healthy humans in well-constructed studies. Me, too! And that's not all I want. To be useful, such drugs have to improve mental performance (by some scale, not necessarily IQ tests) enough to be not only statistically significant, but also *clinically* significant, which is to say, significant from the point of view of a real-life difference. The problem is that with a large enough study, it's quite possible to show that a drug has a definite effect, even though the effect is not enough to make a difference for anyone. The other thing we'd like to know is how LONG the effect lasts, how much the brain adapts, and what the side effects are. There are quite a number of nootropic drugs in which there are well-constructed studies showing a significant mental performance increase for a short time in healthy people (for a review, see the Smart Drugs books by Ward Dean and John Morgenthaler). None of these positive studies, however, are very long-term ones. There is much better evidence for nootropics as short term aids for special occasions (eg., final exams). Don't expect to take them every day and get the same benefit. Why all this should be the case makes sense, if you think about the nootropics you are familiar with, by use or reputation (caffeine, speed, cocaine)-- and if you also think about evolution, and about the way the brain works. If it was easy to increase human intelligence all the time by dumping some simple chemical onto the brain, evolution would figured that easy solution out, and would already have made arrangements to do it (there aren't too many evolutionary advantages in having the same number of neurons, but being relatively stupider all the time). The problem, however, is apparently that "intelligence" is many different things and brain functions, and some are more valuable to goose than others, at different times. Also, all these endogenous chemicals have side effects. Thus, evolution arranges to dump them on the brain only in short bursts, and selectively, when needed, as determined by the situation. *That* arrangement, I believe, is the only thing which allows the so-called "nootropics" to work at all. Your emotions, you see, are markers for what chemicals are being used in your brain to selectively upgrade your performance for a brief time, as needed (a bit like nitromethane injection in a hot rod). You already know your emotions as a color-coded filing system for your memories, but they are also much more. It is useful here to think of the four main functions of the autonomic nervous system which handles those brief, and selective, brain "system boosts": in physiology classes these are generally referred to as the "4 F's" of autonomic organism survival: Fight, Flight, Feeding, and... well... reproductive behavior. The first two are mediated by the sympathetic / adrenergic system, and the second two mostly by the parasympathetic / cholinergic system. (Sexual behavior actually takes both systems working in concert: cholinergic-->adrenergic; the cholinergic influence on arousal is probably why it's impossible to make love to a hungry woman, and the adrenergic influence on orgasm probably explains some of that bondage stuff <g>). Anyway, both autonomic systems have powerful effects on memory and brain performance, since it's very, very important evolutionarily to remember what makes you angry or frightened, or what behaviors get you food or sex. Food is the standard reward for memory tasks in animal experiments, and that's no accident-- memory is cholinergic. It's also no accident that _smell_, so closely tied to feeding and sexual behavior, is a direct tap into the parasympathetic system and memory retrieval (see Proust...). Naturally, the adrenergic or sympathetic drives (adrenalin!) boost processing speed more than memory, especially where time is a critical factor, or pressure. And it makes sense that cholinergic or parasympathetic activations are more selective for memory, since (unless you are Bill Clinton) the task of where to find food and sex usually does not involve the same time pressures that fighting and running do. Nootropics, then, all do for you artificially pretty much what your own system does for you in these categories, and thus it's not too surprising that these drugs all seem to break down very roughly into the same two basic autonomic functions above: one activating and one "vegetative" (growth and reproduction). In short, nootropics are all pretty much either "uppers" or "cholinergic-activating memory drugs". Each class has characteristic side effects. All of the uppers-- purinergics like caffeine and theophylline, herbs like ginkgo and ephedra and coca, adrenergics like amphetamines, and functional ones like Gerovital, deprenyl, and thyroid, all make people naturally feel wired and high strung and irritable. If you're an anxious type, they may do more harm than good, and if you tell your boss one day to get lost, you may later decide that increasing your on- paper job performance wasn't worth the social price. By contrast, the more purely "cholinergic" or sympathetic type drugs (choline itself, DMAE, Lucidril, pantothenate, vinpocetine, vincamine, piracetam and derivatives, vasopressin, etc) all improve memory, but can give you the typical cholinergic side effects also: stuffy nose, GI upset or bowel looseness, stiff muscles, increased joint and tooth pain or sensitivity if you have any pre-existing problems, and general fatigue. All the nootropics of both classes can cause insomnia, since in general autonomic activation is not conducive to sleep (as an organism, you're supposed to be paying attention if your autonomics are firing-- that's what they're THERE for). FINALLY, ALL THESE EFFECTS OF NOOTROPICS ARE SHORT-LIVED, since the brain is an adaptive organ, and is not meant to be goosed by the autonomics in a big way all the time. Thus, if you use these drugs every day, like caffeine or like amphetamine, pretty soon you develop tolerance and need the drug to get back to normal. If you don't have the drug after that, you actually function subnormally until you "kick the habit." If it's a short-lived drug, you use it in rapid cycles. That's not much good for you, so be wise. Perhaps you've been there with caffeine, a very typical nootropic. Note also that nicotine is a powerful nootropic-- this one a cholinergic (people wouldn't use the stuff if it didn't do SOMETHING for them). Aside from smoking and coffee, I've seen nootropic enthusiasts who spent the whole day popping pills just to function. Just like smoking, this was all legal, but it didn't look like much fun. And of course, the pill thing is expensive as hell, even if it has no adverse long term health effects (which I cannot swear to, in the case of all these drugs, either) At least coffee and tea look pretty safe, epidemiologically. Hydergine has been well-studied long term, as well, and at least does no harm. If you have to start somewhere, start with these. But don't overdo it. Steve

From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.med.nutrition Subject: Re: Magnesium pidolate Date: 29 Mar 1999 10:10:31 GMT In <7dnfkd$n5a$1@platane.wanadoo.fr> "gregono" <gregono@wanadoo.fr> writes: >Pidolate comes from pidolic acid, or pyrrolidone carboxylic acid, also >named PCA. PCA is the natural humectant in skin, but it's also pharmacologically active, since it gets into the brain and is ring-cleaved to glutamate, an amino acid which is also a neurotransmitter. That's what the magnesium salt is sold for. Related compounds form a whole class of "nootropic" (thinking enhancer) glutamate analogs, the most well known of which is "Nootropyl" (piracetam), which is PCA with an extra methylene and the COOH made into the carboxamide. These things have been used as antiemetics and antivertigo drugs, and they do give some people a jazzed feeling, a bit like caffeine. But whether or not you think that much better is an open question. Some people think they do. Piracetam is pretty non-toxic, but I personally would not want to take PCA for the same effect, as some people who buy it ostensibly as a skin moisurizer, do. Piracetam is dirt cheap if you can get somebody in Mexico to buy it for you. Glutamate is a neurotransmitter, but in overdose it's a horribly toxic one. In brain injury from seizures and hypoxia it's probably the neurotranmitter most responsible for neuronal death (glutamate sensitive channels let too much calcium into neurons, which wrecks their mitochondria). Not something I personally would fool with too much, buzz or not. Steve Harris, M.D.

From: Steve Harris <sbharris@ix.netcom.com> Newsgroups: sci.med.nutrition Subject: Re: Piracetam? Date: 5 Sep 2005 22:18:38 -0700 Message-ID: <1125983918.593149.3520@g44g2000cwa.googlegroups.com> viv wrote: > Anyone out there have anything positive or negative to say about > Piracetam? I'm considering trying some, but would prefer to hear from > real world users first rather than unquestioningly accepting claims > made about it. > > At 55 my brain could use a jolt of something. > > viv COMMENT: You'll find it's a pretty weak pill. It takes two or three tablets even to give you a mild caffeine-like buzz for a few hours. A lot of money for not much. SBH