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From: ("Steven B. Harris")
Subject: Nootropic Introduction
Date: Wed, 05 Apr 1995

From Steve Harris, M.D.

    Kevin ( 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).

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.


From: B. Harris)
Subject: Re: Magnesium pidolate
Date: 29 Mar 1999 10:10:31 GMT

In <7dnfkd$n5a$> "gregono" <>

>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 <>
Subject: Re: Piracetam?
Date: 5 Sep 2005 22:18:38 -0700
Message-ID: <>

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


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.



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