NOOTROPICS: Complex Interactions, e.g. Nicotine

Crosby_M (
Mon, 5 May 1997 16:20:51 -0400

About a month ago we had a discussion, after some inquiries about
supplements and nootropics, of how to test and measure the effects of
these substances.

Lee Daniel Crocker suggested this was "simple":
<Give a dozen people a euphoric, and another dozen a vitamin or
something, then have them all answer multiple-choice questions about
how they feel. If the answers to some question correlate strongly
enough with those who took the real drug, you've shown a measured
effect (certainly not a conclusive one, but at least better than

While what Lee suggested may be a useful approach for determining if
there is *any* effect, I suggested it wouldn't be very helpful for
quantifying or qualifying the effect because human health, moods and
cognitive capacities, are too complex a system to submit to simple
mechanical measurements. One of the reasons, I suggested, was that
these substances can have multiple effects and the effects may differ
depending on the subject's neurochemical background at the time.

Along these lines, today's Wall Street Journal has several articles
that look at the surprising complexity in the effects of one of the
most commonly used nootropic substances, namely nicotine.

One article, "Kicking the Habit: Personality May Predispose Some to
Nicotine Addiction" by Robert Langreth, notes that "Indeed, nicotine
even seems to have varying effects on the same people at different
times of day" and quotes Neal Benowitz, a tobacco researcher at the
University of California at San Francisco, saying "It is one of the
few drugs that can be a stimulant first thing in the morning, a
tranquilizer later in the day for people who are anxious and a mild
antidepressant for people who are feeling a little down".

One of the difficulties in substantiating nootropic effects is that,
over time, the body acquires a 'tolerance' to them so that the effects
can vary depending on how long someone has used the substance. As
Langreth's article puts it: "Researchers don't know exactly why, but
they suspect that over time, the brain becomes accustomed to operating
with a certain level of nicotine, and eventually depends on nicotine
to produce even normal levels of dopamine and other brain chemicals."

The article also pointed out that genes may be important for who
becomes addicted to nicotine: "Numerous studies of identical twins
show that if one twin smokes, the other also does about 80% of the
time; this is true only about half of the time for fraternal twins,
who don't have matching genes. The commonality between identical twins
exists even in cases where the twins were reared apart, indicating
that genetics -- not environmental factors like the close bond that
often forms between twins -- are at work."

A companion article, "Kicking the Habit: Antidepressants Give New Hope
To Hard Cases Trying to Quit" by Elyse Tanouye, also provides some
insights on the multiple and synergistic effects nicotine and other
nootropics may have. Basically, this article describes how nicotine
affects dopamine and norepinephrine levels but seems not to affect
serotonin levels.

Linda H. Ferry who conducted a study at a California VA medical center
said that "Nicotine is the best and most effective over-the-counter
antidepressant available in the world". Her study found that
Wellbutrin (generic name bupropion, which may soon be approved by the
FDA as Zyban) is an effective substitute for nicotine because it
boosts both dopamine and norepinephrine levels: "In two small trials,
she found that smokers who took the drug were two or three times more
likely to quit than those who took a placebo."

Most interesting to me, as a recovering smoker now using only the
nicotine gum, was the insight that there are "nicotine receptors
inside the mouth and throat" in addition to those in the brain. In
fact, in my own experience, I could do without nicotine most of the
time (I still chew four or five 2 mg pieces per day) except for the
oral craving. Jed Rose, a Duke University nicotine researcher, has
had success "using substances like citric acid" to relieve these
cravings. This confirmed my own experience that grapefruit juice was
a big help in reducing these cravings. I've also noticed that
piracetam somehow almost completely eliminates these cravings, as well
as the more generalized nicotine anxiety which probably originates in
the brain.

The point for Extropians, most of whom are probably not smokers, is
that any of these nootropic substances that work on the brain are
likely to have many, entangled and difficult to measure effects.

Mark Crosby