Title: Neuropeptides: Unlocking the Secrets of the Brain
Publication: D.I.N. Newservice | Do It Now Foundation
Editor: Jim Parker
Date: July-August 1983
Pages: 40-63

1. “Magic Bullets”

They were going to be the “magic
bullets” of psychopharmacology, miraculous chemical keys
to unlock the secrets of pleasure and pain, joy and sorrow, memory,
intelligence, and behavior.

They were supposed to explain
everything from falling in love to falling asleep, and a full
understanding of their actions and effects was going to cure
drug addiction and mental illness, regulate mood and appetite,
and even heighten creativity and sexual response.

They were the endorphins, the
internally-produced morphine-like substances responsible for
an array of drug-like effects in the body, and for a while after
their 1975 discovery, everyone wanted to speculate about them.

According to some scientists
and most reporters, endorphins were clearly the Next Big Thing
in the neurosciences, maybe even the Last Big Thing, and the
imaginations of headline writers across the country lit up like
major league scoreboards on the Fourth of July as they scrambled
to encode news reports in hyperbole.

But the euphoria didn’t last.
Life got complicated. Research findings were confusing, then
contradictory. Somebody even changed the name — as the number
of identified internal body chemicals grew from month to month
and began to defy simple classification — and the catchy “endorphins”
became the colorless “neuropeptides” or, even worse,
the murky “endogenous opioids.”

And when the scientists who’d
started all the buzzing announced that they were settling down
for a few decades’ basic research into nuts-and-bolts issues
of why the compounds worked and how they were going to make every
thing better for everybody forever, the entire phenomenon seemed
to die an unmourned media death.

Reporters stayed away from the
funeral in droves. Research is boring — or at least not as exciting
as science fiction — and members of the press moved on to more
interesting scientific topics — choosing baby’s sex, for example,
or pyramid power.

But the investigators who were
drawn to the study of the linked amino-acid-chain neuropeptides
did not walk away. Instead, they continued to look hard and long
at the powerful new body chemicals and quietly went about the
difficult work of figuring them out — or, at least, figuring
out a way to figure them out.

In the process, they linked them
with a vast array of physical and emotional problems — as both
possible causes and potential cures — and the prognosis is now
good for at least some of the promised early magic bullets to
hit their mark.

What those magic bullets could
mean in scientific terms is anybody’s guess, and some of the
scientists currently engaged in neuropeptide research seem as
unsure where it will all end as anyone else. But in human terms,
for the millions of people afflicted with a wide range of problems
— from alcoholism and obesity to chronic pain and schizophrenia
— the future is looking brighter than many would have dared
to hope even a few years ago.

..2. “Walking Chemistry Sets”

At the bottom of the search for
biochemical magic bullets is the suddenly wide-open study of
the human brain.

Dr. Steve Henricksen, senior
staff scientist at the Salk Institute in La Jolla, California,
knows as much about the brain as anybody, and he just shakes
his head when he thinks about the complexity of it all. “We’re
witnessing an exponential growth in our knowledge of the brain,”
he says. “Our whole conception of how the brain works is
changing right now.”

A key ingredient in the current
revolution in brain research has been the neuropeptides, Henrieksen
says. Where prior to the discovery of neuropeptides, the brain
was thought to be a complicated enough place — with a small
handful of neurotransmitters and a grab-bag of hormones and enzymes
simulating the approximate complexity and organizational efficiency
of an advanced digital computer — today things upstairs are
beginning to look positively like a full-scale riot: “Things
are incredibly complex in the brain,” Henricksen says. “We
used to think the brain was like a computer. Now we think each
cell is like a computer, a separate computer. And one single
cell is like the whole brain.”

If the brain is a collection
of integrated, high-speed, ultra-tech computers, the neuropeptides
may just turn out to be the electrochemical glue that holds them
together — and the communications link that keeps them buzzing
and whirring in unison. But if you’re thinking that the brain’s
communications system is the nice, pat, linear axon-dendrite
chain you learned about in high school, with individual neurons
passing along biochemical signals like so many pails of water
along a volunteer fire department bucket brigade, think again.
“The old concept that the nervous system communicates with
itself from one cell to another by firing a single neurotransmitter
across a synapse is obsolete,” Henricksen says. “Right
now, that’s at best a special case.”

More likely is a composite of
discrete single-cell impulses mingled with and modulated by a
variety of enzymatic, hormonal, and neuropeptide signals, according
to Henricksen. How big a variety is open to question, but pharmacologist
Dr. Thomas Davis of the University of Arizona Neuropeptide Research
Group argues that the possible number of potential neuropeptides
is staggering. “There are a large number — I wouldn’t know
how many millions — of different permutations of amino acids
yielding neuropeptides of different behavioral effects,”
Davis says, pointing out that some of those effects could involve
processes as diverse as appetite, memory, and aging. Factor in
the consideration that dozens, hundreds, thousands are working
simultaneously in different directions — interacting with 20
billion or so brain cells in processing thought and emotion and
sensation while regulating motor control and body maintenance
functions — and you’ve got a system that is almost bewildering
in its complexity. That the system, the entire amalgamation of
chemicals and electricity and blood and tissue, is in operation
— and in perfect balance — in each one of us at every moment
of our lives seems nothing less than miraculous.

The miracle isn’t lost on Davis.
“We’re just a mixture of chemicals,” he says. “We’re
just a chemistry set walking around in total control, most of
the time.” In total control? You wonder.

In total control. Davis smiles.
“All you have to do is trigger a one-part per million concentration
change in the brain and you’re totally out of control.”

..3. “Lock-and-Key” Analogies

To fully appreciate just how
far we’ve come in our current understanding of the brain and
neuropeptide systems — and to fully understand what the systems
are and how they affect our lives — it’s first necessary to
take a backward look at the general context in which the discovery
of the internal chemicals took place.

Neuropeptides were first discovered
in 1975 by a pair of drug addiction researchers in Aberdeen,
Scotland, named John Hughes and Hans Kosterlitz, who were searching
for an internally-produced body chemical similar to opiate drugs
that would plug into existing opiate receptor cells and “turn
on” the body’s own built-in pain-relief system.

The existence of such receptor
cells had been suggested in 1972 by Stanford University psychopharmacologist
Avram Goldstein and verified in 1973 by John Hopkins University
researchers Solomon Snyder and Candace Pert. Goldstein, who hypothesized
that the brain must contain receptor sites of some type for opiate
narcotics for the drugs to exert any effect at all in the brain
and central nervous system, even provided a handy analogy to
describe the system he envisioned. “The places in the brain
cells where morphine and similar molecules combine,” he
said, “must be shaped to accommodate the morphine exactly
as a lock accommodates a particular key.”

In seeking out this biochemical
lock and key, Hughes and Kosterlitz discovered simple amino-acid
chains in a centrifuged extract taken from pigs’ brains, which
they then exposed to tissues of the vas deferens in mice. The
vas deferens, the duct which carries sperm from the testicles
to the prostate gland, seemed an ideal location to measure possible
opiate response since it contains, for still unknown reasons,
a large number of opiate receptor cells.

What Kosterlitz and Hughes discovered
was a heretofore unknown substance binding to their vas deferens
samples, a substance which they quickly learned could block,
like morphine, electrically-stimulated convulsions in the tissue.
They dubbed the substance “enkephalin,” from the Greek
words for “in the head,” where it was produced. After
analyzing the new enkephalin structurally, they discovered that
the substance was actually not one, but two substances, both
amino-acid chains, known as peptides.

As research progressed around
the world in the years following the Hughes-Kosterlitz discovery,
to further test the notion of internal, or endogenous, opiate-like
substances and receptors, the potential applications of the new
substances (often lumped loosely, if inaccurately, under the
generic term “endorphins” after the 1975 discovery
of the beta endorphin molecule became more diverse — and the
supporting evidence a lot more compelling.

At the University of California,
Dr. Huda Akil discovered increased endorphin levels in rats exposed
to electro-acupuncture with a corresponding increase in tolerance
to pain. Administration of the narcotic antagonist naloxone,
a drug that reverses the effects of narcotics by displacing them
at binding sites, immediately reversed that effect.

At John Hopkins University, Solomon
Snyder showed that the central periaqueductal gray (PAG) region
of the brain is particularly high in opiate receptor sites and
that minced extracts of calf-brain PAG tissue blocked electrically-induced
contractions of smooth muscle tissue, like morphine. Naloxone
again blocked the response.

In 1978, Salk Institute researchers
Jean Bossier, Floyd Bloom, and Roger Guillemin found that stimulation
of the PAG region in three patients suffering from peripheral
pain triggered relief from pain and increases of from 50 to 300
percent in the brain’s concentration of beta-endorphin. As in
the other experiments, the effects were blocked by naloxone.

Seemingly all at once, evidence
began piling up around the world implicating the neuropeptides
in a constantly increasing range of activities. From aging to
analgesia, tranquility to transformation, it seemed the endogenous
opioids had a biochemical hand in all the events that shape our
lives — or at least that shape our feelings about our lives.
And it was this sheer accumulation of evidence, and the tantalizing
potential benefits described in early media reports about the
chemicals, that fueled our imagination — and sparked increasing
scientific curiosity about the substances themselves.

..4. Boxcar Molecules

What Hughes and Kosterlitz found,
as did others who followed them, were chains of amino acids,
the large organic molecules often called the “building blocks
of life.”

The amino-acid chains they discovered
in the pigs’ brains were short, only five acids long, compared
to more complex amino-acid groups in the body such as proteins,
which can contain over 100 amino acids.

But it is not the number of amino
acids in neuropeptides that determines their function, it is
their order, according to Davis.

“Amino acids are in a specific
link, a specific pattern. They’re like boxcars on a train, but
each one of these boxcars is in a specific position on that train
because of the activity of the molecule. You can’t exchange boxcars.
Otherwise you change the activity.”

To the best of our current knowledge,
neuropeptides fall into three main categories: enkephalin (two
of which, leu-enkephalin and met-enkephalin, were discovered
by Hughes and Kosterlitz); beta-endorphin ( a large 31-acid molecule
that long served as a basic prototype for understanding the neuropeptides);
and dynorphin, a substance discovered in 1979 with much more
powerful effects than either enkephalin or simple endorphin.

Discovery of the chemicals really
amounted to a jarring, wheelspinning detour off the road neuroscience
had been travelling up to that time. Prior to the discovery of
the neuropeptides, nerve cell transmission was thought to be
a fairly straightforward affair, with individual cells believed
to communicate exclusively through the release of chemical messengers
known as neurotransmitters. These molecular messengers (serotonin,
dopamine, acetylcholine, and norepinephrine are the most common)
squirt across the two-millionth of a centimeter gap between neurons,
urging the connecting nerve cell to turn on or off or fire or
not fire, depending on the nature, and specific instructions,
of the signal.

Although similar to neurotransmitters
in a number of ways, neuropeptides are also different in that
they are made up exclusively of amino acids, rather than inorganic
chemical compounds. And while neurotransmitters seem largely
to researchers to be little more than a transmission medium for
neurological messages, neuropeptides, with the preciseness of
their fit in the biochemical “locks” Goldstein described
and the specificity of their actions, seem increasingly to be
no less than the message itself.

..5. “Do-It-Yourself” Drugs

Probably the most commonly-known
neuropeptide “message” discovered thus far is contained
inside the beta-endorphin molecule. Beta-endorphin, discovered
in 1975, was the first superstar neuropeptide, hailed as the
body’s own “do-it-yourself” drug, a natural, inborn
chemical capable of producing high levels of both pain relief
and tranquilization and a range of other emotional, behavioral,
and physiological effects.

The beta-endorphin molecule itself
has long held a special fascination for many researchers. It
so effectively quashes pain that it was instantly dubbed endorphin
(a contraction for “endogenous morphine”) and served
as a special focus for much early neuropeptide research. But
endorphin is not a simple substance. In fact, researchers know
today that it is not even a single substance, but a class of

The life cycle of the endorphin
molecule in the body probably provides the clearest understanding
of just how complex the neuropeptide system really is. Produced
in the brain and the pituitary gland, the beta-endorphin molecule
is active at binding sites in the brain and in locations throughout
the body, after being released into the bloodstream. It can also
move to the gastrointestinal system, where it is acted on by
enzymes which break down the 31-amino-acid molecule into smaller
fragments that are active in digestion.

Davis believes the endorphins
have “at least a dual function” in the brain and gastrointestinal
system, but he isn’t willing to stop there. “They could
have many functions. They could modulate the function of other
neuropeptides and other neurotransmitters as well as have a central
effect themselves,” he says.

“It’s like this damn thing,”
he says, pulling a Swiss Army knife from his desk drawer. “Like
a little knife that has 42 different facets to it. yet it’s still
a knife. It’s a corkscrew, a file, a screwdriver. The endorphin
molecule is the basic knife and all the different fragments are
all the other parts and their different functions — one can
unlock a door, the other can open a bottle, the other turn a
screw. One endorphin fragment may affect behavior, the other
one memory, the other one acclimation, the other one heat response
and sweating.”

“But it’s not just one chemical.”

..6. Inner Workings

The neuropeptides themselves
are present in great profusion in the brain, particularly in
the limbic system, the emotional center of the brain. Although
more than 20 separate peptides have been identified thus far,
most researchers expect dozens, maybe hundreds, more to be identified
before we get a complete handle on their actions and effects.

How the chemicals work exactly
is poorly understood, but Professor Goldstein’s lock-and-key
analogy still seems the best (or at least the most understandable)
description of what’s going on in there: The neuropeptides are
complex chemical “keys” with a high affinity for certain
types of receptor “‘locks,” and seem to fit them perfectly
— or trigger other chemicals that fit them perfectly. Production
of the neuropeptides themselves may well be regulated by body
enzymes that respond to a bewildering variety of internal and
external signals.

Also poorly understood at the
moment is the reason that external drugs are able to plug into
and turn on various parts of the endogenous neuropeptide system.
While at first many believed that drugs work in the body because
they have structural similarities to neuropeptides, researchers
are less sure today. “Psychoactive drugs may work because
of their structural similarity to endogenous chemicals in the
brain,” Davis explains. “Or they may work because they
trigger release of substances that act on receptors in the brain.

“The drug has to lock in
or it has to affect the chemical that does the locking in,”
he says.

But regardless of which chemical
key snuggles inside which receptor lock, once the key is turned
all sorts of things start to happen. So many, in fact, that the
full range of effects associated with various neuropeptides are
only vaguely beginning to be understood.

The endorphins probably best
demonstrate the complexity of these effects. Beta-endorphin became
something of a showcase neuropeptide because of its effects,
which closely resembled those of the opiates, and which include
the same general feel- good feelings of pleasure and relaxation
over which people have risked life and limb for millions of years.
As a result, early stories on the neuropeptides focused almost
exclusively on beta, and early research linked it to all manner
of pursuits, from acupuncture to runner’s high. But just as with
the other peptides, the longer researchers looked at beta-endorphin,
the less it looked like a simple explanation for anything.

One reason for this, according
to Davis, is that the peptides continually change in the body:
“These things may just break down and break down and exert
all sorts of different effects in different parts of the body
until you get down to small amino acids” he says. “Then
the body does it all over again.”

Further complicating matters,
Davis points out, is that the effects of the peptides seem to
change, sometimes remarkably so, as their structures change.
“The same endorphin molecule can have opposite effects once
it’s cleaved in half,” he says. “You break beta-endorphin
in half…and it’s not beta-endorphin anymore. It can act completely

Can it ever. Because a common
breakdown product of beta is a 17-amino-acid fragment called
gamma-endorphin. Strip away a single amino acid from gamma and
you get alpha-endorphin. The effects of both seem far removed
from the blissed-out, mellow-fellow effects of beta. And according
to Davis, they couldn’t be much more different.

“If you had too much alpha-endorphin,
you might have an amphetamine-type behavior, because it acts
like amphetamines. If you have too little gamma-endorphin, you
may lack the neuroleptic action of gamma-endorphin and, therefore,
you could have a schizophrenic problem.”

And while Davis is quick to point
out that all this is still highly speculative, he is willing
to think out loud about potential applications of neuropeptide
research: “Someday, we may be able to control consciousness
through the homeostatic control of chemicals.”

..7. Problems and Potentials

Leaving all other considerations
and potential applications aside, the neuropeptides provide,
at the very least, built-in circuitry and wiring for the actions
of drugs in the body. This being so, it’s probably not surprising
that pharmaceutical manufacturers have wasted little time in
attempting to translate the explosion of neuropeptide research
into cold cash and a hot new roster of medications. Within months
of the discovery of enkephalin in 1975, dozens of chemical analogues
were under patent by pharmaceutical houses on both sides of the
Atlantic, in spite of the fact that problems seem to pop up as
quickly as new peptide combinations themselves.

For one, there’s been a continual
problem with the sheer unmanageability of manipulating and evaluating
the complex organic molecules that comprise the neuropeptides.

“Peptides are large, and
they’re susceptible to rapid degradation in the body,” says
Dr. Robert Frederickson, a research scientist in the central
nervous system labs at pharmaceutical giant Eli Lilly and Company.

“They’re also not transported
against membrane barriers, which represents quite a problem in
delivering them to appropriate sites in the brain.”

For this reason, much current
research has focused more on the development of substances that
cause the body to increase its own level of specific neuropeptides
than on simply introducing external chemicals that mimic existing
endorphins or enkephalins.

Particularly promising, Davis
says, are the enzymes that trigger the breakdown of neuropeptides
into constituent elements, beta-endorphin into alpha- and gamma-endorphin,
for example, or beta-endorphin into met-enkephalin. “We
know what some of the enzymes are in the brain and the gut, but
we don’t know what all of them are,” says Davis. “If
we could determine what they are, we could model drugs to control
that enzymatic process if it was out of control.”

Ways that enzymatic processes
in the neuropeptide system can manifest their going out of control
are legion, but the specific areas that look most interesting
— and most promising — to researchers today include appetite,
addictions, pain relief, memory and learning, and mental illness.

Some of the most interesting
neuropeptide research — and a type that has potential value
to millions of Americans — investigates the possible role of
neuropeptides in regulating appetite. Current research underway
at a variety of locations around the country is aimed at establishing
the neuropeptides’ role in regulating appetite. If successful,
the research could lead to the development of the first safe
and effective diet pills and unlock the secrets of eating disorders
such as bulimia, in which victims gorge before forcing themselves
to vomit, and anorexia nervosa, in which sufferers are unable
to eat — sometimes to the point of complete starvation.

How are neuropeptides linked
to appetite? One theory suggests that food engages the neuropeptide
system in a manner very similar to drugs and causes the body
literally to become addicted to itself.

The theory, first proposed by
British researchers James and R.F. McCloy, suggests that the
presence of food in the intestines causes local enkephalin release
which, for reasons yet unknown, could have such a strongly reinforcing
effect in some individuals that they become addicted to their
own body chemicals.

Whether or not the McCloys’ “auto-addiction”
obesity theory holds, it is widely conceded that endogenous opioid
systems are involved in appetite regulation, and various compounds
are currently being tested for their effectiveness in blocking
and controlling appetite. Potential treatments include:

  • Naltrexone, an opiate antagonist which blocks opiate
    receptor sites and presumably, the sensation of hunger. The drug,
    which is currently being tested at six medical centers across
    the country, is a long- lasting (6-8 hour) oral derivative of
    the opioid-blocker naloxone.
  • CCK, a newly-discovered neuropeptide called cholecystokinin,
    which researchers at Cornell University believe may be the brain’s
    own satiation signal. In tests, animal subjects given CCK cut
    their food consumption by three-fourths, and simply seemed to
    be not hungry when presented with food. Researchers plan to test
    the substance on human volunteers in the near future.
  • Butorphanol, a pain-killing drug, which has been
    shown to stimulate appetite in animals. University of Minnesota
    researchers who have studied the drug’s effects on appetite hope
    the compound will be effective in treating anorexia nervosa.

Recent advances in memory and
learning have also been spurred by neuropeptide research, and
at least six major pharmaceutical firms are betting there’s money
to be made by the first producer of a reliable memory-boosting,
intelligence-raising drug.

One current entry with links
to the neuropeptides is the anti-diuretic hormone vasopressin.
Secreted by the pituitary gland, vasopressin tripled the memory
length of mice in one study and has been shown to improve recall
in humans, particularly the recall of longs lists of items.

In addition, other neuropeptides
have tentatively been shown to up learning performance. Subjects
in tests involving one, DDAVP, showed increases of up to 20 percent
in learning and memory tests, while another neurohormone, MSH,
has also been shown to increase recall. Scientists believe the
substances work by increasing alertness and attention.

Possible connections between
emotional illness and endogenous substances has been one of the
hottest research topics in the behavioral health field since
neuropeptide pioneer Roger Guillemin first theorized that the
beta-endorphin system could be a “key mechanism” in
sorting out normal and abnormal behavior. If so, Guillemin wondered,
shouldn’t a drug like naloxone, which blocks endorphin’s effects,
have some value in reducing symptoms of a major psychiatric illness
such as schizophrenia?

Tests run to date have yielded
puzzling results, according to the Salk Institute’s Steven Henricksen,
with both beta-endorphin and its antagonist naloxone proving
effective in reducing psychotic symptoms. According to Henricksen,
this factor alone — that both agonists (beta-endorphin-like
compounds) and antagonists (which displace beta molecules at
binding sites) have been shown to alleviate symptoms of schizophrenia
— points out the difficulty in fully understanding the neuropeptide
system, and the nature of the disease. “That should tell
us something about the complexity of the problem,” Henricksen
told Newservice in a recent interview, “when both
the agonist and the antagonist both seem to be involved in the
disease state.” In addition, Henricksen adds, it also tells
researchers that “we’ve got more work to do,” in clarifying
the relationship between neuropeptides and emotional illness.

One research area that has tended
to support the notion of a direct connection between the endogenous
opiate system and emotional illness has been the study of addictions.
In one study involving methadone- stabilized ex-heroin users,
it was shown that, when daily dosage of methadone fell below
critical levels (20 mg/day),that psychotic symptoms consistently
developed in 10-15 percent of the subjects. Symptoms disappeared
when daily dosage was increased to 30 mg. As a result of such
studies, researchers believe that, for a large percentage of
users, drug use and addiction represents an attempt to manage,
and self-medicate, symptoms of major emotional illness that can
otherwise be disabling.

Investigators hope that current
research in the area of addictions will more precisely establish
the hows and whys of addiction and lead to the development of
non-addictive substitutes for narcotics and other drugs. But
other investigators aren’t so sure.

Dr. David Pickar, chief of the
Clinical Studies Section of the National Institute of Mental
Health, believes that addiction is an unavoidable byproduct of
any substance that affects the endogenous opiate system. “The
issue around addiction and withdrawal is, I think, central to
the whole pharmacology of opioids and opiates,” Pickar says,
“I think what you see in heroin, morphine, and codeine (in
terms of dependence and addiction) is going to be duplicated
in endogenous opiates at some level.”

Research into addictions has
also fueled the single biggest area of neuropeptide research
currently under way: the relationship between the chemicals and
the control of pain.

Easily the most interested parties
in the study of neuropeptides and pain relief are the major drug
companies, who stand to benefit most — and most immediately
from the development of an effective, non-addictive, non- narcotic

One of the most interested among
them is Eli Lilly and Co., in Indianapolis, a company that’s
made untold billions of dollars during the past two decades off
its popular prescription pain relievers Darvon and Darvocet.

According to research scientist
Robert Frederickson, Lilly is interested “across the board”
in potential central nervous system applications of neuropeptide
research, although it has concentrated, in its research, on analgesic
applications of internal opioid systems.

Frederickson is optimistic about
the company’s chances of developing — and marketing — an effective
neuropeptide-derived pain reliever in the near future. And although
he says specifics “can’t be discussed” at the moment,
he will say that Lilly is currently clinically testing a “slightly
modified” injectable version of Hughes and Kosterlitz’s
five-amino-acid met-enkephalin molecule, a version he says contains
“specific benefits over existing agents.”

And will it match early researchers’
hopes for an addiction-free side-effect-free drug? Frederickson
isn’t sure. “I don’t know if it will ever be possible to
have a completely side-effect free drug,” he says. “That
is our hope. Whether we will achieve it or not remains to be

“There’s great promise,
but there are great problems, too. When you’re looking at it
from this end, it gets a lot more complicated than just a wish

..8. The DNA of Consciousness

Also remaining to be seen is
how long it will take to fully uncover the remaining mysteries
of the neuropeptides and, through them, learn the secrets of
the brain, personality, and consciousness itself.

It’s generally conceded that
there is simply no way of knowing now what will be known when
about neuropeptides, and how soon that knowledge can be translated
into technologies and treatments to aid people. One reason that
prognostication is such an imperfect art in the neuropeptide
field is because data is turning up so fast on so many fronts
that the sheer volume is difficult to process and assimilate,
much less use to extrapolate what the future may (or may not)
look like.

Tom Davis of the University of
Arizona puts things into perspective this way: “What we
know about receptors today is very different from what we knew
six to eight months ago. We have no way of knowing what we’ll
know six months from now.”

One thing that is generally recognized
among researchers is the critical importance of their work. As
its focus has widened steadily over the years — beyond analgesia
and other drug states to memory, sensation, appetite, and emotion
— researchers have come to grasp the immense significance of
the task before them: deciphering the codes of consciousness.
And as the neuropeptides have emerged as the neurobiological
equivalent of DNA, researchers have glimpsed the incredible potential
of the corkscrew chains and spirals of amino acid permeating
the brain and central nervous system. These chemical clusters
are not, the scientists have come to recognize, merely an artifact
of thought or sensation or emotion; rather, they are the thought
or sensation or emotion — or all of it our brain ever knows.
It’s the ultimate reduction or clarification of Descartes’ famous
argument: My brain is full of neuropeptides; therefore I am.

And regardless of when the breakthroughs
come (and some researchers believe they may occur in the next
five years), and no matter when neuropeptide research “pays
off” in the form of enhanced memory or longer lives or expanded
emotional well-being, thus far it has contributed much to the
study of who — and what — we all are. No less intriguing are
the questions it raises about how we will be in the future. “Magic
bullets” should have to do no more.

..Sidebar |
Mapping the Mind

Just as early phrenologists sought
to link specific areas of the brain with individual attitudes
and aptitudes, researchers today have become increasingly interested
in the overlap between psychology and physiology.

For years, the three-and-a-half
pound glob of grayish-pink tissue each of us carries in our heads
was regarded as the ultimate unknowable object. And for just
as many years, the “science of mind” was more accurately
a philosophy of mind, with elaborate (and often unfounded) conceptual
systems propounded to describe what no one could explain.

But recent breakthroughs in the
study of the brain have revolutionized the way in which people
think of themselves.

“We constantly hear about
things being “just psychological,’ as if they’re somehow
not real,” says Dr. Robert Frederickson of Eli Lilly and
Company’s central nervous system research labs.

“But when you say something
is psychological, what you’re really talking about is the physical
chemistry in the brain. That’s as much physiological as it is

The solution to the traditional
split between the “science of mind” and the rest of
science, according to Frederickson and others like him, must
involve further research into the tangle of chemical codes that
link the brain, its billions of neurons, and their quadrillion

And while no one expects researchers
to devise a system soon that comes anywhere near the simplicity
of the phrenologists’ ancient maps of the mind, scientists do
expect to learn much more about the biochemical connections between
thought and behavior, and to apply that knowledge to a range
of problems that predate even the earliest psychology-physiology

Both sides agree it won’t come
a minute too soon.

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