The Endorphin Story

MINUET ONE

It is difficult to visualize how some can accomplish feats other couldn't even conceive of. Bach wrote the passages of Minuet One played by thousands of music students on violin, piano and flute. For over 200 years the passages of Bach have brought immense pleasure to music lovers all over the world. What is it that Bach wrote? What made him write it? How was he able to conceive of an arrangement so perpetual and unique? These are some of the questions that indirectly relate to the question of how mind alters our actions.

Scientists use a word "paradigm," which means a model, a big model, a world view, a framework into which theories and hypotheses fit like pictures. The scientific paradigm of the brain is that it is an electrochemical powered organ. Other paradigms delve into the reality of mind and brain. Is mind a creation of brain or the mind is an independent or semi-independent element? We will examine these paradigms before embarking on our journey through the electrical and chemical channels of our brain to figure out what made Bach write the Minuet One.

The classical example of how mind alters some 200 trillion body cells is found in the effect of mental behavior on diseases, not perceived but real body disorders. How often have you fallen prey to a cold or headache before taking your Math test? How often has your seven-years old child complained of stomach ache if he did not like the food on the table?

A few years ago, a news report in the Los Angeles Times talked about an "apparent" food poisoning announced on the public address system during the ball game; hundreds of people started throwing up and became ill. Within an hour a correction was announced that there were no signs of food poisoning. Magically, as though, most people started feeling fine to finish enjoying the game.

Understanding these "bizarre" connections requires appreciation of many serendipitous and often danedotal episodes. We find that psychological profiles of a population can be correlated with incidence of cancer, heart disease, hypertension and many other dreadful ailments. The studies in laboratories also confirm this hypothesis. If certain parts of brain are surgically disturbed in animals, many diseases appear in unusually higher proportion.

The immune system of our body, the body's armamentarium to fight off "foreign invaders," seems to be a two-way street to and from our brain. Studies published in conservative medical journals show how patients have been cured of warts and other skin disorders by applying placebo treatment. T-cells, the special blood cells which determine the activity of our immune system, provide the link. The activity of these cells is affected by our emotions and feelings. Placebo is now recognized as often having as much effect as the treatment. Hypnotism is given credibility.

Unified mind-body paradigms are now given credence using the language that scientists understand. Harvard doctor, Richard Bergland, writes, "What is significant is that brain secretions can be stimulated or diminished by thoughts, behavior, feelings, and environment." The Institute for the Advancement of Health publishes a journal, Advances, which explores the relationships between brain, mind and the body- "trying desperately to connect mind and brain through newly founded sciences emerging from chemistry and physics."

The Samoan system of medicine is one case in point. Accordingly, diseases are caused not by infected organs or chemicals but by a complex interaction of interpersonal hostility, stress and poor diet in addition to any physical or organic causes as we define in our Western system of medicine. Similar disease concepts are found in the ancient system of medicine in India, Ayurveda and Siddha (600-1000 B.C.) and Greco-Arabian (Unani) system developed in the mediaeval period.

The Institute of Ayurvedic Studies at the Maharishi Mahesh International University in Iowa is doing extensive work on evaluating the old Indian philosophies of treatment. For example, Dr. Howard Chandler and his associates recently reported on the Maharishi Panchakarma program, a system of physiologic purification that utilizes several herbs. In one study on 43 male volunteers, memory, intelligence, psychomotor speed and alertness were significantly increased using this physiotherapeutic approach. The Ayurvedic system is one of the oldest health science. It focuses on the delicate balance between mind, body, environment and behavior. Diseases are caused by an imbalance of these factors. The teachings of Ayurveda go back thousands of years before Christ perhaps as back when the human consciousness began. A basic text on ayurvedic medicine, Ceraka ,written about 300 A.D. states,"the life stream carried in its own current, its own supporting and protecting wisdom."

Recent investigations in the chemistry of brain now confirm what was already told around 50 B.C. in Huangdi Neijing, The Yellow Emperor's Inner Book, which described health as a constantly changing system of interactions between body cells and the universe; illnesses occur when a balance is lost between yang and yin. Dominance of yin causes "cold diseases" of deficiency, excess of yang ensues in diseases of "overfulness," the "hot diseases."

From prehistoric times, diseases have been considered to be caused by evil spirits and due to victim's willingness to become ill through negative influences. More than 10,000 years ago, exorcism was frequently used to rid the evils from the body to restore health. Diseases were seen caused from inside the body and not from outside--due to imbalance in the forces in the body.

During the Sumerian-Babylonian-Assyrian civilization which lasted for two thousand years starting 2500 B.C., it was a common practice to perform a required critical self-examination of patient, searching for internal causes of disease. The Hebrew culture considered disease as punishment for disobeying or contradicting God's laws. The ancient Greeks were well aware of mind controlling body. According to Socrates, "As it is not proper to cure the eyes without the head, nor the head without the body, so neither is it proper to cure the body without the soul." Patients, in old Greek time, isolated themselves to temples to meditate and seek private spirit for healing through reunification of soul and the afflicted body.

Our concepts of how mind controls body have been changing since the time man started to think. The mind or soul for long was considered an integral part of our body. The mind was considered residing in different parts of our body, the most popular being the heart, as the Bible says. There was apparently no problem in accepting this concept until recently, well, about two hundred years ago.

In the seventeenth century came Rene Descartes who at the tender age of 24 proved to be one of the most influential philosopher of mankind's history. Before the time of Descartes, mind and body were considered one and it was sacrilegious even to consider cutting open or taking apart a cadaver. Descartes suggested that mind is separate from the body, a thought which opened up way for medical breakthroughs since now we could look into cadavers and learn more about the functions of body. In the beginning of the nineteenth century, the teachings of Descartes were fully embraced by the scientists, mind or soul were separated from the body allowing close examination of one without the risk of afflicting the other. However, we got carried away with the philosophy of Descartes. We started treating body as if the flesh and blood were the only entities that made us healthy or sick. Fortunately, we are now rediscovering that in God's world everything is one and mind can not be separated from body. Notice the word mind, not brain. Brain is a physical site where most of the body's activities and functions originate or are controlled. Mind is the totality of what makes us human. They are, however, integral to each other.

The dichotomy created by Descartes has started to heal. Psychobiology, the science of mind's attempt to know itself through the study of the brain has opened new horizons for our brain to explore. Diane Hales writes, "The cause of our vulnerability may lie not in our stars or in the twist of the fate, or in roving pathogens, but in ourselves."

Is brain same as mind? The more we learned about brain, the more this question became difficult to answer. To material scientists only matter is real, nothing else. For them mental phenomena are all products of material phenomena. Logical Positivism asserts the primacy of observations in assessing the truth of statement of facts. Arguments not based on observable data are meaningless. To these philosophies, separation of mind as a non-material entity is absurd. Gregory Bateson puts his theory of unification of mind and brain elegantly, "Mind is no more separate from body than velocity is separate from matter. Or than acceleration is separate from velocity." This is in contrast to Descartes' concept or Cartesian dualism where the observer (you) is separate from the observed (the rest of the universe). According to Descartes mind and the brain are separate and that God is the mediator between the two.

Max Planck saved Newtonian physics on December 14, 1900 when he presented his theory of quantum physics. The Newtonian principles were falling fast, Max Planck showed that these were not wrong, just incomplete. The quantum theory says that energy is emitted in bundles or quanta. It also states that the dualism of observer and observed is an illusion. I and the universe are one. Literally. To a Westerner this concept may seem strange, to a Taoist or Buddhist it is but natural.

The quantum wave function (QWF) is described a probability of something happening. Fred Alan Wolf in his book, Taking The Quantum Leap, suggests that "mind" is a property of all matter or energy, right down to peptides, atoms, electrons and quarks. The molecule's "mind" makes the random choice. For example, if the choice is "up" the molecule will fit into receptor and inhibit a function; if the choice is "down" opposite will happen. Neurons receive hundreds of signals every millisecond leading to either on or off state of the neuron or whether to fire or not to fire withuot question! There are therefore trillions of decisions made every millisecond inside the 3 pound mass of cells we call brain. And all these choices by molecular and atomic centers combine to what we call our mind or sense of awareness or self-consciousness. And that's the theory of reality-relatively speaking.

The monistic paradigm of mind and brain supported by the current scientific theories itself often leads to dualism. Dr. Wilder Penfield, the famous neurosurgeon in the 1930s tried to locate "mind" in the brain. Hundreds of surgeries performed by Dr. Penfield showed that brain itself has no sense of perception and feels no pain. Surgeries performed in conscious subjects showed that there was no "mind" in the brain but there were areas in brain to which mind interacted with. He identified them as supplementary motor areas, SMA, located in both the left and the right brain hemispheres. Dr. Penfield discovered these centers in 1943. These brain centers however did not qualify as mind to Penfield, who suggests that mind and brain are two separate entities or elements, and therefore energy is available in two forms. The energy required for mind to function comes during waking hours through the highest brain-mechanisms. Mind develops and matures independently throughout an individual's life as though it were a continuing element. The mind vanishes when the highest brain-mechanisms cease to function due to injury or due to epileptic interference or anesthetic drugs or even during sleep. Two hypothesis are now possible when mind vanishes. First, the mind no longer exists since it is only a function of brain action. It is recreated each time the highest brain-mechanism goes into normal action. In the second case, the dualistic concept, mind is viewed as a basic element in itself, a medium, an essence, a soma which has continuing existence. Therefore, when mind vanishes, it goes silent, it has no longer any connection to brain but it exists and takes control when the highest brain-mechanism go into action.

Apparently the specialized brain-mechanisms switch off the power that energizes the mind each time it falls asleep. It switches the power on upon awakening-a means of relieving fatigue of brain. In either alternative, the mind has no memory of its own. The brain, like any computer, stores whatever it learns during its lifetime. The recorded data are, however, instantly available while awake and perhaps in a distorted manner during asleep--what we call dreams.

The contributions of Sir Karl Popper and the Nobel laureate neurobiologist Sir John Eccles are note worthy in furthering the concept of "dualism interactionism." According to this concept, humans live in two distinct worlds, the material world and the world of mental processes and consciousness. An interaction of these two worlds leads to the world of knowledge in its various forms-science, religion, philosophy, literature and art.

It is difficult to take side with each paradigm of brain and mind. Whether mind is a creation of brain or mind controls brain, the physicochemical connection between mind and brain is easier to understand, an electrochemical paradigm where brain chemicals such as endorphins, like most other brain chemicals, serve to selectively reduce the electrochemical activity of the brain, without which the body will go into convulsions and death. If brain produces mind, the so called "epiphenomenon" then endorphins are responsible for producing this phenomenon. Endorphins, like other neurotransmitters help mind communicate with brain, such as through supplementary motor areas, to satisfy the dualism concept.

Niaz Fatehpuri, an Asian philosopher and my father, wrote in his famous treatise, I and My God, "The human brain has not yet reached the stage of evolution where it can understand itself. Therefore, attempts to understand it only amount to admitting to its fallibility. The question must not be raised. The answer must be accepted unequivocally, God does exist, though not necessarily in the form we believe."

The problem in raising questions about mind are elusive since the answer, we assume, would be presented in terms and nature understood by us. The entire human universe is perhaps no bigger than a small pebble on a beach, we can see what surrounds us but not what is around our surroundings. Our myopia limits our mental vision to such a small segment of the entire existence of the mega universe that it is pitifully insignificant. Our concept of energy is based on principles of physics which may well be proven wrong in the near future. Perhaps what we see around us is a reflection of our own vision, happening because we are trying to visualize us from outside. Perhaps whatever is around us does not even exist.

The understanding of matter and the understanding of truth may not be complimentary. The paradigms of reality, human brain and positivism are only paradigms not realities, as we best define the word.

Our brain, working through our mind, is our master, regardless of the independence of our actions and our "thoughts." All humans, regardless of their intelligence or other attributes are forced to perform similar functions that promote survival and perpetuation of race. As if we have been programmed like slaves. All species perform functions dictated by their brains and, in the case of mammals, especially humans, by their minds.

If mind does have dimensions other than what we know then mind must know the answer, how it came into existence. Why doesn't it communicate with our brain. One possibility is that we need further evolution to understand it and the second, more fearsome, is that if we are told, we may refuse to obey. One day, sometime in the future, say a few million years from now, we will come to know all the answers. On that day, paraphrasing Penfield, all prophets will smile. For we would have found how Bach wrote Minuet One.

MASTERING THE MIND

I think, therefore, I am.

DESCARTES (1596-1650). Principe de la Philosophie. Bk. i, sec. 7.

Mastering the powers of mind has long been a quest for man. Despite his incessant quest, unfortunately, man has only been able to discover that the big question about the powers and dimensions of human brain are beyond his comprehension. We should know better. It should be intelligible that the intelligence needed to understand intelligence must come later for it is an effect that follows a cause; therefore, all present states must remain undiciphered for the very reason that they exist in a continuous state of evolution. Such paradigms of cause and effect are scattered throughout our universe. The physicists have learned that the velocity and position of an object can never be precisely determined because the very process of determination alters either the velocity or the position of the object--the Heisenberg's Uncertainty Principal. And you thought you knew exactly where you stood and how fast you are going. It is something like if you look at the moon, you change the position and movement of moon. Sounds far out? Not really, because we do know for sure is not any less mind boggling! Take for example, the superficial knowledge about the communication device in your gray matter. Trillions of simultaneous electrical and chemical reactions every second help brain cells communicate with each other and with the rest of our body. This is how we know when to duck and when to blush. This is how we know when to frown and when to smile. This what we call our mind, our personality, our being or perhaps, our soul or what Descartes called the I. For a scientist it is merely an electrochemical soup, the chemical components of which have only been recently identified. We need to delve into the nature of the chemicals that govern our destiny, providing the missing link between our tangible acts to our intangible powers of brain to think, reflect, deduce and rationalize-the so called a group of endorphins, the most recent discovery in the long list of brain chemicals (about forty discovered so far). But more excitingly, it paved the way for linking our body's ability to control our feelings.

Over the past few years we have learned that endorphins are not only involved in the reward system of our body in making us feel happy or sad but also in averting the disease by modulating our body's immune system. To some ambitious scientists endorphins even provide the missing link between the mind and the brain--the most elusive concept for man to comprehend. Whether we can go that far in our extrapolations is questionable but the endorphin connection appears definitely to be the chemical connection that controls our destiny. With proper training of our mind, it appears, we can take charge of these wonder molecules. If endorphins can help a yogi reach the stage of nirvana, stop bleeding while a nail is passed through the hand of a Japanese monk, help a karate master break scores of bricks with his head, give petite characters strength to lift thousands of pound with a flick of finger, help acrobats perform unbelievable feats, allow mourning Muslim Shiites walk on fire without feeling any pain, make us immune to infectious diseases and cancer, explain the mechanisms of mental disorders and treat them, make us fat or lean, help us improve our IQ and help us cope with extreme stresses, conquering these chemicals can certainly make us masters of our body and therefore our destiny.

How we harness the powers of these chemicals will be most hotly debated scientific issue of the nineties. What is the best combination of foods, herb, exercise, meditation and a perhaps a pill that can make us smile at fate? Wouldn't most of us want to know?

ALL ABOUT THE BRAIN

The most unusual marvel of Nature, brain, is also very young. Dr. Paul Pearsall makes an interesting comparison. If all the history of our world were condensed and viewed as a 24-hour day, our brains occurred five minutes before the end of the day. Almost all human history took place in the last minute of that same day."

Modern clichés compare brain with computers, a silly proposition. One simple contrast will be enough to distinguish computers from brain. In computers signals travel to switch on or switch off various circuits. Each digit in computer language is a set of yes and no signals. The similarity between brain cells and computers lies only in that both carry electrical signals but brain cells not only turn on and turn off other cells but also leave them with many shades of gray in between, such as may be's, if you like so, if you do I would too, or see you later attitudes. The dynamic nature of electrical connections in the brain can never be reproduced in a computer which is a mere mechanical instrument, the brain, on the other hand, a living organ.

The human brain weighs slightly more than this book and is no larger than a grapefruit. It has more cells than there are stars in the Milky Way. And no different than the Milky Way, billions of sparks fly through the brain continuously, thousands of chemicals discharge spontaneously throughout the brain, all carrying out the messages of brain. These messages synthesized in response to stimulation, sound and sight, convey the message from I, the soul, to the rest of our body.

The neurons that make up the brain are unique cells which cannot be reproduced; we are born with them and die with them. Whereas brain stimulates and controls tissue repair throughout the body, it is unable to repair itself-an irony of a sort, knowing well its handicap, brain acts as selfish being. It protects itself at all times from being external and internal assaults-it compensates its vulnerability with a well "thought off" protection plan.

Human brain is an excellent example of how nature has preserved the history of evolution. Having evolved from a more primitive type, our brain has three distinct segments or brains in one. The reptilian part of our brain or gray tissue that sit atop the spinal cord, is similar to the brain of today's reptiles and was developed about 500 million years ago when we all used to be less than humans. This part of the brain determines many of our behaviors such as walking in a row, gestures, styles and postures. Part of this brain is dedicated to controlling and regulating temperature, breathing, alertness and above all, perception, the latter through corpus striatum but lacks decisiveness and intelligence. After all lizards never could conceive how to rule the world like Adolf did.

Part of the brain stem is called thalamus, the master file system of the brain. All information is sorted, processed and then sent for storage from this site. Also found in the reptilian part of our brain are all the chemicals called neurotransmitters such as GABA (gamma aminobutyric acid), serotonin, norepinephrine, dopamine, and also endorphins. All of these chemicals have well-defined functions. About 250 million years ago our reptilian brain started to grow and the new growth just about covered the old reptilian brain . Now we had a brain of mammals. The mammalian a part of our brain is connected to reptilian brain, which is still the main "processing and storage unit" of our brain. The mammalian brain also uses similar chemical transmitters as the reptilian brain but unlike the reptilian brain, its cells are much more organized making it a more efficient organ.The main attributes of the mammalian brain are emotion, fear and guilt allowing mammals to make decisions over and above what genetics would dictate--a characteristics very much unlike those of lizards.

The last or the third part of our brain is a "cap" on top of the other two brains. This part of the brain is called limbic system because it resembles a cap or limbus. This is truly a primate brain, and very much unlike the mammalian and reptilian brain. This is analogous to a parallel processing unit in a computer. The unique attribute of the primate brain was that it allowed the mammalian species, for the first time, to make coherent talk about his emotions in different languages--speak German, Yiddish or Hindi.

The limbic system of the brain, developed about 300 million years ago also takes care of fighting, fleeing, feeding and sexual desires. It controls all of our secretions including tears when crying. William Fry wrote a book, Crying: The Mystery of Tears, which suggests that crying is a nature's way to cleanse our body off stress. Women have become more apt at it genetically than men. Women also live longer than men. According to Dr. David Goodman encouraged to cry openly show an adjustment in the level of testosterone, the male hormone responsible for many masculine features including stroke and heart disease. Crying reduces testosterone level if it is high and increases it if it is low--the act of bringing to normal many functions of body related to testosterone levels.

Thus what started as a dumb dinosaur ended up becoming an Einstein through the process of evolution in just over 500 million years trying to understand Pythagorean theorems and Bach's creations.

The history of brain development is vividly repeated every time a sperm and ovum fuse together in the uterus; and now recently, perhaps, in a test tube or a surrogate uterus. The first part of the brain to develop in the fetus is the reptilian brain. Once this brain is developed the pain and breathing centers are installed and simultaneous to that a miraculous (what an inadequate word!) thing happens. Some cells of the reptilian brain start growing tails, the axons that shoot up in the cavity of the skull and form an outline of the future brain. Once this outline is complete, they stop growing. Stimulated by a chemical released from the newly outlined brain, the reptilian brain cells start migrating in the cavity and align themselves like in a marching band until the complex organization of the mammalian and primate brain is complete and the cavity is filled up.

The most important part of the brain is hypothalamus, about the size of the pea and weighing about 4 grams, it is the brain for the brain. It controls the master gland--pituitary which secretes hormones that affect the entire body. Pituitary gland also produces endorphins along with the hormone ACTH as its most important contribution. The role of hypothalamus is best described by Dr. Edward O. Wilson of Harvard: "Our knowledge of self is shaped by the hypothalamus and limbic centers of our brain."

Near the hypothalamus is amygdala, an almond-shaped organ as the name implies, which, if stimulated, causes anger, rage and threatening behavior. Behind the limbic system lies cerebellum, the part of the brain responsible for coordination and balancing.

Through the process of evolution, the reasons for which shall remain elusive to the human mind for quite some time, we have acquired a unique chemical chatter box whose functions are literally "mind-boggling." Unable to understand it completely, we are awed by it and left with an ironic disposition.

The size of our brain has little to do with intelligence. Einstein's brain was of average size, Anatole France's brain was about one-third the average size and he heaviest brain was found in an idiot. The brain of women is about 10 percent smaller. That does not make them any less intelligent. Many animals have much larger brain than human brain, yet they hardly speak Yiddish. Theories relating intelligence to the size of the brain compared to total body weight fail to explain many anomalies.

The right and left parts of brain control opposite sides of our body but intelligence and creativity are not segregated in any part of the brain.

THE CHEMICAL CONNECTION OF BRAIN

Neurons or brain cells make up the gray matter of brain. These are the brain wirings like that of the armature of a motor. They come in different shapes and sizes. Each neuron cell has a body attached to a tail, scientists call axon, equivalent of an electrical cord. The axon can extend a few centimeters or for hundreds, across the brain or across the body, ultimately splitting into many tentacles resembling an octopus or star fish. The end of each neuron is always in close proximity to the end of other neuron making a mesh, without closing the gaps.

Neurons generate electrical charges at a rate of one to sixty pulses per second.(The electrical power in your room outlet has sixty or fifty cycles per seconds.) The more excited a neuron gets, the more electrical pulses it generates. Each electrical pulse fires up other neurons, like dominos.

Simply put, the basic function of brain cells is to excite each other. The brain cells communicate each other through electrical pulses. Hundreds of trillions of electrical pulses generated simultaneously give rise to the overall electrical activity of the brain. The human brain is a live electrical box. The current flowing out of the brain controls the functions of various body cells making them digest food to yawn to writing looks like this one.

Scientists are able to map out the electrical nature of brain with relative ease by placing electrodes in different parts of the brain but the question which bothered them most was how do neurons transfer their electrical charges to other neurons since the ends of neurons never touch each other. Can sparks fly, was the question asked? It was definitely a possibility since the tissues are wet and we know current can be carried through wet medium. Around the turn of this century, this dilemma was solved when specific chemicals were found in the brain tissue suggesting that these may be involved in the transmission of electrical signals. The history of discovery of brain chemicals is however old. Around the sixth century B.C., Pythagoras suggested that brain was the organ of mind, a beginning in linking the functioning of brain with body. In 1901, it was discovered how nerve fibers act like an electric wire and transmit impulses and in 1921 the role of chemicals in transmitting these impulses evolved with the discovery of acetylcholine, the most abundant and important chemical transmitter. These discoveries lead to identifying many brain and body chemicals associated with transmission of electrical signals in the body.

Endocarinologists, specialists of hormone systems of body, suggested that perhaps the transfer of charges takes place through hormones, a plausible suggestion. Neuroscientists called these "hormones" neurotransmitters. The current theory states that when the electrical impulse come to the end of the line in axon, they release neurotransmitters, which travel across the gap, the synapse, make contact with neighboring neurons to activate them in producing electrical impulse. This theory, the chemical basis of brain function, had only one flaw. If the neurotransmitters activate many neurons which in turn can activate many more, wouldn't it result in spreading of electrical activity that the body would short-out? The answer to this question did not come easy. Years of studies, however, paid off and scientists came to a conclusion that there must be specific sites on neurons to which neurotransmitters attach--the receptor sites, a concept which is now proven to be the most significant discovery in understanding how brain works.

A receptor is a large molecules, perhaps made up of thousands of atoms. Jon Franklin compares it with "lily pads" and according to whom, "the exposed section, `lily pad' floats on the surface of the cell membrane, while the `roots' extend deep into the cells." When neurotransmitters attach to "lily pads," the shape of these pads changes and the tail wiggles in a manner to inform the cell how to alter its metabolic rate and other behavior and the information is conveyed to neighboring cells leading to a certain sensation or a response." Receptors are not fixed engravings on the surface of neurons, they are being made and replaced continuously depending on the need of the cell. For example, if a neuron supplying a body cell records lack of oxygen, the neuron will immediately recognize it, form receptors that will attract neurotransmitters that cause slowing down of breathing to conserve energy. If this all sounds complex and confusing, it is. But if you look at the complex functions of creating lovers, poets, daredevils, philosophers and mothers it shapes, it can never be too complicated.

Receptors are also present in other tissues of the body such as muscles. When neuronal cells spray their chemicals on these receptors, muscles responding by contracting or expanding. Since cells can produce just about any type of receptor, cells control their sensitivity to various neurotransmitters affecting its own rate of metabolism. There are over a trillion cells like this in the brain, ever changing, ever modulating their receptors and generating chemical messengers in response to the outside world and the world inside our body, the milieu interior. It is this myriad function of brain cells that we call personality.

An example of how the receptor theory works is the disease myasthenia gravis, loss of muscle tone, the cause of death of Aristotle Onasis. The body muscles have receptors which are activated by nerves through neurotransmitters. At times the body's immune systems starts to chew up these receptors causing loss of nerve control and thereby their rigidity. The chemical neurotransmitters involved in myasthenia gravis is acetylcholine.

How important are the discoveries of the nature of brain can be discerned from the number of Noble prizes awarded in this field. The first Nobel in Medicine in 1908 went to Santiago Ramon y Cajal and Camillo Golgi for their discoveries about the structure of the nervous system. Since then over a dozen Nobel prizes have been awarded to researchers in the area of brain structure and chemistry, more than in any other science--a subtle indication of how scientists consider the importance of these studies.

THE MOST ELUSIVE CHEMICAL-ENDORPHINS

Armed with the chemical key to the functioning of brain, scientists throughout the world are searching, frantically, for the molecules of the brain, and hitting jackpots in herds. To date about forty neurotransmitters have been identified. One such chemical discovered recently attaches to same receptor as morphine does and it was as a result called endogenous morphine, in short--ENDORPHIN. What has enamored the scientists about endorphins is the ability of these molecules to affect brain and body function like no other molecule can.

Endorphins were discovered serendipitously during the research on the mechanism of how morphine works. Morphine creates a feeling of euphoria leading to withdrawal if it is not repeated. The biochemical studies on the mechanism of morphine action lead scientists to specific areas in the brain known as receptors where morphine molecules attach quickly. The question arose why would nature create receptors in brain that will attract a chemical found in the exude of poppy plant? The answer did not come soon. Years of frustrating research revealed that these receptors are actually meant for some chemicals in the brain; it just happens that morphine resembles the structure of these chemicals and thus finds itself fitting snugly and nicely in the holes meant for these endogenous chemicals and thus triggering a response similar to the response of endogenous molecules. The discovery of endorphins thus opened a new area of research on brain receptors, where the brain chemicals cling on to produce what we call the brain response.

A characteristics of morphine is to develop tolerance and dependence, both of which are now classified as chemical phenomenon. Addiction to morphine has been known for long time. Addiction to endogenous morphines has recently been discovered yet practiced since time immemorial. For example, meditation is addicting and so are the rituals of religious prayers. How we contact with realities beyond ourselves is a point of conjecture, yet we know meditation leads to contact with our mind, the one-self inside us. Meditation produces chemical reactions that slow down the firing of certain neuronal system leading to a feeling of calm, relaxation, and often a feeling of "natural high." Zen, trans.

scendental meditation and Centering Prayer all lead to it. Endorphins are definitely involved here.

A recent movie "Dark Angels" is an interesting story indeed. It depicts coming to earth from an alien planet in search of, believe it or not, human endorphins. Yes, the aliens had perfected a technique to concentrate endorphins found in human brain and these potions were sold at very high value in their land of abode. Naturally, there were killings to suck out endorphins and it took an earthling with enough demeanor and courage to square away the mean endorphin hunters. Fantasy or drama, it shows how fast fascinations come down to earth.

Endorphins belong to a class of neurotransmitters called neuropeptides which are found in neurons of the brain and the rest of our body. They are produced by break down of larger amino acids, peptides, found in neurons. The discovery of how brain communicates through neuropeptides is very recent. Neuropeptides are found in the gut, skin, pituitary, pancreas, adrenals and other part of the body where they are intimately involved in controlling such body functions as appetite, sexual drive, recovery from shock, etc.

The peptides which interact with receptors or with morphine or similar molecules attached are called endogenous opiods and include endorphins, enkephalins, and dynorphins. Endogenous opiods affect perception of pain, mood, food intake and scores of other behavioral patterns. The peptides with morphine-like activity have structure quite different from morphine. The most dramatic aspect of these morphine receptors is the reward system associated with these receptors. When we do something that results in brain rewarding us with a shot of this "happy" chemical, we are bound to repeat doing it. But if we did something that shut off this chemical slug, it would made us feel "bad" and perhaps we would not repeat that. This is what scientists call conditional learning.

From learning to control our bowel to smiling at will are all actions that could be described as part of this reward system. Out there in the brain, it seems as if someone is holding a carrot for us. We have seen how dolphins are trained to kick a soccer ball and then receive their reward. Out there or in there we are given a fix in a manner not different from how dolphins receive their reward. We are slaves to our mind.

The mental reward system also explains why people get addicted to drugs. A drug addict gets the good feeling by injecting chemicals, the types which are not otherwise produced in the body, such as heroin. High concentration of heroin would cut off the production of body morphine and perhaps reduce the number of receptors out there, requiring higher dose the next time around--the basis of tolerance. However, if suddenly stopped, it caused withdrawal, principally depression because the body factory which manufactures endogenous morphine is laying dormant and takes a while for it to get going. Until then the addicts suffer. How long they suffer depends on how fast these happy chemical factories started to churn their wares.

Many questions arise when we give credence to the mental reward system. Is it possible for some of us to have defective factories, inadequate production facilities or hyperactivated production? What if something modifies the ability of these factories to reproduce the happy chemicals? Can our environment, our psychological interactions alter the workings of these factories, or perhaps they are only genetically controlled? We know that children who received intellectual stimulation in their early years tend to be more intelligent than who did not. Then is there a conditional reflex that helps us control this amazing plethora of happy chemicals?

Can mother's love help create or stimulate happy chemicals or their receptors in soothing pain? Does embracing causes release of endorphins? Suddenly, we have a basis for explaining effects of a lot of socio-psychologic behavior. The connection between mind and body has been discovered.

The endorphin receptors are found in abundance in pituitary, alongside striatum, intermediate lobe and other parts of the central nervous system(CNS). Outside of CNS, gastrointestinal tract, pancreas, the adrenals, the carotid, the pyloric gland, reproductive system and eyes have reported to exhibit opiod receptors. The receptors are also present in body fluids. The concentration of endorphins is elevated in pregnancy. There is an interesting controversy regarding the nature of these receptors. Are there different types of receptors for different types of endorphins or perhaps same receptor changes its shape to fit different endorphins-sort of fluid or dynamic structure. The latter theory seems plausible since it is difficult to isolate these receptors because removing them from the surroundings where they work, alters their structure.

Endorphins, like other brain and body chemicals, are not merely scattered throughout. These are part of an elaborate body defense system that assures our survival, such as in the handling of famine and feast states. If body suspect famine, it undergoes a remarkable metamorphosis to conserve nutritional and essential resources through a system we will now call ENDORPHINERGIC, wherein all forms of excretion ceases, water, electrolytes, heat and calories are stored; body is motivated to seek more food, water and salt appetites are increased resulting in overeating which leads to obesity and edema. All of these symptoms are quite obvious in shipwreck survivors.

The ENDORPHINERGIC system of our body is our routine for survival. In those times when food was not abundant man survived on whatever catches he could make during good weather and to assure that he is not falling short of nutrition during bad weather, body produced high concentration of insulin which builds the stores necessary to survive famine. Still today, populations of the world which are exposed to the cyclical nature of food availability, such as in Eskimos, storage of body fat is common. Ever seen a slender Eskimo? The endorphinergic system of our body prepares us for hibernation.

The feeding patterns of mammals evolved long before the current era of plentiful food and energy. In those early millennia, only these species survived which could take advantage of infrequent feasts to store enough calories to survive the long intervening periods of famine. It was not uncommon for man to eat all of his daily needs within 10 minutes; overeating and gorging was essential for survival. Today in affluent nations obesity is quite common representation, a preparation for the famine that never comes. The preparation for famine is not all voluntary- body's glandular systems perform all necessary biochemical functions to assure that each calorie goes a long way. Endorphins produce all those conditions which reduce expenditure of energy such as showing rage, getting involved in sexual activity, and providing euphoric feeling--well, what else there is to be happy about in a famine?

In prolonged starvation when opiods are continuously secreted by the body, some tolerance develops requiring higher concentration to achieve the same effect. This is analogous to morphine addition. During starvation, skin is covered with a dirty brown pigment that concentrates around the neck, sump, sides of the torso and on the back of the arms and the thighs. This is because the precursor to endorphins also produce a hormone alpha-melanocyte responsible for producing brown pigment. Could there be any connection between nutritionally deprived citizens of the world and the color of their skin or of morphine addicts being of darker complexion? Or how about the racial differences in the color of the skin related to the habitat of races. Black races mostly come from hot and temperamental climate. High content of pigmentation protects from the ultraviolet energy of sun but it could also have come from excessive beta-endorphin release to conserve body fuels, especially water, in the hot climates. Do these races have a happier disposition as a side effect of endorphin release? There is some indication that darker races generally enjoy more fun-loving things.

In contrast to the endophinergic system, the body has a so called ENDOLOXONERGIC (endogenous naloxone) system with opposite effects. Several chemical together accomplish this action including calcitonin and melanocyte stimulating hormone or corticotropin-inhibiting peptide.

When body expects surplus of nutrient it starts burning them out fast. One symptoms is the "wet dog shakes" that resemble a convulsant condition, to produce heat, elevate body temperature and all other effects that help burn energy faster.

Besides preparing us for famine or feast, endorphins also come handy in our daily behavior such as laughing or crying. When we laugh, anatomically we go through repeated exhalations, one after another. (Try it now). If you were to try to do it without laughing, it will not be easy and may cause discomfort. But during laughing, endorphin levels are high which reduces any feeling of pain in this act of repeated exhalations we call laughing. All physiologic effects of laughing are endorphin effects such as ability to tolerate increases carbon dioxide in blood, which occurs during repeated exhalations, depression in respiration rate.

On the other hand, yawning is an early sign of the withdrawal syndrome in opiod addicted individuals. It is the beginning of the process to reduce levels of carbon dioxide in the blood. Yawn is a prolonged exhalation, an indication of ENDOLOXONERGIC activity building up in the body.

Crying is always accompanied by pain. It is an endoloxonergic activity. Crying is frequent in infants and children because they need it. This happens because they are more sensitive to calcitonin, a hormone needed for growth of bones but which is also endoloxonergic and one of the endoloxonergic activity is to increase secretion of fluids from the body as brought about in crying perhaps due to increased pain. With age, sensitivity to calcitonin decreases and with that comes decreased pain to various stimuli and as a result crying and tears.

Smiles often precede laugh and are also endorphinergic preparing for an inflow.

Stretching is extremely important in exposing receptors to both endorphin and endoloxone hormones. During sexual intercourse endoloxone builds up to orgasm and to ejaculation. Since sexual intercourse involves energy expenditure, it is another indication of it being endoloxone activated. Also supporting this thesis is the spontaneous ejaculation and orgasm as a withdrawal symptom to morphine. After orgasm endorphin is necessary to relax the body. Weaker orgasmic pleasure are produced by stretching of bladder after urination and rectum after bowel movement.

The endorphinergic and endonaloxonergic systems were earlier thought to be active only in humans since earlier studies had suspected that invertebrates have no opiod receptors; now it is well established that all species have these receptors including amoeba which shows naloxone-reversible suppression of pinocytosis by opiate peptides. The earthworm has both enkephalin and endorphin. Insects, mollusks, snails, goldfish, salmon, turtle, pigeons, rabbits and chicken embryo retina all have opiod receptors including those that affect pain sensation. Along with these, rats, mice, guniea pigs, cows and cats have long been demonstrated to have opiod receptors. The concept of receptors and endogenous chemicals occupying these receptors in eliciting various responses opened the doors to recent findings of a diazepam (Valium) receptor, which when activated generates a feeling of peace and security. Amphetamines, the speed drugs, were found to stimulate production of many neurotransmitters.

Through the discovery of endorphins we know now that the poppy plant isn't the only source of opium. The largest storehouse of opium lies within our body, mainly in our brain. The discovery has many meanings. We can get addicted to ourselves, have withdrawal symptoms and perhaps suffer through the miseries of drug addicts with out outside help. Now we have a basis to explain many emotional aspects of our brain or as some say, mind. Brain manufactures chemicals to help curb pain. Brain manufactures chemicals to make us feel happy. Can we produce these chemicals at will? Can we then become addicted to these chemicals?

THE POLITICS OF ENDORPHINS

The discovery of endorphins, perhaps one of the century's most tantalizing scientific tale, is rife with drama that would make Ian Fleming lost for words. The politics of endorphins is as mind boggling as endorphins themselves.

In 1964, Dr. C. H. Li, a professor of biochemistry at the University of California in San Francisco discovered a new compound from brain and pituitary extracts which he called beta-lipotropin. Not knowing what to do with it, Dr. Li shelved his discovery. Seven years later it would be discovered that what he had fumbled onto was a precursor to beta-endorphin, one of the most potent chemicals that control communication between nerve cells.

During all this time while Dr. Li's magic potion sat gathering dust, scientists from California to Stockholm had started to wonder how morphine and other opiates (opium-like drugs) work. One of the suggestion regarding their mechanism came from the well known guru of pharmacology, Dr. Avram Goldstein. He suggested that there may be specific receptors for morphine in the brain as found for other chemical neurotransmitters elsewhere. This receptor concept may be likened to a lock and key mechanism where the keyhole represents the receptor and keys which fit the keyhole and turn the lock represent opiate molecules such as morphine. Opiate antagonists or chemicals which reverse the action of opiates, such as naloxone, might be represented by keys which fit the keyhole, preventing access of opiate keys, but which are incapable of turning the lock.

Dr. Goldstein's idea inspired many scientists to start looking for these receptors in the brain. This included the Snyder-Pert pair of scientists who would within a few years become the most famous names in the history of neurochemistry, the science dealing with the chemical aspects of brain.

By 1970s, the science of neurochemistry was starting to be recognized as a viable science. One of the pioneers of this new discipline was Dr. Solomon Snyder, a young physician at The John Hopkins Medical School in Baltimore. Dr. Snyder had just finished working under the direction of Dr. Julius Axelrod, the Noble laureate, whose interests were to understand the mysteries of "synaptic cleft" (the open area between two neurons).

What fascinated Dr. Snyder was how specific the actions of opium were compared to alcohol. Small doses of morphine will quickly contract pupil, slow down breathing and remove pain. The high specificity of morphine action was enough of a clue to suspect the presence of specific morphine receptors, exactly what Dr. Goldstein had postulated.

The search for these morphine receptors was intensified not because finding these receptors would mean there must be endogenous chemicals that act like morphine because it was unlikely that nature would create a structure in the brain to await man to discover opium poppy. Therefore, in the early 1970s the idea of chemicals similar to morphine floating in the brain had started to catch credibility as Snyder and many others believed.

The catch was to find these receptors. Seemingly, it would be easy to chop brain cells, mix with radioactive morphine, wash out the brain cells to remove unbound morphine and then see, through hot radioactive spots, if morphine sticks to brain cells. Hundreds of scientists throughout the world rushed to perform this simple experiment but they all came out frustrated. There was no sign of morphine sticking to any brain cells. Therefore, no receptor sites for morphine and hence no endogenous morphine type structures, all contrary to what most scientists had hoped for. However, the reward of finding these receptors was too tantalizing for the scientists to give up their search. They next tried heroin, hoping it to adhere much more firmly than morphine but they failed again, rather miserably. But misery brings creativity. The time had arrived to take a fresh look at the hypothesis. In the 1940s it was recognized that small changes in the structure of morphine produce compounds which block the effect of morphine--such as a naloxone. To block the effect of morphine, it was suggested that naloxone must bind somewhere in the brain, it was hypothesized.

Snyder reviewed the hypothesis of how naloxone works again and just when the neuroscientists around the world were ready to throw the towel on finding morphine receptors, Snyder and his new 24-year old pretty graduate student Candace Pert decided to give finding morphine receptors one more try-this time using naloxone as the binding agent in place of morphine or heroin.

In May 1973 a fresh batch of rat brain cells was prepared by Pert and mixed with radioactive naloxone, the cells washed to remove unbound naloxone and the radioactivity retained in the brain cells analyzed. Under the radioscope the sky lit up, Bingo!, naloxone stuck to the brain cells. For the first time, they had the irrefutable evidence of a receptor for naloxone in the brain. Why didn't then morphine or heroin stick to the brain cells? The answer was simple. Morphine and heroin attach to receptor only momentarily. They snap in and snap out; the key gets in the lock, unlock it and get out of the lock. Naloxone sticks there like glue. This is how naloxone overcomes the effect of opiates like morphine-by occupying the brain centers where opiates make their "hit." A colleague of Snyder, Michael Kuhar then repeated the experiment by injecting radioactive naloxone in rats and traced their brain. The hot spots were out there where they were supposed to be-in the pain centers and in the breathing centers of the brain. But more than that he found that naloxone also stuck to a small part of brain which if stimulated produces happiness and bliss, the ultimate effect of opium. The discovery was complete. Many other researchers, almost simultaneous with Snyder and Pert's conclusion, came up with similar observations, notably Eric Simon and Lars Terenius.

The Snyder-Pert discovery was however, only a technical milestone since receptors for other chemicals had already been identified and isolated in other parts of the body. But the discovery of receptors in the brain opened up the possibility that these receptors must be the seats for the chemicals produced in the brain, sort of like brain's opium. And that's what turned-on hundreds of neuroscientists throughout the world to burn the midnight candle. The race was on.

Soon this race was won by Dr. Hughes and his mentor Dr. Kosterlitz from University of Aberdeen, Scotland, who reported finding the first endogenous morphine like compound. They called it ENKEPHALIN, which is derived from "en" meaning "in" and "cephalo" meaning "head." The discovery of enkephalins was followed by findings of many "opium-like" substances named endorphins and dynorphins. Dynorphin, short for dynamic endorphins, are the most potent of all. All of these endogenous opiods (a term referring to opium-like structures found in the brain, whereas opiates refers to opium-like drugs found outside of the body) interact with different parts in the brain and other body tissues.

Nobel Prize, the ultimate recognition of scientists by their peers, is mostly awarded for discoveries that are simple in nature--the most difficult to achieve feat. Discoveries of binding sites of morphine in brain and endorphins was a simple concept worthy of a Nobel. Who will get it remains to be seen but the road to Stockholm is never traveled easily.

Let's understand the dilemma of the Nobel selection committee in Stockholm. First, there was a proposal that there must be morphine receptors made most loudly by Dr. Goldstein. Then there were early discoveries of precursors to endorphins by Dr. Li. The discovery by Snyder-Pert of actual binding of naloxone to brain and the finally extraction of endogenous opium from the brain by Kosterlitz and Hughes. Who should get the prize? But before we project the winner or winners, let us remind ourselves that a Nobel can not be split more than three ways for a single discovery. Snyder, Kosterlitz and Hughes have already received the Laskar award which is generally considered a preamble to Nobel. Pert has apparently missed the boat with lost Laskar. She is crying foul and many agree with her, some go as far as describing it as sex discrimination. Snyder did well professionally and financially. He founded a drug research company, Nova Pharmaceuticals, which made him an instant millionaire. The race for Nobel is however not over yet. Francis Crick, a Nobel laureate for his part in genetic coding, has joined the race, hoping for another big one.

Nobel infightings aside, the discovery of endorphins has made it possible for us to better understand how our mind and body function. For example, the concept of receptors-the lock and key system of our body, helps us explain many phenomena that were a mystery to us before the discovery of endorphins.

THE MAGIC DRAGON

"Puff, the magic dragon, lived by the sea, frolicked in the

autumn mist in a land called Honolee." Peter, Paul and Mary.

Prehistoric man used plants to treat disease and provide food and shelter, long before written history began. He mastered it by his instinct and by trial and error learning that certain plants were useful for treating illness, just as he learned that some were good for food purpose and that eating others would kill him. In the written record, the study of herbs dates back over 5,000 years to the Sumerians who know well the medicinal uses of plants.

The first known "Chinese Book of Herbs" (circa 2700 B.C.) lists some 365 useful medicinal plants. Egyptians, around 1000 B.C., knew the use of garlic, opium, castor oil and various other spices and herbs for food and medicinal purposes. The Old Testament mentions herb use and their cultivation.

Hippocrates advocated, in contrast to Galen' recommendation, the use of few simple herbal drugs but along with fresh air, rest, and proper diet to help body's own "life force" in eliminating diseases.

Opium has for long been used as a panacea for all of mankind's ailments from diarrhea to kidney stones. In the Renaissance period, physician Paracelsus resorted to opium to dissolve disease like "fire dissolves snow." However, what gave opium its place in medicine or culture was its ability to cure the spirit--it cured depression, boredom or even the feeling of lost love. It cured even if there was nothing to cure. Opium did all of it by making us feel good or euphoric and as long we continued to use it we felt "good." But then this goodness of feeling was almost always accompanied by a loss of weight and loss of social responsibility. The only thing an opium user would care for is how to continue to feel "good."

The poppy plant, Papaver somniferum, from where opium is derived, has been known to man for thousands of years. Cuneiform inscriptions on clay tablets excavated from the library of Ashurbanipal in Nineveh describe how the women tended the poppy fields of ancient Mesopotamia and earlier Sumerian writings describe the medicinal use of opium.

How long has opium been used as a drug is debatable but evidence of its use goes back to the third century B.C. in the writings of Theophratus.

However, it was not until 1805, that the active ingredient of opium was isolated by the German pharmacist Serturner (1783-1841). He named it "morpheum" after the Greek god of dream, Morpheus.

Opiates, opium and its various extracts, used for centuries have now become part of many cultures. The word opium itself has become an idiom in many languages. Karl Marx said, "Religion is the opium of the masses." In other contexts the word opium signifies the omnipotent capacity to make things better. Opium is purely a pleasure drug having very little curative property except as analgesic and in the treatment of diarrhea; yet in some parts of the world, it's use is still made to "cure" symptoms ranging from stomach discomfort to miscarriage.

The original use of opium is often associated with China but records indicate that it was introduced in China by Arab traders in the 12th century. The use of opium in China was for medicinal purposes in the early part of 18th century, specifically to control dysentery and other illnesses. Chinese started smoking opium around the middle of the 18th century and that kicked-off the pleasure use of opium and it spread widely. The effect of pleasure use of opium was quickly felt on the social fabric of the society which prompted the emperors in China to ban its sale and use. However, by the time these bans were mandated in the early 19th century, opium had already travelled to India and the Middle East and poppy (Papaver somniferum) had become the largest cash crop and its farms the target of conquest in the 17th and 18th centuries. For example, the British East India Company took over the districts of Bengal and Bihar, the richest opium farmlands in India and thereby controlled the bulk of opium trade to China. The British got exclusive marketing rights to Indian opium and became the largest drug-pushers in the history of mankind.

The British with their marketing genius are held totally responsible for making what opium is today a nuisance to mankind. The British plans to make the entire China an opium den started to falter because of the bans placed by the Chinese Government in 1820 on any vessel carrying opium in the Chinese harbors. The British, overwhelmed by their zealot to conquer the world could not take a no for an answer and came with an audacity to strike militarily in 1839 to seize control of Hong Kong (which will finally be returned to China within a few years). Hong Kong gave the British a routing channel for opium and soon one-fourth of all China had fallen prey to opium.

Just about this time the Chinese laborers had started landing in America and with that came opium to America. At first confined to secluded dens in San Francisco, the opium use spread throughout America by the mid 1800s. However, as entrepreneurial as American brain is, the use of opium was quickly "westernized" and instead of taking those disdainful Chinese fixes, American were getting their high from scores of patented medicines such as Dr. Smith's Backache Cure.

Morphine, much more powerful than opium, from which it is derived, was used widely during the American Civil War for mercy release of pain but those returned from the war also carried with them "the soldier's disease,"- addiction to opium.

Morphine, one of the most humane drug ever discovered also produced the addiction most inhumanely. Much research went into removing the addicting properties of morphine and in 1898 Bayer Laboratories of Germany produced what we call today heroin as a substitute for morphine that would alleviate pain but not cause addiction. The story about heroin is an interesting one. Synthesized as diacetylmorphine by Bayer laboratories in 1889, heroin was Heroin, the brand name of Bayer laboratories. The abuse of heroin became so widespread that Heroin lost its trade-name status and Bayer laboratories happily gave it up disassociating with this new molecule.

The British audacity in pushing opium, however, did not go unnoticed by the humanity at large. In the late 1800s they were forced by the world opinion to stop opium trade which they did half-heartedly and even though the Royal Navy was assigned the task of catching smugglers once financed by the British, they failed miserably, perhaps conveniently. In America, the uproar was heard ever louder and lead to the Harrison Narcotic Act of 1914 which formed the basis for listing ingredients of patent medicines on the label. Before this Act, opium extracts were added to many patent medicines claiming to cure every conceivable ailment. What made these medicines popular was that once used, patients "loved" them and felt so "good" they felt cured.

The crackdown against opium in America was much more successful than the repeated attempts over more than 200 years in China. Opium was made illegal and as a result became very expensive--most housewives and laborers could no longer afford it and were forced to quit, often with severe physical and emotional maladjustments, which became the focal point of study in many detoxification clinics established throughout the country. It was found that addiction to opium was two-fold: physical and psychologic. The physical addiction which takes a longer time to build would result in sweating, heart pounding, skin reaction and a host of other symptoms if opium was stopped. Fortunately, contrary to popular belief, none of the physical withdrawal symptoms are lethal and cured if exposure to opium is avoided. The problem arises in treating the psychologic dependence. Many people who are cleared physically of opium revert back to it for its euphoric properties despite applications of every conceivable Freudian gymnastics. However, a breakthrough was made in treating "pathologic addicts" through use of heroin given as a maintenance dose.

Unfortunately, the successful strides made in America in curbing use of opium were destined to be challenged by a new drug culture. In the late 1800s and early 1900s most people became addicted to opium quite accidentally by using patented medicines they did not know had opium or through unscrupulous prescribing practices of physicians. However, during the Depression and World War II, expanded groups of people who would deliberately make use of opium, morphine or even heroin to get high.

No event in the history of mankind, let alone a silly plant, has ever produced a more indelible mark on the society as opium plant has. Opium use forever changes the social structure of individuals and the society they belong to. Use of opium and its resultant euphoria, the reinforcement is taken as a substitute for the reinforcements received from social environment. In a drug-free society, these reinforcements come at least, in part, from work, interactions with peers, and family, from drinking, eating and other artistic and social endeavors. Opium short circuits this reward reinforcement system, the very fiber of a stable society, and leads to distorted values. Opium was and is a social evil-a dragon of a sort.

The question how opium use makes an individual harmful to society is only answered in light of the rules and principles under which the judgements are to be made. The use of opium may make a person useless but does that make him harmful or perhaps being useless is harmful enough for the society. The societal structure determines the rights and obligations of all individuals. Can an opium addict discharge his obligations? These are the questions for the social scientists to solve. John Stuart Mill writes in his essay On Liberty (1859) that it was an undue infringement on individual liberty for the government to restrict the use of drugs. This statement is still debated today in America.

The chemical technology of the 1960s lead to discovery of what it now seems an unending array of addicting molecules from amphetamines to LSD, from cocaine to crack. The sociologic, biologic and economic impact of addiction to these chemicals would probably take another century to be fully understood. But the chemist of the 1960s has changed the mental fabric of our society forever.

And what started with the silly opium poppy has now grown into a magic dragon and his name is not Puff.

THE FORMONES

Hormones, the wonder chemicals of the body, control such varied functions of body from ovulation to body growth. They are responsible for male virility, female shapes, our vulnerability to cancer, menopause and hundreds of minute functions. Technically, hormones are substances normally produced one part of the body and carried by the blood to distant parts, which it affects for the good of the organism as a whole. Hormones act locally as well as distant sites and thus act as chemical messengers. The definition of hormones needs revision since now we have discovered many "hormone-like" chemicals in our environment, especially our diet. Until such time that scientists can resolve the exact definition of hormones, a new term has been coined, "formones," for hormone like substances in food.

Some formones found in our diet resemble the body endorphins-in their structure and actions. Thus opium that addicts comes not only from poppy plant or from within our brain but can also from over diet as well, making it all plausible for us to get addicted to food. One theory comes to mind instantaneously: eating same food for longer time may make you desire it more often. The differences in ethnic diets and how some cannot give up the taste for that gorgeous piece of pie points to psychologic and physical dependence which can only be instilled by external resources.

The most prominent dietary sources of formones are milk and wheat. The formones found in food resembling endorphins are called the EXORPHINS (exogenous morphine).

Proteins in our diet are particularly important for brain development and their breakdown products, the peptides and the smaller amino acids, are the building blocks of our body neurotransmitters. Our ability or break proteins into peptides and amino acids changes with age; newborns have an enzyme rennin which promotes curdling of milk and subsequent digestion of casein, the milk protein.Peptides secreted in mother's milk provides immunity factors to infant. In some, absorption of large proteins also causes food allergies.

It has long been recognized that the unabsorbed proteins from food cause severe body reactions including loss of blood pressure and death if injected intravenously. Even when absorbed orally they cause diseases such as gluten enteropathy from wheat gluten. Smaller proteins carnosine and anserine produce neurologic diseases and mental retardation. Chicken breast is a good source of carnosine and anserine.

Opiod peptides are mainly formed from gluten and casein in milk. Gluten when broken down yields fractions which have stimulatory and opiate activity. Casein, the milk protein, similar breaks down into many opiod peptides and also non-opiod peptides. In 1973 it was suggested by Dr. F. C. Dohan and his group that some schizophrenic patients improve on gluten-free diet. These studies lead the National Institute of Mental Health to thoroughly investigate whether gluten contains any opiate-like substance. A subtle relationship was established; casein found in milk and wheat gluten shows significant opiate-like activity. In many ways these exorphins appear to be better suited to interact with opiod receptors. Not all people who eat wheat products become schizophrenic or psychotic or even contact celiac disease or other gluten-related disease. Genetic factors are important in eliciting gluten response in terms of their absorption, transport to brain and sensitivity in brain.

Tests confirming the role of food endorphins, exorphins, have included administered then directly in the brain of rats, producing analgesia which is reversed by naloxone, a characteristic of opiod receptor interaction. Also diets high in these exorphins (e.g., hydrolyzed gluten) cause elevation of insulin and glucagon levels in the blood, a characterestic effect of endorphins which was again blocked by naloxone. Hydrolyzed gluten also produces an increase in a neuropeptide in plasma that controls the transit time of food delaying it. Casein exorphin seems to be of same potency as morphine. They have an important role in the growth and development of dopaminergic system, responsible for coordination and body movement. Dr. P. Restani and his colleagues at the University of Milan have shown that newborn rats have completely developed opiod receptors to bind casein-derived exorophins, whose exposure at early life increases body growth through enhanced release of growth stimulating hormone. Increased levels of growth stimulating hormone occur because dopamine, a neurotransmitter in hypothalamus, which depresses production of growth stimulating hormone is itself reduced thus allowing increased levels of growth stimulating hormone.

Food also contains some specific hormones such as thryrotropin releasing hormone (TRH) in alfalfa. TRH not only stimulates thyroid, it has many local effects on stomach acid and pancreatic secretions and the motility of of intestine. Many similar hormones are present in foods that help regulate gastrointestinal activity, a relationship known for centuries but the chemical link to it provided only recently.

These findings make us wonder about the old wive's tales about foods used to treat ailments. A book,"Practical Bazaar Medicines," published in 1936 by G.T. Birdwood in India, talks about the utility of foods of Indian sub-continent on ailments ranging from indigestion to schizophrenia-wonder if Mr. Birdwood knew about endophines.

THE CHEMICAL CONNECTION IN DISORDERS OF THE MIND

The whole world is crazy except for me and thee... and sometime I wonder about thee. OLD QUAKER Farmer

Mental disorders are more common that most of us believe. About 3% of our population can easily earn the laurel of "crazies," about 5 million Americans. This does not include those millions of Americans who are daily scolded with "Are you crazy?" or what Colonel Gaddafi thinks of the American population.

Mental illness as a disease and its chemical connection was recognized only as recently as in the middle 1970s at a great risk to the alcohol and tobacco industry, for now, we can point out to many social addictions on chemicals equally harmful as the prohibit chemicals. The social stigma attached with chemical dependence and mental illness has started to diminish as public understands more about the chemical basis of these diseases.

Like, receptors, neurotransmitters also come in different shapes and forms. These chemicals are essential for communication between brain cells. Some neurotransmitters produce excitatory impulses other transmit "inhibitory" impulses--analogous to the accelerator and brake pedals in a car. However, it appears that the function of most neurotransmitters is that of inhibition -inhibiting, selectively the brain electrical activity to achieve specific actions. By 1970, several chemicals isolated from brain included norepinephrine and serotonin, which govern mental depression. When these chemicals are in short supply, depression sets in. These two neurotransmitters, are broken down by an enzyme called monoamine oxidase, or MAO, in the body. Antidepressant drugs like iproniazid and reserpine act either by reducing the levels of MAO or by elevating the levels of norepinephrine and serotonins. Drug iproniazid reduces the levels of MAO, which means that norepinephrine and serotonin can not be broken down as fast in the body and their levels will rise. Reserpine, on the other hand, works by mobilizing stores of norpeinephrine and serotonin, increasing their levels. Depression as a clinical phenomenon has been with us for centuries and afflicts all ranks in the society. King Saul and Alexander the Great were depressed individuals. Throughout the ages depression has been viewed as caused by evil spirits, moral corruption and disobedience to Gods, grief and anger. The cures for depression have ranged from blood letting, curses, spells to the use of chemicals like tricyclic antidepressant of today. The chemical basis of depression is now starting to be accepted as one of the major causes even though this theory was proposed as early as in the beginning of the nineteenth century.

Another neurotransmitter which has changed many old concepts about human behavior is GABA. Discovered in 1970, it is one of the most fascinating transmitters in the human skull. It's main function is to hold back on all brain centers: those involved in action, thoughts, and beliefs. According to Paul Mandel, a French neurochemist, the world tyrants unleash their potential by suppressing their GABA and serotonin levels through ideologic excitation leaving no inhibition. Lowered levels of GABA and serotonin in our brain are related to our aggressive, often violent behavior. Mandel believes that emotional self stimulation can also change serotonin levels making us more likely to solve life's problems through violent means. Fanaticism, Mandel believes, is linked to reduced levels of brain inhibitors. So, today, we can hold these chemical molecules responsible for all types of bizarre behavior of fanatics. Given the prevalence of such scenarios throughout the world, it can be safely assumed that we are in the age of GABA depression (no pun).

Our brain GABA levels are highly sensitive to our environment. Experiments with rats show that merely watching a rat kill a mouse drops the GABA levels in the bystander rats. Sociologists of our time are now proving that indeed children watching violence on television turn out to be more violent themselves. Ironic as it may sound, publicizing crime and capital punishment may itself lead to more crime and necessity for capital punishment-sort of a Catch 22. The old theory that publicizing crime sentences would discourage people has never withheld, to the amazement of many psychiatrists. Now we know the answer why.

Schizophrenia symptoms are now recognized to be caused by elevated levels of such neurotransmitters as dopamine, though as a result of some physical alteration in the brain, unlike the psychologic involvement of GABA.

The new science of brain chemistry has changed the entire course of the diagnosis and treatment of many illnesses, specifically those of mind. But the present transition in understanding how mental disorders can be caused by chemicals have not come easy. "One Flew Over the Cuckoo's Nest," portrayed, at best or at worst the concept of chemical strait jackets, evoking considerable public outcry and political upheaval. The concept that it is only chemical molecules in our brain that govern our behavior immediately invokes the possibility that our thoughts can be engineered through chemistry, a frightening idea to many, yet it is a reality.

Schizophrenia is a biochemical disorder affecting the brain and also influencing many other systems of the body. Two types of symptoms are associated with schizophrenia:

Type I: acute type, delusions, hallucinations and thought disorders; patients respond to neuroleptic drugs and there is little intellect impairment; caused by increased dopamine receptors, the disease is reversible.

Type II: characterized by poor speech and loss of drive; patients are not responsive to neuroleptic drugs and significant intellect impairment; caused by structural changes in brain, the disease is irreversible.

Type I and type II schizophrenia are not independent diseases, generally type I is followed by type II but not always; similarly type II may appear without type I features.

The causes of schizophrenia are still not clearly understood but genetic factors are important. The possibility that schizophrenia might be caused by a virus was considered by those who observed the psychiatric sequelae of the influenza epidemic of 1918 and of the epidemic of encephalitis lethargica that occurred not long after. Schizophrenia-like psychoses occurred in close relation to both of these illnesses. The viral connection was ruled out.

The current chemical theory of causes of schizophrenia states that high concentration of dopamine, a neurotransmitter in the brain, elicits the symptoms of schizophrenia. It is also suggested that if brain receptors become more receptive to doamine, similar effects as that of increased levels are observed. Drugs which release dopamine produce schizophrenic symptoms, those which block it reverse the schizophrenic effects. Dopamine is found in high concentration in several parts of the brain and affects the emotional and personality centers. If the dopamine system is fouled up, brain's perceptual and emotional system goes berserk. Neuroleptics, a class of drugs with opposite effects, produce chemical lobotomy reducing the exposure of dopamine to the cells and reducing their excitement potential. Dopamine not only controls the perception but also the movements that follow through motor centers in the brain.

The role of endorphins in schizophrenia has been extensively studied. First, endorphins do not bind to dopamine receptors, ruling out any binding connections. Secondly, both low and high levels of endorphins exacerbate schizophrenia, confusing the plausible mechanism. It may be due to amphetamine-like effects of endorphins. The major support of the role of endorphins in schizophrenia comes from the study of opium users who routinely develop psychoses symptoms. Naloxone, an inhibitor of endorphins, only at higher doses shows antischizophrenic activity. Naloxone improvemes auditory hallucinations, some psychotic symptoms, and unusual thought and tension if used in large doses suggesting a possible role of non-opiod receptors which may be affected at high doses.

Therefore stimulation of morphine receptors is not the primary causative factor in schizophrenia; instead, it is suggested that opiod peptides at high concentration stimulate non-opiod receptors, not affected by low naloxone dose, which may be involved in schizophrenic response.

The connection between dietary peptides and schizophrenia was proposed by Dr. F. C. Dohlan in 1966. Peptides from gluten cause diarrhea and intestinal lesions. These patients often show psychiatric disorders and schizophrenic patients often show lesions found in celiac disease patients as shown in many postmortem studies. Epidemiologic studies of women admitted to mental hospitals in a number of countries before, during, and after World War II, when there were large variations in wheat and rye consumption showed a direct correlation between the intake of these grains and schizophrenia, but not other forms of mental illnesses. These observations led Dr. Dohlan to conclude that there must be a genetic factor common to celiac disease and schizophrenia and that gluten peptides may be one of the causative factors in both types of illnesses. To test his hypothesis, relapsed schizophrenics, on admission to locked ward, were randomly assigned to eat either a cereal-grain-free (and milk-free) diet or one high in cereals. The subjects on grain-free diets were discharge at a rate twice as fast as those who received grains in their diet. The same experiment conducted on non-schizophrenics showed no difference in the discharge rate. In a recent study, the suggestive finding was made that 54 percent of a group of mental patients have antibodies to cereal proteins compared with 19 percent of a control group by Dr. I. Mascord and his group in 1978.

Endorphins cause schizophrenia and endorphins prevent schizophrenia--that is the most recent position of scientists in the role of endorphins in schizophrenia.

Another disorder of mind which afflicts just about everyone to a lesser or greater degree is depression. Recent reports suggest that narcotic antagonists such as naloxone may be useful in treating depression suggesting that endorphins attaching to brain cells may be producing depression.

The electro-convulsive therapy (ECT) is often successful in the treatment of depression, schizophrenia and several other disorders of the brain. Electric shocks alter the chemical balance in the brain drastically including the composition of endorphins strengthening the connection between endorphin levels and mental disorders. Since ECT improves control of emotions significantly affected by enkephalins, the endorphins connection is further strengthens. Studies have also shown that higher endorphin levels in blood elicits a self-destructive behavior which is inhibited by naltrexone, an endorphin antagonist. There are several skeptics such as Dr. Gayle A. Olson of the University of Louisiana, who, while agreeing that there is a connection, fail to accept the theories presented so far.

Other observations regarding endorphins and brain disease are sporadic and scientists are still trying to web them together, for example:

. Opiates produce seizures and epilepsy when injected directly into brain. The initiation of seizures is blocked by naloxone.

. levels of endorphins are altered in stroke and spinal injury, perhaps as a result of body's mechanism to fight-off stress.

. connection between endogenous opiates and Alzheimer's disease is suggestive. has been studied inconclusively yet.

. Parkinsonism patients show abnormal levels of opiate peptides.

. Naloxone decreases Cushing's disease symptoms.

. Met-enkephalin may be involved in migraine, since migraine patients have significantly elevated platelet-rich and platelet-poor plasma levels of the peptide.

PLEASINGLY PLUMP - IS IT ALL IN THE MIND?

In Compelling man to eat that he may live, Nature gives an appetite to invite him, and pleasure to reward him.

BRILLAT-SAVARIN (1755-1826), Physiologie du Gout, Ch. 36

Scientists have, for long, debated the question why we get hungry? For finding an answer to this question would mean we can devise means to control hunger, increasing or decreasing; both having significant effect on world sociology and economics.

We get hungry because Nature wanted us to assure there is enough energy in our body to survive. It is nature's way of assuring survival of races. How nature accomplishes this delicate task is quite interesting as we shall see in this chapter.

Food can make us depressed or perk us up, often we do not notice. The reward theory of endorphins also applies in the use of food. Let us examine the "amine" theory. Brain neurotransmitters such as catecholamines and 5-hydroxytryptamine (5-HT) are produced by dietary amino acids, tyrosine and tryptophan respectively. The 5-HT in brain is responsible for lethargy and reduces brain function whereas catecholamines alert the brain function. Since the basic building blocks of these amines is our food, depression or alertness can be created depending on our choice of food. For example, high carbohydrate diets increase tryptophan levels in the brain. Diets rich in proteins decrease tryptophan levels in brain. The mechanism involved here is quite intriguing. High carbohydrate diets results in increased insulin secretion which expedites uptake of most amino acids except tryptophan which then finds its way to brain. When a diet rich in proteins is consumed, proteins are broken down into amino acids which are then absorbed in the blood. The crowding of amino acids in plasma makes it difficult for tryptophan to cross the blood:brain barrier because of competition with other amino acids and as a result the level of tryptophan decreases in the brain. Similarly, starvation increases concentration of tryptophan in the blood by mobilizing fat from body depots. The fatty acids in the blood bind to sites to which tryptophan is generally attached and thus displace tryptophan from binding sites and making it free to enter the brain.

The net effect of a carbohydrate diet would be to make you drowsy, lethargic and sleepy; whereas a high protein diet or starvation will make you alert. It has been suggested that we can alter our diets to beat the jet lag; sleeping according to our time of destination and keeping alert during waking hours of our destination. Unfortunately, our eating customs are not in consonant with this theory. We start our day with a high carbohydrate diet, cereals, bread, etc. and take a high protein diet in the evening. I think a nice steak and lentil breakfast should make us more efficient during the day. A big rice dish should do well to lull us to sleep.

Moving further in our brain to discover the theory of hunger we notice that if the base of brain is damaged in animals, their eating habits and body weight change. If a critical region in brain, ventromedial hypothalamus, is affected, animals start eating too much and become excessively obese. Affecting another part of brain, lateral hypothalamus, reduces eating reflexes. Therefore, we control our eating habits through an intricate interaction of these two centers in our brain, one forcing us to eat and the other providing a satiety response, halting our eating reflex.

However, affecting these centers are several other parts of the brain. For example, around lateral hypothalamus we find many neurones which respond to the sight and/or taste of food when feel hungry. The responses of these neurons reflect the rewarding value or pleasantness of food, for stimulation in this region can mimic the reward value of the food. Once we have eaten a given food, these neurons do not respond to that food but they can still be excited at least partly to other foods which have not been eaten yet; this explains boredom with food or craving for desserts. The addictive response of food however is brought through exorphins.

Satiety in eating is also provided by the sensation of fulness in the stomach and intestine. The temporal lobe portion of brain sorts out the visual stimuli and determines if we are looking at food. This explains why we do not get hungry looking at rocks and trees, but certainly when we see a piping hot pizza or for some, a cold quiche.

Brain controls appetite through a complex play of these chemicals which produce aversion to food at the end of the eating cycle. The recurring desire for food before meals, increased cravings when unusual delay occur between meals, and rapid abolition of hunger by eating food are all chain of complex events trigerred and ended by the gastrointestinal tract. The "set-point" theory states that our body maintains weight what it considers ideal for survival. Each individual has a separate set point which cannot be altered. It appears now that this set point is a fine balance between the activity of these chemicals. What seemed impossible some years ago, seems plausible that we can change the set point-by altering the balance of these chemicals. Many drugs act on appetite control centers through their effect on neuropeptides, for example, clonidine and naloxone increase the activity of CCK, whereas phenoxybenzylamine, tolazoline and yohimbine decrease its activity.

Satietin, a peptide found in the blood of most species is related to the control of all facets of gastrointestinal tract in causing and appeasing hunger. Satientin is a powerful anorectic, which inhibits food in-take, is part of the group of endogenous anorectic agents which include glucagon, prostaglandins, CCK, endorphins, calcitonin, insulin and a variety of other pituitary hormones. Satietin is the essential chemical link connecting the gastrointestinal tract and the brain in the regulation of feeding. High concentration of satietin in brain causes crowding of satiety receptors in brain which leads to aversion from food and a feeling of satiety. Satietin circulates in the blood in an inactive form; upon eating food, satietin is activated and released and causes hunger to suppress immediately. It seems likely that drugs can be developed containing satietin to prodvide hunger satisfaction and weight loss programs.

A number of psychotropic drugs such as antidepressants, antispychotics, lithium, etc., also affect the brain satiety centers possibly through manipulatin of brain peptides and thereby curb appetite.

Drugs useful in weight loss work through several different mechanisms. For example, they may act directly on the brain, on the digestion and absorption function, fat metabolism, or on energy expenditure. Amphetamines, fenfluramine and phenylpropanolamine act by involving either catecholamine or serotonin systems of the brain. The actions of these drugs, however, can also be taking place in other parts of the body such as fenfluramine also slows down stomach emptying. In an interesting study where subjects were videotaped secretly while eating showed that those who received fenfluramine ate slower and were satisfied quicker. Amphetamines act somewhat differently by reducing hunger to begin with. Drugs which affect hunger and not satiety, have their effect last only until eating is commenced. Soon after eating is begun the amount of food taken is often not different from control, explaining the observations of the ineffectiveness of some of these agents.

Opiates are known to induce a relaxed state, drowsiness, and sleep under the appropriate circumstances. The common experience of sleepiness after a heavy meal could be due, at least in part, to the action of opiate peptides formed during food digestion. The behavior of infants after a feeding is particularly striking in that they often fall asleep almost immediately. The high exorphin content of pepsin digests of casein may therefore represent a mechanism for inducing sleep in infants after feeding.

It is often said that unhappy people often resort to compulsive eating. It is possible that these people and opiate addicts share a recluse in endorphins and that they become addicted to food as a source of exorphins rather than to heroin?

Feeding behavior depends to a great degree on choice of foods which depends on senses of taste and smell to discriminate between wholesome and inadequate or offensive foods. The biochemical mechanisms of our body alert us to deficiencies in our body, say of protiens, and then make us choose foods rich in proteins. A possible role of exorphins then could be to signal the brain centers which cause euphoric properties of opiates that nutritionally adeqaute proteins have been eaten. Protein diets makes us happy.

An interesting study by Dr. S. M. Antelman and Dr. H. Szechtman on rats showed that if their tails are subjected to a mild, continuous pressure they eat more perhaps to accumulate exoprhins derived from food to alleviate the pain.

Several elegant studies from the Salk Institute under the supervision of the Nobel laureate Dr. Roger Guillemin show that becoming fat increases beta-endorphin levels and not vice versa. The connection, if any, is highly complex and just modifiying the levels of endorphins in the body is not going to help you loose weight. Back to exercise machines please.

Few studies have evaluated the effects of opiods on food intake and body weight in humans. Obese subjects show elevated levels of beta-endorphin in blood and CSF. Opoid agonists such as methadone and butorphanol tartarate stimulate food intake and naloxone which are antagnoists reduce short-term food intake in obese and lean human subjects.

Specific areas in brain have been identified which stimulate eating reflex upon interaction with opiates. These parts lie in hypothalamus such as paraventricular nucleus, ventromedial hypothalamus.

The researchers are racing to find if antagonists of opiates can be used to curb appetite, food intake and as a result control weight. Fortunately, the experimental findings with antagoinists have been more consistent than with agonists. Some of the compounds which have shown to suppress eating are:

naloxone

naltrexone

naloxonazine

nalmefene

antibodies to beta-endorphin, alpha-neo-endorphin, and to dynorphin

FMRFamide

It now appears that diet itself plays an important role in how eating behaviour is affected by these antagonists. For example rats maintained on a high fat diet show greater suppression than those maintained on a high carbohydrate diet. It is suggested that these compounds may alter palatability to different kinds of foods. For example, obesity-producing effect of a palatable diet, particularly one with sugar, is inhibited by opiate antagonists most. Other variable effects include effect of animal sex. An interesting study shows that deer mouse hoarded more food when given morphine and this behaviour was reversed when an antagonist such as U-50,488H was given. The latter caused increased feeding rather than hoarding.

Logically, the opiate system is related to body weight but not in a straight-forward manner. Initially the increased food intake associated with morphine produces expected weight gain but with the development of tolerance to the drug, weight begins not only to level-off but actually decreases. Thus chronic morphine use lowers body weight specially due to loss of body fat. Attempts to reduce weight in humans with antagonists have been disappointed, suggesting that although they may work in short-term appetite regulation, they probably have little long-term weight reduction. At present there is little scientific value in using these for weight reduction. However, there is a likelihood that they can be developed into drugs for use against anorexia or loss of appetite. In anorexia, physiolgoic processes are down-regulated requiring lesser energy and as a result food requirements are reduced all caused somehow through action of opiate peptides. Antagonists such as naloxone may reverse this effect.

Effect of opiate peptides on fluid and food intake is mediated by their narcotic-like actions.

Effects of fenfluramine, a drug used to treat obesity, are probably mediated through endogenous opiate system. It suppresses eating by releasing serotonin, and this effect is potentiated by morphine pretreatment and antagonized by naloxone. Caffeine also increases eating in rats, an effect reversed by naloxone.

There is some inconsistent observations that antagonists like naloxone also reduce drinking requirements, perhaps through effect on taste. It is still not clear how endogenous peptides regulate drinking which is controlled by many other factors as well. Studies have failed to confirm the interaction between alcohol and endogenous peptides. In humans beta-endorphin levels increase in heavy alcohol consumption.

Anorexia nervosa, refusal to eat, is a deadly disease that kills one in five who get it. It is also the disease of the young. Not surprisingly, anorexia patients show many similarities with those of compulsive joggers, they both have inhibited anger, increased tolerance for pain, and tendency towards depression--the classical symptoms of elevated endorphin levels. Indeed it has been proven in compulsive joggers that their beta-endorphin levels are high. Does it mean that beta-endorphin is in some way responsible for weight loss in anorexics. Perhaps, since administering naloxone, an antagonist of endorphins, reduces the weight loss tendency in anorexics by reducing utilization of body fat.

Is there a hope therefore that perhaps elevated levels of endorphins can help burn off fat better. The studies reported earlier than increased body weight is accompanied by elevated endorphin levels may be precisely for the reason to reduce body fat levels. Much research is needed before the exact role of endorphins in anorexia is established.

Fasting is prescribed in many religions as a means of purifying the soul and body. Muslims throughout the world fast from dawn to dusk during the entire month of Ramadan. No food, no water and not even an evil or sinful thought is allowed throughout the day. As explained earlier, the preparation of an event trains the mind to control release of endorphins just like it does when preparing to begin a fast. In as much as fasting is a trauma, elevated beta-endorphin levels will be expected. But there is some controversy that perhaps these levels are decreased to stimulate eating reflex. The whole topic is so complex and controversial that it is difficult to pass a judgement at this stage.

WHEN THE SOUL HURTS

Living causes stress. Stress is all around us, at home, at work, at school or even at play. Stressors, or stress causing sources, can be emotional, physical, or even pathologic such as germs and viruses. Stress upsets the chemical balance in the body and the mind unleashes its supreme powers to create a fighting mechanism. The first stage of which is called "bells-going-off-stage." The pituitary gland and adrenal cortex produce hormones that prepare us for "fight or flight." The heart rate increases, the blood sugar rises, digestion slows down and pupils dilate. In the second stage, called the "adaptive" stage, body attempts to undo the damge caused to it. The final stage of stress fighting is that of "exhaustion" when body can no longer cope with and gets sick, mentally or physically.

Endorphin levels in the body are raised under acute physical or emotional stress and cause inhibition of digestive or excretory function. Dr. H. J. Teschemacher and his assoiciates from Germany analyzed endorphin levels in students immediately before and after examinations and in athelets before and after their performance. In all instances the levels of beta-endorphins were increased before the event and were even higher in those who were most concerned with achieving a high performance. However, the nervous effects such as increaed heart rate or stomach tightening were not related to blood levels of endorphins.It is suggested that endorphins operate in conjunction with pituitary hormones in adapting to stress situations.The levels of endorphins in blood follow a circadian rhythm like that of other hormones such as ACTH. For exmple, the lowest concentrations are found in the evening and the highest in the morning.

Beta-endorphins are associated with many symptoms of stress. Recent studies show that loss of blood pressure following a stressful situation can be reversed quickly by administering naloxone, an antagonist of endorphins.

Running causes an instantaneous "high." The longer you run and the more tired you get, the higher is the "high." At some point you "get your second wind." What are all those reactions? Can they be anything but endorphins? Probably not.

Recent studies have collected direct evidence showing that upon exercising, the levels of endorphins increase four to five times in the blood. Now we know that the more you exercise the higher is the increase in your endorphin levels which help subdue the pain of exercise. Some researchers argue that endorphins in the blood may not enter brain and therefore endorphins may not be responsible for the observed effect. It is true that the blood:brain barrier protects brain from assault of chemicals but during the stress state the properties of many body membranes change perhaps allowing entry of endorphins to brain. Or, the endorphins in the blood may not be needed, there may be enough endorphins produced in the brain itself and the endorophins in the blood may be affecting other parts of our body.

Running or even prolonged walking is a stress. Human body is not designed to absorb this stress without getting affected. We are no longer monkeys, we often forget. Whether producing this stress is good for the body is a debatable question but the effect of stress on the body are well known. It invariably reduces our longevity by making us more susceptible to diseases. Running or other exercises may help our arteries stay clear of deposits but the means of keeping them clean perhaps causes us to die sooner. The anwswer to dilemma should be given in light of the specific effects of endorphins. For example, met-enkephalins increase the resistance of rats to death from leukemia as shown in studies conducted at the Oral Roberts University. The mechanism is suggested to involve increased production of the fighter T cells. Another study at the University of Texas showed that endorphins decrease B cell production. B cells are needed to make antibodies to infectious organisms.

Lack of oxygen in the breathing air can cause death quickly as observed in mountaineers, pilots, and recent accidents on space shuttle when two astronauts who accidentally walked into an area cleared off oxygen. Similar oxygen deprivation occurs in asthma or emphysema as experienced by many cigarette smokers. Decreased oxygen levels in the blood cause increased acidity in the blood which prompts release of pituitary hormone ACTH and increased levels of beta-endorphin in the blood. Several studies from Japan and in the U.S. have confirmed an almost linear relationship between blood acidity and beta-endorphin levels. Lack of oxygen is a serious stress to the body and endorphins are released to cope with this stress. They reduce the blood pressure, elevate pain and calm down the body muscular activity to conserve whatever oxygen is left in the blood--a very ingenious process to prolong life until the last gasp. People with chronic breathing problems therefore always have higher levels of endorphins in the blood. If the breathing problems are due to cigarette smoking, as is the case in most instances, high levels of endorphins add to the addictive properties of tobacco.

Psychologically we are always under stress. Anxiety, worry, fear and human traits and all of which cause release of endorphins to help us prepare for what is coming. Students before examination show elevated levels of endorphins and so do patients about to be rolled into operating rooms. An interesting study involved applying electrical shock to the foot of six men. They were told they are about to get a shock; their endorphin levels shot up in anticipation even though some of them were never given the shock.

Endorphins are an essential link in obviating the effects of stress. The calming effect of endorphins, reduced blood pressure and decreased sensitivity to pain are all tranquilizing effects which are opposite to what happens when we are suddently faced with an stressful situation. Through evolution we have developed a "fight or flight" syndrome that was necessary when we faced roaming dinosaurs. Today, such responses are not as necessary, yet the clock of evolution is always slower than the clock of immediate events. The "fight and flight" reaction causes severe drain on our body and is responsible for increased heart disease, cancer, and reduced immunity to infectious diseases. Endorphins counteract the "fight and flight" agents in our body and thereby help us survive despite ourselves.

Traumatic shocks result in collapse of circulatory function and we pass out as a measure to conserve energy. Endorphins are clearly involved in these incidences also. Dr. John Holaday at the Walter Reed Institute of Research in Bethesda has shown that naloxone, an antagonist to endorphins, can reverse the loss of blood pressure following a traumatic shock. Therefore, endorphins are involved in exhibiting the symptoms of traumatic shock and they do it by acting in the brain, even though they may be produced elsewhere in the body, such as in pituitary gland, which also produces other hormones to prepare the body for "fight or flight." The studies of these scientists have opened up a new treatment possibility for shock patients--through naloxone. ANALGESIA

Recent studies show that body may have its own endogenous peptide antagonists also such as MIF-1 and Tyr-Mif-1. FMRFamide is also an antagonist.

Other agents that show analgesic effect by binding with specific receptors include phenoxybenzamine, phencyclidine, though not necessary the opiod receptors. A typical model to study the role of endogenous opoiod in pain perception is to administer naloxone or another opiate antagonist to determine its effect on reaction to painful stimuli. Naloxone, however, does not block all receptors. Chronic administration of naltrexone, apparantly causes the development of supersensitivity of opiods, since then analgesic effects are often enhanced rather than attenuated. There is also found in the body endogenous antagonists to opiods with naloxone like properties such as MIF-1 which blocks the analgesic effects of enkephalins and morphine but does not mimic their non-opiate effects, such as reduction in food intake.

Stress causes release of opiods and relieves pain or acts as analgesic. Naloxone increases pain and emotionalism. Stress adaptation is so fast that rats given electric shock or other trauma seem to develop a quick opiod release system even at the cue of the shock rather than actual trauma.

Autonalageis, antinociception produced by classically conditiond fear is also mediated by opiods. Since tolerance to morphine and naloxone does not affect autonalagesia, different type of receptors may be involved in this process. Endogenous opiods are also involved in electroacupuncture whose effect is reversible with naloxone. Low frequency stimulation causes endorphin release but high-frequency stimulation has more of a serotonerrgic action due to nonendorphin system. Serotonin pathways modulate analgesia of morphine and enkephalin and so do pituitary endorphins.

Besides genetics, food deprivation has bearing on pain threshold alongwith diurnal rhythms. Rats are less sensitive to pain in the evening than in the morhing indicating that endorphins system also has a diurnal nature. The levels of endogenous opiods in response to noxious stimulation increase in the afternoon but not in the morning relative to unstressed mice, who had same amount of enkephalins at both times.

**

Spinal administration of opiods provides analgesia of long duration to patients with pelvic cancer. But a tolerance or cross tolerance to narcotics soon develops.

**

The perception of pain, as well as the meaning of pain to the individual, is a complex behavioral phenomenon and involves psychologic and emotional processes in addition to activation of nociceptive pathways. Pain related to malignant diseases can be classified as somatic, visceral, and deaffrenetation in types. The narcotic analgesics are more useful in somatic and visceral type pains.

STRESS:

Endogenous peptides have significant effect on stress. Many of the effects of stress are mediated by opiod peptides such as stress-induced analgesia. For example, electric shock is stressful but it produces a decrease in perception of pain. However, there is considerable variation based on how long or how frequently the shock is applied. Generally, intermitent shock is important for opiate-induced analgesia. There is also large variation between species and even strains of same species in how they respond to stress in producing analgesia. Age is also important alongwith other aspects of stress such as if animal had been restrained or not. There is also a tendency to develop tolerance to shock induced analgesia. An interesting study showed that unstressed rats receiving odors from animals who had received shock developed analgesia just by smelling the stressed rats. Odors of non stressed rats and other novel odors had no effect. This study opens up varied possibilities of communication through odors and how odors can stimulate or depress opiate releases and therefore the sensation of feeling happy or depressed?

Shock also decreases motility of animals, a characaterstic opiate action and lesser tolerance develops to this effect than does for analgesia. If animals are placed in the same environment where they received shock it causes reduced motility even without shock.

Other stresses like restraint, heat and cold increase sensitivty to morphine-induced analgesia. Prolonged exposure to cold in rats produces ulcers which is also the effect of morphine but reversed by morphine antagonist naloxone. Animals forced to swim also develop high levels of opiate peptides and tolerance with repeated challenges.

Mice defeated in fighting also show elevated opiate levels which causes an increase in feeding, a response inhibited by naloxone. Isolation produces an imbalance of eptides in brain for example met-enkephalin may decrease but beta-endorphin increases.

Experiences in early life are just one of the factors which affect the levels of endorphins in the later life. Stress exposure reduces the ability to tolerate pain at later age.

Patients undergoing surgery show elevated plasma levels of beta-endorphins if halothane anesthesia was used and not if fentanyl anesthisa was used indicating perhaps greater stress produced in the use of halothane. Post operative delirium in patients is also related to endogenous opiates. In patients with burns higher levels of endorphins meant lower sensation of pain. Other stresses such as doing mental arithmetic would caused increased blood pressure if naloxone is administered indicating that opiods help keep the pressure down. Persons who are hypertensive might be lacking appropriate opiate inhibition of sympoathetic nervous system.

Plasma levels of beta-endorphin increase after a wide variety of stressors including shock, immobilization, swimming, presurgical stress, and the twitch procedure in horses. Levels of beta-endorphin in pituitary decreased after shock, swimming and several novel stimula including tones, shocks. Opiate peptide are released in response to labor pain. Newborns often have higher levels of beta-endorphins as preparation to handle stress.

PAIN AND ENDORPHINS

"I know how you feel," is the biggest lie. No one can feel the pain of others. Pain is a survival response. Nature has created the feelings of pleasure in those acts which nature wanted us to repeat for our survival such as eating or sexual intercourse. Nature created the feeling of pain in acts that cause damage to our body. Putting your finger on burning iron will cause pain because if you did not know better, Nature knew it is damaging for your finger.

All of the pain feelings are caused by the stimulation of nerves which are in abundance all over our body. In a disease called trigeminal neuralgia, nerves in some parts of our body become dead, such as in the face. People with trigeminal neuralgia of face will cut themselves seriously while shaving without knowing. Just one example to show why pain is such an essential reaction of our body.

However, pain does more than to just discourage us from doing foolish things. Why is there pain involved in the delivery of a child or why does it hurt when we lose someone close to our heart? Why is it painful to see seals clobbered by the poachers? Pain is indeed a varied phenomenon. It serves only one purpose: prepare our body for what is to come.

How does our mind prepare us for the events following a painful episode? For one, it directs the brain to produce endorphins, plenty of it. Just like the effect of morphine, the ultimate pain killer medicine, endorphins immediately kill the feeling of pain and reduce the suffering. How endorphins do it is still a matter of controversy, but one of the mechanism is by shutting down the release of a peptide called Substance P, which is the most potent transmitter of pain sensation.

Dr. Roger Guillemin, a Nobel laureate from the Salk Institute in San Diego, wanted to test the effects of endorphins in killing pain. He sent purified beta-endorphins to Japanese researchers who injected them into spinal cord of cancer patients and women in labor. Invariably, the pain was relieved. Many of the cancer patients who had not slept for days because of pain went into sleep almost immediately after injection of beta-endorphins.

Women who delivered babies reported feeling of great euphoria without any loss of consciousness. All newborns were normal without any trauma generally associated with administration of anesthetics or other pain killers during delivery. Many of these pain killers have often serious effects on the brain of the newborn. The effect of beta-endorphin lasted for about day-and-a-half.

The direct evidence than endorphins are released in the body to relieve pain was obtained by analyzing endorphin levels in the spinal fluids of persons given electric stimulation in brain to relieve pain. All subjects showed elevated levels of endorphins, two to four times higher than normal.

The connection between endorphin release in the body and pain is firmly established. Pain releiving techniques such as acupuncture are directly related to endorphin release. Despite some controversy, the most learned professors such as Avram Goldstein firmly believe in this connection.

The receptors for opiods are found not only in brain but in various other parts of the body. Injections of morphine and endorphins in spinal cord relieves pain and similar effects are found if morphine is injected along the electrical path of the body.

Dr. Leon Silverstone of the University of Colorado School of Dentistry recently proposed an alternative to novocaine. He showed that transcutaneous electrical nerve stimulation (TENS) by placing small electrodes, each inside a cotton roll, placed in the mouth and on the ear lobe or the web of the hand blocked the pain when low-voltage electrical impulses were fired. TENS causes release of endorphins and patients do not even feel the electrical current. In one study of 30 patients requiring cavity fillings and root canal work, 24 were helped by TENS to be effective for 70-80 percent of patients troubled with myofacial pain dysfunction or TMJ syndrome. So next time you go to your dentist ask him if he would like to play with your endorphins.

Naloxone is a drug used to counteract the effects of morphine and heroin. Naloxone also counteracts the effects of endorphins in the body. Several studies have shown that giving naloxone increases pain sensation since it makes difficult for endorphins to act.

We know how each one of us has a different threshold for pain, some will pass out at the site of a needle others will endure surgical removal of their gall bladder without anesthesia. It's all how effective our body and brain are in producing endorphins. Can we train our mind to control brain and body to produce endorphins when we need them?

Gautam Buddha adopted meditation and refused to eat anything until he finds the truth to the existence of God and receives "enlightenement." He found both but went through a most excrutiating bodily trauma that he happily endured it. Ever wonder how?

What causes endorphin release to relieve pain. For one, if there is a physical damage to the body. But how about the state of our mind. In many cultures and religions people subject themselves to unusualy bodily tortures such as walking on flames in Shiite Muslims religion, attempting to pass a needle through hand in many Japanese martial art type activities or how about Judo and Karate requiring demonstration of ultimate physical forebearance. Common to all these situations is a state of concentration of meditation, preparing oneself to go through a traumatic experience. With enough training of the mind we can release enough endorphins to bear these otherwise unbearable pains. In scientific terms we call it a placebo.

The Japanese study where endorphins were injected in the spinal cord of some cancer patients also showed that some patients injected saline also showed relief of pain, even though it was of very short duration. This is a classical example of how placebo effects are elicited.

Placebo effects are most pronounced in the treatment of pain because not only is it a subjective feeling but endorphins have the most profound effect on pain sensation.

Morphine relieves pain but it also causes respiratory depression which can be fatal. Fortunately, biochemists have now come up with a theory that morphine reacts with many receptors in the brain, one of them causes analgesia. Why not design drugs which will interact only with analgesic receptor and thereby circumvent the side effects of morphine. This theory is just about to produce some very effective drugs.

Dynorphin, a type of endorphin, is about 200 times more potent than morphine in blocking pain. It is 700 times more potent than leu-enkephalin. Dynorphin acts at different receptors than does enkephalin. Here's how various pain killers are classified in order of decreasing effect:

dynorphin

human beta-endorphin

D-ala-enkephalin

morphine

met-enkephalin, synthetic

met-enkephalin

leu-enkephalin

The human endorphin is not the strongest one, camel, horse and ostrich produce beta-endorphin more potent than human endorphin, but salmon and turkey produce endorphins which are less effective than human endorpohins. This comparison simply points out to the patience and endurance of camel which can go without food or water for weeks, enduring the harsh deserts without much complain.

MEMORY & LEARNING

Studies from the laboratory of Dr. Eric Zager of Harvard show that the neuropeptides vasopressin, ACTH and beta-endorphin have important bearing on memory and learning. Vasopressin when given through nose results in improved scores on psychometric tests in patients with mild Alzheimer's disease and Korsakoff's psychosis. Even normal volunteers show improved memory. In patients who have received head injury, vasopressin also improves memory. Endogenous opiod peptides such as beta-endorphin and met-enkephalin have shown to have connection with amnesia in animals. Their role in human learning is still uncertain but naloxone, an antagonist of morphine has shown to improve cognitive skills in patients with Alzheimer's disease. Such observations of sporadic nature only tell us how little we know about the memory and learning mechanisms of the human brain.

Applicatins of endorhis are now described in the treatment of Alzheimer disease, a cardinal feature of which is impairment of memory.

Opiod peptides have a definite function in memory and learning. In dementia the balance of opiod peptides in brain is altered alongwith other neurotransmitters. Naloxone seems to cause behavioural arousal with psychomotor retardation at higher doses. There is a conntroversey in the literature on the efffects of naloxone, especially with respect to its dose-effect relationshiop.

Scientists are tickled to death to find that endogenous opiate system may be involved in learning and memory. Generally, opiate peptides impair memory and most antagonists improve it. However, the effects on learning are less clear-cut. It is possible that the antagonists might increase memory in aversive tasks by releasing norepinephrine from opiate inhibition. The studies in humans are only few and inconsistent. Naloxone seems to improve cognitive performance of patients with Alzheimer's disease, including memory facilitation. However, naloxone does not alter cognitive function in depressed patients. The jury is still out.

The hippocampus is considered responsible for transferring memory from short-term to long-term storage among other memory related functions. Opiods might mediate this transfer as evidence by reward system to improve memory and comprehesion.

Memory moleceules, as far as I can remember, are the most favorite hunted molecules in the brain. Every time a new neurotransmitter is discovered, the researchers jump--perhaps this is the one! Endorphins have long been a darling magic molecules, why not study their role as memory entities in our brain.

Well, it is difficult to label any molecule as a memory molecule since we forget easily that memory is a complex phenomenon. For example, our behavior acquired because of aversive events is quickly suppressed by endorphins. This was proven by giving naloxone which resulted in prolongation of memory of a behaviour acquired because of noxious experience. Endorphins help us forget bad memories. Drugs such as levarphenol, which augment the action of endorphins have similar effects. However, the mixture of brain peptides have different effects. Some opiod peptides seem to increase memory and learning ability, others reduce it. Often it is the same peptide showing both types of responses in different circumstances. Endorphins reduce pain-motivated learning because endorphins reduce pain. But endorphins increase the mental acuity of the pleasing events. For example, rats given beta-endorphins were better able to negotiate a course to get to their meal than those who did not receive endorphin injections. Somehow our mind prepares us to forget the bad in our life and get on with the good.

DRUG ABUSE AND TOLERANCE

We all are drug junkies. Some of us use chemicals through veins or snorting through nose to feel high, most of us get our "highs" from within. I wonder if we could have a legislation prohibiting use of internal body opiates? Even if we did, it would be hard to in conquering additions which is so wide spread. Here's some statistics on drug abuse in America:

Age 12-16:

37 percent alcohol

16 percent marijuana

12 percent cigarette

2 percent hallucinogens

Age 18-25:

76 percent alcohol

35 percent marijuana

42 percent cigarette

9 percent cocaine

4 percent hallucinogens

3 percen