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Molecules of Emotion

How Mrs. Dr. Candace B. Pert, Ph.D., explains the inter-organ communication in human body.

Dr. Candace B. Pert, Ph.D., formerly chief of brain biochemistry at the National Institutes of Health (NIH), spent 13 years there mapping and demonstrating biochemicals she now calls "physiological correlates of emotion".  Dr. Pert left NIH after developing a new drug for the treatment of AIDS, but the government wasn't interested.

Dr. Pert believes that virtually all illness, if not psychosomatic in foundation, has a definite psychosomatic component.  Psyche meaning mind or soul, and soma meaning body.  "It is obvious that the public is catching on to the fact that they're the ones paying monstrous health care bills for often worthless procedures to remedy conditions that could have been prevented in the first place."

In understanding Dr. Pert's assessment that there are, in fact, such things as "molecules of emotion", one must first understand some of the fundamentals of biomolecular medicine. Receptors, proteins, and peptides are basic components that make up our bodies and minds.

The Basics

The first component of the molecules of emotion is a molecule found on the surface of cells in the body and brain called the opiate receptor.  Dr. Pert discovered the opiate receptor in the early 1970's when she found a way to measure it and thereby prove its existence.  Dr. Pert says that measurement is the very foundation of the modern scientific methods, the means by which the material world is admitted into existence.  If it can't be measured, science won't concede it exists, which is why science refuses to deal with emotions, the mind, the soul, or the spirit.

A molecule is the tiniest possible piece of a substance that can still be identified as that substance.  The receptor is a molecule, made up of proteins, tiny amino acids strung together in chains.  They are flexible and respond to energy and chemical cues by vibrating. A typical nerve cell may have millions of receptors on its surface.  Basically, receptors function as sensing molecules, or scanners, on a cellular level, much like our eyes, ears, nose, tongue, fingers, and skin.  These receptors float around in the cell membranes, vibrating and wiggling, waiting to receive messages brought by other vibrating creatures that come through the fluids surrounding each cell.  This is called diffusing.  The receptors gather into a cluster in the cellular membrane waiting for the right chemical to make it’s way to them through the extracellular fluid and to attach themselves to them.  This process is called binding. The chemical that binds to the receptor is an element called a ligand.  The ligand causes the receptor to rearrange itself, changing its shape until information enters the cell.

Receptors and ligands are the first components of the molecules of emotion.  Ligand comes from the Latin ligare meaning "that which binds".  It is often used to describe any natural or manmade substance that binds selectively to its own specific receptor on the surface of a cell.  Once the receptor has received a message, it transmits it from the surface of the cell into its interior where the message dramatically changes the state of the cell.  A chain of biochemical events begins.  The life of a cell is determined by which receptors are on its surface and whether those receptors are occupied by ligands or not.  These minute physiological phenomena at the cellular level can translate to changes in behavior, physical activity, and even mood.

The process of binding is very selective.  Only the ligands that have molecules in exactly the right shape can bind to a particular kind of receptor.  This is called receptor specificity.  The opiate receptor can receive only those ligands that are members of the opiate group, like endorphins, morphine, or heroin.  It is this specificity of the receptors that allows for a complex system of organization and ensures that everything gets to where it's supposed to be going.

Ligands are divided into three chemical types:  neurotransmitters, steroids, and peptidesNeurotransmitters are the smallest, simplest molecules manufactured in the brain to transmit information between neurons.  Steroids, including the sex hormones testosterone, progesterone, and estrogen, start out as cholesterol that gets transformed by a series of biochemical steps into a specific kind of hormone.  The peptides, which constitute about 95% of all the ligands, play a wide role in regulating practically all life processes.  Like receptors, peptides are made up of strings of amino acids.  Dr. Pert puts it this way:  "If the cell is the engine that drives all life, then the receptors are the buttons on the control panel of that engine, and a specific peptide (or other kind of ligand) is the finger that pushes that button and gets things started."

In the early days of research, it was known that peptide factors were responsible for regulating digestion and raising and lowering blood pressure in the body's circulatory system.  Peptide components were known to be produced by the pituitary, found at the base of the brain.  It was many years later that many substances not previously identified as peptides turned out to be just that.  Hormones, with the exception of testosterone and estrogen, were peptides, as is insulin.  Prolactin, which causes women's breasts to secrete milk, is also a peptide.

The actual structures of peptides are simple, but the responses in the body that they cause are extremely complex.  Because of this, peptides have been classified as hormones, neurotransmitters, neuromodulators, growth factors, gut peptides, interleukins, cytokines, chemokines, and growth-inhibiting factors.  Francis Schmitt of MIT aptly named them informational substances, because their common function is to distribute information throughout the organism.

Researchers at NIH assumed that any peptide ever found anywhere, at any time, was potentially a neuropeptide with receptors in the brain.  They mapped the location of both the actual peptide containing neurons and the location of their receptors and found that most were clearly shown to have both receptors in the brain and also to be present themselves in the brain.  At first, they thought that peptides existed only in the hypothalamus, but were elated to realize peptides existed in all parts of the brain.  They found peptides in the cortex, the part of the brain where higher functions are controlled, and in the limbic system, or the "emotional" brain.  When they began to understand the distribution of these chemicals throughout the nervous system, they got the first clues that led them to theorize about peptides being the molecules of emotion.

Hofstra University psychology professor Robert Plutchik proposed a theory of eight primary emotions:  sadness, disgust, anger, anticipation, joy, acceptance, fear, and surprise.  Like primary colors, these emotions could be mixed to get other, secondary emotions, i.e., fear + surprise = alarm, or joy + fear = guilt.  Experts also distinguish among emotion, mood, and temperament.  Emotion is the most fleeting, and is easily identifiable by what causes it.  Moods may last hours or days and it is more difficult to determine the cause.  And temperament is genetically based, meaning that we’re generally stuck with it for a lifetime.

Back in the 1920s, human experiments were conducted to show the connection between emotions and those parts of the brain where Dr. Pert and other researchers were locating almost all of the neuropeptide receptors.  Wilder Penfield at McGill University in Montreal worked with conscious, awake individuals during open-brain surgery for severe and uncontrollable epilepsy.  He found that when he electrically stimulated the limbic cortex over the amygdala, he could cause a variety of emotions to display themselves—from reactions of grief, to anger, to joy as patients relived old memories.  The patients also showed body language and physical actions appropriate to the emotions, such as shaking with laughter or crying.


Paul MacLean, a researcher at NIMH, popularized the concept of the limbic system as the seat of the emotions.  He believed that there are three layers to the human brain representing different stages of humanity's evolution:  the brainstem, which is responsible for autonomic functions such as breathing, blood flow, and body temperature; the limbic system, which encircles the top of the brainstem and is the seat of the emotions; and the cerebral cortex, in the forebrain, which is the seat of reason.  If the idea that peptides and other informational substances are the biochemicals of emotions, their distribution in the body's nerves has all kinds of significance.  This very much reflects some of Sigmund Freud's thinking in that the body is the unconscious mind.

Due to the many years of research conducted by Dr. Pert and many others, the emotional brain can no longer be considered confined to the locations of the amygdale, hippocampus, and hypothalamus.  There are many other anatomical locations where high concentrations of almost every neuropeptide receptor exist, such as the back side of the spinal cord.  This is the area within the nervous system where all bodily sensations are processed.   High concentrations of neuropeptide receptors are found in virtually all the locations where information from any of the five senses—sight, sound, smell, taste, and touch—enter the nervous system.  These points have become known as "nodal points", and seem to be designed so that they can be accessed and modulated by almost all neuropeptides as they process and prioritize information.

All sensory information goes through a filtering process as it moves across the synapses of the nervous system, finally reaching the area of higher processes, like the frontal lobes.  There, the sensory input enters our conscious awareness.  The efficiency of the filtering process which chooses what stimuli we pay attention to at any given moment is determined by the quantity and quality of the receptors at the nodal points.

Our bodies use neuropeptides as the cue, and our bodymind retrieves or represses emotions and behaviors.  Columbia University College of Physicians and Surgeons have proved that biochemical change begun at the receptor level is the molecular basis of memory.  When a receptor is flooded with a ligand, it changes the cell membrane in such a way that affects the choice of neuronal circuitry that will be used.  This is important for understanding how memories are stored not only in the brain, but in a psychosomatic network throughout the body, particularly in the receptors between nerves and bundles of cell bodies called ganglia. The decision about what becomes a thought rising to consciousness and what remains an unrealized thought pattern is mediated by the receptors.

Overwhelming amounts of information is being thrust at our brains on a continuous basis.  In order not to be overwhelmed, the brain has a filtering system that allows us to pay attention to some things and ignore others.  While the neuropeptides are directing our attention by their activities, we are not conscious of what is getting processed, remembered, and learned.  We do, however, have the possibility of bringing some of these decisions into consciousness through visualization.  The decision about what sensory information travels to your brain and what gets filtered out depends on what signals the receptors are receiving from the peptides.

Dr. Pert read Anatomy of an Illness by Norman Cousins and was amazed at his experience.  After being diagnosed with a life-threatening illness, Mr. Cousins rejected help offered by his doctors, left the hospital, and checked into a hotel with Charlie Chaplin videos.  He basically laughed himself back to health, having felt that what his body needed was life-affirming, joyous experience of laughter.  He believed that the laughter had triggered a release of endorphins which, by elevating his mood, had somehow brought about a total remission of his disease.  This was a direct implication of what Dr. Pert had been working on with the neuropeptides, the brain chemicals of mood and behavior, and the chemical pathways by which they communicated with the immune system and every other bodily system.

At one point, Dr. Pert and a colleague thought that perhaps cancer cells were really macrophages, somehow mutated and gone awry within the body.  It was their thought that that explained how they replicated so quickly and traveled, or metastasized, so widely.  In their research, they used antibodies that typically bound to macrophages to see if they also bound to the cancer cells.  They did.  What Dr. Pert found out during testing was that the macrophage antibodies had bound to the cancer cells because those cells were macrophages, or more exactly, mutated macrophages.  The cancerous cells had originally arisen not from lung cells, but from macrophages that had migrated to the lung from the bone marrow to participate in the cleanup and repair of damaged tissue.  Somewhere, somehow they had mutated and turned into cancers that metastasized and spread everywhere.  Dr. Pert had found that there was a clear connection between cancer, the immune system, and toxicity in the body, and published a paper in the journal Science.  She began to believe they had found the underlying mechanism that explains how cancer is a response to toxicity from environmental pollutants in the air and chemical additives in the diet.  The paper's summary stated that data suggested the same peptides found in the brain were also found in the immune system, and that the nervous, endocrine, and immune systems are functionally integrated in what looks like a psychoimmunoendocrine network.  Neuropeptides, those chemicals secreted by the brain and known to mediate mood and behavior, were clearly signaling the cancer cells via their receptors and causing them to grow and travel to different parts of the body.  Therefore, the next question was:  Could excess or inappropriate production of neuropeptides released by the immune system, or by the brain, or by any other organ system in the body, promote other forms of cancer as well?

Neuropeptides, the chemicals secreted by the brain that mediate mood and behavior, were signaling the cancer cells via their receptors, causing them to grow and metastasize to different parts of the body.  Dr. Pert showed that besides the immune cells, many different kinds of cancerous cells were chemotaxing according to neuropeptide signals.  This became their basis for thinking about the mind-body basis for cancer and other diseases, especially those that were part of the psychoimmunoendocrine system.  To put it more clearly, cancer cells have neuropeptide receptors.  Dr. Pert also succinctly states that peptides are not the only substances important in understanding cancer.  Sex hormones also play a part in the network, acting to promote growth that may lead to cancer.  Estrogen especially has been shown experimentally to increase the growth of certain breast tumors.


It was known how the mind drugs heroin, opium, PCP, lithium, and Valium entered the network and worked on the receptors, and how the endogenous substance, endorphin, communicated over a wide range.  What the chemicals in the body were doing was affecting the emotional state of the person taking them, making him sad or happy, anxious, or relaxed.  Thinking more about emotions, then, it is interesting that the parts of the brain where there is a higher concentration of peptides and receptors, are also the parts of the brain that have been implicated in the expression of emotion.

In 1985, Dr. Pert published the key paper on their theory of molecules of emotion in the Journal of Immunology.  To quote from the abstract:

“A major conceptual shift in neuroscience has been wrought by the realization that brain function is modulated by numerous chemicals in addition to classical neurotransmitters.  Many of these informational substances are neuropeptides, originally studied in other contexts as hormones, gut peptides, or growth factors.  Their number presently (1985) exceeds 50, and most, if not all, alter behavior and mood states, although only endogenous analogs of psychoactive drugs like morphine, Valium, and phenocyclidine have been well appreciated in this context.  We now realize that their signal specificity resides in receptors rather than the close juxtaposition occurring at classical synapses.  Precise brain distribution patterns for many neuropeptide receptors have been determined.  A number of brain loci, many within emotion-mediating brain areas, are enriched with many types of neuropeptide recept9ors, suggesting a convergence of information processing at these nodes.  Additionally, neuropeptide receptors occur on mobile cells of the immune system:  monocytes can chemotax to numerous neuropeptides via processes shown by structure-activity analysis to be mediated by distinct receptors indistinguishable from those found in the brain.  Neuropeptides and their receptors thus join the brain, glands, and immune system in a network of communication between brain and body, probably representing the biochemical substrate of emotion.”

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