Understanding Neurochemicals

HIGHLIGHTS:

• The average human adult brain weighs around 3 lbs. and contains around 100 billion nerve cells (neurons)
• We’ve identified over 100 neurotransmitters
• Emotions and feelings are formulated at the cellular level through the behaviors of chemical messengers known as neurotransmitters, which are released at the synapses (nerve junctions)
• Neurochemicals are believed to be involved in meditation’s ability to bring about an altered state of consciousness
• The effect of neurotransmitters is either: ionotropic, metabotropic or neuromodulatory
• Neuromodulators, which are heavily affected by meditation, are neurotransmitters that modulate or adjust the normal effect of a particular neurotransmitter (e.g., increasing or decreasing the effect of another neurotransmitter; shortening or prolonging its activity)
• By influencing neurotransmitters and neuromodulators, meditation can help effect permanent changes in the brain and nervous system, thus to our mental health and well-being
• A systemic hormone is a chemical produced by one tissue and conveyed via the bloodstream to another site to effect a particular physiological activity (e.g., growth or metabolism). A neurohormone is a chemical that’s produced and secreted only by nerve cells, even though it may act at other distant sites.

The average human adult brain weighs around three pounds and contains around 100 billion nerve cells (neurons) of different types and sizes. Neurons are around 10 microns wide. (In case you’re curious as to how big that is, you could squeeze about 50 of them into a 10-point-sized period.)

Our emotions and feelings are formulated, literally, at the cellular level. Emotion begins with communication between cells. Cells communicate through messengers, chemical substances called neurotransmitters. Information travels at different speeds. Electrical impulses and chemical signals carry messages across different regions of the brain and between the brain and the rest of the nervous system, a process known as neurotransmission. Neurotransmission can be as slow as 0.5 meters per second or as fast as 120 meters per second, which is tantamount to driving your car at a speed of 268 miles per hour.

Communication — sending and receiving messages — occurs at the tiny gap or junction between neurons called the synapse. Neurotransmitters are released at the neuronal synapses (nerve junctions), where they bind to compatible receptors on the surfaces of cells and transmit information into those cells.

Here’s a model of neurotransmitters at work…

Signals or impulses containing packets of sending chemicals (neurotransmitters) travel down the sending neuron via a single extension called the axon (which range from a fraction of an inch to several feet long) to a terminal. These signals are detected by dendrites, branched extensions of each neuron that collect information from adjacent nerve cells — they receive electrochemical signals and conduct impulses inward toward the cell’s body. Each receiving neuron has receptors for these neurotransmitter molecules. So, a neurotransmitter that’s been released from the sending neuron’s nerve terminals binds to receptors on the membranes of the receiving neuron to either excite (stimulate) or inhibit the target cell.

Each of your individual neurons may easily form a thousand of synaptic connections with other neurons. Your brain probably has somewhere between 100 trillion and a quadrillion synapses, which are all organized into elaborate networks or matrices.

When a neuron is activated, a small difference in electrical charge occurs. This unbalanced charge is called an action potential and is caused by the concentration of ions (atoms or molecules with unbalanced charges) across the cell membrane. Neurotransmitters alter electrical cell membrane potential by opening up channels that allow sodium, potassium, and calcium ions to pass in and out of the nerve cell. Neurotransmitters not only transmit messages from one cell to another, but also selectively facilitate some information and inhibit other information. The action of calcium ions transforms electrical events into molecular changes that can literally alter the functions of the nerve cells permanently; for example, a cell’s function might be permanently changed to serve a particular memory or a learned skill.

As cellular changes are transmitted by nerve impulses across cell membranes, they produce corresponding changes in various aspects of the human existence such as mood, behavior, or physical movements. Some researchers even believe, incidentally, that it is through this mechanism that repressed emotions are stored (Pert, 1997; Butlin, 2001).

Everything we do — every thought, every act, every movement — relies on neurons communicating effectively with each another. Neurotransmitters send chemical messages between neurons. Mental health problems, such as depression, can occur when this process of sending and receiving chemical messages does not work correctly. But communication between neurons can also be electrical, such as in areas of the brain that control movement. Abnormal electrical signals can lead to tremors or other movement disorders, such as Parkinson’s disease.

It is the richness and precision of neural interconnectivity that confers upon us our personhood, makes us who we are. All our memories, emotions, traits, skills, unique abilities and relationships are woven into this vast neural web of connections. And the precision of those connections is achieved and maintained by the subtleties of the electrochemical signals passed between neurons, which are always, at every level, heavily influenced by these silent workhorses, neurotransmitters.

At least 100 different neurotransmitters have been identified. The three main categories are: monoamines and amino acids, which are small molecules, and peptides, which are larger molecules

Neurotransmitters can have one of three main affects on other neurons: ionotropic, metabotropic and neuromodulatory.

Ionotropic neurotransmitters, such as acetylcholine, glutamate and GABA, have “inherent” biological activity and directly increase ionic conductance across postsynaptic cell membranes.

Metabotropic neurotransmitters, which include norepinephrine, epinephrine, dopamine and serotonin, have no direct activity; rather, they act through a “second messenger” to cause metabolic changes in a postsynaptic membrane. Their effects emerge about 30 msec. after release of the neurotransmitter and may last only seconds, or much longer.

Neuromodulators are neurotransmitters that work at the syapse to modulate the normal effect of the neurotransmitter at that synapse. A neuromodulator may either increase or decrease the effect of another neurotransmitter, or it may shorten or prolong its activity. In most cases, neuromodulators exert their effects by second messengers. Most neuromodulators are peptides.

Neurochemicals are believed to be involved in meditation’s ability to bring about an altered state of consciousness, and neuromodulators may play a critical role.

The brain’s evolutionary process created a hierarchy of neurological function, adding higher centers to our primitive nervous system (e.g., the brainstem), which has fundamental control of consciousness and autonomic functions such as breathing. These higher, “smarter” centers have an inhibitory or suppressing influence on the functions of the lower centers. For example, the brainstem is controlled by the higher limbic system, and the limbic system, in turn, is controlled by the still-higher neocortex (known as “new bark”), the outermost part of the cerebral cortex and most recently evolved part of the brain. Our highly evolved neocortex keeps animal tendencies such as involuntary movements, rage and aggression in check so that it can effectively pursue its own highly developed activities of logic, memory, reason, language, calculations and analysis.

This hierarchical relationship between various brain centers is effectively created by neuromodulation — neuromodulators acting to inhibit other neurotransmitters. For instance, the synergistic interaction between dopamine and acetylcholine can inhibit involuntary movements. But imbalance in these neuromodulators can lead to involuntary movements such as chorea (Huntington’s Disease) or tremors (Parkinson’s Disease).

We sprout new neural connections daily. And by influencing the actions of neurotransmitters and neuromodulators, meditation can become an ongoing stimulus to effect permanent changes in the brain and nervous system, thereby to our mental health and well-being.

Neurotransmitters and neuromodulators stimulate neural growth, differentiation, and plasticity, helping to inhibit harmful electrochemical influences while stimulating those that positively effect our capacity to think, reason, and react.

Mental and physical health is also influenced by hormones. A hormone is a chemical, usually a peptide or steroid, produced by one tissue and conveyed via the bloodstream to another site to effect a particular physiological activity, such as a stress response, growth or metabolism. Examples include testosterone, thyroxine or insulin.

A neurohormone, however, is produced and secreted by neurons or nerve cells, even though it may act at other distant sites. Neurohormones are produced in neurosecretory cells (such as those of the brain’s hypothalamus) and released into the bloodstream, cerebrospinal fluid, or intercellular spaces of the nervous system. Some neurohormones are true systemic hormones that influence various organs and systems (e.g., adrenaline). Some are not. A neurohormone that is not a true hormone may be a cell product that triggers the release of another hormone, which in turn stimulates an endocrine gland to release a systemic hormone. For example, ACTH (adrenocorticotropic hormone), stimulates the production of adrenal hormones.

Neurotransmitters, by contrast, only bind to receptors on neurons that either stimulate or inhibit action. But some neurotransmitters function as both neurotransmitters and neurohormones, depending on the action (e.g., dopamine, epinephrine and norepinephrine). Epinephrine acting on the adrenal glands is a neurohormone. Epinephrine acting in the brain is a neurotransmitter. A neurotransmitter’s effect is determined by its receptor.

Following are the characteristics of key neurotransmitters and neurohormones that meditation research thus far has been found to influence…

Neurotransmitters Influenced by Meditation

• Neuromodulator; primary neurotransmitter found at autonomic (involuntary) nervous system synapses.
• Enhances attentional system and the orienting response. While not conclusively confirmed by research, acetylcholine is believed to enhance both attention and orientation in the parietal lobes during meditation as distracting sensory input is deafferentiated or diminished.
• Regulates states of consciousness, including arousal functions of the reticular activating system.
• Rises to dominance during such parasympathetic nervous system responses as sleeping and dreaming.
• Motivation, learning, perception, cognition, and memory consolidation (coding and storing memories for later use).

Decreases in acetylcholine leads to loss of memory and dementia. People with Alzheimer’s disease have decreased acetylcholine in the neocortex and hippocampus.

• Peptide; vasoconstrictor, increases arousal.
• Plays major role in learning and memory consolidation.
• Helps maintain positive affect and decrease self-perceived fatigue.
• Also known as antidiuretic hormone (ADH); facilitates water reabsorption by the kidneys.

Arginine vasopressin (AVP) has also been implicated in autism spectrum disorders. It influences social behavior by mediating secretion of the neurohormone oxytocin.

• Monoamine, produced and secreted by the hypothalamus.
• The primary neurotransmitter involved with reward-motivation neural circuitry, as well as controlling movement/motor activity.
• Associated with feelings of pleasure and reward (in the fronto-limbic affective systems of the brain)
• Heavily modulates attentional systems and enhances learning, memory and the flow of information in frontal brain regions linked to thought and emotion.

Dopamine is involved in the release of natural endorphins, which act as natural mood lifters and have a calming effect on us. Short-term surges of dopamine are normally associated with feelings of pleasure. But excess dopamine has been linked to schizophrenia, psychosis, Attention-Deficit/Hyperactivity Disorder and substance abuse. Dopamine imbalances also cause movement disorders, such as Parkinson’s disease and Huntington’s disease. Some studies indicate that having too little dopamine or problems using dopamine in cognitive and emotional regions of the brain may play a role in disorders like schizophrenia, and Attention-Deficit/Hyperactivity Disorder.

• Monoamine and stress hormone, produced in the adrenal medulla, the outer portion of the adrenal glands.
• Stimulates sympathetic nervous system to produce fight-or-flight responses, such as increased heart rate, increased blood glucose, and increased blood flow to muscles.

• Amino acid; the primary inhibitory amino acid in the central nervous system.
• Induces a calming, anti-anxiety effect on the brain.
• Regulates the activity of other critical mental health neurotransmitters, including serotonin, norepinephrine, epinephrine and dopamine.
• Enhanced activity produces sedative, anxiolytic and anticonvulsant effects.

An inability to produce and circulate adequate levels of GABA has been associated with conditions such as, anxiety, tension, insomnia, and epilepsy. Its effects are similar to anxiolytic and tranquilizing drugs (e.g., benzodiazepines such as Xanax), which reduce anxiety by binding to GABA-A receptors.

• Amino acid, the most commonly found neurotransmitter.
• Excitatory transmitter; its release increases the odds that a neuron will fire. Enhances electrical flow among brain cells required for normal function and plays a role in early brain development.
• Involved in learning, memory and brain plasticity; for example, a sub-type of glutamate receptor appears to mediate the function of brain plasticity essential to learning and memory.

Problems in producing or using glutamate have been linked to several mental health disorders, including autism, obsessive-compulsive disorder (OCD), schizophrenia and even depression.

• Monoamine. Both a stress hormone and neurotransmitter, norepinephrine is secreted by the adrenal medulla and the nerve endings of the sympathetic nervous system; found at autonomic nervous system junctions.
• Causes vasoconstriction and increases in heart rate, blood pressure and blood sugar level.
• Central roles include modulation of arousal, food intake, and mood.

Excess norepinephrine can lead to elation or euphoria, and deficiency can lead to nervous depression.

• Monoamine. Serotonin, a feel-good neurotransmitter, is the primary neurotransmitter regulating mood.
• Plays an important role in sleep cycles and circadian rhythm
• Helps modulate pain, body temperature, blood pressure and endocrine system secretion.
• Plays a role in information processing (learning and memory), aggression, movement and sexual behavior.
• Mediates appetite and satiety, the condition of being gratified or full beyond the point of satisfaction; thus, can be involved in overindulgence behaviors.

Moderately increased levels of serotonin create positive affects, while low levels of serotonin often signify depression and have also been linked to other conditions such as, obesity, insomnia, narcolepsy, sleep apnea, migraine syndrome, premenstrual syndrome, and fibromyalgia. But excess stimulation of cortical 5-HT2 receptors (especially in the temporal lobes) has been known to result in hallucinogenic effects (similar to those caused by tryptamine psychedelics such as LSD), which, in turn, increases serotonin levels.

Both anxiety and depression typically involve a malfunctioning of neurotransmitter pathways and/or imbalances in neurotransmitters such as serotonin and norepinephrine. This mechanism is clearly demonstrated by the effects of the antidepressant class of medications, SSRIs or Selective Serotonin Reuptake Inhibitors (e.g., Prozac, Paxil, and Zoloft), which are widely used to treat depression. SSRIs specifically target serotonin neural receptors, blocking the reabsorption (reuptake) of serotonin, thus leaving more serotonin in circulation throughout the brain.

• Peptide; secreted from the anterior pituitary in response to corticotropin-releasing hormone from the hypothalamus. Corticotropin-releasing hormone is secreted in response to many types of stress.
• Stimulates the adrenal cortex, thus stimulating the production of adrenal (steroid) hormones which are involved in the body’s stress response, including the fight-or-flight response.
• Stimulates secretion of glucocorticoids such as cortisol.

• Natural, endogenous opiate-like peptide.
• Function as the body’s natural painkillers; modulate the body’s pain pathways.
• Create an encompassing sense of happiness and well-being.
• Reduce blood pressure, depress respiration, reduce fear.

• Stress hormone released during fight-or-flight responses.
• Prolonged high cortisol levels have been linked to accelerated aging, compromised immunity, abdominal fat and conditions causing cardiovascular problems and increasing the risk for diabetes.

Prolonged high levels of cortisol in the bloodstream can also lead to decreased bone density, elevated blood pressure, suppressed thyroid function, chronic stress, blood sugar imbalances (e.g., hyperglycemia), decrease in muscle tissue and a decreased immunity and inflammatory response.

• Antioxidant hormone secreted by the pineal gland in the brain, especially at night. Sometimes referred to as the “sleep hormone” or “the hormone of darkness.” Regulates our circadian rhythm (sleeping and waking) patterns — it tells the body when it’s time to sleep.
• Stimulates the immune system and the antioxydative defense system.
• Plays a role in delaying aging, reducing pain sensitivity (sleep deprivation can increase pain perception), and reproduction in humans (skin color changes in amphibians and reptiles)
• Closely linked to serotonin with respect to mood stabilization, positive affect, stress-prevention and aging.
• Melatonin may act as an oncostatic agent; i.e., have cancer-fighting properties.

Melatonin has been closely linked to serotonin with respect to influencing depression (mood instability), positive emotion, stress-prevention and aging. In fact, some of the brain’s serotonin is converted in the pineal gland to melatonin, an antioxidant hormone that regulates sleep patterns and helps you get a good night’s sleep. The body’s natural melatonin levels are high during the evening and low during the day. Some people have found melatonin supplements useful for enhancing sleep quality, fighting jet lag, mitigating Seasonal Affective Disorder and regulating nighttime dementia, but the research is somewhat controversial.

Melatonin’s antioxidant properties help fight the damage wreaked on us by free radicals; for example, melatonin can help stop wear-and-tear damage to DNA. Melatonin deficiency has also been linked to migraine syndrome.

Excess melatonin can directly inhibit memory formation and some research suggests that excess melatonin at bedtime could actually interfere with long-term memory formation since memories of the day’s events are consolidated during sleep.

For details on how meditation influences neurochemicals and brain mechanisms to promote better health, see: Evidence of Meditation’s Impact on Neurotransmitters & Neurohormones.