The Physiology
Of
Addiction
DRUG DISTRIBUTION
Drugs are:
IGNORED
STORED
BIOTRANSFORMED
Into metabolites or chemical variations of the original drug, some of which
can cause an effect
CAUSES AN EFFECT
THE BLOOD-BRAIN BARRIER
Crossover occurs because psychoactive drugs are: FAT-SOLUBLE (Lipophilic)
Most substances that are WATER-SOLUBLE (Hydrophilic) are prevented from
crossover.
ALCOHOL is both!
Within only 10 to 15 seconds after entering the bloodstream the drug will reach the
gateway to the central nervous system.
THE NERVOUS SYSTEM
Central Nervous System (CNS): Brain & Spinal Cord
Peripheral Nervous System (PNS)
Autonomic Nervous System: Controls involuntary internal functions;
circulation, digestion, respiration, glandular output, genital reactions.
Sympathetic division helps the body respond to stress (speed up heart in
response to stress)
Parasympathetic division conserves body’s resources & restores
homeostasis (slow down heart when threat has passed)
Enteric division controls smooth muscles in the gut.
Somatic Nervous System: Transmits sensory information about environment,
limb & muscle position to CNS then back to skeletal muscles which allows the
body to respond voluntarily.
Central Nervous System (CNS)

acts as switchboard/computer, receiving messages from PNS, analyzing
them, sending response to appropriate system

enables us to reason/make judgments
Psychoactive drugs can;

alter information sent to brain from environment,

disrupt messages sent back to various parts of the body,

disrupt our ability to think, reason, interpret sensory input

effect other systems of the body either directly
while passing through or by manipulating nerve cell chemistry in the brain
that then send messages back to that organ.
OLD BRAIN – NEW BRAIN
Brain can be described;

anatomically divided by component parts
(spinal cord, medulla, cerebellum, etc.)

by function (vision center, motor cortex, etc.)

divided by location (hind brain, midbrain, etc.)

in an evolutionary since (looking at physiological changes as survival
adaptations)
Old Brain (Brain stem, cerebellum, & mesocortex)

regulates physiologic functions of the body (respiration, heartbeat, body
temperature, etc.)

experiences basic emotions and cravings (anger, fear, hunger, lust,
pleasure, etc.)
New Brain (neocortex – cerebrum & cerebral cortex)

Processes information that comes in from the old brain, from other areas
of the new brain, or from senses via the peripheral nervous system.

Tries to make sense of the feelings and emotions coming from the old
brain.
The old brain rules the new brain!
THE REWARD/PLEASURE CENTER
The mesolimbic dopaminergic reward pathway
The specific area of the old brain that encourages a human to repeat an action that
promotes survival is called the reward/pleasure center.
Two key parts of this system are:

nucleus accumbens
(Rat research with electrical then drugs)

ventral tegmental area, the lateral hypothalamus, & the prefrontal cortex
(feelings of pleasure or satisfaction when craving is fulfilled – on/off
switch)
REWARD/SATISFACTION NETWORK
Can’t control carvings of instincts or messages from the reward/pleasure center, can
only keep trying to satisfy them until satiation switch kicks in.

involves several neurotransmitters
dopamine & endorphins

developed over millions of years to reinforce survival instincts (thirst,
hunger, sex)

when activated the memory of action causing reward more strongly
imprinted more intense the reward, more ingrained the memory, more
likely to repeat.

is tightly intertwined with physiologic regulatory centers of body
(autonomic nervous system)
DRUGS HIJACK THE REWARD/SATISFACTION NETWORK
The brain is reorganized around the particular drug and in some cases this
reorganization is permanent.
Theories about how psychoactive drugs disrupt the reward/pleasure center and
satiation switches

on-off satiation switch becomes stuck in on position

satiation switch is ignored to continue the euphoria or pain relief

addiction replaces all other problem solving behaviors

communication between two brains disrupted or severed turning off new
brain

desires to act out certain compulsive behaviors (sex, gambling, etc.)
originate in old brain thus subject to addiction
NEUROANATOMY
Nerve Cells
In order to understand how psychoactive drugs affect the user’s physical, emotional, and
mental functioning, you need to understand the precise way messages are transmitted by
the nervous system.
Neurons - building blocks of the nervous system
Has 4 essential parts

dendrites – receive signals from other nerve cells and relay them through
the cell body

cell body – nourishes the organism and keeps it alive

axon – carries the message from the cell body to the terminals

terminals – relay this message to the dendrites, cell body, or terminals of
the next nerve cell.
A single cell might have anywhere from a few contacts up to 150,000 contacts with other
cell dendrites.
Terminals of one nerve cell do not touch dendrites of the adjoining nerve cell but passes
through the synaptic gap that exist between them.
The message jumps this synaptic gap, from the presynaptic terminal to the postsynaptic
dendrite by microscopic messenger chemicals call neurotransmitters.
These bits of chemicals have been synthesized within the neuron and stored in tiny sacs
called vesicles.
The message starts as an electrical signal, travels along the axon to the terminal and at the
presynaptic terminal is then converted to a neurochemical signal, which bridges the
synaptic gap and at the postsynaptic dendrite it is converted back to an electrical signal
for the next phase of the journey.
This transmission process across the gap between nerve cells is called a synapse.
NEUROTRANSMETTERS & RECEPTORS
These are the parts of the central nervous system most affected by psychoactive drugs.
Neurotransmitters:

acetylcholine: mostly active at nerve-muscle junctions; affects mental
acuity, memory, & learning

norepinephrine (NE) & epinephrine (E): classified as catecholamine &
function as stimulants when activated by a demand from the body for
energy. Stimulates autonomic nervous system, affects motivation, hunger,
attention span, confidence & alertness.

dopamine (D): a catecholamine that helps regulate fine motor muscular
activity, emotional stability, satiation, & the reward/pleasure center.

enkephalin: these neuropeptides act on opiate receptors to deaden pain &
trigger the reward/pleasure center when pain is relieved.
serotonin: this neurotransmitter helps control mood stability including
depression & anxiety, appetite, sleep, & sexual activity


GABA (gamma amino butyric acid): an inhibitory neurotransmitter
involved in 25% to 40% of all synapses in the brain. It controls impulses,
muscle relaxation, & arousal. The brains main inhibitory neurotransmitter.

substance “P”: found in sensory neurons, a peptide that conveys pain
impulses from the peripheral nervous system.

anandamide: a neurotransmitter which accommodates’ THC. Found in the
limbic system & the area responsible for integration of sensory
experiences with emotions as well as those controlling learning, motor
coordination, & memory.

glycine: an inhibitory neurotransmitter found mostly in the spinal cord and
brain stem.

histamine: helps regulate emotional behavior and sleep.

nitric oxide: a neurotransmitter involved in message transmission to the
intestines & other organs including the penis (erectile function), also
involved in regulation of emotions.

glutamic acid: a principal excitatory neurotransmitter is one of the major
amino acid.

cortisone: neurochemicals that aid in the immune system, healing, &
stress.
Although each nerve cell produces only one type of neurotransmitter, a single neuron
might receive messages from several neurotransmitters.
Neurotransmitters that open the gate and;

allow positive sodium ions in, increasing cell firings, are called excitatory

allow negative chloride ions in and push positive potassium ions out,
reducing cell firings, are called inhibitory.
Incoming electrical signal forces release of neurotransmitters from the vesicles to the
presynaptic terminal and sends them across the synaptic gap to the postsynaptic dendrite
where the neurotransmitters will slot into precise receptor sites which will cause an ion
molecular gate to open allowing sodium, potassium, or chloride ionic electrical charges
in or out. When enough excitatory neurotransmitters cause sufficient movement of the
positively charged ions & the total voltage reaches a certain action potential it fires a
signal. If enough inhibitory neurotransmitters allow sufficient negative chloride ions in
and positive potassium ions out, the electrical potential is kept below the action potential
level and the cell is inhibited from firing.
This process is called the “first messenger system”
The “second messenger system” is where the slotting in of neurotransmitters makes it
more likely that other neurotransmitters will stimulate or inhibit a signal. It is the
electrical charge sum of all the activated receptor sites that can cause the cell to reach its
action potential and fire off the signal. As the neurotransmitters do their job they are
released back into the synaptic gap and are reabsorbed by the sending nerve cell
membrane reuptake ports and returned to the vesicles, ready to fire again.
The amount of neurotransmitters available for message transmission is constantly
monitored by an autoreceptor on the sending neuron. This autoreceptor either reduces
production/release of additional neurotransmitters or increases it.
There is another system for regulation:
Down regulation: if the cell senses there are too many neurotransmitters, it will reduce
the number of receptor sites to slow message transmission.
Up regulation: If there are too few neurotransmitters available to trigger the message,
the receiving neuron will increase the number of receptor sites so the few
neurotransmitters remaining can be more active.
Agonist: drugs that enhance the activity of neurotransmitters and receptor sites.
Antagonist: drugs that block this activity.
A drug will sometimes disrupt communication in more than one way.
Psychedelic or hallucinogen can produce:
Synesthesia: release of stimulatory neurotransmitters that alter messages from
external environment; sounds become visual distortions & visual images become
distorted sounds.
Hallucinations: images that don’t exist at all in the external world are created by
blocking the action of acetylcholine.
Psychoactive drugs cannot create sensations or feelings that don’t have a natural
counterpart in the body!
Theories of Addiction
Addictive Disease Model (Medical Model)
A chronic, progressive, relapsing, incurable, and potentially fatal condition that is mostly
a consequence of genetic irregularities in brain chemistry and anatomy that may be
activated by the particular drugs that are abused characterized by;

impulsive abuse marked by intoxication throughout the day w/
overwhelming need to use;

loss of control;

repeated failed attempts to control use;

continued use despite adverse consequences;

increased tolerance, blackouts, personality and lifestyle changes.
Behavioral/Environmental Model
Emphasizing the overriding importance of environmental and developmental influences
in leading a user to progress into addictive behavior
Environmental factors (physical/emotional stress) can change brain chemistry
Six levels of drug use: Abstinence, experimentation, social/recreational use, habituation,
abuse, and addiction
Academic Model
Addiction occurs when the body adapts to the toxic effects of drugs at the biochemical
and cellular level with four physiological changes characterizing this process:
1. Tolerance: resistances to the drug’s effects increase, necessitating larger and
larger doses:
2. Tissue dependence: actual changes in body cells occur because of excessive
use, so the body needs the drug to stay in balance;
3. Withdrawal syndrome: physical signs and symptoms of tissue dependence
appear when drug use is stopped:
4. Psychic dependence: the effects of the drug are desired by the user and these
reinforce the desire to keep using.
Diathesis-Stress Theory of Addiction
All existing theories of addiction are true in their own right. It is beneficial to integrate
theories and look at addiction as a process that often encompasses a user’s entire life.
Originally this was a theory in psychological disorders
Diathesis: a constitutional predisposition or vulnerability to develop a given disorder
under certain conditions that leads to the development of the disorder if the person
encounters a level of stress that exceeds stress thresholds or coping abilities.
In addiction, diathesis or predisposition to addiction is: result of genetic and
environmental influences, such as stress + the use of psychoactive drugs or certain
behaviors, then neurochemistry and brain function are further changed to the point that a
return to “normal” is extremely difficult.
HEREDITY, ENVIRONMENT, PSYCHOACTIVE DRUGS, &
COMPULSIVE BEHAVIORS
Addiction is a combination of the three factors of heredity, environment, and the use of
psychoactive drugs!
Heredity
Twin & Retrospective Studies
Biologic family records
1 parent = male child is 34% more likely
Both parents = 400% more likely
Both parents + grandfather = 900%
About 28 million Americans have at least 1 alcoholic parent
Alcoholism-Associated Gene located proves genetic predisposition and indicates a
tendency to a number of compulsive behaviors including; gambling, psychoactive
substance use, attention-deficit disorder, aberrant sexual behavior, overeating, antisocial
personality, and even Tourette’s syndrome.
Referring to this “compulsivity gene” and the process as reward deficiency syndrome
Environment
Environmental influences that determine the level of drug use can be positive or negative
as varied as; Stress, love, violence, sexual abuse, nutrition, living conditions, family
relationships, health care, neighborhood safety, school quality, peer pressure, television,
etc.
Environment & Brain Development
Environmental influences have the greatest impact on the development of the brain
Born with the 100 billion nerve cells in the brain
Environment influences the 100 trillion connections
It molds the brains architecture and neurochemistry, altering the way the brain reacts to
outside influences especially in the first 10 years of life. It may take up to 20 years for the
brain to become “hard wired.”
The brain keeps track through chemical, structural, and biological changes. The stronger
the environmental influence & more often they are repeated, the stronger the imprinting.
If stress continues long enough, the counter-behavior that the child learns also becomes
imprinted. Once connections are made and chemistry altered in response to
environmental challenges, they are very difficult to change but not impossible.
Environment can make a person more liable to use and abuse psychoactive substances

if stress is common in the home,

if drinking or other drug use is common in the home,

if different ways of reacting to stress or anger aren’t ;earned and selfmedication becomes the only solution,

if there are mental health problems triggered by the home environment,

or if their diet lacks sufficient vitamins and proteins needed for healthy
brain chemistry.
One is also more susceptible to drug use if society tells them in word and deed that
drinking, smoking, drug use will solve their problems.
Nutrition is an overlooked environmental influence for brain cells need proteins to
produce neurotransmitters. Unbalanced diet can impact brain chemistry and increase
susceptibility to addiction.
Psychoactive Drugs
Affect not only susceptible and predisposed people but everyone.
Excessive, frequent, or prolonged use of alcohol/drugs inevitably modifies many of the
same nerve cells and neurochemistry that are affected by heredity and environment.
Tolerance, tissue dependence, withdrawal, and psychic dependence demonstrate this
affect. Compulsive behaviors also influence the progression to addiction.
These changes in various parts of the brain can be imaged.
SPECT scans
Looks at blood flow and metabolic activity in the brain to show how the brain functions
during a given activity (such as taking drugs).
Shows that psychoactive drug use (initial & chronic) decrease vital functioning of the
brain neocortex impairing reason and thinking key to maintaining compulsive use.
Compulsive Behaviors
Compulsive behaviors (gambling, sexual activity, & eating disorders) also accelerate,
supplant, or even cause compulsive drug use. Gambling causes the brain to be rewired,
particularly the reward/pleasure center.
These compulsions are actual dysfunctions of brain chemistry.
These compulsions are different from obsessive-compulsive disorder (OCD) which has
been shown to occur along a different brain and neurotransmitter pathway. These
compulsions associated with a pleasurable experience whereas OCD actions are not.
ALCOHOLIC MICE & SOBER MICE
Two generic strains of mice developed to help understand alcoholism;
One loved alcohol, when given a choice between water and 70% concentration of alcohol
they would choose the alcohol..
Other hated alcohol, when given a choice between water and even 2% concentration
alcohol they would choose the water.
EXPERIMENT
Injected alcohol-hating mice with high levels of alcohol = to heavy drinker. Within a few
weeks if mice weren’t stopped they would drink themselves to death.
EXPERIMENT
Subjected alcohol hating mice to stress, within a few weeks mice came to prefer higher
and higher concentrations of alcohol. (Stress + exposure)
EXPERIMENT
Restricted diet of alcohol-hating mice of vitamin B and some essential proteins, after
several months there was an increased alcohol use.
EXPERIMENT
Alcohol loving mice given alcohol drank themselves to death, even when given electrical
shocks aimed at preventing drinking, even when shocks came close to being fatal.
EXPERIMENT
When forced drinking, stress induced, and nutritional restricted alcohol-hating mice were
taken off alcohol they did not return to their non-drinking self. They had been
transformed into alcohol loving mice.
When the brains of these mice were examined, all had similar brain cell changes and
neurotransmitter imbalances that made them prefer alcohol.
Compulsion Curve
Human beings are more complex, it usually takes a combination of heredity,
environment, and psychoactive drugs use to increase compulsive use. If heredity is low
then the other two needs to be higher, if heredity and environment is low then more drug
use or more potent drugs are needed to result in compulsive use.
Drugs & routes of entry that push the hardest & quickest towards addiction
smoking tobacco
smoking “crack” cocaine
smoking or injecting heroin
injecting methamphetamines
snorting cocaine
ingesting opioid painkillers
ingesting methamphetamines
ingesting sedative hypnotics
drinking alcohol
smoking marijuana
ingesting PCP
ingesting caffeine
ingesting MDMA
ingesting LSD
ingesting peyote
When people stop using drugs or stop compulsive behaviors they drop below critical
susceptibility but not back to the level they were before they started. This is because they
have permanently altered their brain chemistry making them forever liable to redevelop
uncontrolled use or behavior quicker than before.
IMPLICATION
The recovering person can’t control the heredity and they can’t control their drug use
when using and they can’t control their altered brain chemistry, so they need to control
their stress and environment in order to reduce their susceptibility.