Neurobiology of Addiction:

the rewired system.

Joseph Zannella M.A., L.A.D.C.
Copyright 2010
203-362-8369

1
 Post Acute Withdrawal Syndrome is a
framework that helps explain the Biological
changes people go through in recovery.

This allows the Therapist to explain how

the brain and biology relate to what the
client feels.

Thoughts…Feelings…Actions
2
 Post Acute Withdrawal Syndrome
Racing Thoughts Frustration Sleep Disorders
Confusion Moodiness Exhaustion
Easily Overloaded Pink Cloud Pain Issues
Memory Problems Anger Over/Under Eating
Loss of Skills Anxiety Digestion Issues
Obsession Hopeless Accident Prone
Distractibility Depression Compulsive Actions
Dissociation Alexithymia Agitation

Why are these symptoms grouped this way?

What do all these things have in common?

3
 • The Brain Is…Biological

Yes…you really need to know these parts of the brain.

The Reward System, where addiction starts.
4
 There are many myths about the brain.
• ‘We only use only 10% of our brain.’
There is no scientific basis for this assertion. This misconception most likely arose from a
misunderstanding of neurological research in the late 1800s and early 1900s when
researchers either discovered that only about 10% of the neurons in the brain are firing at
any given time and announced that they had only mapped the functions of 10% of the brain
up to that time. Another possible origin of the misconception is that only 10% of the cells in
the brain are neurons; the rest are glial cells that, despite being involved in learning, do not
function in the same way that neurons do.

• ‘Someplace in our brain we remember everything that ever happened to us.’

There is no proof we can remember that much. We have plenty of proof that we forget,
permanently, lots of thing. We also have good proof that when we recall memories we are
re-writing and changing those memories each time we access them. There are a few people
who have Hyperthymesia, an extraordinary recall for most of the events in their lives.

• ‘We don’t really know how the Brain works.’

We understand very well how the major areas and functions of the brain work. We know
how most of those interact and we are quickly learning the fine details about the remaining
areas. We know a huge amount about how individual neurons work.

Please do not state myths to your clients as facts.

That is malpractice! 5
 And some more myths about the
• ‘We kill thousands of Brain cells when brain.
we drink alcohol (use drugs).’
It is very hard to examine the effects of drug abuse on a living brain. We have to rely on
scanning and other non-invasive techniques. While we can see more and less activation
in some areas due to substance abuse we cannot accurately say how many nerve cells
are being damaged or destroyed.

• ‘I’m a left/right brain thinker.’

Some mental functions such as speech and language tend to be localized to specific
areas in one hemisphere. If one hemisphere is damaged at a very early age, however,
these functions can often be recovered in part or even in full by the other hemisphere.
Other abilities such as motor control, memory, and general reasoning are spread
equally across the two hemispheres.

• ‘Once you are an adult you don’t get new brain cells, they only die as you get older.’
In fact, new neurons can grow within the mature adult brain; this process is known as
neurogenesis. The scientific consensus, however, is that neurogenesis only occurs in the
hippocampus and the olfactory bulb (and maybe Cerebellum). Regardless of neuron
growth or death, brain function and capabilities can be learned and developed
throughout life.

Please do not state myths to your clients as facts.

That is malpractice! 6
 Human Brain: Facts, Anatomy & Mapping Project
by Tanya Lewis, LiveScience Staff Writer
Date: 06 May 2013 Time: 06:28 PM ET

– Brain mapping project

• In April 2013, President Barack Obama announced a new research program known as
the Brain Research through Advancing Innovative Neurotechnologies (BRAIN)
Initiative, which will provide $100 million in funding starting in 2014 to map the
structure and function of the human brain.
• Sometimes called the Brain Activity Map, the project has been planned for some time.
In June 2012, six scientists put forth general proposals for developing sensors and
protocols for experimenting on single cells within neural networks. Obama first
referenced the project in his 2013 State of the Union address in February, and in
March 2013, the project's backers outlined their goals in the journal Science, calling
for a sustained effort over several years to create tools to understand how brain
networks function.
• Supporters of the project argue that it will provide the missing piece in how the brain
operates at a level between that of single neurons and the whole brain.

7
 The Reward System is several different structures deep in the brain between the top of
the spinal cord and the Cerebrum (the big part of the rest of the brain). It manages many
different basic functions like hunger, thirst, sleep, sex, motivation, and rewarding
successful behaviors. It also regulates our emotions and attaches emotions to memories.

The Reward System is part of the Limbic System, which manages all of the above as well
as many of the basic operations of our brains that are below our level of awareness and
control. These are deep structures that are shared by all mammals, and run the basic
functions needed to keep us alive. Elephants, mice, whales, marmosets, dogs, whatever,
all have these structures in their brains. Non-mammals do have similar structures as well.

8
 Why a Reward System.
Rewards come from different
sources…

Natural Rewards
•Food
•Water
•Nurturing
•Sex

Natural Rewards stimulate the Reward System of the Brain. That system tells
us what feels good or relieves a need, and makes us want to repeat the same
behavior when needed to relieve the need again (Reinforcement). When
things don’t feel good, we don’t usually repeat the behavior.
This is real important; if we didn’t have a reward system there could be no
such thing as addiction.
9
Addiction
•A state in which an organisms engages
in repeated, compulsive behaviors.

•The behaviors are Reinforced by the

brain. (Labeled as Pleasurable, or they
relieve Displeasure such as Anxiety or
Withdrawals.)

•There is a loss of control in limiting the

behaviors despite damage to the
organism.
10
The Reward System cannot use words to communicate with the rest of the brain. It uses feelings and
emotions. Feelings like Hunger, Craving, Pain and Fear are the ways the it tries to influence us to
satisfy it. It will send a craving for the drug, or the gambling, or whatever to the Frontal Lobes of the
brain, our center for planning and judgment. It uses the only language it has, feelings. This is why
addicts may have trouble finding words to describe what they are going through. The Reward System
has been rewired and is now an Addiction System(copyright).

11
Time to talk about Vocabulary. You really need to know
these words and get comfortable using them all the
time. These are the words of our profession.

• Central Nervous System  Addiction

(CNS)  Post Acute Withdrawal
• Frontal Lobes Syndrome (PAWS)
• Neuron  Harm Reduction
• Axon  Reward System
• Dendrite  Reinforcement
• Synapse  Extinguish
• Receptor Site  Synaptic Pruning
• Neurotransmitter  Neuroplasticity
• Reuptake

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 Neuroplasticity
• The ability of the brain to continually rewire itself through changes in Synapses, Neural
pathways and Neural Networks. These changes are ongoing and are from numerous causes.
Changes in behavior, environment, thinking, emotions, as well as bodily injury lead to changes
in the neural networks. Recovery from Stroke damage is a good example of Neuroplasticity.

• A 2005 study found that the effects of neuroplasticity can occur rapidly. Medical students'
brains were imaged during the period when they were studying for their exams. In a matter of
months, the students' gray matter increased significantly in the posterior and lateral parietal
cortex.

• Drug addiction and obsessive-compulsive disorder are deemed examples of "negative

plasticity" as the synaptic rewiring resulting in these behaviors is highly maladaptive and
difficult to change.

• A surprising consequence of neuroplasticity is that the brain activity associated with a given
function can move to a different location; this can result from normal experience and also
occurs in the process of recovery from brain injury.

• "neurons that fire together, wire together, neurons that fire apart, wire apart,"
 But what are these Systems made from?
Really tiny parts. Neurons!

One Hundred Million Neurons in One Cubic Milliliter of Brain.

86 Billion Neurons in the total Human Brain.
14
Synapses

Which are understood in great detail.

15
 Simpler can be better. The basic structure of a
synapse, the connection between two neurons.

16
 Lets get back to
the basics…

Neurons talk to
each other using
chemicals at
their Synapses.
Neurotransmitters
Here’s how three important Neurotransmitters
may interact to create our moods. 17
We have lots of Neurotransmitters. No, don’t try to memorize these.

Small Molecule Acetylcholine (ACh) Dopamine (DA) Norepinephrine (NE)

Neurotransmitter
Serotonin (5-HT) Histamine Epinephrine
Substances.

Amino Acids Gamma-Aminobutyric acid (GABA) Glycine Glutamate

Aspartate

Neuroactive Peptides bradykinin beta-endorphin bombesin calcitonin

–it’s a partial list. cholecystokinin enkephalin dynorphin insulin
gastrin substance P neurotensin glucagon
secretin somatostatin motilin vasopressin
oxytocin prolactin thyrotropin angiotensin II
thyrotropin-
sleep peptides galanin neuropeptide Y
releasing hormone
gonadotropins- growth hormone- luteinizing vasoactive
releasing hormone releasing hormone hormone intestinal peptide

Soluble Gases Nitric Oxide (NO) Carbon Monoxide

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 More about Neurotransmitters.
• Different types of cells secrete different neurotransmitters. Each brain chemical works in widely spread but fairly specific brain locations
and may have a different effect according to where it is activated. Some 60 neurotransmitters have been identified and many more
suspected, but some of the most important, seem to be:
• Dopamine
• Controls arousal levels in many parts of the brain and is vital for giving physical motivation. Your ability to generate ideas and take action is
regulated by dopamine. Dopamine is the master power switch controlling our drive to pursue life and all it has to offer. Abundant dopamine
in the brain gives you a feeling that you can do anything and feelings of euphoria. When levels are severely depleted, as in Parkinson's
disease, people may find it impossible to move voluntarily. Drugs of addiction tend to increase levels of dopamine.
• Serotonin
• Serotonin is key to regulating sleep, appetite, happiness, sexual arousal and very important for regulating emotions. It helps defend against
both anxiety and depression. Shortages of serotonin can cause depressed moods, anxiety, panic attacks, low energy, migraines, sleeping
problems, obsession or compulsions, irritability, sweets cravings, and reduced sex drive. This is the neurotransmitter enhanced by Prozac,
and has thus become known as the 'feel-good' chemical. It has a profound effect on mood and anxiety -- high levels of it, or sensitivity to it,
are associated with serenity and optimism.
• Acetylcholine (ACh)
• This plays an essential role in enabling us to learn and remember. Acetylcholine helps regulate the plasticity of our neural network. It helps
manage how our brain re-wires connections between neurons in response to new activities and experiences. People with Alzheimer's
disease typically have low levels of ACh, and drugs that boost its action may improve their memory.
• Adrenalin and Noradrenalin
• Mainly excitatory chemicals that induce attention, mental focus, physical/mental arousal, and cognition. When levels are too low in the
brain, you can experience fatigue, lack of focus, and low motivation. Production is centered in an area of the brain called the Locus
Coeruleus, which is one of several components of the brain's 'pleasure' center.
• GABA (Gamma Aminobutyric acid)
• The chief inhibitory neurotransmitter in the CNS. It plays a role in regulating Neuron excitability throughout the nervous system; similar to
the brakes on a car it can slow things down.
• Glutamate
• The brain's major excitatory neurotransmitter, vital for forging the links between neurons that are the basis of learning and long-term
memory. Makes it more likely any neuron affected will send a signal. Can be thought of as a gas pedal for the brain.
• Enkephalins and Endorphins.
• These are internal opioids that, like the drugs heroin and morphine, modulate pain, reduce stress and promote a sensation of floating,
oceanic calm. They also depress physical functions like breathing and may produce physical dependence.

19
There are many ways that a drug can act to enhance (Agonize) a given neurotransmitter:

An agonistic drug can increase the production of particular neurotransmitters. When those
neurotransmitters are then released into the synapse, they are more numerous than they
would normally be, and more of the neurotransmitter molecules find their way over to the
post-synaptic receptors on the dendrites of the next neuron (L-Dopa and L-Tryptophan).
An agonistic drug can interfere with the re-uptake of neurotransmitter molecules which has
the effect of forcing them to remain in the synapse and interacting with receptors longer than
normal (an excellent example is Cocaine).
An agonistic drug can bypass the neurotransmitter entirely, and simply float out into the
synapse and itself bind with and activate the neurotransmitter's receptors (Heroin).

Similarly, there are many ways that a drug can act to interfere with (Antagonize) a given
neurotransmitter:
An antagonistic drug can interfere with the release of neurotransmitters into the synapse.
(Alcohol suppresses Glutamate and increases the effect of GABA).
An antagonistic drug can compete with the neurotransmitter for binding to the
neurotransmitter's receptor. The antagonistic drug binds to the receptor but does not activate
it, thus blocking receptors from being activated by the neurotransmitter (Naloxone/Narcan).
An antagonistic drug can causes neurotransmitters to leak out of their containers in the
terminal button, into the fluid of the pre-synaptic neuron itself, making the neurotransmitter
substance unavailable for release into the synapse. When the neuron is activated, there is
less neurotransmitter available to be released into the synapse (Reserpine).

Most of the drugs that get abused are agonists of various neurotransmitters - they work to
enhance the natural effect of neurotransmitters. 20
 Neurotransmitters
are released,
enhanced, reduced, Food
imitated or affected Love Sleep
by…

Meditation Laughter

Neurotransmitters

Everything we
experience is Gambling Sex
because of, and
affects, our
Neurotransmitters.
Exercise Music
All of our reality is a
dance of chemicals
Drugs

in our brain.
21
Addiction A state in which an organisms engages
in a repeating, compulsive behavior.

The behavior is initially reinforcing. “Wow…that was great!”

“Thank god…my anxiety is going away!”

There is a loss of control in delaying or “Just one more hit.”

offsetting the behavior. “Of course I can stop anytime I want.”
“This machine is ready to pay off.”

The behavior is often continued when “I musta got some bad stuff.”
there is no further reinforcement. “I don’t get why I keep using, I don’t
even like it anymore.”

The behavior is often continued “My wife left me, I’m going to jail
to the point of damaging or and my liver is shot…but I can
destroying the organism. stop anytime I want to.”

22
 Alcohol CH3CH2OH

•Alcohol affects the brain’s neurons in several ways. It alters their membranes as well as
their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for
acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate.

•GABA’s effect is to reduce neural activity by allowing chloride ions to enter the post-
synaptic neuron. These ions have a negative electrical charge, which helps to make the
neuron less excitable. This physiological effect is amplified when alcohol binds to the GABA
receptor, probably because it enables the ion channel to stay open longer and thus let more
Cl- ions into the cell.

•The neuron’s activity would thus be further diminished, this explains the sedative effect of
alcohol. This effect is accentuated because alcohol also reduces glutamate’s excitatory
effect on NMDA receptors.

•However, chronic consumption of alcohol gradually makes the NMDA receptors

hypersensitive to glutamate while desensitizing the GABAnergic receptors. It is this sort of
adaptation that would cause the state of excitation, up to seizures, characteristic of alcohol
withdrawal.
23
Endorphins
• At least 20 types of endorphins have been
demonstrated in humans. Endorphins can be
found in the pituitary gland, in other parts of the
brain, or distributed throughout the nervous
system.
• Stress and pain are the two most common
factors leading to the release of endorphins.
Endorphins interact with the opiate receptors in
the brain to reduce our perception of pain and
act similarly to drugs such as morphine and
codeine. In contrast to the opiate drugs,
however, activation of the opiate receptors by
the body's endorphins does not lead to
addiction or dependence.
• In addition to decreased feelings of pain,
secretion of endorphins leads to feelings of
euphoria, modulation of appetite, release of sex
hormones, and enhancement of the immune
response.

24
 • The reason that opiates such as heroin and morphine

Opiates
affect us so powerfully is that these exogenous
substances bind to the same receptors as our
endogenous opioids. There are many kinds of opiate
receptors widely distributed throughout the brain.

• These receptors, through second messengers, influence

the likelihood that ion channels will open, which in
certain cases reduces the excitability of neurons. This
reduced excitability is the likely source of the euphoric
effect of opiates.

• This euphoric effect also appears to involve another

mechanism in which the GABA-inhibitory interneuron's
of the ventral tegmental area come into play. By
attaching to their receptors, exogenous opioids reduce
the amount of GABA released.

• Normally, GABA reduces the amount of dopamine

released in the nucleus accumbens. By inhibiting this
inhibitor, the opiates ultimately increase the amount of
dopamine produced and the amount of pleasure felt.

25
The Locus Coeruleus is one of the centers of brain activation. It is intimately connected to
PTSD and Opiate withdrawals. Opiates inhibit the firing of neurons in the locus coeruleus.
When opioid consumption is stopped, the increased activity of the locus coeruleus
contributes to the symptoms of opiate withdrawal. The alpha2 adrenoceptor agonist
Clonidine is used to counteract this withdrawal effect by decreasing adrenergic
neurotransmission from the locus coeruleus.

26
Cocaine • Cocaine acts by blocking the reuptake of
certain neurotransmitters such as dopamine,
norepinephrine, and serotonin. By binding to
the transporters that normally remove the
excess of these neurotransmitters from the
synaptic gap, cocaine prevents them from
being reabsorbed by the neurons that released
them and thus increases their concentration in
the synapses. As a result, the natural effect of
dopamine on the post-synaptic neurons is
amplified.
• The group of neurons thus modified produces
the euphoria (from dopamine), feelings of
confidence (from serotonin), and energy (from
norepinephrine) typically experienced by
people who take cocaine.
• Because the norepinephrine neurons in the
locus coeruleus project their axons into all the
main structures of the forebrain, the powerful
overall effect of cocaine can be better
understood.
• The Ventral Tegmental Area (VTA) creates the
impulse to repeat the behavior. This is where
the “craving” comes from.

27
Amphetamines
• Like cocaine, amphetamines increase the concentration
of dopamine in the synaptic gap, but by a different
mechanism. Amphetamines are similar in structure to
dopamine, and so can enter the terminal button of the
presynaptic neuron via its dopamine transporters as
well as by diffusing through the neural membrane
directly. Once inside the presynaptic neuron,
amphetamines force the dopamine molecules out of
their storage vesicles and expel them into the synaptic
gap by making the dopamine transporters work in
reverse.

• Amphetamines also seem to act by several other

mechanisms. For example, they seem to reduce the
reuptake of dopamine and, in high concentrations, to
inhibit monoamine oxydase A (MAO-A).

• Amphetamines may also excite dopaminergic neurons

C9H13N via glutamate neurons. Amphetamines would thus
remove an inhibiting effect. By thus releasing this
natural brake, amphetamines would make the
dopaminergic neurons more readily excitable.

28
Nicotine
• Nicotine imitates the action of a natural neurotransmitter
called acetylcholine and binds to a particular type of
acetylcholine receptor, known as the nicotinic receptor.

• Whether it is acetylcholine or nicotine that binds to this

receptor, it responds in the same way: it changes its
conformation, which causes its associated ion channel to
open for a few milliseconds. This channel then allows
sodium ions to enter the neuron, depolarizing the
membrane and exciting the cell. Then the channel closes
again, and the nicotinic receptor becomes temporarily
unresponsive to any neurotransmitters. It is this state of
desensitization that is artificially prolonged by continual
exposure to nicotine.

• Tobacco dependency, which then develops very quickly,

arises because nicotinic receptors are present on the
neurons of the ventral tegmental area which project their
terminations into the nucleus accumbens. In smokers,
The chemical repeated nicotine stimulation thus increases the amount of
formula for nicotine dopamine released in the nucleus accumbens.
is C10H14N2
29
Cannabis • Cannabinoid receptors are present almost everywhere
in the brain, and an endogenous molecule that binds to
them naturally has been identified: anandamide. We
are thus dealing with the same kind of mechanism as in
the case of opiates that bind directly to the receptors for
endorphins, the body’s natural morphine.

• Anandamide is involved in regulating mood, memory,

appetite, pain, cognition, and emotions. When cannabis
is introduced into the body, its active ingredient, Delta-
9-tetrahydrocannabinol (THC), can therefore interfere
with all of these functions.

• THC begins this process by binding to the CB1 receptors

for anandamide. These receptors then modify the
activity of several intracellular enzymes, including cAMP,
whose activity they reduce. Less cAMP means less
protein kinase A. The reduced activity of this enzyme
affects the potassium and calcium channels so as to
reduce the amount of neurotransmitters released. The
general excitability of the brain’s neural networks is thus
reduced as well.

• However, in the reward circuit, just as in the case of

other drugs, more dopamine is released.

30
 K2 (Synthetic THC’s)
• K2 products are synthetic
cannabinoid-laced, marijuana-like
drugs of abuse, use of which is often
associated with clinical symptoms
atypical of marijuana use, including
hypertension, agitation,
hallucinations, psychosis, seizures and
panic attacks. JWH-018, a prevalent
K2 synthetic cannabinoid, is
structurally distinct from Δ9-THC, the
main psychoactive ingredient in
marijuana. Since even subtle
structural differences can lead to
differential metabolism, formation of
novel, biologically active metabolites
may be responsible for the distinct
effects associated with K2 use.

31
 Ecstasy
• Ecstasy (MDMA) is a synthetic drug. It acts simultaneously as a stimulant and a hallucinogen
because of its molecular structure, which is similar to that of both amphetamines and LSD. Like
amphetamines and cocaine, ecstasy blocks the reuptake pumps for certain neurotransmitters,
thus increasing their levels in the synaptic gap and their effect on the post-synaptic neurons’
receptors.

• While ecstasy also potentiates the effects of norepinephrine and dopamine, it is distinguished
from other psychostimulants by its strong affinity for serotonin transporters. The initial effect of
ecstasy is thus an increased release of serotonin by the serotonergic neurons. The individual may
then experience increased energy, euphoria, and the suppression of certain inhibitions in relating
to other people.

• A few hours later, there is a decrease in serotonin levels. This decrease can last much longer than
the initial increase. Once again, an artificial increase in the level of a neurotransmitter exercises
negative feedback on the enzyme that manufactures it. As a result, when intake of the drug
ceases, the excess turns into a shortage.

• Like all psychoactive drugs that produce a sensation of pleasure, ecstasy also increases the release
of dopamine into the reward circuit.

32
 PCP C17H25N Part 1
• PCP affects several major neurotransmitter systems, resulting in many different internal and external
consequences. Primarily, PCP is a sympathomimetic drug, causing a high, maintained level of sympathetic
nervous system activity (the flight or fight response). Sympathetic activation, though, is also the reason
why patients became "unmanageable". The reason for the sympathetic reaction is an increased level of
norepinephrine (NE), caused by the blocking of NE reuptake into the presynaptic neuron. In addition to
activating the sympathetic reaction, increased NE helps stimulate the reward center of the brain. It also
contributes to an irritable mood, heightened general arousal, heightened anxiety, and heightened senses
of panic.

• At the same time the sympathetic system is being activated, the parasympathetic system (responsible for
relaxation) is inhibited by a decrease in acetylcholine (Ach). The blocked parasympathetic reaction allows
high levels of arousal to be maintained without interruption. In addition, decreased Ach levels contribute
to increased muscular rigidity, dilated pupils, disorientation and confusion, and amnesia.

• The dopamine (Da) system is also effected. The reuptake of Da is blocked by PCP, and Da levels rise. High
levels of Da cause the expansive mood, dissociation, hallucination, and psychosis involved in a PCP high.
High levels of Da also are at the root of schizophrenia, hence the similarity of a PCP high to schizophrenic
symptoms. Excess Da also creates a risk for seizures and convulsions. High Da levels also have a negative
effect on coordination and movement, affecting the nigrostriatal pathway for movement (PCP can remain
in the substantia nigra for over three weeks (Palfai & Jankewicz, 1991)). Dopamine is also the foremost
neurotransmitter involved in the reward center of the brain through the mesolimbic pathway.
Interestingly, monkeys will seek PCP reinforcement just as much as they will seek reinforcement from
cocaine or amphetamines (Ray & Ksir, 1999). Other hallucinogens will not support animal self-
administration like PCP will. Hence, PCP generates psychological dependence, and uniquely so.

33
 PCP C17H25N Part 2
• Levels of serotonin also rise under the effects of PCP, though it the exact cause for this is undetermined (it
does not seem that the reuptake is blocked) Due to increased serotonin levels, PCP highs do not involve
any sleep. Increased serotonin also leads to increased confidence, expansive mood, and delusions involved
with the schizophrenic-like symptoms observed in the PCP high. High levels of serotonin are believed to be
partially involved in schizophrenia (American Family Physician, 1985).

• New discoveries show that the receptors for the neurotransmitter glutamate are the primary sites of
action for PCP. There appears to be an endogenous PCP-like substance that PCP, when administered,
throws out of balance. The receptor site at which glutamate and PCP are involved is the NMDA (N-methyl-
D-aspartate) receptor. PCP acts as an NMDA antagonist, lowering the levels of glutamate in the brain.
Lower levels of glutamate add to, and are possibly the most responsible for, the schizophrenic like
symptoms of a PCP high.

• The level of GABA, an "inhibitory" neurotransmitter, is raised through its reuptake being blocked by the
effects of PCP. Increased levels of GABA are responsible for the inhibition of pain associated with the PCP
high. GABA works on the same receptor complex as alcohol and benzodiazepines, and therefore, is
responsible for PCP's alcohol-like effects. This is the same reason, though, that there is a deadly synergistic
effect between PCP, alcohol, and benzodiazepines. This synergy is the leading cause of PCP overdose.

• Finally, the levels of endorphins are also raised by PCP. Endorphins are the body's natural opiates, creating
pleasure. Endorphins also work to mask pain. The absence of pain in a PCP high is one of the most
important factors in PCP's risk for behavioral toxicity.

34
Benzodiazepine
• Benzodiazepines, such as diazepam (Valium) and
clonazepam (Rivotril) are anxiolytics that can also have
hypnotic or amnesia-inducing effects. Like alcohol, these
drugs increase the efficiency of synaptic transmission of
the neurotransmitter GABA by acting on its receptors.

• A GABA receptor is actually a macromolecular complex

that, in addition to containing sites for binding GABA,
also contains sites for binding other molecules such as
benzodiazepines that modulate GABA’s activity.

• When benzodiazepines bind to a specific site on a GABA

receptor, they do not stimulate it directly. Instead, they
make it more efficient by increasing the frequency with
which the chlorine channel opens when GABA binds to
its own site on this receptor. The resulting increase in
the concentration of Cl- ions in the post-synaptic neuron
immediately hyperpolarizes this neuron, thus making it
less excitable.

35
 Gambling Addiction
• Serotonin in the cerebral spinal fluid of problem gamblers is a little deficient from that of
people who don't have a gambling addiction. The SSRIs [selective serotonin reuptake
inhibitors] are medications that affect serotonin, which are most popularly the
antidepressants: Prozac, Paxil. These have shown benefit in gambling addiction. So serotonin
may have something to do with gambling addiction.
• Neurotransmitters don’t act alone, they act in concert with each other. Dopamine is
associated with rewarding experiences. When researchers looked again at cerebral spinal fluid
dopamine seemed to be a little deficient compared to people who don't have a gambling
addiction.
• Most interesting is the case of Parkinson's disease. Parkinson's represents depleted
dopamine, so when these patients take medications that increase dopamine, many of them
developed a gambling addiction, even people who have never gambled before. An intriguing
concept. Why is this?
• Bupropion is a medication with a dopamine effect—it's also called Wellbutrin and Zyban. It's
used to treat smoking problems. It has also been shown in some early studies to be effective
against gambling addiction.
• And then last are endorphins, the opiate system of the brain, which gets revved up and tells
us something's pleasurable. We've found out that when you look at different parts of the
opiate system, metabolites in the cerebral spinal fluid, again, it's a little out of whack in
people who have a gambling addiction. And we have used opiate antagonists, the most widely
known being Naltrexone, which is a medication to treat alcoholism and the urges of
alcoholism, and we've used that in gambling addiction as well. Some people say that when
they are on the medicine they gamble and it isn't any fun any more. They don't get that rush.

36
 Addictions of Impulse Control?
• In some people with Impulse Control issues the ventral medial prefrontal
cortex, which is the front part of the lower part of the brain, does not
seem to be as activated, and this is the part of the brain that would say,
"Don't do it. Not a good idea." It seems to be less activated in people who
have a gambling addiction compared to people who don't have a gambling
addiction.

• People who have manic depression, which is an illness partly defined by its
impulsivity, tend to have the same finding on fMRI brain scans. That's not
to say that they're the same illness, but perhaps the same part of the
brain is involved when someone cannot control impulses. You could look
at this in terms of sexual addictions and other disorders defined by lack of
ability to put off rewards, control impulses.

• Of course gambling, eating and sex all activate the reward system as well.
They feel good so we want to do them. Does this mean the reward system
is altered in these people as well?

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 How To Treat the Re-Wired Brain
Use P.A.W.S. as a framework to explain to your client how to repair the
changes they have made to their brain.

Abstain!
Decrease Stress.
Teach Coping Skills.
Let them talk, talk, talk.
Take medications as prescribed .
Convince them of the value of Learning!
Reframe their experiences as healthy brain growth.
Use P.A.W.S. as one of your tools to explain things.
Remind them this is all temporary.
Meditation. Diet. Exercise. Sun.
Teach clients how to have fun.
Model ways to Laugh.

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