Substance-

Related Disorders
 SUBSTANSE ABUSE

Use of any drug, usually by

self-administration, in a manner
that deviates from approved
social or medical patterns.
 ADDICTION
 An addiction is a complex brain disease
causing physical and mental dependence on
drugs, harmful chronic symptoms both
physical and mental, and making it hard for
the addict to stop.
 Prolonged use of a drug
causes the brain to change it’s structure and
communication method causing the addiction
and effects.
 Though drug addictions can be
treated with long grueling rehab sessions,
relapses and chronic diseases will remain.
 Withdrawal
 A substance-specific syndrome that occurs after
stopping or reducing the amount of the drug or substance
that has been used regularly over a prolonged period of time.

 The syndrome is characterized by physiological signs and

symptoms in addition to psychological changes such as
disturbances in thinking, feeling, and behavior. Also called
abstinence syndrome or discontinuation syndrome.
 Tolerance
Phenomenon in which, after repeated
administration, a given dose of drug produces a decreased
effect or increasingly larger doses must be administered to
obtain the effect observed with the original dose.
 Cross-tolerance

Refers to the ability of one drug to be

substituted for another, each usually producing the same
physiological and psychological effect (e.g., diazepam and
barbiturates). Also known as cross-dependence.
 Neuroadaptation
Neurochemical or neurophysiological changes
in the body that result from the repeated
administration of a drug. Neuroadaptation
accounts for the phenomenon of tolerance.
Your Brain on Drugs
Addiction is Like Other Diseases…
 It is preventable
 It is treatable
 It changes biology
 If untreated, it can last a lifetime
Decreased Brain Metabolism
in Drug Abuser

Healthy Brain Diseased Brain/

Cocaine Abuser
 Why Do People Take Drugs in The
First Place?

To Feel Good To Feel Better

To have novel: To lessen:
feelings anxiety
sensations worries
experiences fears
AND depression
to share them hopelessness
 Why Do People
Abuse Drugs?

Drugs of Abuse
Engage Motivation and
Pleasure Pathways
of the Brain
 Movement

Motivation

Dopamine

Addiction Reward & well-being

EFFECTS OF DRUGS OF ABUSE ON
DOPAMINE PATHWAYS
Dopamine-Very important Neurotransmitter
 Certainly Dopamine is released
 Dopamine is commonly (particularly in areas such as
associated with the 'pleasure the nucleus accumbens and
system' of the brain, providing striatum) by naturally
feelings of enjoyment and rewarding experiences such as
reinforcement to motivate us to food, sex, abuse of drugs and
do, or continue doing, certain neutral stimuli that become
activities. associated with them.

 This theory is often discussed in

terms of drugs (such as
Cocaine) which seem to directly
produce dopamine release in
these areas, and in relation to
neurobiological theories of
addiction, which argue that
these dopamine pathways are
pathologically altered in
addicted persons.
But Dopamine is only Part of the Story

• Scientific research has shown that other

neurotransmitter systems are also affected:
I. Serotonin
II.GABA
III.Glutamate
 Science Has Generated Much
Evidence Showing That…

Prolonged Drug Use Changes

the Brain In Fundamental
and Long-Lasting Ways
Functionally…
Dopamine D2 Receptors are Decreased by Addiction

Cocaine

DA D2 Receptor Availability
Meth

Alcohol

Heroin
Control Addicted
 Vulnerability

Why do some people

become addicted to drugs
while others do not?
 Individual Differences in Response to
Drugs: DA Receptors influence drug liking
High DA high
receptor

Low DA
receptor

low
As a group, subjects with low receptor levels found MP pleasant while those
with high levels found MP unpleasant
Adapted from Volkow et al., Am. J. Psychiatry, 1999.
Genetics is a Big Contributor to the
Risk of Addiction…

And…
The Nature of this Contribution
Is Extremely Complex
COMORBIDITY
 Why do Mental Illnesses and
Substance Abuse Co-occur?
• Self-medication
– substance abuse begins as a
means to alleviate symptoms of
mental illness
• Causal effects
– Substance abuse may increase
vulnerability to mental illness
• Common or correlated causes
– the risk factors that give rise to
mental illness and substance
abuse may be related or overlap
 What Environmental
Factors Contribute to Addiction?

• Stress
• Early physical or sexual abuse
• Witnessing violence
• Peers who use drugs
• Drug availability
 Substance Abuse&Dependence
8 Classes of Pharmacological Agents

Alcohol  Hallucinogens
Amphetamines  Nicotine
Caffeine  Opioids
Cannabis  Phencyclidine (PCP)
Cocaine  Sedatives
 STIMULANTS
• Stimulants are central nervous system
activators that include caffeine, nicotine,
amphetamines and cocaine.
• Caffeine is found in coffee (125 mg/cup),
tea (65 mg/cup), cola (40 mg/cup),
nonprescription stimulants, and over-the-
counter diet agents.
 STIMULANTS cont’

• Nicotine is a toxic substance present in

tobacco.
• Cigarette smoking decreases life expectancy
more than the use of any other substance.
 STIMULANTS cont’
Amphetamines are used clinically and also are drugs of
abuse.
1.They are medically indicated in the management of
attention deficit/hyperactivity disorder (ADHD) and
narcolepsy. They are sometimes used to treat depression in
the elderly and terminally ill, and depression and obesity in
patients who do not respond to other treatments.

2. The most common clinically used amphetamines are

dextroamphetamine (Dexedrine),methamphetamine
(Desoxyn), and a related compound, methylphenidate
(Ritalin).
3. “Speed,” “ice” (methamphetamine), and “ecstasy”
(methylenedioxymethamphetamine[MDMA]) are street
names for amphetamine compounds.
 STIMULANTS cont’
• Cocaine
1. “Crack” and “freebase” are cheap, smokable
forms of cocaine; in expensive, pure form, cocaine
is snorted.
2. Hyperactivity and growth retardation are seen in
newborns of mothers who used cocaine during
pregnancy.
3. Tactile hallucinations of bugs crawling on the skin
(i.e., formication) are seen with the use of cocaine
(“cocaine bugs”).
 Effects of Use and Withdrawal of Stimulant Agents
Substances Effects of Use Effects of
Withdrawal
Psychological Lethargy
Caffeine, Nicotine Mild depression of
Increased alertness and
mood
attention span
Mild improvement in
Caffeine, Nicotine mood
Agitation and insomnia
Physical
Decreased appetite Increased appetite
Increased blood
with slight weight
pressure and heart rate
(tachycardia) gain
Increased Fatigue
gastrointestinal activity Headache
 Effects of Use and Withdrawal of Stimulant Agents
Substances Effects of Use Effects of Withdrawal
Psychological Significant depression of
Significant elevation of mood mood
(lasting only 1 h with cocaine) Strong psychological craving
Increased alertness and
(peaking a few days after the
attention span
Aggressiveness, impaired last dose)
judgment Irritability
Psychotic symptoms (e.g.,
Amphetamines, Cocaine paranoid delusions
with amphetamines and
formication with cocaine)
Agitation and insomnia
Physical
Loss of appetite and weight
Pupil dilation
Increased energy
Hunger (particularly with
Tachycardia and other
cardiovascular effects, amphetamines)
which can be life-threatening Pupil constriction
Seizures (particularly with Fatigue
cocaine)
Reddening (erythema) of the
nose due to“snorting” cocaine
Hypersexuality
 Neurotransmitter associations
1. Stimulant drugs work primarily by increasing the
availability of dopamine (DA).
2. Amphetamine use causes the release of DA. Cocaine
primarily blocks the reuptake of DA.
Both the release of DA and the block of DA reuptake result in
increased availability of this neurotransmitter in the synapse.
3. Increased availability of DA in the synapse is apparently
involved in the euphoric effects of stimulants and opioids (the
“reward” system of the brain). As in schizophrenia, increased
DA availability may also result in psychotic symptoms.
 SEDATIVES
1. Sedatives are central nervous system depressants that
include alcohol, barbiturates, and benzodiazepines.
2. Sedative agents work primarily by increasing the
activity of the inhibitory neurotransmitter g-aminobutyric
acid (GABA).
3. Hospitalization of patients for withdrawal from
sedatives is prudent; the withdrawal syndrome may include
seizures, psychotic symptoms such as hallucinations and
delusions and cardiovascular symptoms that are life
threatening.
 Effects of Use and Withdrawal of Sedative Agents

Substances Effects of Use Effects of

Withdrawal
Psychological Mild depression of mood
Alcohol, Increased anxiety
Alcohol,
Benzodiazepines, Benzodiazepines, Insomnia
Psychotic symptoms (e.g.,
Barbiturates Barbiturates
delusions and formication)
Mild elevation of mood Disorientation
Decreased anxiety
Somnolence
Behavioral disinhibition

Physical Tremor
Sedation Seizures
Poor coordination Cardiovascular symptoms
such as tachycardia
Respiratory depression
and hypertension
 Alcohol
Acute associated problems
a.Traffic accidents, homicide, suicide, and rape are
correlated with the use of alcohol.

b. Child physical and sexual abuse, spouse abuse, and elder

abuse are also associated with alcohol use.
 Alcohol cont’
Chronic associated problems
a. Thiamine deficiency resulting in Wernicke syndrome and
ultimately in Korsakoff syndrome is associated with long-term use
of alcohol.
b. Liver dysfunction, gastrointestinal problems (e.g., ulcers), and
reduced life expectancy also are seen in heavy users of alcohol.
c. Fetal alcohol syndrome (including facial abnormalities, reduced
height and weight, and mental retardation) is seen in the offspring of
women who drink during pregnancy.
d. A childhood history of problems such as ADHD and conduct
disorder correlates with alcoholism in the adult.
 Alcohol cont’
Intoxication
a. Legal intoxication is defined as 0.08%–0.15% blood alcohol
concentration, depending on individual country laws.
b. Coma occurs at a blood alcohol concentration of 0.40%–
0.50% in non-alcoholics.
c. Psychotic symptoms (e.g., hallucinations) may be seen in
alcohol intoxication as well as in withdrawal .
 Alcohol cont’
Delirium tremens (“the DTs”)
a. Alcohol withdrawal delirium (also called delirium
tremens or “the DTs”) may occur during the first week of
withdrawal from alcohol (most commonly on the third day
of hospitalization).
It usually occurs in patients who have been drinking
heavily for years.
b. Delirium tremens is life threatening; the mortality rate is
about 20%.
 Barbiturates
1. Barbiturates are used medically as sleeping pills,
sedatives, antianxiety agents (tranquilizers),anticonvulsants,
and anesthetics.
2. Frequently used and abused, barbiturates include
amobarbital, pentobarbital, and secobarbital.
3. Barbiturates cause respiratory depression and have a low
safety margin. As such they are very dangerous in overdose.
 Benzodiazepines
1. Benzodiazepines are used medically as tranquilizers,
sedatives, muscle relaxants, anticonvulsants,and anesthetics,
and to treat alcohol withdrawal (particularly long-acting agents
such as chlordiazepoxide and diazepam .
2. Benzodiazepines have a high safety margin unless taken
with another sedative, such as alcohol.
3. Flumazenil (Mazicon, Romazicon), a benzodiazepine
receptor antagonist, can reverse the effects of benzodiazepines
in cases of overdose.
 OPIOIDS
1. Narcotics or opioid drugs include agents used medically as
analgesics (e.g., morphine) as well as drugs of abuse (e.g.,
heroin).
2. Compared to medically used opioids such as morphine and
methadone, abused opioids such as heroin are more potent,
cross the blood–brain barrier more quickly, have a faster
onset of action, and have more euphoric action.

3. In contrast to barbiturate withdrawal, which may be fatal,

death from withdrawal of opioids is rare unless a serious
physical illness is present.
 Methadone and related agents
1. Methadone and buprenorphine (Temgesic, Suboxone [when
combined with naloxone-opioid blocker]) are synthetic opioids used
to treat heroin addiction ; they can also cause physical dependence
and tolerance.
2. These legal opioids can be substituted for illegal opioids, such as
heroin, to prevent withdrawal symptoms.
3. Advantages of methadone and buprenorphine over heroin:
a. Methadone is dispensed by federal health authorities without
charge to registered addicts.
b. Buprenorphine is an opioid receptor partial agonist-antagonist
(making it unlikely to cause respiratory depression) that can block
both withdrawal symptoms and, when combined with naloxone, the
euphoric action of heroin.
 Methadone and related agents
Buprenorphine can now be prescribed by physicians in private
practice who complete a brief training program.

c. Both agents can be taken orally. The intravenous method of drug

use employed by many heroin addicts may involve sharing
contaminated needles, thus contributing to AIDS and hepatitis B
infection.
d. Both agents have a longer duration of action.

e. Both agents cause less euphoria and drowsiness, allowing people

on maintenance regimens to keep their jobs and avoid the criminal
activity.
 Effects of Use and Withdrawal of Opioid Agents

Psychological Depression
Heroin, Methadone, Other Anxiety
Opioids Insomnia
Elevation of mood
Relaxation
Somnolence
Heroin, Methadone, Other
Opioids
Physical Sweating, muscle aches,
Sedation fever
Analgesia Rhinorrhea (running nose)
Respiratory depression Piloerection (goose bumps)
(overdose may be fatal) Yawning
Constipation Stomach cramps and diarrhea
Pupil constriction (miosis) Pupil dilation (mydriasis)
 HALLUCINOGENS AND RELATED
AGENTS
1. Hallucinogens and related agents include lysergic acid
diethylamide (LSD), phencyclidine (PCP or “angel dust”),
cannabis (tetrahydrocannabinol, marijuana, hashish),
psilocybin (from mushrooms), mescaline (from cactus), and
ketamine (“Special K”).
2. Hallucinogens promote altered states of consciousness
which are usually pleasurable but can also be frightening
(“bad trips”).
3. Increased availability of serotonin is associated with the
effects of these agents (e.g., LSD).
 Effects of Use and Withdrawal of Hallucinogens and Related Agents
Substances Effects of Use Effects of Withdrawal
Cannabis (marijuana, Psychological Few, if any, psychological
hashish), Altered perceptual states withdrawal symptoms
Lysergic acid diethylamide (auditory and visual
(LSD, hallucinations,
Phencyclidine (PCP or alterations of body image,
“angel dust,” distortions of time and space)
Psilocybin, Mescaline Elevation of mood
Impairment of memory (may
be long term)
Reduced attention span
“Bad trips” (frightening
perceptual states)
“Flashbacks” (a re-experience
of the sensations associated
with use in the absence of the
drug even months after the
last dose)
 Effects of Use and Withdrawal of Hallucinogens and Related Agents

Substances Effects of Use Effects of Withdrawal

Cannabis (marijuana, Physical Few, if any, physical
hashish), Impairment of complex withdrawal symptoms
Lysergic acid diethylamide motor activity
(LSD, Cardiovascular symptoms
Phencyclidine (PCP or Sweating
“angel dust,” Tremor
Psilocybin, Mescaline Nystagmus (PCP)
 Marijuana
1. Tetrahydrocannabinol (THC) is the primary active
compound found in marijuana.

2. In low doses, marijuana increases appetite and relaxation, and

causes conjunctival reddening.

3. Chronic users experience lung problems associated with

smoking and a decrease in motivation (“the amotivational
syndrome”) characterized by lack of desire to work, and
increased apathy.
 LSD and PCP
1. LSD is ingested and PCP is smoked in a marijuana or other
cigarette.
2. While LSD and PCP both cause altered perception, in contrast
to LSD, episodes of violent behavior occur with PCP use.
3. Emergency department findings for PCP include hyperthermia
and nystagmus (vertical or horizontal abnormal eye movements).
4. PCP binds with N-methyl-D-aspartate (NMDA) receptors of
glutamate-gated ion channels.
5. Consumption of more than 20 mg of PCP may cause seizures,
coma, and death.
Management (in Order of Utility, Highest to Lowest) of Abuse of Sedatives,
Opioids, Stimulants, and Hallucinogens and Related Agents
Category Immediate
Management/Detoxification
Minor Stimulants: Eliminate or taper from the
Caffeine, Nicotine diet
Analgesics to control
headache due to withdrawal
Stimulants: Amphetamines, Benzodiazepines to decrease
Cocaine agitation
Antipsychotics to treat
psychotic symptoms
Medical and psychological
support
Extended
Management/Maintenance
Peer support group (e. g.,
“Smokenders”)
Antidepressants
(particularly bupropion
[Zyban]) to prevent smoking
Support from family
members or nonsmoking
physician
Hypnosis to prevent smoking
Nicotine-containing gum,
patch, or nasal spray
Education for initiation and
maintenance of abstinence
Management (in Order of Utility, Highest to Lowest) of Abuse of Sedatives,
Opioids, Stimulants, and Hallucinogens and Related Agents cont’
Category Immediate
Management/Detoxification
Hospitalization
Flumazenil (Mazicon) to
reverse the effects
of benzodiazepines
Substitution of long-acting
Sedatives: Alcohol, barbiturate
Benzodiazepines, (e.g.,phenobarbital) or
Barbiturates benzodiazepine
(e.g., chlordiazepoxide
[Librium] in decreasing
doses); IV diazepam
(Valium), lorazepam
(Ativan), or phenobarbital if
seizures occur
Specifically for alcohol:
Thiamine (vitamin
B1) and restoration of
nutritional state
Extended
Management/Maintenance
Education for initiation and
maintenance of abstinence
Specifically for alcohol:
Alcoholics Anonymous (AA)
or other peer support group
, disulfiram (Antabuse),
psychotherapy,
behavior therapy, naloxone
(Narcan), naltrexone
(ReVia), acamprosate
(Campral), topiramate
(Topamax)
Management (in Order of Utility, Highest to Lowest) of Abuse of Sedatives,
Opioids, Stimulants, and Hallucinogens and Related Agents cont’
Category Immediate
Management/Detoxification
Hospitalization and naloxone
(Narcan) for overdose
Clonidine(alpha-adrenergic
Opioids: Heroin, agonist)to stabilize the
Methadone, Opioids autonomic nervous
used medically system during withdrawal
Substitution of long-acting
opioid (e.g., methadone) in
decreasing doses to decrease
withdrawal symptoms
Extended
Management/Maintenance
Methadone or
buprenorphine (Temgesic)
(partial agonist of mu-opioid
receptor)- maintenance
program
Naltrexone(opioid
antagonist) or
buprenorphine plus
naloxone (Suboxone)-
(competitive antagonist of
opioid receptors) used
prophylactically to block the
effects of abused opioids
Narcotics Anonymous (NA)
or other peer support
program
Management (in Order of Utility, Highest to Lowest) of Abuse of Sedatives,
Opioids, Stimulants, and Hallucinogens and Related Agents cont’
Category Immediate Extended
Management/Detoxification Management/Maintenance
Calming or “talking down” Education for initiation and
the patient maintenance of abstinence
Benzodiazepines to decrease (self-restraint )
Hallucinogens and agitation
Related Agents: Antipsychotics to treat
Marijuana, Hashish, psychotic symptoms
LSD, PCP, Psilocybin,
Mescaline
THANK YOU…