Substance Abuse and

Dependence
Manu Karthik
Substance Abuse and Dependence

Important Definitions
• Tolerance
• Dependence
• Addiction
• Compulsive substance taking behavior
• Withdrawal
• Craving
• Substance Abuse
• Gateway Substances
 Tolerance

• 1. Previous exposure to a drug or to a similar one

• 2. Quantitative response characterized by either:
a. A usual dose no longer evokes its desired
effect.
b. A larger dose than the previous one must
be used to produce the same effect.
 Dependence:
• This is an adaptive psychological,
physiological and
biochemical state caused by the repeated
exposure to a drug.
• Continued use of the drug becomes
necessary for the well-being of the
organism.
• Sometimes the word "dependence" is
used as a synonym of addiction.
 Withdrawal

* Withdrawal syndrome: psychological

or physiological symptoms may
occur.
* A closely related substance is taken
to relieve or avoid withdrawal
symptoms.
Compulsive substance taking behavior:
* The substance is taken in larger amounts or
over a longer period than intended.
* Unsuccessful efforts to cut down or control
substance use.
* A great deal of time is spent in
obtaining, using and recovery from
substance effects.
* Social, occupational or recreational activities
are given up or reduced.
* Continuing despite physical or
psychological problems.
 Craving:

• it is a strong subjective drive to use the

substance. It is likely to be experienced by
most (if not all) individuals with substance
dependence.
 Substance Abuse:

• It is repetitive use of substances resulting in

recurrent and significant adverse
consequences, e.g.
• * Failure to fulfill major role obligations at
work, school or home.
• * Recurrent substance use in situations in
which it is physically hazardous (e.g. driving an
automobile).
• * Recurrent substance related legal problems.
 Gateway Substances
• These are addictive substances their frequent
use has been directly related to subsequent
abuse and dependence of other more dangerous
substances, such as Heroin and Cocaine.
• They include:
1. Tobacco
2. Cannabinoids (Hashish, Marijuana,
Bango)

• They are the best predictor of other drug use

during adolescence.
 Addiction:

• The diagnosis of addiction implies the

use of a drug with the following clinical
criteria:

* The use of the drug is not upon medical

indication
* Tolerance
* Withdrawal
 Types of Drugs of Abuse and Dependence

• Most of substances known to be amenable for

abuse and dependence (Addiction) can be
grouped into the following classes:

1. Alcohol.
2. Sedatives, hypnotics or anxiolytics.
3. Cannabinoids [e.g. Bango - Hashish - Marijuana].
4. Opioids [e.g. Heroin, Opium, Morphine, Codeine
and Codeine-containing cough sedatives].
5. Cocaine.
Types of Drugs of Abuse and Dependence

6. Amphetamines and other stimulants.

7. Tobacco.
8. Caffeine.
9. Hallucinogens [e.g. LSD, Anticholinergics, Mescaline ...]
10. Phencyclidine [e.g. Ketamine]
11. Volatile solvents.

• N.B. Poly-substance abuse and dependence is

common.
Substances may be mixed with others.
 (1) Nicotine

• Nicotine, in mild to moderate doses, is a

central nervous system stimulant.
• It enhances central cholinergic receptors
(activated by acetyl choline).
• The dependence-producing effects of
nicotine appear to be modulated by
dopamine (nicotinic-cholinergic receptors
lie on dopamine neurons, nicotine
increases dopamine).
 (1) Nicotine

• Nicotine also increases nor epinephrine,

epinephrine, and serotonin and these
increases may modulate some of the
reinforcing effects from cigarettes.
• In large toxic doses, it exerts an inhibitory
effect on peripheral cholinergic receptors.
 Nicotine Withdrawal (Nicotine
Abstinence Syndrome)
* Subjective symptoms:
o Dysphoria or depressed mood.
o Irritability.
o Anxiety.
o Decreased concentration.
o Restlessness, impatience, confusion then rapidly appears.
o Desire for nicotine.
* Objective symptoms (signs):
o Decreased heart rate.
o Insomnia.
o Increased reaction time (reaction is slowed down).
 Nicotine Toxicity: In low doses:

• signs and symptoms of nicotine toxicity include:

* Pallor
* Weakness
* Salivation
* Abdominal pains & diarrhea
* Cold sweats
* Headache
* Nausea & vomit
* Dizziness
* Tachycardia
* Increased blood pressure.
 Nicotine Toxicity: At higher doses:

• * Seizures
• * Hypotension
• * Respiratory arrest can develop
 Hazards of smoking
• Death is the primary adverse effect of cigarette
smoking.
• Causes of death include:
* Chronic bronchitis.
* Emphysema.
* Bronchogenic cancer.
* Cerebrovascular disease.
* Cardiovascular disease.
 Hazards of smoking
• In pregnant women, nicotine crosses the
placenta freely and is in the amniotic fluid and
umbilical cord blood of neonates.
• Sustained exposure of the fetus causes:
*Slow growth in utero and lower than average
birth weights.
*Increased incidences of newborns with
persistent pulmonary hypertension.
Cannabinoids
 Cannabinoids
• The psychoactivecompound in
cannabinoids is delta-9-
tetrahydrocannabinol (THC).
• Cannabinoids are usually smoked, but may be
taken orally and are sometimes mixed with tea or
food.
• Common forms of Cannabinoids include
Hashish. Marijuana, and Bango.
 Cannabinoids
• THC is lipid soluble and rapidly absorbed after
inhalation.
• It is redistributed from blood into other
tissues.
• It is then released from its adipose tissue
stores into the blood stream. This explains the
prolonged effects of THC after acute intake.
 Effect of cannabinoids
• Cannabinoids exert many of their actions by
influencing several neurotransmitter systems.

• These include acetylcholine, dopamine, gamma-

amino-butyric acid (GABA), histamine, serotonin,
norepinephrine, opioid peptides, and
prostaglandins.
 cannabis intoxication
• in the form of impaired motor
coordination, euphoria, anxiety, sensation of
slowed time, impaired judgment and social
withdrawal.
 Cannabis withdrawal
• have been described in association with the
use of high doses in the form of:
* Irritable or anxious mood
* Tremor
* Perspiration
* Nausea
* Sleep disturbances
 Hazards of cannabinoids
• Chronic cannabinoids use is associated with poor social
and vocational functioning due to the development of
Amotivational Syndrome.

• A number of psychiatric disorders such as bipolar mood

disorder, anxiety, depersonalization, and dissociative
episodes are reported as a consequence of cannabinoid
abuse.

• Affective disorders and paranoid symptoms may be

exacerbated after cannabinoid abuse
 Opioids

• Opioids are highly addicting.

• Forms of Opioids include opium, morphine,
heroin, codeine and some analgesic opiate
derivatives.
 Acute effects of Opioids
• 1. Central nervous system effects: Opioids are
central nervous system suppressants
(endogenous opioid receptors).
Their effects include:
* Analgesia
* Mood changes
* "Mental clouding",
* Sedation
* Central nausea and vomiting
• 2. Gastrointestinal effects:
• 3. Pupillary constriction
• 4. Respiratory depression
 Over dose of opiates
Severe intoxication is diagnosed by the triad of:
• 1- Coma
• 2- Pinpoint pupils
• 3- Respiratory depression.

• It is a medical emergency that requires

immediate attention.
 Opioids Withdrawal Syndrome

• Time of onset differs according to the half-life of

the drug used: e.g. 4-6 hours after the last use of
heroin but up to 36 hours after the last use of
methadone.
• Severity varies with the dose and duration of
drug use.
• Early findings may include
tachycardia, hypertension, pupillary
dilatation, and diffuse musculo-skeletal pains
 Opioids Withdrawal Syndrome

• Central nervous system symptoms include restlessness,

irritability and insomnia
• Gastrointestinal symptoms are
• anorexia, vomiting, abdominal colics, and diarrhea
• Cutaneous and mucocutaneous symptoms include
lacrimation, rhinorrhea and piloerection , also know
• Opioids Craving
n as "gooseflesh"
 Alcohol

• 90% of USA population are using

alcohol, whereas only 12% or 18% have abuse
or dependence problem, respectively.
Effect of alcohol on
the brain
• * Alcohol is a CNS suppressant.
• It exerts this suppressant effect in a
descending manner, where higher cortical
centers are inhibited first, resulting in
euphoria and then disinhibition.
• In larger doses, lower vital centers are
inhibited, leading to hypotension and
respiratory depression.
Effect of alcohol on neurotransmitters

• * It is found that ion channel activities

associated with acetyl choline, serotonin
and GABA receptors are enhanced by
alcohol.
• Ion channel activities associated with
glutamate receptors are inhibited.
• * Death is due to central respiratory
depression or inhalation of vomitus
 Alcohol-Related Disorders

* Alcohol abuse and dependence.

* Alcohol withdrawal
* Alcohol induced dementia.
* Alcohol induced amnestic disorders.
*Alcohol induced psychotic disorders
* Alcohol related mood disorder.
 Alcohol withdrawal
• The classic signs of alcohol withdrawal are due
to sympathetic over activity and tendency to
develop epileptic convulsions.
• Symptoms include
tremulousness, sweating, restlessness and even
excitement.
• They may include psychotic symptoms (such as
delusions and hallucinations).
• Seizures and symptoms of delirium tremens may
eventually develop.
• Treatment is Benzodiazepines.
 Fetal alcohol syndrome

• It occurs when fetuses are exposed in utero to

alcohol by their mothers' drinking alcohol.
• This syndrome is the leading cause of mental
retardation in the United States.
• Women with alcohol related disorders have a
35 percent risk of having a child with deficits.
 Hallucinogens
• Agents that induce a state of marked perceptual
alterations.
• They are CNS stimulants.
• Examples are:
• lysergic acid diethylamide (LSD) and
amphetamines.
• They have both an antagonist and an agonist
effect on serotonergic systems.
 lysergic acid diethylamide (LSD)
• LSD is synthetic derivative of ergot fungus.
• It is extremely potent and is effective in
extremely low doses.
• It is ingested orally or through other mucous
membranes (sublingual, orally or corneal).
• Tolerance quickly develops, leading to
ingestion of larger doses or increased
frequency of use.
• It is not highly addicting,
 Hazards of hallucinogen use
1.A drug precipitated psychosis may
continue following the cessation of
hallucinogen use.
2.Flashbacks are brief spontaneous
recurrences of perceptual changes, such
as experienced while using
hallucinogens.
They have been reported days, months or
years after drug use.
 Cocaine
• Cocaine is one of the most addictive of
commonly abused substances and one of the
most dangerous.
• Cocaine, variously referred to as
crack, snow, cock, girl and lady,
• It is a white powder that is inhaled, smoked or
injected.
 Effect of cocaine on CNS
• Cocaine is a psychoactive stimulant.
• Its primary pharmacologic action is related to its
competitive blockade of dopamine reuptake by
dopamine transporters.
• This leads to marked elevation of dopamine in
synaptic clefts.
• Cocaine has powerful addictive qualities.
• psychological dependence on cocaine can
develop after a single use.
Withdrawal symptoms of cocaine
• Withdrawal symptoms are mild compared to
those of opioids.
• They include depressed
mood, dysphoria, fatigue, hypersomnolence.
• Suicidal ideations may occur.
• Symptoms persist for a few days up to one
week.
• Craving is very strong.
 Over dose of cocaine
• Intoxication by high doses is associated with
delirium, seizures, cerebrovascular diseases
and myocardial infarction which may lead to
death.
 Psychiatric disorders with cocaine abuse

They include:
• psychotic disorders,
• mood disorders,
• anxiety disorders,
• sexual dysfunction and
• sleep disorders.
 Benzodiazepines (BDZ)

• Benzodiazepines are psychoactive depressant

drugs that are used to control anxiety and
epilepsy and in induction of anesthesia.
• Tolerance to benzodiazepines is common.
• Benzodiazepines are widely used in
combination with heroin, cocaine, alcohol and
stimulants.
 Intoxication of BDZ

• includes somnolence and behavioral

disinhibition.
• In higher doses, they cause hypotension and
central respiratory depression, particularly if
taken with another depressant drug
(e.g., alcohol).
 Withdrawal of BDZ
• symptoms include rebound anxiety, restlessness,
agitation, hypertension, an d tachycardia.
• Epileptic seizure is a serious emergency and may
be fatal.
• Hospitalization and gradual withdrawal of
benzodiazepines are the main lines of treatment
of benzodiazepine addiction.
• Prevention of seizures by antiepileptics may be
needed.
 Management of Substance
Abuse/Dependence

• Two major goals:

• the first is abstinence from the
substance;
• the second is physical, psychiatric, and
psychosocial well-being of the patient.
 Management of Substance
Abuse/Dependence
• * Inpatient or outpatient settings.
• * Detoxification,
• * Rehabilitation.
• * Throughout
treatment, individual, family, and group
therapies (alcoholic & narcotic anonymous)
can be effective.
• * Any underling psychiatric disorder should be
diagnosed and appropriately treated.
Rehabilitation centre
 Pharmacological Treatment of
Substance Abuse
• * Because substance abuse/dependence is
in part a neuropharmacological
phenomenon, there is at present an
aggressive search for agents that may:
o decrease the reinforcing properties of
substances (block the drug euphoric effect)
o decrease craving associated with substances
o function as replacements for the drug of
abuse
 Pharmacological Treatment of
Substance Abuse
• * Naltrexone (an opiate receptor blocking agent)
decreases alcohol consumption and relapse in
alcoholic patients, also in opiate abuse.
• * Nicotine replacement using nicotine
gum, patch, spray and inhalation have been used
with successful results in nicotine dependence.
• * Methadone - an opiate receptor agonist -
proved to be highly effective in abstinence from
opiate use.
• Thank You