Substance Use

Disorders
Dr. Mohammed Ridha
M. B. Ch. B., F.I.C.M.S. (Psych.)
The presentation of alcohol and drug misuse is not limited to any
particular psychiatric or indeed medical specialty. Alcohol and
drug use may play an important part in all aspects of psychiatric
practice, and is relevant, e.g., to the assessment of a patient with
acute confusion on a medical ward, a suicidal patient in the ER,
an elderly patient whose self-care has deteriorated, a troubled
adolescent, or a disturbed child who may be inhaling volatile
substances.
DIAGNOSIS AND DSM-5 CRITERIA
Substance use disorder characterized by a problematic pattern of substance use →
impairment or distress manifested by at least two of the following within a 12-
month period (note that these criteria are the same regardless of the substance):

1. Using substance more than originally intended

2. Persistent desire or unsuccessful efforts to cut down on use
3. Significant time spent in obtaining, using, or recovering from substance
4. Craving to use substance
5. Failure to fulfill obligations at work, school, or home
6. Continued use despite social or interpersonal problems due to the substance use
7. ↓ social, occupational, or recreational activities because of substance use
8. Use in dangerous situations (e.g., driving a car)
9. Continued use despite subsequent physical or psychological problem
10. Tolerance
11. Withdrawal
Categories of drugs of abuse
• Opiates: e.g. heroin, dihydrocodeine, methadone, codeine,
buprenorphine, pethidine.
• Depressants: e.g. BDZs, barbiturates, alcohol, GHB.
• Stimulants: e.g. amfetamines, cocaine, MDMA.
• Hallucinogens: e.g. LSD, PCP, mushrooms, ketamine.
• Others: e.g. cannabis, volatile substances, anabolic steroids
EPIDEMIOLOGY
■ Over 2% of the world population has an alcohol or illicit drug
addiction
■ More common in men than women.
■ Alcohol and nicotine are the most commonly used substances.
Pathophysiology/Aetiology
PSYCHIATRIC SYMPTOMS
■ Mood symptoms are common among persons with substance use
disorders.
■ Psychotic symptoms may occur with some substances.
■ Personality disorders and psychiatric comorbidities (e.g., major
depression, anxiety disorders) are common among persons with
substance use disorders.
■ It is often challenging to decide whether psychiatric symptoms are
primary or substance-induced.
■ Withdrawal: The development of a substance-specific syndrome due
to the cessation (or reduction) of substance use that has been heavy
and prolonged.
■ Tolerance: The need for ↑ amounts of the substance to achieve the
desired effect or diminished effect if using the same amount of the
substance.
History taking
make rapport and ask with empathy, active listening and a non-
judgemental attitude.
Enquier about current use (including ‘TRAP’ [Type, Route,
Amount, Pattern] and exploring the signs of dependency, risk
assessment (suicide/ self-harm as well as IV use/needle sharing),
possible triggers or stressful life events, past substance use,
physical, psychological and social complications of drugs abuse
(e.g. future use), and coping strategies.
Investigations
• Bloods including:
(1) HIV screen, Hep B, Hep C and tuberculosis testing → risk of
blood-borne infections is thought to be greater through needle
sharing;
(2) U&Es to check renal function;
(3) LFTs and clotting to check hepatic function;
(4) Drug levels.
• Urinalysis: drug metabolites (e.g. cannabis, opioids) can be
detected in urine.
• ECG for arrhythmias, ECHO if endocarditis suspected
(secondary to needle sharing).
General Management
• A keyworker with a therapeutic alliance is best placed to offer
psychosocial support.
• Hep B immunization must be considered for those at risk.
• Motivational interviewing to help with controlling the substance
misuse and CBT (for co-morbid depression or anxiety) may be offered.
• Contingency management is a technique that focuses on changing
specified behaviours by offering incentives (e.g. financial) for positive
behaviours such as abstinence.
• Supportive help can be in housing, finance and employment. Help
with co-existing alcohol misuse and smoking cessation should be
offered.
• Self-help groups, e.g. Narcotics Anonymous and Cocaine
Anonymous.
• Consider the issue of driving and review the DVLA guidelines.
Alcohol (EtOH)
■ Alcohol activates gamma-aminobutyric acid (GABA), dopamine, and
serotonin receptors in the central nervous system (CNS), and inhibits
glutamate receptor activity and voltage-gated calcium channels. GABA
receptors are inhibitory, and glutamate receptors are excitatory. Thus,
alcohol is a potent CNS depressant.
■ AUDs are among the most prevalent mental disorders globally,
affecting 8.6% of men and 1.7% of women in 2016 (total prevalence
5.1%).
■ Alcohol is metabolized in the following manner:
1. Alcohol → acetaldehyde (enzyme: alcohol dehydrogenase).
2. Acetaldehyde → acetic acid (enzyme: aldehyde dehydrogenase).
There is upregulation of these enzymes in heavy drinkers. Secondary to
a gene variant, Asians often have less aldehyde dehydrogenase,
resulting in flushing and nausea, and likely reducing their risk of alcohol
use disorder.
CAGE questionnaire
A simple and popular questionnaire to screen patients for alcoholism

C – cut
“Have you ever tried to cut down on your drinking?”
A – annoyed
“Have you ever been annoyed by others’ criticizing your drinking?”
G – guilty
“Have you ever felt guilty about your drinking?”
E – eye-opener
“Have you ever had a drink first thing in the morning to steady your
nerves or to get rid of a hangover?”

Two “yes” responses should be investigated further.

INTOXICATION

Clinical Presentation
■ The absorption and elimination rates of alcohol are variable
and depend on many factors, including age, sex, body weight,
chronic nature of use, duration of consumption, food in the
stomach, and the state of nutrition and liver health.
■ In addition to the above factors, the effects of EtOH also
depend on the blood alcohol level (BAL). Serum EtOH level or an
expired air breathalyzer can determine the extent of intoxication.
the effects/BAL may be ↓ if high tolerance has been developed.
Clinical Presentation of Alcohol Intoxication
Treatment
■ Monitor: Airway, breathing, circulation, glucose, electrolytes, acid–base
status.
■ Give thiamine (to prevent or treat Wernicke’s encephalopathy) and
folate.
■ Naloxone may be necessary to reverse effects of co-ingested opioids.
■ A computed tomographic (CT) scan of the head may be necessary to rule
out subdural hematoma or other brain injury.
■ The liver will eventually metabolize alcohol without any other
interventions.
■ Severely intoxicated patient may require mechanical ventilation with
attention to acid–base balance, temperature, and electrolytes while he or
she is recovering.
■ Gastrointestinal evacuation (e.g., gastric lavage, induction of emesis, and
charcoal) is not indicated in the treatment of EtOH overdose unless a
significant amount of EtOH was ingested within the preceding 30–60
minutes.
WITHDRAWAL

Clinical Presentation
■ Signs and symptoms of alcohol withdrawal syndrome include
insomnia, anxiety, hand tremor, irritability, anorexia, nausea, vomiting,
autonomic hyperactivity (diaphoresis, tachycardia, hypertension),
psychomotor agitation, fever, seizures, hallucinations, and delirium.
■ The earliest symptoms of EtOH withdrawal begin between 6 and 24
hours after the patient’s last drink and depend on the duration and
quantity of EtOH consumption.
■ Generalized tonic-clonic seizures usually occur between 12 and 48
hours after cessation of drinking, with a peak around 12–24 hours.
■ About a third of persons with seizures develop delirium tremens
(DTs).
■ Hypomagnesemia may predispose to seizures; thus, it should be
corrected promptly.
■ Seizures are treated with benzodiazepines. Long-term treatment with
anticonvulsants is not recommended for alcohol withdrawal seizures.
Delirium Tremens (DTs)
■ The most serious form of EtOH withdrawal.
■ Usually begins 48–96 hours after the last drink but may occur later.
■ While only 5% of patients who experience EtOH withdrawal develop
DTs, there is a roughly 5% mortality rate (up to 35% if left untreated).
■ Physical illness predisposes to the condition.
■ Age > 30 and prior DTs increase the risk.
■ In addition to delirium, symptoms of DTs may include hallucinations
(most commonly visual), agitation, gross tremor, autonomic instability,
and fluctuating levels of psychomotor activity.
■ It is a medical emergency and should be treated with adequate doses
of benzodiazepines.
Treatment
■ Benzodiazepines (chlordiazepoxide, diazepam, or lorazepam)
should be given in sufficient doses to keep the patient calm and
lightly sedated, then tapered down slowly. Carbamazepine or
valproic acid can be used in mild withdrawal.
■ Antipsychotics (be careful of lowering seizure threshold) and
temporary restraints for severe agitation.
■ Thiamine, folic acid, and a multivitamin to treat nutritional
deficiencies (“banana bag”).
■ Electrolyte and fluid abnormalities must be corrected.
■ Careful attention must be given to the level of consciousness,
and the possibility of trauma should be investigated.
■ Check for signs of hepatic failure.
ALCOHOL USE DISORDER

Medications for Alcohol Use Disorder

➢ Naltrexone :
■Opioid receptor blocker.
■Works by ↓ desire/craving and “high” associated with alcohol.

➢ Acamprosate:
■ Thought to modulate glutamate transmission.

➢ Disulfiram (Antabuse):
■ Blocks the enzyme aldehyde dehydrogenase in the liver and causes
aversive reaction to alcohol (flushing, headache, nausea/vomiting,
palpitations, shortness of breath).
■ Contraindicated in severe cardiac disease, pregnancy, psychosis.
■ Liver function should be monitored.
■ Best used in highly motivated patients, as medication adherence is an
issue.
Long-Term Complications of Alcohol Intake
■ Wernicke’s encephalopathy:
■ Caused by thiamine (vitamin B1) deficiency resulting from poor
nutrition.
■ Acute and can be reversed with thiamine therapy.
■ Features: Ataxia (broad-based), confusion, ocular abnormalities
(nystagmus, gaze palsies).
■ If left untreated, Wernicke’s encephalopathy may progress to
Korsakoff syndrome:
▪ Chronic amnestic syndrome.
▪ Reversible in only about 20% of patients.
▪ Features: Impaired recent memory, anterograde amnesia,
compensatory confabulation (unconsciously making up answers
when memory has failed).
 stimulants
Cocaine

Cocaine blocks the reuptake of dopamine, epinephrine, and

norepinephrine from the synaptic cleft, causing a stimulant
effect. Dopamine plays a role in the behavioral reinforcement
(“reward”) system of the brain.
INTOXICATION
■ General: Euphoria, heightened self-esteem, ↑ or ↓ blood pressure, tachycardia
or bradycardia, nausea, dilated pupils, weight loss, psychomotor agitation
or depression, chills, and sweating.
■ Dangerous: Respiratory depression, seizures, arrhythmias, hyperthermia,
paranoia, and hallucinations (especially tactile). Since cocaine is an indirect
sympathomimetic, intoxication mimics the fight-or-flight response.
■ Deadly: Cocaine’s vasoconstrictive effect may result in myocardial infarction
(MI), intracranial hemorrhage, or stroke.
Management
■ For mild-to-moderate agitation and anxiety: Reassurance of the patient
and benzodiazepines.
■ For severe agitation or psychosis: Antipsychotics (e.g., haloperidol).
■ Symptomatic support (i.e., control hypertension, arrhythmias).
■ Temperature of > 102ºF should be treated aggressively with ice bath, cooling
blanket, and other supportive measures.
COCAINE USE DISORDER
Treatment of cocaine use disorder
■ There is no FDA-approved pharmacotherapy for cocaine dependence.
■ Off-label medications are sometimes used (disulfiram, modafinil, topiramate).
■ Psychological interventions (contingency management, relapse prevention,
NA, etc.) are efficacious and the mainstay of treatment.

WITHDRAWAL
■ Abrupt abstinence is not life threatening.
■ Produces post-intoxication depression (“crash”): Malaise, fatigue,
hypersomnolence, depression, anhedonia, hunger, constricted pupils, vivid dreams,
psychomotor agitation, or retardation. Occasionally, these patients can become
suicidal.
■ With mild-to-moderate cocaine use, withdrawal symptoms resolve within
72 hours; with heavy, chronic use, they may last for 1–2 weeks.
■ Treatment is supportive, but severe psychiatric symptoms may warrant
hospitalization.
Amphetamines
■ Classic amphetamines:
■ Block reuptake and facilitate release of dopamine and norepinephrine
from nerve endings, causing a stimulant effect.
■ Examples: Dextroamphetamine (Dexedrine), methylphenidate (Ritalin),
methamphetamine (Desoxyn, “ice,” “speed,” “crystal meth,” “crank”).
■ Methamphetamines are easily manufactured in home laboratories
using over-the-counter medications (e.g., pseudoephedrine).
■ They are used medically in the treatment of narcolepsy, attention deficit/
hyperactivity disorder (ADHD), and occasionally depressive disorders.
■ Substituted (“designer,” “club drugs”) amphetamines:
■ Release dopamine, norepinephrine, and serotonin from nerve endings.
■ Examples: MDMA (“ecstasy”).
■ These substances are associated with dance clubs and raves.
■ Have both stimulant and hallucinogenic properties.
INTOXICATION
Clinical Presentation
■ Amphetamine intoxication causes symptoms similar to those of
cocaine.
■ Overdose can → hyperthermia, dehydration (especially after a
prolonged
period of dancing in a club), rhabdomyolysis, and renal failure.
■ Complications of their long half-life can cause ongoing
psychosis, even during abstinence.
■ Amphetamine withdrawal can → prolonged depression.
Treatment
Rehydrate, correct electrolyte balance, and treat hyperthermia.
Sedative-Hypnotics
Agents in the sedative-hypnotics category include benzodiazepines, barbiturates, zolpidem,
zaleplon, gamma-hydroxybutyrate (GHB), meprobamate, and others. These medications,
especially benzodiazepines, are highly abused in the United States, as they are more readily
available than other drugs such as cocaine or opioids.

➢ Benzodiazepines (BDZs):
■ Commonly used in the treatment of anxiety disorders.
■ Easily obtained via prescription from physician offices and emergency departments.
■ Potentiate the effects of GABA by modulating the receptor, thereby ↑ the frequency of
chloride channel opening.

➢ Barbiturates:
■ Used in the treatment of epilepsy and as anesthetics.
■ Potentiate the effects of GABA by binding to the receptor and ↑ the duration of chloride
channel opening.
■ At high doses, barbiturates act as direct GABA agonists, and therefore have a lower margin of
safety relative to BDZs.
■ They are synergistic in combination with BDZs (as well as other CNS depressants such as
alcohol); respiratory depression can occur as a complication.
INTOXICATION
Clinical Presentation
■ drowsiness, confusion, hypotension, slurred speech, incoordination, ataxia, mood
lability, impaired judgment, nystagmus, respiratory depression, and coma or death in
overdose.
■ Symptoms are synergistic when combined with EtOH or opioids/ narcotics.
■ Long-term sedative use may → dependence and may cause depressive symptoms.

Treatment
■ Maintain airway, breathing, and circulation. Monitor vital signs.
■ Activated charcoal and gastric lavage to prevent further gastrointestinal
absorption (if drug was ingested in the prior 4–6 hours).
■ For barbiturates only: Alkalinize urine with sodium bicarbonate to promote
renal excretion.
■ For benzodiazepines only: Flumazenil in overdose.
■ Supportive care—improve respiratory status, control hypotension.
WITHDRAWAL
Abrupt abstinence after chronic use can be life threatening. While
physiological dependence is more likely with short-acting agents,
longer-acting agents can also cause dependence and withrawal
symptoms.

Clinical Presentation
Signs and symptoms of withdrawal are the same as these of EtOH
withdrawal. Tonic-clonic seizures may occur and can be life threatening.

Treatment
■ Benzodiazepine taper.
■ Carbamazepine or valproic acid taper not as beneficial.
Opioids
■ Opioid medications and drugs of abuse stimulate mu, kappa, and delta
opiate receptors (normally stimulated by endogenous opiates), and are
involved in analgesia, sedation, and dependence. Examples include heroin,
oxycodone, codeine, dextromethorphan, morphine, methadone, and
meperidine (Demerol).
■ Opioids also have effects on the dopaminergic system, which mediates
their addictive and rewarding properties.
■ Prescription opioids (OxyContin [oxycodone], Vicodin [hydrocodone/
acetaminophen], and Percocet [oxycodone/acetaminophen]), not heroin,
are the most commonly used opioids.
■ Behaviors such as losing medication, “doctor shopping,” and running out
of medication early should alert clinician of possible misuse.
INTOXICATION
Clinical Presentation
■ Opioid intoxication causes drowsiness, nausea/vomiting, constipation,
slurred speech, constricted pupils, seizures, and respiratory depression,
which may progress to coma or death in overdose.
■ Meperidine and monoamine oxidase inhibitors taken in combination may
cause the serotonin syndrome: hyperthermia, confusion, hyper- or
hypotension, and muscular rigidity.

Treatment
■ Ensure adequate airway, breathing, and circulation.
■ In overdose, administration of naloxone (opioid antagonist) will improve
respiratory depression but may cause severe withdrawal in an
opioiddependent patient.
■ Ventilatory support may be required.
WITHDRAWAL
■ While not life threatening, abstinence in the opioid-dependent
individual leads to an unpleasant withdrawal syndrome characterized
by dysphoria, insomnia, lacrimation, rhinorrhea, yawning, weakness,
sweating, piloerection, nausea/vomiting, fever, dilated pupils,
abdominal cramps, arthralgia, myalgia, hypertension, tachycardia, and
craving.

Treatment includes:
■ Moderate symptoms: Symptomatic treatment with clonidine (for
autonomic signs and symptoms of withdrawal), nonsteroidal anti
inflammatory drugs (NSAIDs) for pain, dicyclomine for abdominal
cramps, etc.
■ Severe symptoms: Detox with buprenorphine or methadone.
■ Monitor degree of withdrawal with COWS (Clinical Opioid Withdrawal
Scale), which uses objective measures (i.e., pulse, pupil size, tremor) to
assess withdrawal severity.
Opioid dependence
• Biological therapies include methadone (first-line) or
buprenorphine for detoxification AND maintenance.

• Naltrexone is recommended for those who were formerly

opioid-dependent but have now stopped and are motivated to
continue abstinence.
Hallucinogens
Hallucinogenic drugs of abuse include psilocybin (mushrooms),
mescaline (peyote cactus), and lysergic acid diethylamide (LSD).
Pharmacological effects vary, but LSD is believed to act on the
serotonergic system. Hallucinogensdo not cause physical
dependence or withdrawal, though users can rarely develop
psychological dependence.
 ➢ INTOXICATION
■ Effects include perceptual changes (illusions, hallucinations, body image
distortions, synesthesia), labile affect, dilated pupils, tachycardia,
hypertension, hyperthermia, tremors, incoordination, sweating, and
palpitations.
■ Usually lasts 6–12 hours, but may last for several days.
■ May have a “bad trip” that consists of marked anxiety, panic, and
psychotic symptoms (paranoia, hallucinations).
■ Treatment: Monitor for dangerous behavior and reassure patient. Use
benzodiazepines first-line (can use antipsychotics) if necessary for agitated
psychosis.

➢ WITHDRAWAL
No withdrawal syndrome is produced, but with long-term LSD use, patients
may experience “flashbacks” later in life.
Marijuana
■ Cannabis (“marijuana,” “pot,” “weed,” “grass”) is the most
commonly used illicit substance in the world.
■ The main active component in cannabis is THC
(tetrahydrocannabinol).
■ Cannabinoid receptors in the brain inhibit adenylate cyclase.
■ Marijuana has shown some efficacy in treating nausea and
vomiting in chemotherapy patients, ↑ appetite in AIDS patients,
in chronic pain (from cancer), and ↓ intraocular pressure in
glaucoma.
INTOXICATION
■ Marijuana causes euphoria, anxiety, impaired motor coordination,
perceptual disturbances (sensation of slowed time), mild tachycardia,
anxiety, conjunctival injection (red eyes), dry mouth, and ↑ appetite (“the
munchies”).
■ Cannabis-induced psychotic disorders with paranoia, hallucinations, and/
or delusions may occur. There is no overdose syndrome of marijuana use.
■ Cannabis use disorder occurs in approximately 10% of those who use (up
to 50% of daily users).
■ Chronic use may cause respiratory problems such as asthma and chronic
bronchitis, suppression of the immune system, cancer, and possible effects
on reproductive hormones.
■ Treatment: Supportive, psychosocial interventions (e.g., contingency
management, groups, etc.).
WITHDRAWAL
■ Withdrawal symptoms may include irritability, anxiety,
restlessness, aggression, strange dreams, depression, headaches,
sweating, chills, insomnia, and ↓ appetite.
■ Treatment: Supportive and symptomatic.
Inhalants
■ Inhalants include a broad range of drugs that are inhaled and
absorbed through the lungs.
■ Inhalants generally act as CNS depressants.
■ User is typically a preadolescent or adolescent; rate of use is
similar between boys and girls (but rare in adult females).
■ Examples: Solvents, glue, paint thinners, fuels, isobutyl nitrates
(“huff,” “laughing gas,” “rush,” “bolt”).
INTOXICATION
■ Effects: Perceptual disturbances, paranoia, lethargy, dizziness, nausea/
vomiting, headache, nystagmus, tremor, muscle weakness, hyporeflexia,
ataxia, slurred speech, euphoria, hypoxia, clouding of consciousness, stupor,
or coma.
■ Acute intoxication: 15–30 minutes. May be sustained with repeated use.
■ Overdose: May be fatal secondary to respiratory depression or cardiac
arrhythmias.
■ Long-term use may cause permanent damage to CNS (e.g., neurocognitive
impairment, cerebellar dysfunction, Parkinsonism, seizures), peripheral
neuropathy, myopathy, aplastic anemia, malignancy, metabolic
acidosis, urinary calculi, glomerulonephritis, myocarditis, myocardial
infarction, and hepatotoxicity).
■ Treatment: Monitor airway, breathing, and circulation; may need oxygen
with hypoxic states.
■ Identify solvent because some (e.g., leaded gasoline) may require
chelation.
WITHDRAWAL
A withdrawal syndrome does not usually occur, but symptoms
may include irritability, sleep disturbance, anxiety, depression,
nausea, vomiting, and craving.
Caffeine
Caffeine is the most commonly used psychoactive substance in
the United States, usually in the form of coffee or tea. It acts as
an adenosine antagonist, causing ↑ cyclic adenosine
monophosphate (cAMP) and stimulating the release of excitatory
neurotransmitters.
OVERDOSE
■ > 250 mg (2 cups of coffee): Anxiety, insomnia, muscle
twitching, rambling speech, flushed face, diuresis, gastrointestinal
disturbance, restlessness, excitement, and tachycardia.
■ > 1 g: May cause tinnitus, severe agitation, visual light flashes,
and cardiac arrhythmias.
■ > 10 g: Death may occur secondary to seizures and respiratory
failure.
■ Treatment: Supportive and symptomatic.
WITHDRAWAL
■ Caffeine withdrawal symptoms occur in 50–75% of caffeine
users if cessation is abrupt.
■ Withdrawal symptoms include headache, fatigue, irritability,
nausea, vomiting, drowsiness, muscle pain, and depression.
■ Usually resolve within 1½ weeks.
Nicotine
■ Nicotine is derived from the tobacco plant, and stimulates nicotinic
receptors in autonomic ganglia of the sympathetic and parasympathetic
nervous systems. It is highly addictive through its effects on the
dopaminergic system.
■ Smoking → tolerance and physical dependence (i.e., prominent craving
and withdrawal).
■ Cigarette smoking is the leading cause of preventable morbidity and
mortality in the United States, posing many health risks including chronic
obstructive pulmonary disease (COPD), cardiovascular diseases, and various
cancers.
■ Current smoking prevalence is about 21% of US adults.
■ Effects: Restlessness, insomnia, anxiety, and ↑ gastrointestinal motility.
■ Withdrawal symptoms: Intense craving, dysphoria, anxiety, poor
concentration, ↑ appetite, weight gain, irritability, restlessness, and
insomnia.
TREATMENT OF NICOTINE
DEPENDENCE
FDA-approved pharmacotherapy:
■ Varenicline (Chantix): a4b2 nicotinic cholinergic receptor
(nAChR) partial agonist that mimics the action of nicotine,
reducing the rewarding aspects and preventing withdrawal
symptoms.
■ Bupropion (Zyban): Antidepressant that is an inhibitor of
dopamine and norepinephrine reuptake; helps reduce craving
and withdrawal symptoms.
■ Nicotine replacement therapy (NRT): Available as transdermal
patch, gum, lozenge, nasal spray, and inhaler.
■ Behavioral support/counseling should be part of every
treatment.
■ Relapse after abstinence is common.