Alcohol dependence

Drinking patterns
None no alcohol in last year
Occasional no alcohol in last month
Light (males) less than 22 units / week
Light (females) less than 15 units / week
Moderate (males) 22-35 units
Moderate (female) 15-25 units
Heavy (males) 36-50 units
Heavy (female) 26-35 units
Very Heavy (male) > 50 units
Very Heavy (female) > 35 units

Recommended drinking limits

• 10 ml of absolute alcohol = 8.0 g of absolute alcohol = 1 unit
• no more than ½of total units should be consumed in one session
• 2 drink free days per week
• during pregnancy: 1-2 units / day a couple of days a week, but preferably nil
• 1-2 units / day has a beneficial effect on the coronary arteries

Blood alcohol levels

• one unit of alcohol can give a blood alcohol level of 15-25 mg %
• blood alcohol levels fall due to excretion at a rate of about 15-20 mg % per hour

Blood alcohol concentration (mg %) Typical effects

20 • enhanced sense of well-being
• visual reaction time reduced
40 • somewhat disinhibited
• reduced driving ability at speed
60 • judgement impaired
80 • physical coordination impaired
100 • evident loss of social judgement
• poorly coordinated
130 • clearly intoxicated
300 • coma
• stupor
• loss of bladder control
500 + • coma
• respiratory depression, death

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Blood, Urine, and breath alcohol equivalents
Blood (mg / 100ml) Urine (mg / 100 ml) Breath (µg / 100 ml)
50 67 22
80 (legal limit) 107 35
150 200 66
200 267 88
250 333 110

Alcohol and the brain

Experience Transmitter/ receptor

Activation NA
DA
Euphoria/ pleasure DA
opioids
5-HT2
Anxiolysis/ ataxia GABA
Sedation/ amnesia increase GABA
block NMDA
Nausea stimulate 5-HT3
Withdrawal increase Ca2+ flux
decrease magnesium
reinforcing actions of alcohol NA
DA

Opioids
• alcohol increases concentrations of plasma endorphins
• mu and delta receptors are involved in the reinforcing effects of alcohol

GABA
• at low doses, alcohol increases the ability of GABA to open the chloride channel
on GABAA receptors
• at higher concentrations, alcohol has a direct action on the receptor, causing a
prolonged opening of the channel which is GABA-independent
• this action is mimicked by barbiturates but not benzodiazepines – excessive
chloride influx will result in paralysis of the neurons responsible for respiratory
drive, so causing asphyxiation

Glutamate
• alcohol blocks NMDA channels, opposing the effects of glutamate, and contributes
to the causation of amnesia and other cerebral depressant effects
• the brain attempts to compensate by increasing the number of NMDA channels
• once alcohol consumption drops, there is a relative excess of NMDA function,
which explains the hyperexcitability of alcohol withdrawal

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Harmful use of alcohol (F10.1)
• a maladaptive pattern of alcohol use:

DCR-10
A. There must be clear evidence that the substance use was responsible for (or
substantially contributed to) physical or psychological harm, including impaired
judgment or dysfunctional behaviour
B. The nature of the harm should be clearly identified (and specified)
C. The pattern of use has persisted for at least 1 month or has occurred repeatedly
within a 12-month period
D. The disorder does not meet the criteria for any other mental or behavioural disorder
related to the same drug in the same time period (except for acute intoxication)

Alcohol dependency syndrome (F10.2)

• Edwards, G. & Gross, M. M. (1976) Alcohol Dependence: provisional
description of a clinical syndrome. British Medical Journal 1: 1058-61

1. narrowing of repertoire
2. salience of drinking
3. tolerance
4. withdrawal symptoms
5. relief drinking
6. compulsion to drink
7. reinstatement after abstinence

DCR-10
• at least three of the following:
A. A strong desire or sense of compulsion to drink
B. Difficulty in controlling the amount drunk
C. Physiological withdrawal state after drinking stops, with the possible use of
alcohol to relieve this
D. Evidence of tolerance may appear
E. Progressive neglect of alternative pleasures and interests
F. Persistence of drinking in spite of evidence of harmful effects

Epidemiology

Hospital admissions
• in the USA 30 % of medical and surgical cases are suffering from alcohol problems
• 25 % of psychiatric cases, 19 % of neurology, and 12.5 % of Obstetric and
Gynaecology
• alcohol accounts for 10 % of all psychiatric admissions in the UK

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General population surveys
Men over 15 Women over 15
England & Wales 14.9 units per week 4.0
Scotland 1.2 3.4
Northern Ireland 6.7 1.3

• annual consumption of 4.2 litres of absolute alcohol per capita (population surveys)
• ECA study found a 14 % lifetime prevalence of alcoholism
• M:F = 4:1
• 20-30 % of patients in general health care have alcohol-related disabilities
• 10 % of the population are totally abstinent from alcohol

Specific groups
• disproportionate rise in females
• rise in adolescents
• 35 % of homeless have alcohol disorders
• 4-6 % of medical profession abuse alcohol

• age of onset in late teens or 20s for males

• onset later in females, who are more likely to:
• drink alone
• delay seeking help
• have co-morbid depression
• have a stronger genetic predisposition
• develop physical complications, especially cirrhosis
• higher rates in:
• urban areas
• divorced/ separated
• those who manufacture, or sell alcohol
• commercial travellers, frequent overseas travellers
• entertainers, doctors, journalists
• North American, Afro-Caribbean, Irish
• lower rates in:
• ‘middle’ social groups
• Jewish, Chinese

Aetiology

Genetic
1. Family Studies:
a) 7-fold increase in risk of alcoholism among 1st degree relatives of
alcoholics
2. Twin Studies:
a) MZ: DZ = 70 %: 43 % for males

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 47 %: 32 % for females
3. Adoption Studies:
a) sons of alcoholics are 4 x more likely to be alcoholic than sons of non-
alcoholic, regardless of the drinking patterns of adoptive parents
b) sons of alcoholics raised by non-alcoholic adoptive parents are no more
susceptible to other non-alcoholic adult psychiatric disorder
c) higher rates of childhood conduct disorder in male offspring of
alcoholics
d) alcoholism and antisocial personality disorder were genetically
independent disorders for both males and females
4. Chromosomes:
a) recent associations between D2 dopamine receptor and alcoholism are
controversial
b) variations in allele compositions for alcohol dehydrogenase and
aldehyde dehydrogenase may contribute to risk patterns of alcoholism
among oriental populations
5. Vulnerability markers:
a) abnormalities in P300 event-related potential associated with familial
alcoholism > P300 predicts alcohol abuse (Berman et al. 1993)
6. Risk factors:
a) family history

Biochemical
• alcohol’s reinforcing effects are modulated by dopamine, serotonin, and GABA
systems
• DA antagonists, SSRIs, GABA agonists, and opioid antagonists have all been
shown to reduce alcohol consumption in animal studies

1. Dopamine:
a) alcohol stimulates DA release in nucleus accumbens
b) increased DA may underlie ‘craving’
2. 5-HT:
a) alcohol potentiates effects of serotonin at 5-HT3 receptors
i) increased DA release in nucleus accumbens may be via this
mechanism
b) some reports of 5-HT agonists in reducing alcohol craving
3. MAO:
a) decreased platelet MAO activity is linked to type 2 alcoholism
4. Other receptor/ neuropeptides:
a) alcohol inhibits NMDA receptor channels in glutamate receptor
i) possible glutamate excitotoxic model for CNS damage with
alcohol
b) potentiation of effects of GABA receptor complex

Psychodynamic
• intoxication is a gain to the patient, with disinhibition allowing the expression of
aggression
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• maternal overprotection is described among some alcohol problems clinic attendees
• childhood sexual abuse is more commonly reported in women alcoholics than in the
general population

Behavioural
• models include drinking becoming a conditioned response to a wide range of
circumstances
• modelling from parents, relatives, peers, etc. is clearly demonstrated
• the euphoriant effect of alcohol is an important reinforcer for continued drinking

Stress and negative life events

• bereavement
• separation
• impending court case

Personality
1. Type 1 alcoholic – more dependent, anxious, rigid, less aggressive, more guilty,
with either the mother or father an alcoholic
2. Type 2 alcoholic – early onset, severe problems, socially detached, distractible,
confident, and whose behaviour is linked to a similar pattern in the biological father
• can be seen as alcoholism secondary to antisocial personality disorder

Characteristic Type 1 Type 2

Onset after age 25 before age 25
Gender either male
Antisocial traits no common
Type of drinking binge steady
Other drugs rare common
Guilt about drinking marked slight
Impulsivity low high
Brain 5-HT function high low
Mcpp responsess anxiety high

Alcohol related disabilities

Hepatic:
1. may be due to toxic effects of acetaldehyde / damage to immune system by
alcohol
2. women are more susceptible than men
3. Fatty liver:
a) may be present in 90 % of drinkers
b) reversible with abstinence
4. Alcoholic hepatitis:
a) abstinence aids resolution, but cirrhosis may follow
5. Cirrhosis:
a) 10 % of chronic alcoholics
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 b) more common in women
c) vulnerability may be due to HLA-B8 antigen, found in 25 % of
population
d) HLA-A28 may have a protective effect
e) fibrosis of the liver and decompensation of liver function
f) stigmata of liver disease may be present
6. Carcinoma:
a) 15 % of patients with cirrhosis go on to develop hepato-cellular
carcinoma
7. Portal hypertension

Gastrointestinal:
1. Barrett’s oesophagitis
2. Oesophageal varices
3. Mallory-Weiss tears
4. Gastritis and gastric erosions
5. Peptic ulceration – 20 % of alcoholics; bleeding may be exacerbated by Vitamin
K deficiency secondary to cirrhosis
6. Pancreatitis – both acute and chronic
7. Gastric carcinoma
8. Possible association with colorectal carcinoma
9. Diabetes mellitus

Haematological:
1. alcoholism is the commonest cause of macrocytosis
2. Thrombocytopenia and anaemia may also occur
3. Zieve’s syndrome is a rare form of alcoholic haemolysis

Neurological:
1. Delirium Tremens
2. Alcoholic Hallucinosis:
a) rare conditions in which auditory hallucinations occur alone in clear
consciousness
b) usually clears in a few days, but may be followed by secondary
delusional misinterpretation
c) up to 50 % go on to develop symptoms of schizophrenia (Benedetti,
1952)
3. Epilepsy of late onset (> 25 yrs) is the most common neurological complication
a) trauma
b) alcohol withdrawal
c) brain damage
4. Peripheral neuropathy is probably due to thiamine deficiency (Dry Beriberi)
5. Optic atrophy:
a) loss of visual acuity
b) blindness associated with methanol poisoning, thiamine and B12
deficiency, and heavy tobacco smoking
6. Korsakoff’s syndrome is caused by global cortical brain impairment
7. Wernkicke’s encephalopathy
8. Central pontine myelinolysis
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9. Cerebellar atrophy/ degeneration
10. Widening of sulci on CT scan
11. EEG abnormalities – P300 is decreased, and other wave abnormalities have
been reported in detoxified alcoholics

Cardiovascular:
1. moderate drinking is beneficial, due to changes in the lipoprotein profile
2. heavy drinking has the following effects:
a) increase in blood pressure
b) weakened contraction of myocardium, leading to heart failure
c) cardiac arrhythmia
d) cardiomyopathy

Alcohol in pregnancy
• alcohol in pregnancy associated with increased risk of:
• stillbirth
• neonatal mortality
• low birth weight
• later difficulties with attention
• distractibility
• Foetal Alcohol syndrome (FAS):
• incidence of 1.9 per 1000 live births in US
• microcephaly, mental retardation, low birth weight, cleft palate, ptosis,
scoliosis, abnormal dermatoglyphics, congenital heart disease, congenital
renal disease
• may occur at alcohol intake of 4-5 units per day

Social
• increased rates of:
• physical / sexual abuse of partner
• divorce
• child abuse
• later alcoholism in children

Employment
• 2 ½times as many days off work
• decreased productivity
• increased accidents at work

Accidents
• 80 % of fatal car accidents involve alcohol
• 40 % of casualty trauma involves alcohol

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Laboratory tests
• MCV may be raised
• GGT may be raised after a single heavy drinking bout
• CDT (carbohydrate deficient transferrin) can detect if someone has been drinking
more than 7 units a day for a week
• AST > ALT in alcoholism

Psychiatric disorders associated with alcoholism

• 47 % of alcoholics meet criteria for another psychiatric disorder

Affective disorders
• 70-90 % of alcoholics have depressive symptoms
• depression is associated more commonly with women
• most symptoms remit in treatment, by detoxification and social support
• about 25 % of completed suicides (15 % in women, 45 % in men) are associated
with heavy drinking
• alcoholics have at least 7 times the expected suicide rate

Anxiety
• the anxiolytic effects of alcohol wear off as tolerance develops, with a rebound
effect occurring when the effects wear off
• tranquilizers are used with dual dependency resulting

Schizophrenia
• schizophrenic symptoms can occasionally be triggered by heavy drinking, which
remit when the patient is detoxed
• a number of these patients go on to develop more permanent schizophrenic features

Personality disorder
• almost any personality disorder may be associated with alcohol abuse

Morbid jealousy
• may be associated with an alcoholic paranoid state

Delirium tremens
• risk develops when intake is 12 units per day
• used to have a 30 % mortality
• 1-4 days after withdrawal
• trauma or infection present from outset in up to 50 % of cases
• biochemical evidence of liver damage in up to 90 %
• classic triad of:
1. clouding of consciousness and confusion
• patient is disorientated
2. vivid hallucinations
• usually visual (rats, insects, Lilliputian) or tactile
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 3. marked tremor
• primary disorder of reticular activating system – suggested by inattention,
overarousal, insomnia, and overactivity
• REM rebound, with REM sleep occupying whole of sleep time
• marked autonomic hyperactivity
• epileptic fits are common

Marchiafava-Bignami disease
• presents with:
• ataxia
• dysarthria
• epilepsy
• severe impairment of consciousness
• due to extensive demyelination of the corpus callosum, the optic tracts, and the
cerebellar peduncles

Central Pontine Myelinolysis

• consists of demyelination involving the pyramidal tracts within the pons
• presents with rapid onset of:
• pseudobulbar palsy
• quadriplegia
• loss of pain sensation in the limbs and trunk
• vomiting, confusion, and coma are common

Alcoholic Amblyopia
• caused by a retrobulbar neuritis
• presents as a painless bilateral loss of vision over 1-2 weeks, in association with
alcohol misuse
• the majority of patients are also smokers
• thiamine deficiency has been strongly implicated - the condition responds to
treatment with B-vitamins

Alcoholic dementia
• mild cognitive deficits frequent, but reversible with abstinence
• dementia rarely occurs before 40 years
• associated with CT and MRI evidence of ‘atrophy’

Treatment
• none of the following have any proven efficacy in the treatment of alcohol misuse:
1. Antabuse
2. Group therapy

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 3. Individual counselling
4. In-patient detoxification
5. Alcoholics anonymous

Pharmacotherapy
1. NALTREXONE
a) is an opioid antagonist
b) is more effective than placebo in reducing the number of relapses and lowering
consumption
c) the main action seems to reduce the likelihood that a lapse would lead to a
relapse, probably by reducing the reinforcing actions of alcohol
2. ACAMPROSATE
a) proven efficacy in relapse prevention
b) pharmacodynamic actions are those of reducing endogenous excitatory
neurotransmitters and enhancing GABA transmission
c) probably acts by reducing the reinforcement caused by endogenous opioids
3. BUSPIRONE
a) is a 5-HT1A agonist
b) can improve outcome in anxious alcoholics

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Alcohol and Wernicke-Korsakoff syndrome

Biochemistry

Thiamine (Vitamin B1)

• co-enzyme involved three major enzyme systems:
• pyruvate dehydrogenase (energy production - involved in Kreb’s cycle)
• transketolase (maintenance of myelin sheaths in the nervous system)
• exists in two or more forms in different patients
• 2-oxo-glutarate dehydrogenase (synthesis of Acetlylcholine, GABA, and
glutamate)
• recommended daily amount is 1.5 mg (more required in alcoholism)
• body stores:
• liver 4 mg
• total body 30 mg
• absorption:
• by active transport across basal membrane of enterocytes
• displays saturable (Michaelis-Menten) kinetics
• energy-dependent and is therefore compromised in deficient states
• an alcoholic will absorb about 0 - 1.3 mg of a 10 mg dose - increased doses
will not result in increased absorption
• excretion:
• rapid clearance
• excreted in urine

Ethanol
• increases Mg2+ excretion (co-factor in similar enzymes to thiamine)
• damages apo-enzyme of which thiamine is a co-enzyme
• interferes with the active uptake of thiamine

Types of alcohol
• caloric content of two bottles of whisky is equal to the daily requirement
• beer and port provide the highest carbohydrate load, and therefore the highest risk
to thiamine deficient alcohol abusers

Wernicke’s syndrome
• occurs in people with gradual thiamine depletion who then have an acute event
(e.g. glucose load) which causes a sudden fall in thiamine
• characterized by:
1. abrupt onset of confusion and impairment of consciousness
2. ataxia
3. ophthalmoplegia

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• may also present with unexplained hypothermia and hypotension
• of those who get Wernicke’s, 10 % recover
20 % die
70 % develop Korsakoff’s

Korsakoff Psychosis

Epidemiology
• F:M = 1:1.7
• females tend to present 10-20 years earlier than men
• 1 in 9 long stay psychiatric patients have alcohol brain damage
• large increase between 1990 and 1995 - due to withdrawal of Parenterovite® from
the market

Clinical features
• presentation of Korsakoff psychosis is often insidious
• features include:
1. amnesia
2. disorientation
3. confabulation

Pathology
• specific topographic pattern of lesions:
• mammillary bodies (maintenance of consciousness and waking state)
• periventricular thalamic nuclei
• structures in the floor of the fourth ventricle
• involvement of the dorso-medial nucleus of the thalamus appears to be
particularly associated with memory disturbance

Investigations
• SPECT scanning reveals:
• reduced blood flow in:
• anterior temporal lobe and frontal lobe
• atrophy of the thalamus and mamillary bodies

Treatment & Prophylaxis

• at least 500 mg of thiamine is required for 3-5 days
• there is some evidence that ophthalmoplegia responds more rapidly than confusion
• anaphylaxis with Pabrinex is:
• 1 in 5,000,000 for IM
• 1 in 250,000 for IV

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Alcoholic Pellagra Encephalopathy
• due to deficiency of niacin in association with chronic alcohol misuse
• much less common than WKS

Clinical features
• encephalopathic syndrome:
• confusion
• oppositional hypertonus
• myoclonus
• cogwheel rigidity
• grasping and sucking reflexes
• hallucinations
• insomnia
• tremor
• ataxia
• urinary and foecal incontinence

Treatment
• responds rapidly to treatment with nicotinic acid

Vitamin B6 deficiency
• pyridoxine is crucial co-enzyme for glutamic acid decarboxylase (GAD), the
enzyme which synthesizes GABA from glutamic acid
• deficiency can result in epileptic seizures
• in nutritional seizures states, clinical response and normalization of EEG can occur
within minutes of giving parental pyridoxine

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 Drug Misuse

Epidemiology
• % of US population who have tried cannabis = 33 %; cocaine = 11 %; crack = 1 %
• 3.5 % have used BZDs for non-medical reasons
• lifetime prevalences (ECA study, Regier et al. 1991):
• 6.1 % substance abuse (SA) disorder (excluding alcohol)
• 13.5 % alcohol abuse
• 1.1 % alcohol and other drugs
• 3.2 % substance abuse co-morbidity with other mental disorders
• age, sex:
• 80 % begin SA before age 18
• peak abuse period in 20-30s in males, 20-24 in females
• risk lessens after 40
• overall, M:F = 4:1
• social class:
• lower groups over-represented
• pattern of abuse:
• episodic use generally seen with less addictive drugs, continuous course with
highly addictive drugs
• cannabis is first drug of abuse in 70 % of opiate addicts
• 90 % of opiate abusers also abuse BZDs
• only 1/3 of opiate users in contact with treatment agencies at any time
• average duration of use before seeking treatment = 9 years
• average duration of IV use before seeking treatment = 4 years
• co-morbidity:
• 70 % of opiate users have another current diagnosis (affective disorder,
antisocial personality disorder, anxiety disorder)
• 87 % meet lifetime criteria for another psychiatric diagnosis
• 50 % meet lifetime criteria for ≥ 2 psychiatric disorders
• high prevalence of SA (30-60 %) in schizophrenic patients
• Vulnerability hypothesis:
• SA may precipitate schizophrenia in predisposed individuals
• Self-medication hypothesis:
• SA counteracts negative symptoms and depressed mood
• SA counteracts side-effects of treatment

Aetiology
1. Genetics:
a) putative association of dopamine DR D2 allele with polysubstance abuse
may suggest vulnerability of SA
2. Pharmacological/ Biochemical:
a) abnormalities observed in many neurotransmitter systems:
i) opiate receptor
ii) dopamine
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 iii) serotonin
b) neuropharmacology of craving:
i) may relate to ability to increase DA activity in nucleus
accumbens
ii) reinforcing effects may occur from stimulation of corticofugal
DA pathways
c) Behavioural theories:
i) modelling
ii) primary direct reinforcement (psychic effect of SA promotes
continued abuse)
iii) secondary reinforcement (interaction of environmental cues and
pharmacological effects of drugs)
d) Analytic theories:
i) regression/ fixation at oral stage of development
e) Sociocultural theories:
i) 50 % of heroin addicts from single parent/ divorced families
ii) high rates of parental alcoholism
iii) ‘peer group activation’, e.g. ecstasy abuse
f) Access and availability:
i) ease of availability of ‘crack’ cocaine led to increased misuse in
high-risk groups – medical personnel, prostitutes

Drugs of abuse

Drug Pharmacology Symptoms

Opioids • bind to opioid receptors; NALTREXONE and •
NALOXONE are competitive antagonists
• tolerance develops with usage; also cross-
tolerance within opioid group
• withdrawal commences 4-6 hours after last
dose, peaks 24-48 hours, lasts 7-10 days
Cocaine • blocks reuptake of serotonin and • formication;
catecholamines, especially dopamine – the ‘cocaine
inhibits transporter uptake site bug’
• various DA agonists/ autoreceptors studied • reduced
for ↓ craving prolactin
• increased GH
levels
Amphetamines • sympathomimetics •
Hallucinogens (LSD, • sympathomimetics •
mescalin, psilocybin, • 5-HT agonists
dimethyltryptamine - • onset of effects in 1 hour, last 8-12 hours
DMT)
Phenylcyclidine (PCP) • receptor sites located in calcium ion •
channel of NMDA subtype of glutamate
receptor
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Cannibis • G-protein receptor for cannabinoids •
(tetrahydrocannabinol) recently discovered
• onset of effect is minutes - 1 hour, lasts 6-
12 hours
Barbiturates • CNS depressants •
Benzodiazepines • bind to benzodiazepine - GABA receptor •
complex
Ecstasy (MDMA – 3,4 • neurotoxic effect on serotonin nerve •
methylenedioxymeth- terminals (stimulates 5-HT release and
amphetamine) blocks 5-HT reuptake), especially in frontal
cortex and hippocampus
Volatile substance • CNS depressants •
abuse (VSA)

Opioids
• exert their effect through µ receptors

Clinical effects
• euphoria
• analgesia
• respiratory depression
• constipation
• reduced appetite
• low libido
• tolerance develops rapidly
• withdrawal symptoms (onset within 6 hours, and peak at 36-48 hours) include:
• intense craving
• restlessness
• insomnia
• pain in muscles and joints
• running nose and eyes
• sweating
• abdominal cramps
• vomiting
• piloerection
• dilated pupils
• disturbance of temperature control

Barbiturates
• these people are usually middle aged and took the drugs as hypnotics
• in aqueous solution, these drugs are highly irritant
• tolerance develops less rapidly than to opioids – the danger exists that tolerance to
the sedating effect occurs to a greater extent than tolerance to the CNS depressant
effects
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• withdrawal is dangerous, and leads to delirium, seizures, and can result in
cardiovascular collapse and death:
• anxiety
• restlessness
• disturbed sleep
• anorexia
• nausea
• vomiting, hypotension, pyrexia, tremor, seizures, disorientation, hallucinations,
a la delirium tremens

Clinical features
• drunkeness, with slurred speech and incoherence
• drowsiness
• depression
• nystagmus

Hallucinogens
• a.k.a. psychotomimetics
• synthetic hallucinogens include:
• LSD
• DMT – dimethyl tryptamine
• found in normal subjects’ urine
• found in increased amounts in urine during acute psychotic episodes
• MDMA
• natural drugs include:
• psilocybin
• tolerance can occur
• withdrawal syndrome has not been described
• dependence may occur in long term users, but is rare

Physical effects
• tachycardia
• hypertension
• dilation of the pupils

Psychological effects
• onset within 2 hours
• last 8-14 hours
• distortions or intensifications of sensory perception
• synaesthesia
• passage of time is reduced
• distortion of the body image
• panic, fears of insanity
• mood may be exhilaration, distress, or acute anxiety

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Cannabis

Clinical effects
• exaggeration of the pre-existing mood
• increased enjoyment of aesthetic experiences
• distortion of the perception of time and space
• reddening of the eyes
• dry mouth
• irritation of the respiratory tract

Adverse effects
• anxiety
• mild paranoid ideation
• toxic confusional states can occur
• psychosis (rare)

Tolerance, dependence, and withdrawal

• tolerance can occur but only for those using high doses
• withdrawal can lead to irritability, nausea, insomnia, and anorexia
• dependence can occur, but only of the non-physiological type

Stimulants
• effects are due to the release of, and blocking of the reuptake of, dopamine and
noradrenaline

Clinical effects
• overtalkativeness
• over-activity
• insomnia
• dryness of the lips, mouth, and nose
• anorexia
• dilated pupils
• tachycardia and hypertension – cardiac arrythmia and CVA can occur with large
doses

Adverse effects
• dysphoria
• irritability
• insomnia
• confusion
• anxiety, and panic
• paranoid psychosis may be induced by repeated high doses
• stereotyped behaviour, e.g. tidying

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Tolerance, dependence, and withdrawal
• tolerance is recognized
• withdrawal consists of:
• low mood
• decreased energy
• depression, anxiety, lethargy, fatigue, and nightmares in some cases
• craving can be intense
• suicidal ideation may be present

Cocaine
• similar effects to amphetamine (see above)
• powerful positive reinforcer in animals

Pharmacology
• blocks the re-uptake of dopamine into presynaptic dopamine terminals
• leads to high levels of extracellular dopamine in the nucleus accumbens
• activation of the physiological reward system

Clinical effects
• excitement
• increased energy
• euphoria
• tachycardia, hypertension, dilated pupils

Adverse effects
• grandiose thinking, impaired judgement, sexual indiscretion
• higher doses can lead to visual and auditory hallucinations
• paranoid ideation
• violent behaviour
• formication (the ‘cocaine bug’)
• cardiac arrythmias, MI, myocarditis, cardiomyopathy
• seizures
• respiratory arrest

Tolerance, dependence, and withdrawal

• tolerance is recognised
• withdrawal symptoms include:
• dysphoria
• anhedonia
• anxiety
• irritability
• fatigue
• hypersomnolence

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Phencyclidine (PCP)
• originally developed as a dissociative anaesthetic
• related to ketamine

Pharmacology
• both ketamine and PCP antagonize neurotransmission at NMDA receptors

Clinical effects
• drunkenness
• analgesia, and even anaesthesia
• agitation
• depressed consciousness
• nystagmus
• high blood pressure

Adverse effects
• aggressiveness
• ataxia
• muscle rigidity
• convulsions
• hypertensive heart failure
• CVA
• malignant hyperthermia

Tolerance, dependence, and withdrawal

• tolerance occurs
• withdrawal symptoms are rare in humans
• dependence can occur in heavy users

Management

Pharmacological treatments
1. Methadone
a) long acting opiate
b) maintenance therapy at 20-70 mg per day
c) less physical morbidity, slower progression of HIV infection
d) moderate/ high dosage of METHADONE required to maintain abstinence
2. Naltrexone
a) opiate antagonist
b) used in detoxification and maintenance
c) less acceptable to user than METHADONE
3. Buprenorphine
a) mixed agonist-antagonist
b) useful in opiate and cocaine abuse

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 c) withdrawal from BUPRENORPHINE may be easier than from
METHADONE
4. Other agents under investigation
a) DESIPRAMINE – may decreased craving for cocaine
b) AMANTADINE – decreases craving
c) AMPEROZIDE – novel antipsychotic for schizophrenia, but may reduce
craving for cocaine

Psychosocial treatments
• aims:
• tackle underlying factors perpetuating SA
• increase awareness
• develop alternative coping strategies
• foster cognitive-behavioural strategies to manage craving and eliminate
reinforcing behaviours
• psychosocial treatments may be as effective as pharmacological therapy, especially
when combined with self-help groups

Improvement at 6 months
1 counselling session per month 25 %
1 counselling session per week 60 %
1 counselling session per week plus > 60 %
family/ psychiatric intervention

Prognosis
• high initial relapse after treatment
• follow-up is associated with:
• high psychiatric morbidity
• continued use
• high mortality (suicide, accidents, physical complications, HIV)
• factors associated with poor outcome:
• early age of initial abuse
• long history of abuse
• IV abuse
• early drop-out from maintenance programmes
• antisocial personality disorder
• 45 % of treated opiate addicts are abstinent and living in the community at 6 months
• 85 % used opiates at some time during 6 months

Pathological gambling

Epidemiology
• males > females (4 % attending gamblers’ anonymous are female)

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• females present earlier (< 5 years)
• addiction usually begins in adolescence

Aetiology
1. Predisposing factors:
a) family history of addiction
b) parental rejection or criticism resulting in chronic low self-esteem
2. Precipitating factors:
a) death of parent or relative
b) birth of child
c) physical illness or personal threat to life
d) job demotion or promotion
e) other substance abuse

Clinical features
• categorized as Habit and Impulse Disorder in ICD-10
• frequent, repeated episodes of gambling that dominate the individual’s life to the
detriment of social, occupational, material, or family commitments
• 4 phases:
1. winning
2. losing
3. desperation
4. giving up
• stress-related physical illness, depression, DSH, criminal behaviour are common in
phases 3 and 4

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