4 Psychoactive Substance

Use Disorders

A drug is defined (by WHO) as any substance that, renal failure or idiosyncratic sensitivity) even a low
when taken into the living organism, may modify one dose may lead to intoxication. The intensity of intoxi-
or more of its functions. This definition conceptual- cation lessens with time, and effects eventually disap-
ises ‘drug’ in a very broad way, including not only pear in the absence of further use of the substance. The
the medications but also the other pharmacologically recovery is therefore complete, except where tissue
active substances. damage or another complication has arisen.
The words ‘drug addiction’ and ‘drug addict’ were The following codes may be used to indicate
dropped from scientific use due to their derogatory whether the acute intoxication was associated with
connotation. Instead ‘drug abuse’, ‘drug dependence’, any complications:
‘harmful use’, ‘misuse’, and ‘psychoactive substance i. uncomplicated (symptoms of varying severity,
use disorders’ are the terms used in the current nomen- usually dose-dependent, particularly at high
clature. A psychoactive drug is one that is capable of dose levels);
altering the mental functioning. ii. with trauma or other bodily injury;
There are four important patterns of substance use iii. with other medical complications (such as hae-
disorders, which may overlap with each other. matemesis, inhalation of vomitus);
1. Acute intoxication, iv. with delirium;
2. Withdrawal state, v. with perceptual distortions;
3. Dependence syndrome, and vi. with coma;
4. Harmful use. vii. with convulsions; and
viii. pathological intoxication (only for alcohol).
Acute Intoxication
According to the ICD-10, acute intoxication is a Withdrawal State
transient condition following the administration of A withdrawal state is characterised by a cluster of
alcohol or other psychoactive substance, resulting symptoms, often specific to the drug used, which
in disturbances in level of consciousness, cognition, develop on total or partial withdrawal of a drug, usu-
perception, affect or behaviour, or other psychophysio- ally after repeated and/or high-dose use. This, too, is
logical functions and responses. This is usually associ- a short-lasting syndrome with usual duration of few
ated with high blood levels of the drug. hours to few days.
However, in certain cases where the threshold is Typically, the patient reports that the withdrawal
low (due to a serious medical illness such as chronic symptoms are relieved by further substance use.
 34 A Short Textbook of Psychiatry

The withdrawal state is further classified as: 5. Progressive neglect of alternative pleasures or
i. uncomplicated; interests because of psychoactive substance use,
ii. with convulsions; and increased amount of time necessary to obtain or
iii. with delirium. take the substance or to recover from its effects.
6. Persisting with substance use despite clear evi-
Dependence Syndrome dence of overtly harmful consequences, such as
According to the ICD-10, the dependence syndrome is harm to the liver through excessive drinking,
a cluster of physiological, behavioural, and cognitive depressive mood states consequent to periods of
phenomena in which the use of a substance or a class heavy substance use, or drug-related impairment
of substances takes on a much higher priority for a of cognitive functioning; efforts should be made
given individual than other behaviours that once had to determine that the user was actually, or could
greater value. be expected to be, aware of the nature and extent
A central descriptive characteristic of the de- of the harm.
pendence syndrome is the desire (often strong and A narrowing of personal repertoire of patterns of
sometimes overpowering) to take psycho active psychoactive substance use has also been described as
substances (which may or may not have been medi- a characteristic feature of the dependence syndrome
cally prescribed), alcohol, or tobacco. There may be (e.g. a tendency to drink in the same way on weekdays
evidence that return to substance use after a period and weekends, regardless of the social constraints that
of abstinence leads to a more rapid reappearance of determine appropriate drinking behaviour).
other features of the syndrome than occurs with non- The dependence syndrome can be further coded
dependent individuals. as (ICD-10):
A definite diagnosis of dependence should usually i. currently abstinent;
be made only if at least three of the following have ii. currently abstinent, but in a protected environment
been experienced or exhibited at sometime during the (e.g. in hospital, in a therapeutic community, in
previous year: prison, etc.);
1. A strong desire or sense of compulsion to take the iii. currently on a clinically supervised maintenance
substance. or replacement regime (controlled dependence,
2. Difficulties in controlling the substance-taking e.g. with methadone; nicotine gum or nicotine
behaviour in terms of its onset, termination, or patch);
levels of use. iv. currently abstinent, but receiving treatment with
3. A physiological withdrawal state when the sub- aversive or blocking drugs (e.g. naltrexone or
stance use has ceased or reduced, as evidenced disulfiram);
by the characteristic withdrawal syndrome for v. currently using the substance (active dependence);
the substance; or use of the same (or a closely vi. continuous use; and
related) substance with the intention of relieving vii. episodic use (dipsomania).
or avoiding withdrawal symptoms. The dependence can be either psychic, or physical,
4. Evidence of tolerance, such that increased doses of or both.
the psychoactive substance are required in order to
achieve effects originally produced by lower doses Harmful Use
(clear examples of this are found in the alcohol- Harmful use is characterised by:
and opiate-dependent individuals who may take 1. Continued drug use, despite the awareness of
daily doses that are sufficient to incapacitate or harmful medical and/or social effect of the drug
kill non-tolerant users). being used, and/or
 Psychoactive Substance Use Disorders
35

2. A pattern of physically hazardous use of drug (e.g. 6. Hallucinogens, e.g. LSD, phencyclidine (PCP)
driving during intoxication). 7. Sedatives and hypnotics, e.g. barbiturates
The diagnosis requires that the actual damage 8. Inhalants, e.g. volatile solvents
should have been caused to the mental or physical 9. Nicotine, and
health of the user. Harmful use is not diagnosed, if a 10. Other stimulants (e.g. caffeine).
dependence syndrome is present. DSM-IV-TR uses the The various psychoactive substances are sum-
term substance abuse instead, with minor variations marised in Table 4.1.
in description.
The other syndromes associated with the psycho- Aetiology
active substance use in ICD-10 include psychotic dis- The various aetiological factors in substance use dis-
order, amnesic syndrome, and residual and late-onset orders are briefly summarised in Table 4.2.
(delayed onset) psychotic disorder.
ALCOHOL USE DISORDERS
Psychoactive Substances
The major dependence producing drugs are: Alcohol dependence was previously called as alcohol-
1. Alcohol ism. This term much like ‘addiction’ has been dropped
2. Opioids, e.g. opium, heroin due to its derogatory meaning.
3. Cannabinoids, e.g. cannabis According to Jellinek, there are five ‘species’ of
4. Cocaine alcohol dependence (alcoholism) on the basis of the
5. Amphetamine and other sympathomimetics patterns of use (and not on the basis of severity).

Table 4.1: Psychoactive Substance Use Disorders

Drug Usual Route of Physical Psychic Tolerance
Administration Dependence Dependence
1 Alcohol Oral ++ ++ +
2 Amphetamines Oral, Parenteral ++ ++ +++
3 Barbiturates Oral, Parenteral ++ ++ +++
4 Benzodiazepines Oral, Parenteral + + +
5 Caffeine Oral + ++ +
6 Cannabis Smoking, Oral ± ++ +
(Marihuana)
7 Cocaine Inhalation, Oral, ± ++ –
Smoking, Parenteral
8 Lysergic acid Oral – + +
diethylamide (LSD)
9 Nicotine Oral, Smoking + ++ +
10 Opioids Oral, Parenteral, Smoking +++ +++ +++
11 Phencyclidine (PCP) Smoking, Inhalation,
Parenteral, Oral ± + +
12 Volatile solvents Inhalation ± ++ +
– = None; ± = Probable/Little; + = Some/Mild; ++ = Moderate; +++ = Severe.
The dependence can be either psychic, or physical, or both.
 36 A Short Textbook of Psychiatry

Table 4.2: Aetiological Factors in Substance Use A. Alpha (α)

Disorders i. Excessive and inappropriate drinking to relieve
physical and/or emotional pain.
1. Biological Factors
i. Genetic vulnerability (family history of substance ii. No loss of control.
use disorder; for example in type II alcoholism) iii. Ability to abstain present.
ii. Co-morbid psychiatric disorder or personality B. Beta (β)
disorder i. Excessive and inappropriate drinking.
iii. Co-morbid medical disorders ii. Physical complications (e.g. cirrhosis, gastritis and
iv. Reinforcing effects of drugs (explains continu- neuritis) due to cultural drinking patterns and poor
ation of drug use) nutrition.
v. Withdrawal effects and craving (explains con- iii. No dependence.
tinuation of drug use) C. Gamma (γ); also called as malignant alcoholism
vi. Biochemical factors (for example, role of i. Progressive course.
dopamine and norepinephrine in cocaine, ii. Physical dependence with tolerance and with-
ethanol and opioid dependence) drawal symptoms.
2. Psychological Factors iii. Psychological dependence, with inability to con-
i. Curiosity; need for novelty seeking trol drinking.
ii. General rebelliousness and social non-conform- D. Delta (δ)
ity i. Inability to abstain.
iii. Early initiation of alcohol and tobacco ii. Tolerance.
iv. Poor impulse control iii. Withdrawal symptoms.
v. Sensation-seeking (high) iv. The amount of alcohol consumed can be control-
vi. Low self-esteem (anomie)
led.
vii. Concerns regarding personal autonomy
v. Social disruption is minimal.
viii. Poor stress management skills
E. Epsilon (ε)
ix. Childhood trauma or loss
i. Dipsomania (compulsive-drinking).
x. Relief from fatigue and/or boredom
xi. Escape from reality
ii. Spree-drinking.
xii. Lack of interest in conventional goals Earlier, it was believed that γ-alcoholism was more
xiii. Psychological distress common in America, while δ-alcoholism was com-
3. Social Factors moner in the wine-drinking countries such as France.
i. Peer pressure (often more important than At present the existence of this pattern of distribution
parental factors) is doubted and its inclusion in this book is mainly for
ii. Modelling (imitating behaviour of important historical reasons.
others) Cloninger has classified alcoholism into two types,
iii. Ease of availability of alcohol and drugs on the basis of the relative importance of genetic and
iv. Strictness of drug law enforcement environmental factors (Table 4.3).
v. Intrafamilial conflicts Alcohol dependence is more common in males,
vi. Religious reasons and has an onset in late second or early third decade.
vii. Poor social/familial support The course is usually insidious. There is often an
viii. ‘Perceived distance’ within the family associated abuse or dependence of other drugs. If the
ix. Permissive social attitudes onset occurs late in life, especially after 40 years of
x. Rapid urbanisation. age, an underlying mood disorder should be looked for.
 Psychoactive Substance Use Disorders
37

Table 4.3: Classification of Alcoholism

Factors Type I Type II
Synonym Milieu-limited Male-limited
Gender Both sexes Mostly in males
Age of onset > 25 years < 25 years
Aetiological factors Genetic factors important; strong Heritable; environmental
environmental influences are influences are limited
contributory
Family history May be positive Parental alcoholism and antisocial
behaviour usually present
Loss of control Present No loss of control
Other features Psychological dependence; Drinking followed by aggressive
and guilt present behaviour; spontaneous alcohol
seeking
Pre-morbid Harm avoidance; Novelty-seeking
personality traits high reward dependence

Certain laboratory markers of alcohol dependence Acute Intoxication

have been suggested. These include:
i. GGT (γ-glutyl-transferase) is raised to about After a brief period of excitation, there is a generalised
40 IU/L in about 80% of the alcohol dependent central nervous system depression with alcohol use.
individuals. GGT returns to normal rapidly (i.e. With increasing intoxication, there is increased reac-
within 48 hours) on abstinence from alcohol. An tion time, slowed thinking, distractibility and poor
increase of GGT of more than 50% in an abstinent motor control. Later, dysarthria, ataxia and incoordina-
individual signifies a resumption of heavy drinking tion can occur. There is progressive loss of self-control
or an abnormality of liver function. with frank disinhibited behaviour.
ii. MCV (mean corpuscular volume) is more than The duration of intoxication depends on the
92 fl (normal = 80-90 fl) in about 60% of the amount and the rapidity of ingestion of alcohol. Usu-
alcohol dependent individuals. MCV takes ally the signs of intoxication are obvious with blood
several weeks to return to normal values after levels of 150-200 mg%. With blood alcohol levels
abstinence. of 300-450 mg%, increasing drowsiness followed
iii. Other lab markers include alkaline phosphatase, by coma and respiratory depression develop. Death
AST, ALT, uric acid, blood triglycerides and CK. occurs with blood alcohol levels between 400 to 800
GGT and MCV together can usually identify three mg% (Table 4.6).
out of four problem drinkers. In addition, BAC (blood Occasionally a small dose of alcohol may produce
alcohol concentration) and breath analyser can be used acute intoxication in some persons. This is known as
for the purpose of identification. pathological intoxication. Another feature, sometimes
For detection of the problem drinkers in the com- seen in acute intoxication, is the development of
munity, several screening instruments are available. amnesia or blackouts.
MAST (Michigan Alcoholism Screening Test) is
frequently used for this purpose whilst CAGE ques- Withdrawal Syndrome
tionnaire (Table 4.5) is the easiest to be administered The most common withdrawal syndrome is a hangover
(it takes only about 1-2 minutes). on the next morning. Mild tremors, nausea, vomiting,
 38 A Short Textbook of Psychiatry

weakness, irritability, insomnia and anxiety are the Multiple seizures (2-6 at one time) are more com-
other common withdrawal symptoms. Sometimes mon than single seizures. Sometimes, status epilep-
the withdrawal syndrome may be more severe, char- ticus may be precipitated. In about 30% of the cases,
acterised by one of the following three disturbances: delirium tremens follows.
delirium tremens, alcoholic seizures and alcoholic 3. Alcoholic hallucinosis
hallucinosis. It is important to remember that alcohol Alcoholic hallucinosis is characterised by the presence
withdrawal syndrome can be associated with marked of hallucinations (usually auditory) during partial or
morbidity as well as significant mortality, and it is complete abstinence, following regular alcohol intake.
important to treat it correctly. It occurs in about 2% of patients.
1. Delirium tremens These hallucinations persist after the withdrawal
Delirium tremens (DT) is the most severe alcohol syndrome is over, and classically occur in clear con-
withdrawal syndrome. It occurs usually within 2-4 sciousness. Usually recovery occurs within one month
days of complete or significant abstinence from heavy and the duration is very rarely more than six months.
alcohol drinking in about 5% of patients, as compared
to acute tremulousness which occurs in about 34%
Complications of Chronic Alcohol Use
of patients. Alcohol dependence is often associated with several
The course is short, with recovery occurring within complications; both medical and social (Table 4.4).
3-7 days. This is an acute organic brain syndrome Some withdrawal and intoxication related complica-
(delirium) with characteristic features of: tions have described above whilst the neuropsychiatric
i. Clouding of consciousness with disorientation in complications are discussed below.
time and place. Wernicke’s encephalopathy
ii. Poor attention span and distractibility. This is an acute reaction to a severe deficiency of
iii. Visual (and also auditory) hallucinations and illu- thiamine, the commonest cause being chronic alcohol
sions, which are often vivid and very frightening. use. Characteristically, the onset occurs after a period
Tactile hallucinations of insects crawling over the of persistent vomiting. The important clinical signs
body may occur. are:
iv. Marked autonomic disturbance with tachycardia, i. Ocular signs: Coarse nystagmus and ophthal-
fever, hypertension, sweating and pupillary dilata- moplegia, with bilateral external rectus paralysis
tion. occurring early. In addition, pupillary irregulari-
v. Psychomotor agitation and ataxia. ties, retinal haemorrhages and papilloedema can
vi. Insomnia, with a reversal of sleep-wake pattern. occur, causing an impairment of vision.
vii. Dehydration with electrolyte imbalance. ii. Higher mental function disturbance: Disorien-
Death can occur in 5-10% of patients with delirium tation, confusion, recent memory disturbances,
tremens and is often due to cardiovascular collapse, poor attention span and distractibility are quite
infection, hyperthermia or self-inflicted injury. At common. Other early symptoms are apathy and
times, intercurrent medical illnesses such as pneumo- ataxia.
nia, fractures, liver disease or pulmonary tuberculosis Peripheral neuropathy and serious malnutrition
may complicate the clinical picture. are often co-existent. Neuropathologically, neuronal
2. Alcoholic seizures (‘rum fits’) degeneration and haemorrhage are seen in thalamus,
Generalised tonic clonic seizures occur in about 10% hypothalamus, mammillary bodies and midbrain.
of alcohol dependence patients, usually 12-48 hours Korsakoff ’s psychosis
after a heavy bout of drinking. Often these patients As Korsakoff’s psychosis often follows Wernicke’s
have been drinking alcohol in large amounts on a encephalopathy; these are together referred to as
regular basis for many years. Wernicke-Korsakoff syndrome.
 Psychoactive Substance Use Disorders
39

Table 4.4: Some Complications of Alcohol Dependence

I. Medical Complications ii. Foetal alcohol syndrome (craniofacial anomalies,
A. Gastrointestinal System growth retardation, major organ system malfor-
i. Fatty liver, cirrhosis of liver, hepatitis, liver cell mations)
carcinoma, liver failure iii. Alcoholic hypoglycaemia and ketoacidosis
ii. Gastritis, reflux oesophagitis, oesophageal varices, iv. Cardiomyopathy, cardiac beri-beri
Mallory-Weiss syndrome, achlorhydria, peptic v. Alcoholic myopathy
ulcer, carcinoma stomach and oesophagus vi. Anaemia, thrombocytopenia, Vitamin K factor
iii. Malabsorption syndrome, protein-losing enter- deficiency, haemolytic anaemia
opathy vii. Accidental hypothermia
iv. Pancreatitis: acute, chronic, and relapsing viii. Pseudo-Cushing’s syndrome, hypogonadism,
B. Central Nervous System gynaecomastia (in men), amenorrhoea, infertility,
i. Peripheral neuropathy decreased testosterone and increased LH levels
ii. Delirium tremens ix. Risk for coronary artery disease
iii. Rum fits (Alcohol withdrawal seizures) x. Malnutrition, pellagra
iv. Alcoholic hallucinosis xi. Decreased immune function and proneness to
v. Alcoholic jealousy infections such as tuberculosis
vi. Wernicke-Korsakoff psychosis xii. Sexual dysfunction
vii. Marchiafava-Bignami disease II. Social Complications
viii. Alcoholic dementia i. Accidents
ix. Suicide ii. Marital disharmony
x. Cerebellar degeneration iii. Divorce
xi. Central pontine myelinosis iv. Occupational problems, with loss of productive
xii. Head injury and fractures. man-hours
C. Miscellaneous v. Increased incidence of drug dependence
i. Acne rosacea, palmar erythema, rhinophyma, vi. Criminality
spider naevi, ascitis, parotid enlargement vii. Financial difficulties.

Table 4.5: CAGE Questionnaire Table 4.6: Body Fluid Alcohol Levels

The CAGE questionnaire basically consists of four BAC* (mg%) Behavioural Correlates
questions: 25-100 Excitement
i. Have you ever had to Cut down on alcohol (amount)? 80 Legal limit for driving (in UK)**
ii. Have you ever been Annoyed by people’s criticism 100-200 Serious intoxication, slurred speech,
of alcoholism? incoordination, nystagmus
iii. Have you ever felt Guilty about drinking? 200-300 Dangerous
300-350 Hypothermia, dysarthria, cold sweats
iv. Have you ever needed an Eye opener drink (early
350-400 Coma, respiratory depression
morning drink)?
>400 Death may occur
A score of 2 or more identifies problem drinkers.
Urinary Diagnostic Equivalent BAC
Clinically, Korsakoff’s psychosis presents as an Alcohol (mg%) Use (mg%)
organic amnestic syndrome, characterised by gross >120 Suggestive 80
memory disturbances, with confabulation. Insight >200 Diagnostic 150
is often impaired. The neuropathological lesion is *BAC - Blood Alcohol Concentration
usually wide-spread, but the most consistent changes **30 mg/100 ml in India (Section 185 of the Motor
are seen in bilateral dorsomedial nuclei of thalamus Vehicle Act, 1988)
 40 A Short Textbook of Psychiatry

and mammillary bodies. The changes are also seen unless the risks of acute discontinuation are felt to be
in periventricular and periaqueductal grey matter, high by the treating team. This decision is often based
cerebellum and parts of brain stem. on several factors including chronicity of alcohol
The underlying cause is believed to be usually dependence, daily amount consumed, past history of
severe untreated thiamine deficiency secondary to alcohol withdrawal complications, level of general
chronic alcohol use. health and the patient’s wishes.
Marchiafava-Bignami disease The usual duration of uncomplicated withdrawal
This is a rare disorder characterised by disorientation, syndrome is 7-14 days. The aim of detoxification is
epilepsy, ataxia, dysarthria, hallucinations, spastic symptomatic management of emergent withdrawal
limb paralysis, and deterioration of personality and symptoms.
intellectual functioning. There is a widespread demy- The drugs of choice for detoxification are usually
elination of corpus callosum, optic tracts and cerebel- benzodiazepines. Chlordiazepoxide (80-200 mg/day in
lar peduncles. The cause is probably an alcohol-related divided doses) and diazepam (40-80 mg/day in divided
nutritional deficiency. doses) are the most frequently used benzodiazepines.
The higher limit of the normal dose range is used in
Other Complications delirium tremens.
These include: A typical dose of Chlordiazepoxide in moderate
i. Alcoholic dementia. alcohol dependence is 20 mg QID (four times a day)
ii. Cerebellar degeneration. on day 1, 15 mg QID on day 2, 10 mg QID on day 3,
iii. Peripheral neuropathy. 5 mg QID on day 4, 5 mg BD on day 5 and none on
iv. Central pontine myelinosis. day 6. However, in more severe dependence, higher
doses are needed for longer periods (up to 10 days).
Treatment These drugs are used in a standardised protocol, with
Before starting any treatment, it is important to follow the dosage steadily decreasing everyday before being
these steps: stopped, usually on the tenth day. Clormethiazole (1-2
i. Ruling out (or diagnosing) any physical disorder. g/day) and carbamazepine (600-1600 mg/day) are
ii. Ruling out (or diagnosing) any psychiatric disorder experimental drugs and should not be used routinely
and/or co-morbid substance use disorder. for detoxification.
iii. Assessment of motivation for treatment. In addition, vitamins should also be administered.
iv. Assessment of social support system. In patients suffering from (or likely to suffer from)
v. Assessment of personality characteristics of the delirium tremens, peripheral neuropathy, Wernicke-
patient. Korsakoff syndrome, and/or with other signs of vita-
vi. Assessment of current and past social, interper- min B deficiency (especially thiamine and nicotinic
sonal and occupational functioning. acid), a preparation of vitamin B containing 100 mg
The treatment can be broadly divided into two of thiamine (vitamin B1) should be administered
categories which are often interlinked. These are parenterally, twice everyday for 3-5 days. This should
detoxification and treatment of alcohol dependence. be followed by oral administration of vitamin B1 for
at least 6 months.
Detoxification Care of hydration is another important step; it is
Detoxification is the treatment of alcohol withdrawal extremely important not to administer 5% dextrose
symptoms, i.e. symptoms produced by the removal of (or any carbohydrate) in delirium tremens (or even in
the ‘toxin’ (alcohol). The best way to stop alcohol (or uncomplicated alcohol withdrawal syndrome) without
any other drug of dependence) is to stop it suddenly thiamine.
 Psychoactive Substance Use Disorders
41

Although detoxification can be achieved on an religious in nature, many patients derive benefits
outpatient (OPD) basis, some patients do require from the group meetings which are non-professional
hospitalisation. These patients may present with: in nature.
i. Signs of impending delirium tremens (tremor, iv. Deterrent agents
autonomic hyperactivity, disorientation, or per- The deterrent agents are also known as alcohol sen-
ceptual abnormalities), or sitising drugs.
ii. Psychiatric symptoms (psychotic disorder, mood Disulfiram (tetraethyl thiuram disulfide) was dis-
disorder, suicidal ideation or attempts, alcohol- covered in 1930s, when it was observed that workers
induced neuropsychiatric disorders), or in the rubber industry developed unpleasant reactions
iii. Physical illness (caused by chronic alcohol use or to alcohol intake, due to accidental absorption of
incidentally present), or antioxidant disulfiram. The mechanism of action of
iv. Inability to stop alcohol in the home setting. disulfiram is summarised in Figure 4.1.
Detoxification is the first step in the treatment of When alcohol is ingested by a person who is on
alcohol dependence. disulfiram, alcohol-derived acetaldehyde cannot be
oxidised to acetate and this leads to an accumulation
Treatment of Alcohol Dependence of acetaldehyde in blood. This causes the important
After the step of detoxification is over, there are sev- disulfiram-ethanol reaction (DER) characterised
eral methods to choose from, for further management. by flushing, tachycardia, hypotension, tachypnoea,
Some of these important methods include: palpitations, headache, sweating, nausea, vomiting,
i. Behaviour therapy giddiness and a sense of impending doom associated
The most commonly used behaviour therapy in the with severe anxiety.
past has been aversion therapy, using either a sub- The onset of the reaction occurs within 30 minutes,
threshold electric shock or an emetic such as apomor- becomes full blown within 1 hour, and subsides usu-
phine. Many other methods (covert sensitisation, ally within 2 hours of ingestion of alcohol. In sensitive
relaxation techniques, assertiveness training, self- patients or in those who have ingested a large amount
control skills, and positive reinforcement) have been of alcohol, DER can be very severe and life threatening
used alone or in combination with aversion therapy. due to one or more of the following: shock, myocardial
Currently, in most settings, it is considered unethical infarction, convulsions, hypoxia, confusion and coma.
to use aversion therapy for the treatment of alcohol Therefore, treatment with disulfiram is usually
dependence. begun in an inpatient hospital setting, usually after
ii. Psychotherapy a challenge test with alcohol to demonstrate that
Both group and individual psychotherapy have been unpleasant and dangerous side-effects occur, if either
used. The patient should be educated about the risks alcohol or alcohol-containing eatable/drink is con-
of continuing alcohol use, asked to resume personal sumed whilst treatment is continued with disulfiram.
responsibility for change and be given a choice of The usual dose of disulfiram is 250-500 mg/day
options for change. Motivational enhancement therapy (taken before bedtime to avoid drowsiness in daytime)
with or without cognitive behaviour therapy and life- in the first week and 250 mg/day subsequently for
style modification is often useful, if available. the maintenance treatment. The effect begins within
iii. Group therapy 12 hours of first dose and remains for 7-10 days after
Of particular importance is the voluntary self-help the last dose. The patient should carry a warning card
group known as AA (Alcoholics Anonymous), with detailing the forbidden alcohol-containing articles, the
branches all over the world and a membership in hun- possible effects and their emergency treatment, along
dreds of thousands. Although the approach is partly with patient identification details.
 42 A Short Textbook of Psychiatry

Fig. 4.1: Disulfiram: Mode of Action

The contraindications of disulfiram use are first Acamprosate (the Ca++ salt of N-acetyl-homotaurinate)
trimester of pregnancy, coronary artery disease, liver interacts with NMDA receptor-mediated glutamater-
failure, chronic renal failure, peripheral neuropathy, gic neurotransmission in the various brain regions
muscle disease and psychotic symptoms presently or and reduces Ca++ fluxes through voltage-operated
in the past. channels.
In selected patients (such as an older age group, Naltrexone (oral opioid receptor antagonist) prob-
good motivation, good social support, absent under- ably interferes with alcohol-induced reinforcement
lying psychopathology and good treatment concord- by blocking opioid receptors. Fluoxetine (and other
ance), the response can be dramatic. In addition to SSRIs) have been occasionally used as anti-craving
oral preparations, subcutaneous disulfiram implants agents in their usual antidepressant doses.
are also now available. However, they provide unpre- vi. Other medications
dictable blood levels of disulfiram. A variety of other medicines such as benzodia-
Other deterrent agents zepines, antidepressants, antipsychotics, lithium,
1. Citrated calcium carbimide (CCC): The mecha- carbamazepine, and even narcotics have been tried.
nism of action is similar to disulfiram but onset of These should be used only if there is a special indi-
action occurs within 1 hour and is reversible. The cation for their use (for example, antidepressants for
usual dosage is 100 mg/d in two divided doses. underlying depression).
2. Metronidazole. vii. Psychosocial rehabilitation
3. Animal charcoal, a fungus (Coprinus atramen- Rehabilitation is an integral part of the multi-modal
tarius), sulfonylureas and certain cephalosporins treatment of alcohol dependence.
also cause a disulfiram like action.
v. Anti-craving agents OPIOID USE DISORDERS
Acamprosate, naltrexone and SSRIs (such as fluoxet-
ine) are among the medications tried as anti-craving Dried exudate obtained from unripe seed capsules of
agents in alcohol dependence. Papaver somniferum has been used and abused for
 Psychoactive Substance Use Disorders
43

Table 4.7: Opioid Derivatives

centuries. The natural alkaloids of opium and their
synthetic preparations are highly dependence produc- A. Natural Alkaloids of Opium
ing. These are listed in Table 4.7. 1. Morphine
In the last few decades, use of opioids has in- 2. Codeine
creased markedly all over the world. India, surrounded 3. Thebaine
on both sides by the infamous routes of illicit transport,
4. Noscapine
namely the Golden Triangle (Burma-Thailand-Laos)
and the Golden Crescent (Iran-Afghanistan-Pakistan) 5. Papaverine
has been particularly severely affected. B. Synthetic Compounds
The most important dependence producing de- 1. Heroin
rivatives are morphine and heroin. They both like 2. Nalorphine
majority of dependence producing opioids bind to 3. Hydromorphone
μ (mu) opioid receptors. The other opioid receptors 4. Methadone
are k (kappa, e.g. for pentazocine), δ (delta, e.g. for a 5. Dextropropoxyphene
type of enkephalin), σ (sigma, e.g. for phencyclidine),
6. Meperidine (Pethidine)
ε (epsilon) and λ (lambda).
7. Cyclazocine
Heroin or di-acetyl-morphine is about two times
more potent than morphine in injectable form. Apart 8. Levallorphan
from the parenteral mode of administration, heroin can 9. Diphenoxylate
also be smoked or ‘chased’ (chasing the dragon), often
in an impure form (called ‘smack’ or ‘brown sugar’ yawning, tachycardia, mild hypertension, insomnia,
in India). Heroin is more addicting than morphine raised body temperature, muscle cramps, generalised
and can cause dependence even after a short period bodyache, severe anxiety, piloerection, nausea, vomit-
of exposure. Tolerance to heroin occurs rapidly and ing and anorexia.
can be increased to up to more than 100 times the first There are marked individual differences in pres-
dose needed to produce an effect. entation of withdrawal symptoms. Heroin withdrawal
syndrome is far more severe than the withdrawal
Acute Intoxication syndrome seen with morphine.
Intoxication is characterised by apathy, bradycardia,
hypotension, respiratory depression, subnormal core Complications
body temperature, and pin-point pupils. Later, delayed The important complications of chronic opioid use
reflexes, thready pulse and coma may occur in case may include one or more of the following:
of a large overdose. In severe intoxication, mydriasis 1. Complications due to illicit drug (contaminants):
may occur due to hypoxia. Parkinsonism, degeneration of globus pallidus,
peripheral neuropathy, amblyopia, transverse
Withdrawal Syndrome myelitis.
The onset of withdrawal symptoms occurs typically 2. Complications due to intravenous use: AIDS,
within 12-24 hours, peaks within 24-72 hours, and skin infection(s), thrombophlebitis, pulmonary
symptoms usually subside within 7-10 days of the embolism, septicaemia, viral hepatitis, tetanus,
last dose of opioid. endocarditis.
The characteristic symptoms include lacrimation, 3. Drug peddling and involvement in criminal activi-
rhinorrhoea, pupillary dilation, sweating, diarrhoea, ties (social complication).
 44 A Short Textbook of Psychiatry

Treatment argue that one type of dependence is often replaced

Before treatment, a correct diagnosis must be made by another (methadone).
on the basis of history, examination (pin-point pupils 2. Clonidine is an α2 agonist that acts by inhibiting
during intoxication or withdrawal symptoms) and/or norepinephrine release at presynaptic α2 recep-
laboratory tests. These tests are: tors. The usual dose is 0.3-1.2 mg/day, and drug
1. Naloxone challenge test (to precipitate withdrawal is tapered off in 10-14 days. It can be started after
symptoms). stoppage of either the opioid itself or the substitu-
2. Urinary opioids testing: With radioimmunoassay tion drug (methadone). The important side effects
(RIA), free radical assay tech nique (FRAT), of clonidine are excessive sedation and postural
thin layer chromatography (TLC), gas-liquid hypotension. Clonidine treatment is usually started
chromatography (GLC), high pressure liquid in an inpatient psychiatric or specialist alcohol and
chromatography (HPLC) or enzyme-multiplied drug treatment centre setting.
immunoassay technique (EMIT). 3. Naltrexone with Clonidine: Naltrexone is an orally
The treatment can be divided into three main types: available narcotic antagonist which, when given to
1. Treatment of overdose. an opioid dependent individual, causes withdrawal
2. Detoxification. symptoms. These symptoms are managed with the
3. Maintenance therapy. addition of clonidine for 10-14 days after which
clonidine is withdrawn and the patient is continued
Treatment of Opioid Overdose on naltrexone alone. Now if the person takes an
An overdose of opioid can be treated with narcotic opioid, there are no pleasurable experiences, as
antagonists (such as naloxone, naltrexone). Usually an the opioid receptors are blocked by naltrexone.
intravenous injection of 2 mg naloxone, followed by a Therefore, this method is a combination of detoxi-
repeat injection in 5-10 minutes, can cause reversal of fication and maintenance treatment. The usual
overdose. But as naloxone has a short half-life repeated dose of naltrexone is 100 mg orally, administered
doses may be needed every 1-2 hours. This should be on alternate days. Once again treatment is usually
combined with general care and supportive treatment. started in an inpatient psychiatric or specialist
alcohol and drug treatment centre setting.
Detoxification 4. Other Drugs: The other detoxification agents
This is a mode of treatment in which the dependent include LAAM (levo-alpha-acetyl-methadol),
person is ‘taken off’ opioids. This is usually done propoxyphene, diphenoxylate, buprenorphine
abruptly, followed by management of emergent (long acting synthetic partial μ-agonist which can
withdrawal symptoms. It is highly recommended that be administered sublingually), and lofexidine (α2
detoxification is conducted in a safe manner under agonist, similar to clonidine).
expert guidance of a specialist. In particular, Buprenorphine has recently been
The withdrawal symptoms can be managed by one used widely for detoxification as well as for main-
of the following methods: tenance treatment in many parts of the World. Care
1. Use of substitution drugs such as methadone (not must be exercised as there is potential for misuse
available in India at present) to ameliorate the with buprenorphine.
withdrawal symptoms. Maintenance Therapy
The aim is to gradually taper off the patient from
methadone (which is less addicting, has a longer After the detoxification phase is over, the patient is
half-life, decreases possible criminal behaviour, maintained on one of the following regimens:
and has a much milder withdrawal syndrome). 1. Methadone maintenance
However, relapses are common and its opponents (Agonist substitution therapy)
 Psychoactive Substance Use Disorders
45

This a very popular method used widely in the 4. Psychosocial rehabilitation

Western World. 20-50 mg/day of methadone is given This is a very important step in the post-detoxification
to the patients to ‘shift’ them from ‘hard’ drugs, thus phase, in the absence of which relapse rates can be
decreasing IV use and criminal behaviour. Its use very high. Rehabilitation should be at both occupa-
in India has not been recommended by an expert tional and social levels.
committee for de-addiction services.
Other drugs such as LAAM and buprenorphine CANNABIS USE DISORDER
can be used for maintenance treatment.
2. Opioid antagonists Cannabis is derived from the hemp plant, Cannabis
Opioid antagonists have been in use for a long time sativa, which has several varieties named after the
but they were either partial antagonists (such as nalor- region in which it is found (e.g. sativa indica in India
phine) or had to be administered parenterally (such as and Pakistan, and americana in America).
naloxone). Now with the availability of orally effective Cannabis (street names: grass, hash or hashish,
and very potent antagonists, such as naltrexone, the marihuana) produces more than 400 identifiable
use of opioid antagonists in routine practice has been chemicals of which about 50 are cannabinoids, the
simplified. The usual maintenance dose is 100 mg on most active being Δ-9-tetrahydrocannabinol (Δ9-
Mondays and Wednesdays, and 150 mg on Fridays. THC). The pistillate form of the female plant is more
Naltrexone combined with clonidine, as described important in cannabis production (Table 4.8).
above, is a very effective method for detoxification Recently, a Gi-protein (inhibitory G-protein) linked
as well as for maintenance treatment. cannabinoid receptor has been found (in basal ganglia,
3. Other methods hippocampus and cerebellum) which inhibits the ade-
These include individual psychotherapy, behaviour nylate cyclase activity in a dose-dependent manner.
therapy, interpersonal therapy, cognitive behaviour Cannabis produces a very mild physical depend-
therapy (CBT), motivational enhancement therapy, ence, with a relatively mild withdrawal syndrome,
self-control strategies, psychotropic drugs for asso- which is characterised by fine tremors, irritabil-
ciated psychopathology, family therapy, and group ity, restlessness, nervousness, insomnia, decreased
therapy (e.g. in therapeutic communities such as Syna- appetite and craving. This syndrome begins within
non, self-help groups such as Narcotic Anonymous or few hours of stopping cannabis use and lasts for 4 to
NA). These methods have to be tailored for use in an 5 days. However, some health professionals feel that
individual patient. there is no true physical dependence with cannabis.

Table 4.8: Cannabis Preparations

Cannabis Portion of Plant THC Content (%) Potency
Preparation (as compared to ‘Bhang’)
1 Hashish/Charas Resinous exudate from the flowering 8-14 10
tops of cultivated plantsh
2 Ganja Small leaves and brackets of inflorescence 1-2 2
of highly cultivated plants
3 Bhang Dried leaves, flowering shoots and 1 1
cut tops of uncultivated plants
4 Hash oil Lipid soluble plant extract 15-40 25
 46 A Short Textbook of Psychiatry

On the other hand, psychological dependence 2. Amotivational syndrome: Chronic cannabis use is
ranges from mild (occasional ‘trips’) to marked (com- postulated to cause lethargy, apathy, loss of inter-
pulsive use). All the active ingredients are called as est, anergia, reduced drive and lack of ambition.
marijuana or marihuana. Cannabis can be detected The aetiological role of cannabis in this disorder
in urine for up to 3 weeks after chronic heavy use. is however far from proven.
3. ‘Hemp insanity’ or cannabis psychosis: Indian
Acute Intoxication hemp insanity was first described by Dhunjibhoy
Mild cannabis intoxication is characterised by mild in 1930. Thereafter, several reports appeared
impairment of consciousness and orientation, light- in literature from India, Egypt, Morocco and
headedness, tachycardia, a sense of floating in the Nigeria. It was described as being similar to an
air, a euphoric dream-like state, alternation (either acute schizophreniform disorder with disorien-
an increase or decrease) in psychomotor activity and tation and confusion, and with a good prognosis.
tremors, in addition to photophobia, lacrimation, The validity of this specific disorder is currently
tachycardia, reddening of conjunctiva, dry mouth and doubted.
increased appetite. There is often a curious splitting of 4. Other complications: Chronic cannabis use some-
consciousness, in which the user seems to observe his times leads to memory impairment, worsening
own intoxication as a non-participant observer, along or relapse in schizophrenia or mood disorder,
with a feeling that time is slowed down. chronic obstructive airway disease, pulmonary
Perceptual disturbances are common and can malignancies, alteration in both the humoral and
include depersonalisation, derealisation, synaesthe- cell-mediated immunity, decreased testosterone
sias (sensation in one sensory modality caused by a levels, anovulatory cycles, reversible inhibition
sensation in another sensory modality, e.g. ‘seeing’ of spermatogenesis, blockade of gonadotropin
the music) and increased sensitivity to sound. How- releasing hormone, and increased risk for the
ever, hallucinations are seen only in marked to severe developing foetus (if taken during pregnancy).
intoxication. These are often visual, ranging from
elementary flashes of lights and geometrical figures Treatment
to complex human faces and pictures. As the withdrawal syndrome is usually very mild, the
Mild cannabis intoxication releases inhibitions, management consists of supportive and symptomatic
which is expressed in words and emotions rather than treatment, if the patient comes to medical attention.
in actions. ‘Flashback phenomenon’ has been descri- The psychiatric symptoms may require appropriate
bed, and is characterised by a recurrence of cannabis psychotropic medication and sometimes hospitali-
use experience in the absence of current cannabis use. sation. Psychotherapy and psychoeducation are
very impor tant in the management of psychic
Complications dependence.
The complications of cannabis use can include:
1. Transient or short-lasting psychiatric disorders: COCAINE USE DISORDER
Acute anxiety, paranoid psychosis, hysterical
fugue-like states, suicidal ideation, hypomania, Cocaine is an alkaloid derived from the coca bush,
schizophrenia-like state (which is characterised by Erythroxylum coca, found in Bolivia and Peru. It was
persecutory delusions, hallucinations and at times isolated by Albert Neimann in 1860 and was used by
catatonic symptoms), acute organic psychosis and, Karl Koller (a friend of Freud) in 1884 as the first
very rarely, depression. effective local anesthetic agent.
 Psychoactive Substance Use Disorders
47

Cocaine (common street name: Crack) can be output may be present. Later, judgement is impaired
administered orally, intranasally, by smoking (free and there is impairment of social or occupational
basing) or parenterally, depending on the preparation functioning.
available (Fig. 4.2). Cocaine HCl is the commonest
form used, followed by the free base alkaloid. Both Withdrawal Syndrome
intravenous use and free base inhalation produce a Cocaine use produces a very mild physical, but a
‘rush’ of pleasurable sensations. very strong psychological, dependence. A triphasic
Cocaine is a central stimulant which inhibits the withdrawal syndrome usually follows an abrupt dis-
reuptake of dopamine, along with the reuptake of continuation of chronic cocaine use (Table 4.9).
norepinephrine and serotonin. In animals, cocaine
is the most powerful reinforcer of the drug-taking Complications
behaviour. A typical pattern of cocaine use is cocaine The complications of chronic cocaine use include
‘runs’ (binges), followed by the cocaine ‘crashes’ acute anxiety reaction, uncontrolled compulsive
(interruption of use). Cocaine is sometimes used in behaviour, psychotic episodes (with persecutory delu-
combination with opiates like heroin (‘speed ball’) sions, and tactile and other hallucinations), delirium
or at times amphetamines. Previously uncommon, and delusional disorder. High doses of cocaine can
cocaine misuse appears to be recently a growing often lead to seizures, respiratory depression, cardiac
problem in the metros of India. arrhythmias, coronary artery occlusion, myocardial
infarction, lung damage, gastrointestinal necrosis,
Acute Intoxication foetal anoxia and perforation of nasal septum.
Acute cocaine intoxication is characterised by pupil-
lary dilatation, tachycardia, hypertension, sweating, Treatment
and nausea or vomiting. A hypomanic picture with Before starting treatment, it is essential to diagnose
increased psychomotor activity, grandiosity, ela- (or rule out) co-existent psychiatric and/or physical
tion of mood, hypervigilance and increased speech disorder, and assess the motivation for treatment.

Fig. 4.2: Cocaine Preparations

 48 A Short Textbook of Psychiatry

Table 4.9: Phases in Cocaine Withdrawal Syndrome

Phase Sub-stage Duration Clinical Features
I (Crash phase) i 9 hours Agitation, depression, anorexia,
to craving +++
ii 4 days Fatigue, depression, sleepiness, craving +
iii after discontinuation Exhaustion, hypersomnia with intermittent
awakening, hyperphagia, craving ±
II i 4 to 7 days Normal sleep, improved mood, craving ±
after
discontinuation
ii Anxiety, anergia, anhedonia, craving ++
III (Extinction phase) After 7-10 days of No withdrawal symptoms, increased
discontinuation vulnerability to relapse

Cocaine use disorder is commonly associated with therapy, are useful in the post-withdrawal treatment
mood disorder, particularly major depression and and in the prevention of relapse.
cyclothymia.
AMPHETAMINE USE DISORDER
Treatment of Cocaine Overdose
The treatment of overdose consists of oxygenation, Though synthesised by Edleano in 1887, it was intro-
muscle relaxants, and IV thiopentone and/or IV duced in Medicine in 1932 as benzedrine inhaler, for
diazepam (for seizures and severe anxiety). the treatment of coryza, rhinitis and asthma. Later, it
IV propranolol, a specific antagonist of cocaine- was recommended for a variety of conditions such as
induced sympathomimetic effects, can be helpful, narcolepsy, postencephalitic parkinsonism, obesity,
administered by a specialist. Haloperidol (or pimoz- depression, and even to heighten energy and capac-
ide) can be used for the treatment of psychosis, as ity to work.
well as for blocking the cardio-stimulatory effects of Amphetamine refers to a unique chemical which
cocaine. These must be administered very carefully is basically phenyl-iso-propylamine or methyl-
by an expert specialist. phenethylamine. It is a powerful CNS stimulant,
with peripheral sympathomimetic effects too. The
Treatment of Chronic Cocaine Use dextro-amphetamine isomer is nearly 3-4 times more
The management of underlying (or co-existent) psy- potent than the levo-isomer. It acts primarily on nore-
chopathology is probably the most important step in pinephrine release in brain, along with an action on
the management of chronic cocaine use. the release of dopamine and serotonin.
The pharmacological treatment includes the Although still clinically indicated for narcolepsy
use of bromocriptine (a dopaminergic agonist) and and attention deficit hyperactivity disorder (and very
amantadine (an antiparkinsonian) in reducing cocaine rarely for obesity and mild depression), one of the
craving. commonest patterns of ‘use’ is seen amongst the
Other useful drugs are desipramine, imipramine students and sports-persons to overcome the need for
and trazodone (both for reducing craving and for sleep and fatigue. Tolerance usually develops to the
antidepressant effect). The goal of the treatment is central as well as cardiovascular effects of ampheta-
total abstinence from cocaine use. mines.
The psychosocial management techniques, such as Recently, there has been a resurgence of amphe-
supportive psychotherapy and contingent behaviour tamine use in USA and Europe, with the availability of
 Psychoactive Substance Use Disorders
49

‘designer’ amphetamines, such as MDMA (3,4-methy- Treatment

lenedioxy-amphetamine; street name: ecstasy or Treatment of Intoxication
XTC).
Acute intoxication is treated by symptomatic meas-
Intoxication and Complications ures, e.g. hyperpyrexia (cold sponging, parenteral
The signs and symptoms of acute amphetamine antipyretics), seizures (parenteral diazepam), psy-
intoxication are primarily cardiovascular (tachycar- chotic symptoms (antipsychotics), and hypertension
dia, hypertension, haemorrhage, cardiac failure and (antihypertensives). Acidification of urine (with oral
cardiovascular shock) and central (seizures, hyperpy- NH4Cl; 500 mg every 4 hours) facilitates the elimina-
rexia, tremors, ataxia, euphoria, pupillary dilatation, tion of amphetamines.
tetany and coma). The neuropsychiatric manifestations
include anxiety, panic, insomnia, restlessness, irrita-
Treatment of Withdrawal Symptoms
bility, hostility and bruxism. The presence of severe suicidal depression may necessitate
Acute intoxication may present as a paranoid hal- hospitalisation. The treatment includes symptomatic
lucinatory syndrome which closely mimics paranoid management, use of antidepressants and supportive
schizophrenia. The distinguishing features include psychotherapy. The management of withdrawal syndrome
rapidity of onset, prominence of visual hallucinations, is usually the first step towards successful management
absence of thought disorder, appropriateness of affect, of amphetamine dependence.
fearful emotional reaction, and presence of confusion.
However, a confident diagnosis requires an estimation LSD USE DISORDER
of the recent urinary amphetamine levels. Ampheta-
mine-induced psychosis usually resolves within seven Lysergic acid diethylamide, first synthesised by Albert
days of urinary clearance of amphetamines. Hoffman in 1938 and popularly known as ‘acid’, is a
Chronic amphetamine intoxication leads to severe powerful hallucinogen. It is related to the psychedelic
and compulsive craving for the drug. A high degree compounds found in the ‘morning glory’ seeds, the
of tolerance is characteristic, with the dependent lysergic acid amides. As little as 100 μg of LSD is
individual needing up to 15-20 times the initial dose, sufficient to produce behavioural effects in man. LSD
in order to obtain the pleasurable effects. A common presumably produces its effects by an action on the
pattern of chronic use is a cycle of runs (heavy use 5-HT levels in brain.
for several days) followed by crashes (stopping the Although tolerance as well as psychological
drug use). dependence can occur with LSD use, no physical
Tactile hallucinations, in clear consciousness, dependence or withdrawal syndrome is reported. A
may sometimes occur in chronic amphetamine common pattern of LSD use is a trip (occasional use
intoxication. followed by a long period of abstinence).

Withdrawal Syndrome Intoxication

The withdrawal syndrome is typically seen on an The characteristic features of acute LSD intoxication
abrupt discontinuation of amphetamines after a period are perceptual changes occurring in a clear conscious-
of chronic use. The syndrome is characterised by ness. These perceptual changes include deperson-
depression (may present with suicidal ideation), alisation, derealisation, intensification of perceptions,
marked asthenia, apathy, fatigue, hypersomnia alterna- synaesthesias (for example, colours are heard, and
ting with insomnia, agitation and hyperphagia. sounds are felt), illusions, and hallucinations.
 50 A Short Textbook of Psychiatry

In addition, features suggestive of autonomic hy- it has been described separately as it has some distinc-
peractivity, such as pupillary dilatation, tachycardia, tive features.
sweating, tremors, incoordination, palpitations, raised Since their introduction in 1903, barbiturates have
temperature, piloerection and giddiness, can also be been used as sedatives, hypnotics, anticonvulsants,
present. anaesthetics and tranquilisers. The commonly abused
These changes are usually associated with marked barbiturates are secobarbital, pentobarbital and amo-
anxiety and/or depression, though euphoria is more barbital. Their use has recently decreased markedly
common in small doses. Persecutory and referential as benzodiazepines have replaced barbiturates in the
ideation may also occur. majority of their clinical uses.
Sometimes, acute LSD intoxication presents with Barbiturates produce marked physical and psy-
an acute panic reaction, known as a bad trip, in which chological dependence. Tolerance (both central and
the individual experiences a loss of control over his metabolic) develops rapidly and is usually marked.
self. The recovery usually occurs within 8-12 hours of There is also a cross tolerance with alcohol.
the last dose. Rarely, the intoxication is severe enough
to produce an acute psychotic episode resembling a Intoxication and Complications
schizophreniform psychosis. Acute intoxication, typically occurring as an epi-
sodic phenomenon, is characterised by irritability,
Withdrawal Syndrome increased productivity of speech, lability of mood,
No withdrawal syndrome has been described with disinhibited behaviour, slurring of speech, incoor-
LSD use. dination, attentional and memory impairment, and
However, sometimes, there is a spontaneous recur- ataxia. Mild barbiturate intoxication resembles alcohol
rence of the LSD use experience in a drug free state. intoxication; severe forms may present with diplopia,
Described as a flashback, it usually occurs weeks to nystagmus, hypotonia, positive Romberg’s sign and
months after the last experience. Such episodes are suicidal ideation. Drug automatism may sometimes
often induced by stress, fatigue, alcohol intake, severe lead to lethal accidents.
physical illness or marihuana intoxication. Intravenous use can lead to skin abscesses, cel-
lulitis, infections, embolism and hypersensitivity
Complications reactions.
Long-term LSD use is not a common phenomenon.
The complications of chronic LSD use include psy- Withdrawal Syndrome
chiatric symptoms (anxiety, depression, psychosis or The barbiturate withdrawal syndrome can be very
visual hallucinosis) and occasionally foetal abnor- severe. It usually occurs in individuals who are taking
malities. more than 600-800 mg/day of secobarbital equivalent
for more than one month.
Treatment It is usually characterised by marked restlessness,
The treatment of acute LSD intoxication consists tremors, hypertension, seizures, and in severe cases,
of symptomatic management with antianxiety, anti- a psychosis resembling delirium tremens. The with-
depressant or antipsychotic medication, along with drawal syndrome is at its worst about 72 hours after
supportive psychotherapy. the last dose. Coma, followed by death, can occur in
some cases.
BARBITURATE USE DISORDER
Treatment
Barbiturate use disorder is now subsumed under seda- The barbiturate intoxication should be treated sympto-
tive, hypnotic and anxiolytic use disorders. However, matically. If patient is conscious induction of vomiting
 Psychoactive Substance Use Disorders
51

and use of activated charcoal can reduce drug absorp- to heavy doses (more than 60-80 mg per day of dia-
tion. If coma ensues, intensive care measures should zepam), is characterised by marked anxiety, irritability,
be employed on an emergency basis. tremors, insomnia, vomiting, weakness, autonomic
The treatment of withdrawal syndrome is usually hyperactivity with postural hypotension, and seizures.
conservative. However, pentobarbital substitution Depression, transient psychotic episodes, suicidal
therapy has been suggested for treatment of withdrawal ideation, perceptual disturbances and rarely delirium
from short-acting barbiturates. After detoxification have also been reported in withdrawal period.
phase is over, follow-up supportive treatment and
treatment of associated psychiatric disorder, usually Treatment
depression, are important steps to prevent relapses. The treatment of benzodiazepine intoxication is
usually symptomatic. However, in cases of coma
BENZODIAZEPINES AND OTHER caused by benzodiazepine overdose, flumazenil (a
SEDATIVE-HYPNOTIC USE DISORDER benzodiazepine receptor antagonist) can be used in a
dose of 0.3-1.0 mg IV, administered over 1-2 minutes.
Since the discovery of chlordiazepoxide in 1957 The treatment of low dose dependence syndrome
by Sternbach, benzodiazepines have replaced other (~15 mg/day of diazepam) is abrupt withdrawal and
sedative-hypnotics in treatment of insomnia and symptomatic management of withdrawal symptoms.
anxiety. These are currently one of the most often pre- However, moderate to high dose dependence is best
scribed drugs. Benzodiazepines produce their effects managed by gradual withdrawal in a step-wise manner
by acting on the benzodiazepine receptors (GABA- (a reduction of ~10% of the dose every day). Sometimes
benzodiazepine receptor complex), thereby indirectly a slower withdrawal is clinically indicated (see Ashton
increasing the action of GABA, the chief inhibitory Manual in Suggested Further Reading List).
neurotransmitter in the human brain. The best treatment is probably prevention by limit-
Benzodiazepine (or sedative-hypnotic) use disor- ing benzodiazepine use to no more than 2-4 weeks of
der can be either iatrogenic or originating with illicit prescription at most.
drug use. Dependence, both physical and psychologi- After the detoxification phase, an adequate follow-up
cal, can occur and tolerance is usually moderate. and supportive treatment is essential to prevent relapses.

Intoxication and Complications INHALANTS OR VOLATILE SOLVENT

Acute intoxication resembles alcohol intoxication USE DISORDER
whilst chronic intoxication causes tolerance, espe-
cially to the sedative and anticonvulsant actions of The commonly used volatile solvents include gaso-
benzodiazepines. Excessive doses can lead to respira- line (petrol), glues, aerosols (spray paints), thinners,
tory depression, coma and death while chronic use has varnish remover and industrial solvents. The active
been reported to cause amnestic syndrome. ingredients usually include toluene, benzene, acetone
Some of the other complications of benzodi- and halogenated hydrocarbons.
azepines, particularly with high dose and chronic Volatile solvent misuse is more common in early
use, include behavioural disinhibition, impulsivity, adolescence as a group activity, particularly in low
blackouts, memory loss, worsening of depression and socioeconomic status groups (e.g. rag-pickers in
interactions with other prescribed medications. Mumbai and Delhi).

Withdrawal Syndrome Intoxication and Complications

A typical withdrawal syndrome, after cessation of Inhalation of a volatile solvent leads to euphoria, ex-
prolonged use (more than 4-6 weeks) of moderate citement, belligerence, dizziness, slurring of speech,
 52 A Short Textbook of Psychiatry

apathy, impaired judgement, and neurological signs depression and impairment in cognitive functions
(such as decreased reflexes, ataxia, nystagmus, incoor- have been reported.
dination and coma). Death can occur due to respiratory
depression, cardiac arrhythmias, or asphyxia. Treatment
The complications include irreversible damage to The treatment of PCP intoxication is symptomatic and
liver and kidneys, peripheral neuropathy, perceptual usually involves gastric lavage, isolation, and use of
disturbances and brain damage. anticonvulsants (for seizures) and antipsychotics (for
There appears to be no specific treatment of the PCP induced psychosis).
inhalant use disorder. There is often an associated psy- There is no specific treatment for phencyclidine
chiatric disorder (usually schizophrenia or personality withdrawal syndrome.
disorder, particularly in solitary sniffers), or there is
a history of criminal background. The prognosis is OTHER USE DISORDERS
usually guarded.
Caffeine and nicotine are among the most widely used
PHENCYCLIDINE USE DISORDER substances, as they are both legally available. Both of
these can cause intoxication, dependence, tolerance,
Phencyclidine (PCP) was introduced as a dissociative and withdrawal syndrome.
anaesthetic agent (similar to ketamine) in 1950s. Nicotine use (often in the form of smoking) is more
However, its use was soon restricted to veterinary common in schizophrenia and depression. Smoking
anaesthesia as some human subjects developed predisposes to increased risk of cardiovascular dis-
delirium while emerging from anaesthesia. Classified ease, respiratory disease and cancer, and can affect
as an atypical hallucinogen (street names: Peace pill; metabolism of several psychotropic drugs. Smoking
angel dust), PCP selectively antagonises the neuronal also decreases serum levels of clozapine (and other
action of NMDA (N-methyl-D-aspartate). drugs such as olanzapine, duloxetine, fluphenazine)
PCP is usually taken either occasionally or in by up to 50%. Clozapine levels can therefore rise
binges (called as runs); however, some individuals do significantly after smoking cessation even whilst the
take PCP in a regular manner. It can be administered patient is on nicotine replacement therapy. This is due
orally, intravenously or by snorting. to induction of liver enzymes CYP1A2 (cytochrome
P450 1A2) by hydrocarbons in tobacco smoke rather
Intoxication and Complications than nicotine.
Acute PCP intoxication produces euphoria in small Nicotine withdrawal can occur 12-14 hours after
doses; higher doses produce dysphoria. Other features last smoke and can present with anxiety, restless-
may include impulsiveness, agitation, impaired social ness, poor concentration, decreased sleep, increased
judgement, assaultativeness, feeling of numbness appetite and exacerbation of psychiatric symptoms in
and inability to move. PCP intoxication can some- those with pre-existing psychiatric disorder(s).
times present with psychiatric syndromes (catatonic Nicotine replacement therapy is widely used
syndrome, delirium, stupor, paranoid hallucinatory despite equivocal evidence, delivered in a variety
psychosis, mania or depression) and/or neurological of preparations such as a sublingual tablet (2 mg),
symptoms (nystagmus, ataxia, dysarthria, rigidity, lozenge (1, 2 or 4 mg), chewing gum (2 or 4 mg),
seizures or coma). nasal spray (0.5 mg), inhalator (10 mg), and patches
(7, 14 or 21 mg).
Withdrawal Syndrome In addition, bupropion (also called as amfeb-
Although no clear-cut withdrawal syndrome has utamone; a norepinephrine and dopamine reuptake
been described, craving, social withdrawal, anxiety, inhibitor – NDRI antidepressant) and varenicline
 Psychoactive Substance Use Disorders
53

(a partial α4β2 nicotinic acetylcholine receptor partial arrhythmia, periods of inexhaustibility and psychomo-
agonist) are pharmacological agents recently used in tor agitation.
promoting smoking cessation as adjuncts to behav- These symptoms should be accompanied by
ioural or cognitive behavioural treatment(s). These clinically significant distress or impairment in social,
should only be initiated after a discussion of possible occupational or other areas of functioning, and the
adverse effects with the patient. symptoms should not be better accounted by a general
Similarly, caffeine is widely used in general medical condition or another mental disorder.
population as well as in patients with psychiatric The typical content of caffeine in the commonly
disorders. DSM-IV-TR defines caffeinism (caffeine used drinks is usually as follows: tea (45 mg/cup),
intoxication) as a recent consumption of caffeine, instant coffee (60 mg/cup), brewed coffee (100 mg/
usually in excess of 250 mg per day, along with five cup), and cola drinks (25-50 mg/can). Caffeine is also
or more of the following: restlessness, nervousness, present in chocolate. Caffeine can affect metabolism
excitement, insomnia, flushed face, diuresis, GI (gas- of several psychotropic drugs, most importantly
trointestinal) disturbance, muscle twitching, rambling clozapine. It can elevate the levels of clozapine (and
flow of thought and speech, tachycardia or cardiac other drugs) by inhibiting CYP1A2.