University of Oxford

Psychoactive Substance Misuse Disorders

 Psychoactive Substance Misuse Disorders

A. Psychopathology:

ALCOHOL:

Alcohol is a widely used recreational drug (even in our culture) because of its relaxing and disinhibiting effect. It is also an extremely common cause of physical and psychiatric morbidity. The psychiatric manifestation of alcohol use form the basis of this lecture, providing the conceptual framework of all substance related disorders.

Mechanism of action:

The biochemical action of alcohol is complex and only partly understood. It has a number of effects on various neurotransmitter system of the brain. The primary effects are thought to be stimulation of GABA receptors and inhibition of excitatory glutamate receptors, causing sedation, relief of anxiety, and amnesia. In addition, alcohol appears to affect noradrenergic, dopaminergic, serotoinergic and opioids systems, giving rise to other effects such as nausea, euphoria and craving.

Metabolism:

Approximately 75% of this takes place in the liver. There are two mechanisms:

  • Alcohol dehydrogenase converts alcohol to acetaldehyde; this is then converted to acetate by acetaldehyde dehydrogenase
  • Mixed-function oxidases metabolism alcohol within the endoplasmic reticulum hepatocytes

The classification of substance misuse disorder (clinical syndromes caused by excessive use of alcohol and other psychoactive substances):

The terms ‘alcoholism’ and ‘alcohol misuse should be avoided; they are often loosely applied and cause confusion.

1. Acute intoxication:

Acute intoxication is the most common manifestation of alcohol use and will be suffered by most users in our culture. The term denotes the acute dose-related effects of a substance which resolve once the substance (or its active metabolites) are expelled from the body.

In the case of alcohol, which is a CNS depressant, low blood alcohol concentrations produce an enhanced sense of wellbeing, greater confidence, relief of anxiety, and social disinhibition. Mood changes vary and include depression, elation, and aggression. Visual reaction times are reduced and motor coordination becomes impaired.  As blood alcohol levels increase, coordination, judgment, and level of consciousness deteriorate, leading to ataxia, disorientation, amnesia, incontinence, and eventually death secondary to respiratory depression.

Pathological intoxication:

The term denotes the rare syndrome of uncharacteristic violent or aggressive behaviour after drinking small quantities of alcohol that would not cause intoxication in most people.

2. Harmful use:

The term describes the secondary damaging effects of alcohol or other psychoactive substance misuse.

Using alcohol to illustrate, a number of consequences may result:

  1. Physical: alcohol adversely affects most systems of the body.
  • Neurological: epilepsy-alcohol withdrawal, head injury, cerebellar degeneration, polyneuropathy, delirium tremens/ Wernick’s encephalopathy/ Korsakoff’s syndrome (see later)
  • Cardiovascular: hypertension, cardiomyopathy, arrthymias, ischeaemic heart disease (IHD)
  • Gastrointestinal: acute gastritis, carcinoma oesophagus/rectum, pancreatitis, haemochromatosis, alcoholic hepatitis/cirrhosis
  • Metabolic: hyperuricaemia, hyperlipidemia, hypoglycemia, hypomagnesaemia
  • Respiratory: pneumonia
  • Endocrine: pseudo-Cushing’s syndrome
  • Musculoskeletal: acute & chronic myopathy, osteoporosis, osteomalacia
  • Haematological: macrocytosis, thrombocytopenia, leukopenia
  • Reproduction: premature babies, foetal alcohol syndrome ( small stature, low birth weight, intellectual impairment, facial abnormality, over-activity)
  1. Psychological: increased alcohol consumption gives rise to a range of symptoms and behaviours, such as increased depressive symptoms and violence (see later)
  2. Social: this might include increased absenteeism from work, increased financial difficulties or debt, recurrent drink-driving offences, and problems sustaining relationship

3. Dependence syndrome:

Whereas the previous disorder may occur with sporadic rather than regular consumption, a dependence syndrome develops against a backdrop of heavy, regular consumption. Diagnosis depends on identification of three or more of the following:

  • Ø Compulsion to take the substance
  • Ø Stereotyped pattern of substance use
  • Ø Physiological withdrawal symptoms ‘the shakes’ leading to ‘eye-opener’
  • Ø Tolerance
  • Ø Neglect of other interest
  • Ø Reinstatement after abstinence

4. Withdrawal state with delirium:

This state occurs when a withdrawal syndrome develops characteristic delirium. This is particularly important to diagnose given the life-threatening nature of a delirium. It occurs around two days (48 hours) after cessation of drinking in about 5% of alcohol- dependent individuals (see above for criteria), usually in association with a physical illness such as pneumonia. It is characterised by:

  • Ø Clouding of consciousness
  • Ø Disorientation
  • Ø Memory impairment
  • Ø Extreme agitation
  • Ø Distressing illusions, hallucinations (Lilliputian hallucinations: visual hallucinations are fleeting miniature humans or animals e.g. spiders)
  • Ø Other symptoms of CNS excitation

An even rarer neurological syndrome known as Wernicke’s encephalopathy may occur. This is related to chronic deficiency of vitamin B1(thiamine), it is characterised by:

  • Ø Impaired consciousness
  • Ø Disorientation
  • Ø Memory problems
  • Ø Ataxia (broad gait)
  • Ø Ophthalmoplegia (ocular palsies, nystagmus and fixed pupils)

The syndrome is thought to develop from haemorrhagic lesions within the cerebellum, thalamus, ventricular system, brainstem and mamilary bodies (sub-cortical structures)

5. Psychotic disorder:

Develop within two days of consuming the substance. It is distinct from previous disorders and the effects of intoxication, in that it occurs in clear consciousness and persists beyond the period the original substance exerts its effect. This disorder resolves spontaneously, usually within one month (brief psychotic episode), but may at times appear indistinguishable from an affective psychosis or schizophrenia

Alcohol hallucinosis is a commonly described condition whereby the patient describes persistent second-person auditory hallucinations. These occur in clear (i.e. not during intoxication or withdrawal and sometimes years after stopping the alcohol) and usually consist of simple words or phrases.

6. Amnesic disorder:

Alcohol -induced amnesic syndrome, or Korsakoff’s psychosis, is related to vitamin B1 deficiency and is a common sequel of Wernicke’s encephalopathy (Wernicke’sà acute, Korsakoff’sàchronic).

7. Dementia syndrome:

This present similarly to the typical dementia syndrome (see dementia lecture), although, like amnesic syndrome, must be clearly related to prolonged heavy use of the substance. It is considered as a reversible dementia (as opposed to irreversible dementias, which is the majority of the dementias e.g. Alzheimer’s).

OTHER PSYCHOACTIVE SUBSTANCES

Problems related to the use of illegal (and some time, legal) psychoactive drugs are extremely common in mental health services, particularly among younger population. Some of the main classes of drugs and their mechanism of action will be described below:

Amphetamine:

Route of administration: oral, IV, smoked, snorted

Acute effect: dilated pupils increased or decreased blood pressure and pulse, perspiration, agitation, euphoria, hypervigilance, insomnia, and mood changes.

Chronic effect: weight loss, tolerance, craving and paranoid psychosis. On withdrawal, there may be several days of sleep disturbance, increased appetite, low mood, fatigue, and psychomotor changes.

Mechanism of action: CNS stimulant

  • Inhibition of noradrenaline, dopamine, and serotonin uptake
  • Increased release of dopamine

Ecstasy or MDMA is similar in effect but additionally gives rise to hyperpyrexia, dehydration and hyponatraemia, due to direct effect on temperature regulation and antidiuretic hormone (ADH) production.

Cocaine:

Route of administration: smoked, snorted, inhaled, IV

Acute effect: similar to those of amphetamine. Vivid hallucinations are often described, including formication (the sensation of insects crawling beneath the skin, so called cocaine bug). In overdose, death may occur from hypertensive crisis or arrhythmias.

Chronic effect: Nasal septum perforation or ulceration. The withdrawal syndrome is similar to amphetamine

Mechanism of action:CNS stimulant:

  • Sympathomimetic activity
  • Direct action on temperature regulation
  • Local anesthetic
  • Increase dopamine release, block dopamine, noradrenaline and serotonin reuptake

LSD (Lysergic acid diethylamine):

Route of administration: Oral, IV, smoked

Acute effect: Dilated pupils, tachycardia, perspiration, blurred vision, incoordination, euphoria (or depression), impaired judgment and perceptual disturbances. ‘Synaesthesia’ describes blending of sensation e.g. tasting smell

Chronic effect: tolerance and craving. Rarely may cause psychosis, although ‘flashbacks occur- these are re-experiencing of the disturbances after use.

Mechanism of action: hallucinogenic that may causes hyperarousal of the CNS by mediation of the serotonin system

Cannabis (marijuana, grass, hash, weed):

Route of administration: Oral, IV, smoked, snorted

Acute effect: conjunctival injection, dry mouth, tachycardia, euphoria, relaxation and altered time-perception and judgment

Chronic effect: tolerance, craving, psychosis (maybe only in predisposed individuals, great debate regarding if it causes psychosis), flashbacks and withdrawal (rare) in heavy users consisting of sleep disturbance, nausea and tremor.

Mechanism of action: direct action on cannabinoid receptors sites

Opioids (heroin, morphine, pethidine, methadone):

Route of administration: oral, IV, smoked, snorted

Acute effect: conjunctival injection, constructed pupils, slurred speech, euphoria, apathy, and impaired judgment.

Chronic effect: constipation, tolerance, and intense craving. Withdrawal syndrome can last for between six hours and ten days. Symptoms comprise low mood, agitation, dilated pupils, vomiting, muscle pain, lacrimation, diarrhea, cramps, fever, piolerection, gooseflesh (cold turkey), and sleep disturbance. In overdose pupils dilated, respiratory depression, hypotension and coma.

Mechanism of action: direct action on opioid receptors sites (central & peripheral)

Benzodiazepine (BDZ):

Route of administration: Oral, IV

Acute effect: impaired consciousness, nystagmus, disinhibition, mood changes, and perceptual disturbance

Chronic effect: effects are similar to alcohol

Mechanism of action: CNS depressant that causes potentiation of GABA transmission

Inhalants (solvents, glue, paints, petrol):

Route of administration: Inhaled (heated to increase speed of action)

Acute effect: impaired consciousness, nystagmus, unsteady gait, vomiting, euphoria, disinhibition and psychosis.

Chronic effect: weight loss, tolerance, craving and paranoid psychosis. On withdrawal, there may be several days of sleep disturbance, increased appetite, low mood, fatigue, and psychomotor changes.

Mechanism of action: similar to alcohol, initial CNS stimulant then depressant.

Clinical syndromes associated with the use of psychoactive substances:

Drug

Intoxication state

Dependence state

Withdrawal state

Psychotic disorder

Amnesic syndrome/ dementia

Amphetamine

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Cocaine

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LSD

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Phenylacyclidine

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Cannabis

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Opioids

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Benzodiazepine

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Inhalants

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B. Aetiology:

ALCOHOL:

It is widely accepted that the aetiology for substance misuse is multifactorial (Bio-Psycho-Social)

1. Biological theories:

Genetic predisposition: most family studies show an increase risk of dependence among relatives of dependent individuals; adoption studies indicate heritable component, as offspring of dependent parents have higher rates of dependence than their non-dependent adoptive parents. The nature of this influence is unclear. It may operate at the level of heritable personality characteristic or it might relate to the body’s biochemical susceptibility to alcohol and its consequences. For example, 50% of east-Asian populations have a deficiency in one of the aldehyde dehydrogenase enzymes, leading to flushing and palpitation after small amount of alcohol; this may explain reduced rates of consumption and dependence in these cultures

Biochemical: the biochemical basis of dependence remains uncertain. A current model postulates decreasing activity of GABA system and increasing activity of glutamate systems in response to chronic alcohol administration. The former is facilitated by increasing calcium channels which reduce chloride ion flow. By decreasing the inhibitory action of GABA to counteract the CNS depressant effect of alcohol, the neurons become more excitable and this leads to the symptoms of CNS excitability that occur on sudden alcohol withdrawal.

2. Psychological theories:

Psychodynamic: several theories. One suggests there are unconscious gains resulting from both intoxication (allows release of aggression) and the personal damage caused (sympathy from others).

Cognitive-behavioural:based on associative learning (classical and operant conditioning), cognitive learning, and social learning theories. In the associative learning theory, a neutral (unconditioned) stimulus such as hotel becomes associated with alcohol; this then becomes a conditioned stimulus, leading to psychological craving. An alternative explanation, according to social learning theory, is that the patterns of alcohol consumption are modeled on the drinking behaviour of relatives or peers. Family studies support the idea that drinking habits follow those of older relatives.

Personality factors: there is little support for the notion of ‘addictive personality’, although there is link with premorbid dissocial (antisocial) and borderline personality traits.

Psychiatric disorders: psychotic, affective and anxiety disorders appear to increase the risk.

3. Social theories:

Level of alcohol consumption: population levels of alcohol consumption are closely related to levels of alcohol-related disorders which in turn are related to the easily measurable number of death cirrhosis. There are wide variations among populations in this prospect, e.g. levels in Italy and France are greater than those of the UK and USA (as usual figures are not present for our culture, but it is reasonable that one could assume that levels are much less than the west). Level of consumptions are influenced by the real cost of alcohol and availability (here it is expensive àless use, in the west cheap àmore use). Cultural attitude also has a major influence (less consumption in Muslim cultures).

Occupation: there is a clear link between certain occupations and death from cirrhosis; again, issues of availability and subcultural attitudes interplay. The highest-risk professions are members of leisure and catering trades, and those involved with shipping and travel. However, when one looks at the overall picture, higher rates of dependence are noted in unskilled workers and the unemployed.

Significant life events: these appear to increase the amount of alcohol consumed and therefore the risk of dependence.

ILLICIT-DRUG DEPENDENCE

The aetiological factors for illicit-drug dependence are even less well understood, although would again appear to be related to a mixture of biopsychosocial factors. Factors of price, availability, and cultural attitudes again appear to operate at a population level. Moreover, social deprivation, family environment, conduct disorder in childhood (see childhood lecture), dissocial personality, psychiatrist prescription habits (major source of addiction in UAE) and severe mental illness increase the likelihood of substance-misuse problems.

The introduction of harsher legal penalties for suppliers and users of illcit drugs (which is the case in this country) and increase education about the ‘real’ effect of drug use (which is not the case in this country), surprisingly does not result in significant decrease in illicit drug use (as opposed to alcohol use)

C. Epidemiology:

ALCOHOL

Prevalence:

Accurate figures are difficult to obtain in western cultures (non-existent in ours) to obtain given the complexity of assessing what is still stigmatized and socially undesirable behaviour. Estimates are based on population surveys (weak evidence based method for collecting information), hospital-admission statistic, and cirrhosis statistic (only gives small sample of ‘real’ users due to legal ramification).

Demographic factors are:

  • Marital status: divorced/separated > single > married
  • Age: the highest consumption of alcohol in the west, occur for both sexes in the age band 18-24 (maybe higher in our culture), but problem related to dependence tend to emerge at a later age.
  • Social class: as has been mentioned above, alcohol consumption is higher in social class V and the unemployed. This picture applies particularly to men. In women, higher rates of consumption are seen in the higher social classes.

ILLICIT-DRUG DEPENDENCE

Prevalence:

As with alcohol, overall illicit-substance use has increased over the 30 years almost worldwide. Rates are particularly high within urban, socially deprived areas.

Type of drug used:

In the west in general cannabis is the most commonly used, followed by amphetamine, ecstasy and LSD; heroin is used less frequent and cocaine is even less. Here one can presume that BDZ are the most commonly used drug, heroine and cannabis are used more than LSD, ecstasy and cocaine.

Sex difference:

Almost worldwide males are more than females in the UK 3:1; here one can guess that it is much more by males 10:1.

D. Investigations:

Physical examinations: the physical examination is an important part of any assessment of substance-use problems and requires an awareness of the acute and long-term effects of substance use.

The following areas should be considered:

  • Evidence of acute use or intoxication e.g. papillary constriction associated with opiates use
  • Immediate and short-term medical complications of substance use, e.g. head injury following alcohol intoxication, local infection and abscesses caused by intravenous substance use
  • Signs of substance withdrawal, e.g. raised blood pressure, tachycardia, sweating, and pupil dilatation, associated with alcohol or BDZ withdrawal.
  • Long-term medical complications, e.g. stigmata of liver disease associated with alcohol (or infectious hepatitis caused by intravenous drug use)

Physical investigations:   a wide range of non-specific investigations can be useful when the longer-term medical complications of substance misuse are suspected, these include:

  • Ø FBC
  • Ø U&E
  • Ø LFT
  • Ø ECG
  • Ø Chest X-ray
  • Ø Hepatitis serology
  • Ø HIV

    Other specific investigations for evidence of excessive alcohol consumption include:

    • Ø ? MCV: occurs in 60%, females more than males and is due to deficiency of vitamin B or as a direct effect on erythropoiesis
    • Ø ? ?-GT: this occur in 80%; other LFTs are raised once there is an advanced liver disease
    • Ø ? Blood alcohol or breathalyzer detects recent use (with 24 hours)
    • Ø ? serum carbohydrate-deficient transferring detects excessive use in the previous seven days
    • Ø ? TG & cholesterol
    • Ø ? WCC, ? ESR and ? LFTs, these occur in DT

    In illicit-substance use urine test is the most commonly used and should be considered for all psychiatric patient presenting in the A&E (provide presence or absence of a drug), blood test(provide quantity, more detailed), hair (good to detect use where there is a time gap, e.g. three month able to detect cannabis use), also salivary test is available.

    E. Complications:

    Medical:alcohol dependence gives rise to significant morbidity and reduction in life expectancy. This derives from both direct and indirect effect.

    Ten % of alcohol-dependent patients develop cirrhosis; females are more susceptible than males. The 5-years mortality figures are 10% if abstinence achieved 40% if drinking continues, and 65% in advanced disease.

    Indirect effect of alcohol include increased accident, obesity (or malnutrition), and neglect of other conditions (e.g. diabetes).

    Overall mortality rate is twice the expected. Drinkers who remain within safe drinking limits appear to have a lower mortality than lifelong abstainers; this may be related to a cardioprotective effect of alcohol.

    Morbidity associated with illicit-substance misuse particularly affects injectable drug users (e.g. HIV, Hepatitis)

    Psychological: there is a close association between substance misuse and psychotic, affective and anxiety disorders; lifetime risks of suicide for both alcohol and illicit drugs dependence are around 10%.

    Social: the social cost of alcohol can be measured in several ways:

    • Drink driving: even al low limit, inexperienced drivers are at a five times higher risk of an accident and a third of all killed drivers are above the legal limits (in the UK, here the rate is probably lower, but present)
    • Violent crimes: in a high percentage of murders, alcohol is in one of the participants. Also higher percentage of violence is precipitated by alcohol.

    F. Management: (Bio-psycho-social)

    The principles of management are similar for both alcohol and substance dependence:

    • Short term-treating the acute effect of the substance, such as intoxication or withdrawal syndrome
    • Medium term-rehabilitating patient after withdrawal syndromes
    • Long term-dealing with the medical, psychological and social consequences

    Good prognostic factors:

    • Ø A stable relationship
    • Ø Employed
    • Ø Stable living conditions with good social support
    • Ø Good insight into problems and self-motivation to change

      

    Reference:

    •1.      Stevens L, Rodin I. Psychiatry: An illustrated colour text, Churchill Livingstone 2001

    •2.      Steple D. Oxford Handbook of Psychiatry, Oxford University Press, 2006

    •3.      Guthrie E & Creed F. Seminars in Liaison Psychiatry. Royal college of Psychiatrist 2007

    •4.      World Health Organization (WHO). ICD-10 Classification of mental and behavioural disorders. Churchill Livingstone

    •5.      American Psychiatric Association (APA). DSM-IV-TR. Fourth Edition Text Revision. APA Publication

    •6.      King D. Seminars in clinical psychopharmacology. Second Edition 2004. Royal College of Psychiatrists

    •7.      Smith G et al. Key topics in Psychiatry. Bios scientific publisher limited, 1996.

    •8.      Boyle D, Davies S. Psychiatry, Mosby’s crash course 2002

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