Addiction Treatment Blog

If we heard it said of Orientals that they habitually
drank a liquor which went to their heads, deprived
them of reason and made them vomit, we should
say: ‘How very barbarous!’

Jean de la Bruyere (1645-96), ‘Les Caracteres’.

In 1994, the UK spent nearly £12 billion on alcohol.

History of Alcohol

Alcohol has been available to man for several thousand years. Ethyl alcohol, or ethanol, is produced by the action of yeasts on sugars found in fruit and other plant material. Compared with most other substances of abuse it has a very simple chemical structure. One tends to assume that it was one of the first intoxicants used by man because it is so easy to make. However most of the fruits grown today have been selected for their high sugar content and so the manufacture of fruit wines is a relatively simple process. This was no so in prehistoric times, when sugar-rich plants and sugars themselves were rare. Therefore other plant-derived psychotropic substances that could simply be eaten without preparation probably pre-date alcohol. The first cultures to produce alcohol are thought to have been based in the eastern Mediterranean and Mesopotamia. During the 4th millennium BC they probably fermented dates. The warm climate and the high sugar content of the dates were ideal for the purpose. As the process spread, a whole range of naturally occurring substances were used to produce alcoholic drinks.

The discovery of distillation enabled early civilisations to make more concentrated alcoholic drinks. This process was probably discovered independently by several ancient societies. Concentrating the active constituent in this way enabled the alcohol to act as a preservative and beverages could be stored for longer. In Britain, the strength of alcohol-containing drinks was traditionally measured in terms of ‘percentage proof‘; 100 percent proof was equal to 57.1 per cent ethanol by volume. However, it is now the standard practice to state alcohol content in terms of percentage by volume and to refer to the content of individual drinks in terms of ‘units’.

Alcohol is a very widely accepted substance, even being used as a central part of many Christian ceremonies such as the Communion. It is commonly associated with major events in peoples’ lives: weddings, birthdays and special celebrations. A vast and profitable industry exists to supply the public with this inebriant which can have very pleasurable effects but which can also kill. It is not surprising that many younger people feel that Society has a rather hypocritical attitude to abuse of street drugs: condemning illicit substances on the one hand while condoning the widescale use of alcohol on the other. In 1994, the population of the UK spent nearly 12 billion pounds on alcohol. In Islamic countries the consumption of alcohol is illegal.

The 1992 Health Survey for England revealed that 88 per cent of men and 75 per cent of women interviewed drank alcohol at least once every two months (’alcohol consumers’). Of these, 20 per cent of men and 13 per cent of women felt that they should reduce their intake. The survey teams classified 9 per cent of male alcohol consumers and 4 per cent of female consumers as problem drinkers. There has been increasing concern that teenagers may be encouraged to consume large amounts of alcohol by the marketing of several concentrated alcoholic beverages in forms similar to soft drinks, such as lemonades and other sweet, fruit-flavoured drinks. A recent survey of 758 schoolchildren aged 12 to 15 in Dundee concluded that over half of them had been drunk at least once. Another study of 7722 pupils aged 15 and 16 from across the UK revealed that 94 per cent of participants had already consumed alcohol and 78 per cent of these had become drunk at least once.

Natural products used to produce alcoholic beverages

Effects Sought

Alcohol is a central nervous system (CNS) depressant which encourages disinhibition because the highest levels of brain function are most susceptible to it. Depression of the cerebral cortex causes: reduced inhibition, merriment, loquacity, risk-taking behaviour and impaired judgement. As with nearly all psychoactive substances, the precise effects vary according to the dose, the mood of the user and the environment. Blood alcohol concentrations of 0.2 to 0.7 g/L are required for these effects to occur.

It has been shown that moderate daily intake of alcohol can reduce the risk of mortality from coronary heart disease in men over 40 and post-menopausal women, perhaps by increasing the concentrations of high density lipoprotein.

Alcohol content of different drinks

Administration

Alcohol is taken orally, primarily in the form of a drink. The alcohol content of these varies considerably (see the table above). Alcoholic drinks are used to flavour other foods such as cakes and desserts. Alcohol is also used as a solvent and fuel (e.g. liquid metal polishes, aftershaves, methylated spirits). Unfortunately, these products are sometimes consumed by alcoholics as a cheap source of concentrated alcohol.

Pharmacokinetics and Pharmacology

Alcohol has a variety of actions on the brain. It does affect specific neurotransmitter systems and is not a non-specific CNS depressant as was once thought. However, there is unlikely to be an ethanol receptor; it is more likely that the drug interacts with other CNS receptors by altering their configuration, thus affecting the binding of endogenous chemicals. Alcohol seems to augment the actions of the inhibitory neurotransmitter GABA and to antagonise certain effects of the excitatory glutamate. This is probably the mechanism of many of the CNS depressant actions of alcohol. The effects on GABA, plus an ability to trigger the release of neurotransmitters such as endorphins and dopamine may explain the pleasurable feelings evoked by alcohol. Stimulation of 5-HT₃ receptors may be the reason for alcohol causing nausea and vomiting.

Alcohol is absorbed passively from the gastrointestinal tract – a process which begins as soon as alcohol enters the mouth. It is absorbed from the stomach but passes across the mucosa of the small intestine much more rapidly because of the larger surface area. Hence food in the stomach will decrease the rate of absorption by delaying the passage of alcohol into the small intestine. The alcohol will continue to be absorbed from the stomach but at the slower rate. Peak concentrations are achieved in blood 20 to 60 minutes after ingestion depending on the amount of alcohol ingested. Its concentration and whether there is food in the stomach.

Alcohol is eliminated mainly via liver metabolism, although about 5 per cent lost in the breath, urine and sweat. The majority of alcohol ingested is metabolised by alcohol dehydrogenase to acetaldehyde. However, part of the cytochrome P450 oxidase system also facilitates the conversion as does, to a small extent, catalase. Alcohol dehydrogenase is only available in small amounts in infants under the age of 5 years, hence their comparatively increased sensitivity of alcohol.

The long-term ingestion of large amounts of alcohol induces certain of the cytochrome P450 enzymes of the liver so that the metabolism of alcohol, and other drugs which are eliminated via this system, is accelerated. Acetaldehyde is further degraded to acetic acid mainly by aldehyde dehydrogenase in the liver. Acetic acid is then either converted to carbon dioxide and water in peripheral tissues and excreted or, because acetic acid is formed by a variety of means in the body, incorporated into the metabolic pathways of carbohydrate or lipid.

The half-life is dose-dependent because the amount of alcohol ingested is usually too great for enzyme systems to handle (i.e. zero-order kinetics). The conversion of alcohol to acetaldehyde is the limiting step. The rate of human elimination of ethanol varies from 80 to 150 mg/kg/h; the average clearance is 100 mg/kg/h.

Adverse effects of alcohol

It has been estimated that 33,000 people a year die as a result of alcohol in the UK.

Acute effects

• Intoxication (see text) leading to accidents, aggression, risk-taking behaviour and criminal acts
• Incoordination, dulled mentation, slurred speech, reduced audiovisual acuity, ataxia, drowsiness, loss of consciousness, respiratory depression, death.
• Flushing, hypothermia
• Diuresis, dehydration
• Gastritis, nausea, vomiting, oesophageal reflux, haematemesis
• Sleep apnoea, inhalation of vomit
• Hypoglycaemia
• Arrhythmiass

Acute intake of alcohol can produce a wide range of effects. Intoxication is an important factor in many accidents involving both the affected individual (drowning, falling, suffocation) and other people (road traffic accidents). It is a significant factor in a high proportion of violent crimes and acts of aggression, and may seriously disrupt an individual’s social and family life. The behavioural changes produced by disinhibition can result in aggression, fights and other forms of violence, unprotected sex and the desire to use other substances of abuse.

As the concentration of alcohol in the bloodstream increases to about 1 to 1.5 g/L, basic brain functions become affected (loss of taste, reduced audiovisual acuity, slurred speech, awkward gait, etc.). The ultimate sequelae of CNS depression – loss of consciousness, respiratory depression and death – are seen at blood alcohol concentrations greater than 3 to 4 g/L.

Acute adverse effects of alcohol are well known. Flushing occurs because alcohol depresses the vasomotor centre in the medulla, resulting in dilation of blood vessels in the skin. Alcohol can sometimes cause hypothermia in cold weather when cutaneous vasodilation is coupled with inhibition of the thermoregulatory centre in the hypothalamus. Diuresis is a consequence of the inhibition of antidiuretic hormone production from the pituitary. One or two units of alcohol will encourage sleep through simple CNS depression but larger doses tend to cause poor sleep because the somatic sympathetic nervous system is activated as the effects of ethanol wear off. Sleep in the early morning is therefore often restless and punctuated by vivid dreams. Alcohol may cause or exacerbate snoring and obstructive sleep apnoea which also gives rise to poor quality sleep in those affected.

Gastritis, vomiting and oesophageal reflux can result from acute intake of large amounts of alcohol. This probably is the result of irritation of the gastric mucosa, both as a direct action of alcohol and because it stimulates the production of gastric acid. Haematemesis may occur in severe cases. When unconsciousness occurs, death may arise from inhalation of vomit. Arrhythmias are a rare acute effect of ethanol intoxication in non-alcoholics.

Effects of chronic use (chronic heavy ingestion)

• Liver cirrhosis, alcoholic hepatitis, liver cancer, oesophageal varices Mallory-Weiss tears (rupture of oesophageal mucosa)
• Pancreatitis, gastric cancer
• Alcohol cardiomyopathy, tachyarrhythmias (especially atrial fibrillation), sudden death
• Hypertension, hyperlipidaemia
• Malnutrition, weight loss, dehydration
• Peripheral neuropathy, sensory and motor polyneuritis, Wernicke’s encephalopathy, Korsakoff’s psychosis, stroke, CNS infection, tobacco-alcohol amblyopia, cerebellar degeneration, central pontine myelinolysis
• Myopathy, muscle weakness, muscle pain
• Gynaecomastia, decreased libido, impotence
• Depression, paranoia, anxiety, memory loss, blackouts

Chronic regular high-dose alcohol intake (alcoholism) can cause a range of adverse effects. The liver can experience serious damage. Cirrhois, alcoholic hepatitis, liver cancer, gastric cancer and pancreatitis are all linked to excessive long-term alcohol intake. Alcoholic cardiomyopathy is a recognised consequence of long-term heavy drinking which is probably reversible in the early stages if alcohol consumption is abandoned. Tachyarrhythmias, especially atrial fibrillation are also associated with alcoholism, as is sudden death (perhaps due to ventricular fibrillation). It is likely that those who experience cardiac toxicity are predisposed to it by some means (e.g. genetic make-up, pre-existing disease) because cases of atrial fibrillation have been reported in those consuming a single large amount of alcohol. Electrolyte disturbances may play a part in some cases of cardiac toxicity: hypo-magnesaemia is a well known problem. Women and individuals under 50 years of age seem to be the groups most at risk of dying early (from any cause) as a result of prolonged heavy intake.

Neurological disorders are also common in alcoholics. Many of these arise as a result of poor diet. Malnutrition results when alcoholics come to depend upon alcohol as a source of energy to the exclusion of food. 1g alcohol supplies about seven calories. Water-soluble vitamins are particularly susceptible to depletion: vitamin B₁ (thiamine) deficiency is the primary cause of Wernicke’s encephalopathy. Alcoholics have reduced dietary intake but in addition the absorption of thiamine is reduced and the metabolic activation of thiamine is also inhibited by alcohol. Korsakoff’s psychosis is another serious brain disorder that is probably linked to a thiamine deficiency; unlike Wenicke’s, to which it may be a sequel, it does not appear to be reversible. Sensory and motor neuropathies and cerebellar degeneration may also occur as a result of thiamine deficiency. Cerebellar malfunction manifests primarily as ataxia and dysarthria. Tobacco-alcohol amblyopia involves progressive blindness and is thought to be linked to vitamin B₁₂ deficit. Strokes occur as a result of: alcohol decreasing blood coagulability; emboli arising due to cardiac toxicity; or secondary to alcohol-induced hypertension and/or hyperlipidaemia. Central pontine myelinolysis is characterised by demyelination of neurones at the base of the pons. This can result in paralysis. The condition is probably caused by iatrogenic over-rapid correction of hyponatraemia but the exact mechanism is not known.

The endocrine effects of alcohol are largely confined to carbohydrate metabolism and reproductive function. Alcohol causes hypoglycaemia 6 to 36 hours after heavy intake in those suffering from malnutrition. In other alcoholics, hyperglycaemia may occur for reasons which are not full understood. This can develop into diabetes. Chronic alcohol administration may cause gynaecomastia and decreased libido in men largely because of inhibition of hormone production at both pituitary level and testis. In women, alcohol may be the cause of absent or irregular menstruation.

Alcohol Withdrawal

In the alcoholic, symptoms of withdrawal usually begin within 12 hours of the last intake of alcohol. These include tremors, sweating, anxiety, flushing, confusion, disorientation, vomiting, anorexia, diarrhoea, insomnia and a variable level of consciousness. This can progress to delirium tremens, which may be fatal. It is characterised by severe hallucinations, delirium, violent behaviour, severe depression, hyperpyrexia, dehydration, electrolyte, abnormalities and convulsions. Hallucinations often evoke extreme fear. Arrhythmias, hypertension, paraesthesiae, suicidal ideation and hepatic dysfunction are less common but can develop at any stage of the withdrawal process. Some heavy consumers of alcohol do not experience withdrawal symptoms at all.

Many alcoholics have intermittent periods of reduced alcohol intake when symptoms of withdrawal may occur but this usually encourages a return to old habits (negative reinforcement). Full scale ‘detoxification’ usually requires admission to a psychiatric hospital, specialised alcohol detoxification unit or a general medical ward. Chlordiazepoxide or chlormethiazole are generally used to make withdrawal more bearable. These drugs alleviate many of the symptoms; it is important to realise that their function is to make withdrawal more bearable – they do not prevent it. High doses are used on the first day of withdrawal: 60 mg or more of chlordiazepoxide and up to 12 chlormethiazole capsules. Lower doses should be used in the elderly and in patiens with severe liver impairment where hepatic encephalopathy is a potential adverse effect. The daily dose is reduced in a stepwise fashion over the next seven days and then stopped completely. Courses should not be extended because of the risk of adding sedative dependence to the patient’s existing problems. Similarly patients should not be allowed to take supplies of medication home with them – not only because of the risk of dependence but because in the (common) event of recidivism the effects of alcohol and sedatives are additive. Alcoholics might also sell sedative drugs on the black market. One US study successfully used chlordiazepoxide capsules on an ‘as required’ basis rather than via a fixed reducing dose regimen. Patients in the ‘as required’ group received a dose of chlordiazepoxide whenever an evaluation of their symptoms exceeded a predetermined score on a rating scale. This method was as effective as a fixed detoxification regimen but the ‘as required’ method, although more labour intensive, allowed individualisation of therapy and resulted in usage of less drug. Chlormethiazole infusion is used when the oral route is unavailable or inappropriate but respiratory depression must be guarded against.

Clonidine relieves some of the withdrawal symptoms mediated by the sympathetic nervous system (e.g. tremors, palpitations) but has no anxiolytic, sedative or anticonvulsant actions. It is therefore not widely used. Fitting can usually be controlled with a regular anticonvulsant (e.g. carbamazepine) or diazepam rectal tubes when required. The anticonvulsant action of chlordiazepoxide or chlormethiazole is often sufficient to prevent withdrawal seizures.

Thiamine should be given to all alcoholics admitted to hospital because most are likely to be deficient to some extent, even if this is not clinically apparent. Thiamine has good oral bioavailability in the non-alcoholic but in alcoholics its absorption can be markedly impaired. Furthermore, if not treated early with thiamine, Wernicke’s encephalopathy is irreversible. The usual dose is 100 to 300 mg daily parenterally if possible. Vitamin B compound tablets are of no value in this situation because the thiamine content is too low. They may be useful dietary supplements for general health once the patient in several B-group vitamins but unsupervised alcoholics in the community are unlikely to comply with any medication. Some alcoholics are discharged on ‘maintenance‘ doses of thiamine (e.g. 25 mg daily). Thiamine should be given parenterally if the patient is not able to receive it orally and especially if showing signs of neurological damage. A patient presenting with symptoms suggestive of Wernicke’s encephalopathy requires a very high doses of thiamine reaches the CNS. Very high doses such as this maintain a diffusion gradient for thiamine across the blood-brain barrier, enabling larger quantities to pass through.

Haloperidol is sometimes advocated for the alleviation of distressing hallucinations or aggressive behaviour. However, neuroleptic agents with antidopamine actions in the CNS may exacerbate delirium. Furthermore, most antipsychotic drugs tend to lower the seizure threshold and can cause liver damage, hepatic encephalopathy or interfere with temperature regulation. Neuroleptics such as haloperidol must therefore be used with extreme caution. It is rare to encounter a situation where the simple sedative actions of benzodiazepines or chlormethiazole are insufficient, and many detoxification units never use neuroleptics.

During the process of withdrawal, many alcoholics will require rehydration and correction of electrolyte abnormalities according to their individual circumstances.

Maintaining Abstinence

After passing through the period of acute withdrawal, the patient requires other forms of support to maintain abstinence. Especially during the first six months of abstinence there may be craving for alcohol, often associated with depression. Aspects of lifestyle which help to fuel addiction need to be addressed, e.g. unemployment, homelessness and problems with relationships. Some alcoholics also suffer from specific psychiatric disorders such as depression, schizophrenia or anxiety which may require treatment. Various forms of counselling and support are available but the self-help methods offered by Alcoholics Anonymous remain popular. However, some drug therapies are available which may also help.

Disulfiram is occasionally used to try to control alcohol intake. It usually produces unpleasant symptoms if the recipient imbibes alcohol during the course of treatment. Drugs of this kind are termed antidipsotropics. Disulfiram irreversibly inhibits the enzyme aldehyde dehydrogenase, and this result in greatly increased plasma levels of acetaldehyhde if alcohol is ingested. Symptoms of acetaldehyde accumulation include facial flushing, pulsing headache, nausea, dizziness, weakness, orthostatic hypotension and palpitations. Some of these effects can last for several days. The effects of inhibition are permanent and one dose of disulfiram are limited – not all alcoholics will accept this treatment and even those that appear to accept it may not comply. In addition, some alcoholics do not experience the so-called ‘disulfiram reaction‘ with alcohol or may experience symptoms which can be tolerated; for others the reaction may cause a wide range of serious adverse effects (e.g. arrhythmias, heart failure, hepatoxicity).

Nitrefazole and calcium carbamide also inhibit aldehyde dehydrogenase. They both have a more selective action than disulfiram, which inhibits dopamine beta-hydroxylase and so increases the plasma concentration of several biogenic amines (which may account for some of its side effects). Calcium carbamide has the advantage of a short duration of action (24 hours). Both drugs have fewer side effects than disulfiram.

Acamprosate is used to maintain abstinence in alcoholics following withdrawal. In alcohol-dependent laboratory animals it reduces the voluntary ingestion of alcohol in a dose-related manner. A derivative of the amino acid taurine, acamprosate potentiates the actions of the inhibitory neurotransmitter GABA in the CNS and antagonises the excitatory transmitter glutamate, i.e. it has a similar action to alcohol. It does not produce intoxication or dependence. Glutamate receptors have been observed to proliferate in the brains of alcoholics, suggesting that overactivity of excitatory neurosystems in the brain upon withdrawal of alcohol may be at least partly responsible for craving. Acamprosate may increase the likelihood of maintaining abstinence in alcoholics after withdrawal. It does not have a dramatic effect and many studies have only assessed effectiveness after three months treatment. However, a study from Austria has investigated the ability of acamprosate to maintain complete abstinence for longer periods. 41 acamprosate-treated individuals (18.3 per cent of the total) and 16 placebo-treated (7.1 per cent) were abstinent continuously for one year. The benefits of acamprosate were also demonstrated in a six-month acamprosate versus placebo trial: 31.8 per cent acamprosate recipients were abstinent at the end of the study compared with 18.6 per cent in the placebo group. Note that in both studies the abstinence rates fell after the active treatment was stopped. Acamprosate does not treat withdrawal, prevent intoxication with alcohol, interact with it or lessen any of the harmful effects of alcohol. A dose of 666 mg three times daily is given.

Naltrexone is an opioid antagonist which has recently been licensed in the USA as an adjunct to the psychosocial treatment of alcoholism. Like acamprosate, laboratory work has shown that alcohol-dependent animals will choose to take alcohol less often when administered naltrexone. However, the two published human studies are small-scale end each was only of three months duration. One study revealed a 54 per cent abstinence rate in the treatment group and 23 per cent in the placebo group but only 70 patients participated. The second study utilised an unnecessarily complex four-treatment group design which had a high drop-out rate (65 per cent) making interpretation of results difficult, although naltrexone did seem to be better than placebo. The dose used was 50 mg daily.

Limited work suggests that drugs which inhibit the neuronal reuptake of serotonin such as citalopram and fluoxetine may reduce the desire to consume alcohol. In animal studies, the boosting of central serotonin levels seems to reduce the voluntary consumption of alcohol. In humans, only small-scale, short-term studies are available and these have shown that although selective serotonin reuptake inhibitors may significantly reduce craving for alcohol, this does not always correspond to a marked decrease in intake. The ability of this group of drugs to maintain abstinence in the detoxified alcoholic has not been demonstrated.

Are You Addicted To Alcohol?

The Causeway Retreat, Europe’s leading alcohol addiction treatment centre in the UK uses the latest treatment methods under the leadership of our medical director, Dr. Mike McPhillips. We do take alcohol addiction treatment very seriously and believe that treating alcohol addiction relies on a deep analysis of the patient, both psychologically and physically.

One of the most luxurious treatment centres of the world, The Causeway Retreat is based on a 400 acre private island, and just 40 miles east of central London. If you have are addicted to alcohol or any other substances mentioned in this article, please call us directly on 0207 100 7260 to talk to a clinical nurse specialist on addiction treatment who will be able to help you immediately. Alternatively, you can fill the form below to get in touch with us and let us know your circumstances. Please note that The Causeway Retreat is takes client confidentiality as a very serious matter, therefore all of the information you supply to us will always remain confidential. Call us now! 0207 100 7260.