Dr. Abu Bakar Abdul Majeed
The Sun, July 18,1995
ALCOHOL IS A DRUG THAT IS MOST used throughout the world. It has been found in almost every civilisation that has left evidence of its existence. It is currently recognised as an official drug in the British and the United States Pharmacopoeias (lists of accepted drugs in use), although the various alcoholic beverages as such are no longer listed for medical use.
Previously, doctors used to prescribe alcohol as a tranquiliser, sedative or hypnotic. This is because this drug is a central nervous system depressant. However, the drug has been found to be addictive, whereby it reinforces it's own consumption through activation of the brain's reward circuits.
Today alcoholism, alcohol dependence or alcohol addiction is considered as a disease which is characterised by four main features - craving, impaired control over drinking, physical dependence, and tolerance.
Craving refers to the hunger for alcohol before drinking begins. Impaired control over drinking is the difficulty that an alcoholic experiences in stopping once drinking has started. Physical dependence is an adaptive state manifested by intense physical disturbances that takes place when drinking is discontinued.
These include profound anxiety, tremulousness, intense hyperactivity, sleep disturbances, hallucinations and possibly, seizures. These symptoms are known as the alcohol withdrawal syndrome.
Finally, repeated consumption of alcohol can induce tolerance, which means the amount necessary to produce the desired effect must be progressively increased.
But if you are an alcoholic, do not despair. Scientists have made great strides toward understanding how alcohol acts on the brain. This knowledge has launched a burgeoning era of research efforts to develop medications that impede the progress of alcoholism and lessen the risk of relapse to the disease. Here we look at some of the research strategies adopted in developing drugs to combat this menace.
Altering drinking behaviour
The first strategy involves designing drugs which decrease craving, block the reinforcing effects of alcohol or produce aversive reactions when combined with alcohol. In the brain, there exists a number of chemicals which act as postmen which carry messages from one nerve cell to the other. Diminished level of one of these chemicals, or neurotransmitters (known as serotonin), may influence the the appetite for alcohol.
Thus, the use of a new group of drugs, known as serotonin uptake inhibitors, would enhance brain serotonin activity, and thus, reduce consumption by abating craving for alcohol experienced by many alcoholics.
These drugs are particularly useful during the early stage of recovery. In studies with human volunteers, one of these drugs, citalopram, caused alcoholic individuals to consume less alcohol and remain abstinent for a greater number of days.
Aversive agents, such as disulfiram, which reduce drinking by causing an unpleasant effect when combined with alcohol, have been used to treat alcoholism for more than 40 years. However, due to failure of compliance with medication regimen, many patients do not benefit from these agents.
Dopamine, another neurotransmitter influenced by alcohol consumption, may play a role in the expression of the alcohol induced euphoria that appears to reinforce continued drinking.
Drugs that mimic dopamine, such as bromocriptine, may lessen craving and drinking in dependent persons by blocking this reinforcing effect. The neurotransmitter gamma-aminobutyric acid (GABA) also influences drinking behaviour. Drugs which mirror the actions of this neurotransmitter, for example the benzodiazepines (anti-anxiety drugs), have increased abstinence in alcoholics (see figure 1).
Inducing sobriety
Alcohol produces its effects by influencing a myriad of brain systems, making it difficult to find a single agent that reverses its intoxicating effects. Currently, researchers are focusing on a range of medications that counteract specific aspects of intoxication.
These agents may be useful in certain life-threatening conditions. An experimental benzodiazepine compound called Ro15-4513 appears to block several of the intoxicating effects of alcohol. This finding has laid the foundation for enhanced research efforts in the coming decade to develop new medications that induce sobriety.
Treating impairments
Alcoholics suffer from severe cognitive impairment. The most extreme damage can be seen in alcoholics with Wernicke-Korsakoff's syndrome who have amnesia for recent events and an inability to form new memories.
These deficits are seen to be the greatest hindrance to the success of the present forms of alcoholism therapy, i.e. verbal, psychological and cognitive therapy.
Thus, the development of drugs which enhance the recovery of brain function may offer a patient the potential and better benefit from traditional treatment approaches. These include fluvoxamine and clonidine.
Managing alcohol withdrawal
Managing alcohol withdrawal is the first step in alcoholism treatment. Research conducted in the past 10 years has provided a greater understanding of the physiological processes involved in alcohol withdrawal.
The production of the neurotransmitter noradrenaline appears to increase drug withdrawal. Thus, the use of drugs which antagonise the action of noradrenaline such as clonidine and lofexidine, can help to treat the symptoms of alcohol withdrawal and hasten a patient's entry into rehabilitation therapy.
Because of the complex nature of alcoholism, it is unlikely that a single anti-alcoholic agent will be developed to treat this disease. Instead, researchers are concentrating on developing agents to manage the specific events that occur in the clinical course of alcoholism and hasten the recovery process.
It is hoped that these new drugs can improve long-term treatment outcome when coupled with traditional verbal and behavioral therapies.
