How does baclofen work?
It is vitally important that you understand and believe why there is great cause for optimism that, for many individuals, Baclofen holds real genuine hope.
All the various bits of your nervous system communicate with each other by electrical impulses travelling along nerve fibres. When the electricity reaches the end of the nerve cell it causes the release of tiny amounts of a highly specific chemical that passes across a small gap (the synapse) to the next nerve cell or, more usually, lots of cells. In order for the chemical to work, it must attach itself to a highly specific receptor that that particular cell will have so that the system works properly. When this chemical attaches to another nerve cell with the appropriate receptor it triggers another electrical impulse to pass the message on along it. And so on, until the final end-point is reached and something actually happens (e.g. making a muscle contract or a hormone to be released). These higly specific chemicals are called neurotransmitters (or neuromodulators), and there are lots of different ones for different functions in different parts of your brain / nervous system and elsewehere in your body. Importantly, nature has made a system where, within whatever the bodily process you are considering, one neurotransmitter might speed the process up, whilst another slows it down. This vital process allows for fine control or regulation.
Next, imagine your nervous system as a train set. The appropriate neurotransmitter, in the right amount, makes the train run smoothly in the direction you want; performing the precise physiological action required.
Scientists now routinely develop synthetic forms of these neurotransmitters (analogues) for therapeutic use. They are laboratory- created chemicals that are similar enough in structure to be able to attach onto the receptors that the naturally occurring neurotransmitter does. Some do what the transmitter does (agonists); some block or even reverse its actions (antagonists).
Consequently, these analogue drugs might have any or more of the following effects when administered to an individual:
Make the train go the way nature intended. It might help the taker considerably or not, depending on the dose and why it is being taken;
Make the train go in precisely the opposite direction. This again might help some diseases or make things worse;
Make the train stand still and not go at all. This might be beneficial if intentional and prescribed;
And some might make the train do really crazy things and mess the whole thing up. Many illicit drugs work in this fashion;
Lastly, the effects of some drugs make the train go in one direction at a low dose and do precisely the opposite at a higher dose.
Add in other brain altering drugs (e.g. alcohol) and the mix could be wholly unpredictable, and frequently is.
One such natural neurotransmitter is Gamma Aminobutyric Acid (GABA). Very simply, it is an inhibitory chemical. It makes the train run much slower. In general, it slows down many areas of your nervous system; regulating the degree of excitability of how the system works. If it wasn't there, or not working properly, the system would run out of control - in a sense, if would 'overheat'. There would be chaos. As such, GABA is intimately involved in regulating the tone of your muscles. Abnormalities of GABA's working result in your muscles becoming excessively toned, or spastic.
There is actually more than one type of GABA. There are at least two currently known - GABAa and GABAb. For our present purposes, we needn't concern ourselves too much with this. Baclofen is important in relation to GABAb.
Baclofen is the ONLY drug that, as yet, mimics GABAb.
For reasons discussed next, GABA also appears to be fundamentally important in the development of chronic alcoholism, and holds the key to why Baclofen is so effective in treating it.
Baclofen is a synthetic analogue agonist of GABA and enhances the effects of GABA. It makes the 'train' go in the direction nature intended. That is, to calm the system down. For individuals with problems with how their GABA works, it replaces or reinforces GABA, helping it to do the job nature intended.
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Next, there is a very small area of the brain called the Amygdala(because it's shape resembles an almond), involved in a wide range of normal behavioural functions and psychiatric conditions. Until recently, it attracted very little interest from scientists, but recently has become the focus of a great deal of research. Why? It is because it is now extremely evident that the Amygdala is integral to how humans process their emotions (such as fear; sexual activity; pleasure; eating; aggression). It is essentially a bit of brain that thrives on excitement of whatever kind. It is often referred to as the pleasure centre. It also appears to have an important role in your development and retention of your emotional memories; and perception of your environment and perceived stresses applied to it.
In short, abnormalities of the Amygdala interfere with the individual's processing of the emotional significance of external stimuli; e.g. normal daily problems and activites get blown totally out of proportion and cause inappropriate stress. Further, and importantly, the Amygdala appears to be important in binge-drinking, and is damaged by repeated episodes of excessive drinking and alcohol withdrawal. Alcoholism is now known to interfere with the nerve pathways (including the Amygdala) that are responsible for the processing of your emotions.
Consequently, scientists now believe (although the details have yet to be worked out completely) that a malfunctioning or damaged Amygdala has a crucial role in the development of a wide range of psychological and psychiatric conditions. To date, these include:
· Alcoholism and other addictions, especially if they are caused by chronic anxiety
· Panic Attacks
· Bipolar Disorder
· Clinical Depression
· General Anxiety Disorder
· Obsessive Compulsive Disorder
· Post-Traumatic Stress Disorder
· Panic Attacks
Recent studies have also shown that a naturally occurring brain peptide (CRF) has an additional effect when combined with alcohol. Both appear to influence activity within the Amygdala by increasing its transmission of GABA.
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We now have to consider a little about how drugs exert their effects on our brains and bodies and how other administered drugs (medicines) might help treat addiction.
In 'positive reinforcement', the individual feels really great when they take the drug. This is clearly very important in why people initially take drugs or drink alcohol. For people like you and me, our positive reinforcement is that our anxiety was relieved when we drink. Medicines that reduce positive reinforcement to another drug might help block the euphoria that the individual feels after taking it, and help the individual stop taking it.
In 'negative reinforcement', the individual has to take the drug to get rid of the horrible feelings of NOT taking the drug. This is clearly important in why people find it difficult to come off drugs or stop drinking alcohol. Medicines that help reduce negative reinforcement might make the individual not feel the need to take the drug in order to stop the horrible feelings of coming off that particular drug.
It appears that different parts of the brain are involved in both of these elements.
In order to test whether a new drug works in helping any addiction, scientists have to devise experiments that look at both positive and negative reinforcement. They often use laboratory rats. After all, rats know nothing of the 'psychology' or 'sociology' of why they do what they do. They just do it. Consequently, if they voluntarily take a drug when it is offered to them, they do it because it does something that they feel as beneficial. If they are then given medicines, scientists can look at how that medicine affects their behaviour with the other drug in question.
In laboratory rats, it has been shown that Baclofen seems to reduce the positive reinforcement of many drugs, including alcohol. Rats given Baclofen were less likely to drink and become 'alcoholic' when offered alcohol. Simply, they just didn't get anything from it.
Further, in rats made 'alcoholic', Baclofen makes it less likely that they will exhibit many of the horrible effects of coming off alcohol. They stop craving alcohol to get rid of these effects; taking less or no alcohol when offered it.
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In conclusion, it is thought that Baclofen exerts its beneficial effects in patients taking it by doing what GABA should be doing when you take alcohol; diluting or eliminating the euphoric 'beneficial' effects of alcohol - eventually removing the craving for it. After all, it is not then providing you with any perceived ‘benefit’. It also alleviates many of the unpleasant effects of not taking alcohol.
Further, Baclofen also ‘calms your Amygdala down’, so helping to treat your chronic anxiety / panic attacks that caused you to drink in the first place.
This is all very rudimentary and the research still has a considerable way to go. However it is fair to say that, already, the whole focus on chronic alcoholism as a physical disease has shifted dramatically in recent years.