So, now we know quite a lot about Baclofen. But what made Olivier Ameisen feel that it might help him? Did he just pluck it out of thin air? No, of course, he didn't. Like any excellent doctor, he did his research. And it is clear that he has a much more enquiring, inventive mind than many of his colleagues. Thank God he has! As briefly as I can .....
Several preclinical (ie mostly experimental laboratory) studies, often in rats, have demonstrated that synthetic agonist analogues of GABA, especially Baclofen are likely to help in the promotion and maintenance of abstinence from a wide range of drug abuse.
In simple terms, laboratory rats don’t have any concept of what drugs are, obviously. They’re rats. So, if you make drugs available to them, they only take them if they need them, in the addictive sense. To use the technical language, they ‘self-administer’. If you make them drug addicts by giving them drugs beforehand, you can test how effective drugs such as Baclofen might be in helping them to abstain, ie to not self-administer. Does that make sense?
Such prevention of self-administration has been shown to occur with Baclofen, for rats addicted to (amongst others) cocaine, nicotine, heroin, methamphetamine and alcohol. Further, Baclofen appears to also have a beneficial effect in reducing the signs of opiate withdrawal in rats dependent on morphine.
What is currently known about how this might happen?
We need to very briefly consider two different, but related, concepts.
In positive reinforcement, the reward of feeling really great when the rat takes the drug obviously makes the rat want to do it again, and again.
In negative reinforcement, the drug is craved in order to prevent or alleviate signs and symptoms that are unpleasant or outright painful, ie the effects of withdrawal.
Still with me? Excellent.
It seems that different bits of the brain might be involved in these different effects.
The important point is that Baclofen may have a valuable role in both of these reinforcement pathways. The details of the neurophysiology are far too complicated for this particular discussion. That is the sort of thing that I sal be discussing on the www.medic-al.org site
The bits of brain that appear to be involved in the positive reinforcement pathway appear to be associated with a great sense of well-being (euphoria) for cocaine, heroin, nicotine and alcohol. Baclofen, through its action as a synthetic GABA analogue and agonist reduces this sense of euphoria.
Conversely, there is now evidence, in rats, that Baclofen also reduces the horrible, often painful signs and symptoms of withdrawal of opioid drugs, such as morphine.
So, a double whammy.
So far so good for rats, then! What about humans?
There are fewer studies in humans, as yet, but the evidence of the benefit of Baclofen is becoming a little clearer.
Whilst the data needs further investigation, it does appear that Baclofen does have the same potential for ameliorating both the positive and negative in humans.
This therefore, was the background to why it was considered possible that Baclofen might have a potentially valuable role in the management of both the cravings for alcohol and other symptoms of alcohol withdrawal, and also the underlying chronic anxity state that appears to be so common in alcoholics.
