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December 2, 2011

Alcoholism: Can it be Cured?


Alcoholism to this day is one of the most deadly and chronic diseases, that is interestingly controversial with regards to symptoms, treatment, diagnosis, and even heritability. How can a disease be so dangerous and historical and yet not even be remotely understood? As medicine, science, and technology move forward we are rapidly moving towards this inconceivable goal, but treatment is still only moderately successful along with progressive pharmacotherapies for all addictions.

A huge part of this lack of understanding of this disease is the fact that alcoholics are all different in a variety of ways; including their symptoms. There are numerous biological mechanisms as a result of alcohol addiction, all of them varying in their manners and withdraw. So recent studies show that these different mechanisms represent different stages of alcoholism, which could be relieved by different treatments. Regardless, these treatments have to block motivation to seek and consume alcohol.

Researchers have determined two categories: relief and reward drinkers. Reward drinkers drink to reward themselves the same way many drugs work, by activating brain reward pathways. Relief drinkers drink to relieve negative emotions, such as anxiety and feelings of withdrawal. Obviously these two varying types of alcoholics require different treatments.

It has also been discovered that alcoholism is marginally heritable. Genetic susceptibility is an alcoholic trait that can be passed down from generation to generation, however these varying types of alcoholism are largely based on environmental factors. These would include things such as how often the individual is exposed to stress or put in a circumstance of reward.

So now, is it possible to treat either one or both of these forms of alcoholism? Studies show that the reward system of alcoholism is mediated by a collaboration of endogenous opioids and dopamine release. Activation of dopamine in the mesolimbic pathway has been correlated to many other sorts of drug addictions. Dopamine is regulated in the corticomesolimbic system by a receptor known as MOR (mu-opioid receptor), which if blocked, prevents dopamine release caused by alcohol consumption. A drug known as naltrexone is an antagonist of opioid receptors, and is currently being researched as treatment for reward alcoholics.

Next is relief drinking. Relief drinkers drink to suppress stress, anxiety, discomfort, pain, and dysphoria. These alcoholics generally end up setting the stage for routine and frequent alcohol consumption to escape negative emotions. Recently, it has been discovered that release of CRF is central to this behavior. CRF (Corticotropin-releasing factor) is a peptide that is released into the anterior pituitary by alcohol consumption in relief drinkers, which in turn releases ACTH and stimulates cortisol release, reducing stress. CRF regulation and function is somewhat genetically determined, which makes a pharmacological cure more difficult and less likely to be successful. However, studies have shown that in individuals with naturally decent regulation of CRF could likely be treated for relief alcoholism; via CRF1 antagonism. Research is still ongoing as to whether this would be a sufficient method to treat alcoholics.

Alcoholism is a very complex disease, by which human understanding is challenged and pushed to therapeutic limits. This blog marks a tremendous step in the right direction towards understanding alcoholism and possibly curing the disease one day, but until that day comes there is plenty more to learn and to gain.

Heilig, Markus, David Goldman, Wade Berrettini, and Charles P. O'Brien. "Pharmacogenetic Approaches to the Treatment of Alcohol Addiction : Article : Nature Reviews Neuroscience." Nature Publishing Group : Science Journals, Jobs, and Information. 20 Oct. 2011. Web. 02 Dec. 2011. .

http://www.nature.com/nrn/journal/v12/n11/full/nrn3110.html
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October 23, 2011

Can You Fool Yourself Out Of Depression?


Major depression has long been a disorder weighing down on its victims, but fascinating neuroscientists. Can we use the placebo effect to leave the confines of a depressed world? What exactly lies behind the mechanisms of the placebo analgesic effect? To find out, researchers compared the effect of fluoxetine and a placebo and using neural imaging techniques, compared which regions of the brain showed activity/change at the beginning of the study, at six weeks, and at the end. What they found was that each treatment method caused an increase in activity in the prefrontal and posterior cingulate and decreases in subgenual cingulate. Fluoxetine worked better, and the results of the placebo were inconclusive. Although not tested in an extended study, researchers also compared the effect of various psychotherapies as opposed to placebos and found that they each affected different regions of the brain and that, unfortunately the placebo effect only worked for a little while.

But hold up! If our emotions are strictly based on the balance of chemicals in our brain, then how could we possibly fool ourselves of how we really feel even for a second? The placebo analgesic effect is when our brains signal to generate endorphins in order to alleviate pain.

The expectation of getting better plays a huge role in how well the placebo effect works and the way this is tested is through the use a drug called naloxone. Naloxone counters the effect of opioids and is used to reverse heroin/morphine overdoses in modern clinical practice. It was found that in patients where the placebo analgesic was brought on by strong expectations, the response could be blocked by naloxone. However, if the expectation cues were decreased, naloxone would not work. This concludes that in order for naloxone to work, there needs to be a large amount of endogenous opioid concentration.
Let�??s delve into this a little further. If the patients were exposed to various opioid drugs, the placebo effect could be reversed by naloxone, but if they were not, they were insensitive to naloxone. It can be concluded that naloxone only works in certain physiological conditions.

A typical side effect of opioids is respiratory depression. It was hypothesized that a placebo could mimic the effects of a drug which causes mild respiratory depression. Repeated injections of buprenorphine during the study and then a final injection of a placebo showed that the placebo was able to induce respiratory depression in the same way that the opioid did.

Placebo analgesics only work on certain people and in certain physiological conditions. But we know that they can induce extreme physiological changes, for the better or worse. Further studies need to be conducted to prove how exactly our brain can practice �??mind over matter�??.

all info was taken from http://www.jneurosci.org/content/25/45/10390.full.pdf+html
Posted by      Dora P. at 11:55 PM MDT




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