My Immoral Research Proposal

I got a very thoughtful email from a former colleague of mine (he's still a neuroscientist), who wondered why I would invest in scientific research for drug addicts over those with mental illness. After all, schizophrenics didn't commit a crime; they just inherited a flawed cortex. Why not first invest in cures for patients who 1) have an illness through no fault of their own and 2) can't already be cured by a combination of willpower, therapy and methadone.

This is an excellent point, and my priorities were certainly morally skewed. But I still won't change my answer. The reason I find addiction such a tantalizing research topic is that it's one of the few remaining areas in neuroscience where there's hope for a big breakthrough. Twenty years ago we naively assumed that schizophrenia was caused by a small constellation of genes which upset a few neurotransmitter receptors. Now we know better. Dozens of genes probably underlie schizophrenia, and the more we know the less likely it seems that the different varieties of schizophrenia are even the same disease. Our increased knowledge, in other words, has made things very, very complicated. Such is the nature of scientific progress. If we know anything about the brain, it's that there aren't any easy answers.

So what about addiction? Certainly addiction is an extremely complicated phenomenon, and I don't want to sound glib when I refer to the promise of the dopamine reward pathway. But it does seem that the brain utlizies a single chemical mechanism for everything from heroin to gambling to cigarettes to music. Of course, the details differ - sex, drugs and rock n' roll all excite our dopamine in different ways - but the general idea is the same. And while only time will tell if this addiction pathway is a chimera - just another biological tease, which ends up being much more complicated in reality - I would still lob gobs of money at scientists just in case. If, by chance, we do end up engineering an anti-addiction drug, the payoff would be immense.

[Another example of a neural mechanism which seemed simple but then devolved into a mess of feedback loops and endless acronyms is CREB. A decade ago, CREB seemed like the magic bullet of long-term memory. But then came this, and this. Or what about nerve growth factor(NGF)? When Rita Levi-Montalcini discovered NGF in the 1950's, it was believed to be the magic stimulant of neurons. Now we know that NGF isn't very important in the brain, and have discovered in its place a maze of other trophins, such as BDNF, sonic-hedghog, and GDNF. Life is rococo.]

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Actually, as you probably know, there has been modest progress in this area, such as the use of Campral and Revia for alcohol addiction; also, there is some interest in possibly using Provigil for cocaine addiction.

So far, all of these appear to reduce the probability of relapse, or reduce the severity of a relapse if one occurs.

Most clinicians think of these treatments as adjucts that might help, at best. Like you, though, I remain hopeful that a big breakthrough eventually will be found.

I can't believe how you responded to your former colleague, Jonah! Have you known many addicts in the past? I'm not talking simple cigarrette smoking, I'm talking crack, coke, something hardcore... or even pot smoking or alcoholism taken to an extreme degree.

Let's evaluate the questions propose to you by your former colleague:
1) have an illness through no fault of their own and 2) can't already be cured by a combination of willpower, therapy and methadone.

What if, and let's get theoretical here, the person has an obsession with receiving a huge dopamine release of some kind (coke, whatever)... wouldn't it be logical that they might do this because of a constant inadequate amount of dopamine on a daily basis inhibiting their ability to feel motivated, or good in general? I can tell you quite honestly that I've never met a true addict that didn't show signs of being bipolar, or out-and-out OCD.

So here's the answer for your friend: most true addicts ARE mentally ill. By curing addiction, you are curing a form of mental illness. If a person is an addict because they are trying to make themselves FEEL GOOD, perhaps there is a reason why they constantly feel bad and it has existed since their childhood?

Thanks for your stimulating comment. And I agree that most hard core addicts are mentally ill. But many hard core addicts also learn to live with their past addiction, and recover some semblance of balance.

In my post, I was merely trying to draw a distinction between inescapable mental illnesses - like schizophrenia - and mental illnesses which can be effectively modified through behavioral therapy, lifestyle modifications, etc. Of course, from the perspective of neuroscience, both types of illnesses are the same thing: a deficiency of neurotransmitter is a deficiency of neurotransmitter. But I believe that society must do a much better job of distinguishing between mental illnesses which are incurable and deterministic and mental illnesses which can be treated through plasticity and resolve. After all, the miracle of the brain is that we have the power to alter ourselves. It's important to remember that feelings and thoughts - and not just pills - can also rearrange our cortical cells.

"It's important to remember that feelings and thoughts - and not just pills - can also rearrange our cortical cells."

A very valid point. And in fact, OCD has been known to be cured through cognitive behavioral therapy... so it is implied that their dopamine levels must have learned regulation.

There is also the issue of operant conditioning treating illnesses (such as schizophrenia) which are not supposed to be treated... through EEG biofeedback.
Check out http://www.eegspectrum.com/Applications/InfoNetwork/ for a list of case studies put together by just their site. There's plenty of abstracts on pubmed to be found as well.

Definition is important, but the fact is... what we define is inescapable may not be all that inescapable.

Some researchers are developing new models of addiction which are uprooting many old ideas, including the very idea that addicts can be "cured". Many addicts seem to bounce from one addiction to another in varying degrees until age seems to take "the edge" off things for them. This is more than likely a result of the risks/rewards equation changing, or due to hormone levels and biological changes occuring with the onset of age. Often, "recovering" addicts seem to have simply refocused whatever psychological/mental issues were responsible for their addiction in a new direction, which might be giving them the same rewards the maladaptive behavior was giving them before (just look at AA).

So, to say the mental illness of addiction has been "cured" by therapy may be overly optimistic. It's just the manifestation has taken a form which is acceptable in our society, whether that be "addiction" to spirituality, self-help groups, work, academics, etc...