Archive for October, 2009

To be A1 or not to be A1; that is the question

Saturday, October 24th, 2009

I’m at the ASAM State of the Art Conference in Washington and just heard 2 really good talks on Addiction where food is the drug or overeating is the process. Of course, the presenters didn’t put it quite that way. The first talk was by Gene-Jack Wang who has done a lot of the neuroimaging in Addiction and found a lot of evidence that Addiction is a single disease. Unfortunately, he interprets his findings differently and so titled his talk, “Overlapping Neural Circuits in Addiction and Obesity.” You can see from the title of the talk the focus on obesity still doesn’t look at the disease but the result; we might as well try to study diabetes by focusing on people who lost their feet. The other place I differ with Dr Wang’s conclusions is that he interprets his findings to mean that it’s the increased dopamine reward response that makes us eat more. I don’t think that’s true for most of the addicts I treat, and they are the target of his work.

The second talk was by Eric Stice called “Reward Circuitry Responsivity Predicts Weight Gain.” While Dr Wang’s talk was quite good, it’s Dr Stice’s talk that really gives us some information we didn’t have. He presented a number of studies that built a picture of determines who gains weight over the next year and who doesn’t.  Right there, you can see this is new because he’s not talking about rats and he’s not looking at people after the fact. He’s looking at the biology that determines their eating, not the biology caused by their eating. Rather than going into all the studies he presented, I want to just give you the pricture he presented as I see it.

He showed that one would normally expect a dopamine response in the brain from food and even from thinking about food. He’s the first scientist I’ve heard who has said what addicts have long known, that the problem is low dopamine in the brain, not the dopamine from the drug.

In the studies they looked at people who had two different forms of the dopamine receptor. One form has a lower response to seeing the brain’s dopamine and the other was normal. So those with the first form will presumably have a lower dopamine tone and need more of something to feel the dopamine release caused by it. The second form will feel normal dopamine release with a normal reward. Let’s call these two forms of the dopamine receptor A1 and A2.

For the A1 people the less their brain lit up when presented with food, the more likely they were to gain weight over the next year. That makes sense because they will need more food to feel the dopamine. For the A2 people it was just the opposite. For them, the more their brain responded to food the more likely they were to gain weight. Both groups can become obese.

The A2 people seem to act like Dr Wang expects; they far outnumber A1 people at about 75% to 25%, so he would mostly see the A2 people. The A1 people are the people I’m used to seeing that come for treatment for addiction regardless of what food or behavior they use.

For A2 people the more rewarding foods are the more they’ll gain weight – just like Dr Wang suggests. However for the A1 people it’s the less reward they feel from food, the more they’ll eat to feel normal and the more they’ll gain weight. So not every obese person has Addiction, it depends on why they’re obese. Just as I’ve suggested with alcohol.

Again we come to the importance of knowing our genetic makeup. It’s really important for us to know what risks there are in genes so we can know how to modify our lives. Also, it’s important for treatment Dr Stice’s A1 people need augmentation of their dopamine tone so that they can eat less food and the A2 people perhaps need attenuation of their dopamine tone so they can eat less and lose weight. I recommend to all my patients that they go to 23andme.com to get their genetic testing done.

Definitions

Monday, October 5th, 2009

By the time we learn to use words to describe things like medical interventions or public policy we’ve heard most of the words in other contexts, and we have our own idea of what they mean. Long before we heard the word Addiction in any adult setting we heard it as children. It’s meaning to us reflects our oldest understanding of the word. That is, we learned what we think Addiction is long before we learned about what it really is.

Most people I talk to about Addiction are talking about something else. They are talking about drug taking, or substance abuse or criminal behavior or just being bad. They are talking about will and decision, self-deception and lying. To be sure all of these things can be associated with Addiction, but none of them are Addiction.

I’ve written before here about separating out the core phenomena of the illness called Addiction from the surrounding epiphenomena that become associated with it. What keeps getting in the way are the definitions. Before we can actually discuss what we have learned scientifically we’re going to have to let go of our old definitions of words that we think we know the meaning to. Addiction is one of those words.

One colleague suggested that the word Addiction is so filled with false meaning to people that we need a new word to mean the illness that we treat. I came up with Subcortical Hedonic Attachment Syndrome, but there were two problems. First, it didn’t quite capture everything that is core to Addiction as an illness and second, SHAS is a stupid sounding acronym.

So here are some definitions of Addiction and related syndromes that I’ve put together for discussion and feedback. Perhaps we can get to a place of common ground starting from these:

ADDICTION: A permanent dysfunction of the midbrain reward system and resulting hypofrontality with characteristic symptoms relieved by the use of at least one rewarding substance or behavior and resulting in the compulsive use of that behavior.

It must be permanent – a temporary dysfunction brought about by combat or domestic violence is not addiction even if accompanied by attempts at self treatment with rewarding substances.

Resultant hypofrontality –  can be tested for by reward/risk test such as the Iowa Gambling Task and measures of impulsivity such as the Continuous Performance Task

Characteristic symptoms of midbrain reward system dysfunction include irritability, easily frustrated, relative anhedonia, poor focus, poor memory, difficulty making attachments to others, procrastination. Compulsive use of some substance without these symptoms would be a different syndrome such as a hypofunctioning GABAb input to the reward system leading over reactivity of the reward system and temporary production of these symptoms only in the case of drug use.

Substance or behavior must be used to control and be effective in controlling or mitigating at least some of the symptoms. Use cannot be solely for oblivion from some life situations, in response to external stressors or, in the case of anxiolytic substances, for the control of anxiety.

TEMPORARY REWARD SYSTEM DYSFUNCTION USE SYNDROME: The temporary production of symptoms of reward system dysfunction brought about by an environmental agent or situation leading to the compulsive use of a rewarding substance which completely resolves with the removal of the causative environmental agent or situation.

Clinically will look like Addiction and will be differentiated from it by history.

Temporary Reward System Dysfunction Use Syndrome can become Addiction with continued use and resulting damage to the midbrain reward system.

COMPULSIVE USE SYNDROME: The temporary compulsive use of a substance or rewarding behavior brought about only in the aftermath of a rewarding stimuli not accompanied by chronic symptoms of midbrain reward system dysfunction and hypofrontality.

Temporary – often seen as repeated binging episodes and not present between episodes until triggered by another reward powerful enough to cause a high and resultant crash leading to compulsive use

Between episodes there are no symptoms of reward system dysfunction  or hypofrontality.

Compulsive Use Syndrome can become Addiction with continued use and resulting damage to the midbrain reward system.

ANXIETY INDUCED SUBSTANCE USE: The use, compulsive or otherwise, of any anxiolytic substance, rewarding or otherwise, to quell the symptoms of anxiety, even when done in spite of adverse consequences, coupled with an absence of symptoms of midbrain reward system dysfunction.

Use must be solely for relief of anxiety and not for relief of symptoms of midbrain reward system dysfunction. There must be no symptoms of midbrain reward system dysfunction except in the immediate aftermath of a rewarding anxiolytic substance.

Anxiety induced substance use can become Addiction with continued use and resulting damage to the midbrain reward system.

SUBSTANCE OR REWARDING BEHAVIOR ABUSE: The recurrent, non-compulsive use of a substance, in spite of knowledge of possible adverse consequences, for purposes of experimentation, fitting in with peers, to avoid social stigma or other social reason without evidence of compulsive use, anxiety relief from use or symptoms of midbrain reward system dysfunction.

SUBSTANCE OR REWARDING BEHAVIOR USE: The occasional, voluntary, and non-problematic use of rewarding substances or behaviors in socially acceptable situations without compulsive use, symptoms, or symptom relief.

© Howard C Wetsman MD FASAM

To Prevent Addiction

Saturday, October 3rd, 2009

It’s everybody’s dream. Don’t just treat the illness, or even find a cure for the illness; prevent the illness. It’s a wonderful dream, and with regard to addictions it seems easy to fulfill. Don’t ever drink and you won’t get addicted to alcohol. Don’t allow cocaine in the country and no one will ever get addicted to cocaine. To quote Hemingway, “Isn’t it pretty to think so.”

We’ve got to ask ourselves, “How long have we been at this? And when is it going to work?” Surely, if this were true prohibition in the twenties would have gotten rid of much of Addiction if Addiction could be prevented by preventing use of the drug. However, as I show in Questions and Answers on Addiction, while prohibition temporarily decreased the amount of alcohol used in the US it just caused a switch to another drug. Drinking went down but not Addiction.

I keep asking my Addiction Medicine colleagues to show me one study that shows that any preventive measures aimed at Addiction as a whole have ever worked. I’ve put this challenge out numerous times to the leadership of Addiction Medicine and have yet to get a single response. I get lots of responses about preventing alcoholism or cocaine abuse, but nothing that shows prevention of Addiction as a whole.

Of course, no one has to worry about my thesis on this if they don’t believe Addiction is an illness. If they believe that alcoholism or cocaine dependence is an illness, but that they are different illnesses, then I can be safely shunted aside. It’s probably more convenient for a lot of people treating Addiction to not see the single disease. It’s hard to see your own overeating as a form of the illness while telling someone else to stop drinking.

It also helps when you’re making drug policy not to have to look at Addiction as an illness. It’s hard to get an illness to change by making a policy; it’s so much easier to have a policy about a drug. We’ve had “drug policy” for a long time in this country and spent billions of dollars to implement it. At this point one would have to conclude that either the original thesis of the policy was incorrect or that the implementation was completely botched. Generation after generation of administrations have been able to point to their predecessor and claim a botched implementation, thereby preventing anyone from having to critically look at the original premise.

So if I’m right, can Addiction be prevented? Sure, about as well as Diabetes is prevented or Hypertension. These are largely genetic, chronic illnesses with lifestyle and behavioral components just like Addiction. We can have tertiary prevention and secondary prevention, but primary prevention of a largely genetic illness is going to be hard.

What would we have to prevent to have primary prevention of the Addiction that isn’t genetically derived? We’d have to prevent anyone feeling less than anyone else. We’d have to prevent anyone from feeling isolated from others. In short we’d have to prevent bigotry, prejudice, poverty, inequality, and the list goes on. Really, it’s much easier to just shoot down drug smugglers.

But we have a lot we can do about secondary and tertiary prevention whether something is genetic or not. We can find it quickly and intervene before it gets worse. We can treat it as an illness rather than as a social problem that we hope goes away. We can make sure that people who don’t get better get more treatment, not less. But in order to do any of these things that can be good secondary and tertiary prevention of Addiction, we have to recognize that we can’t do primary Addiction prevention by getting rid of drugs and alcohol. Unless of course you can show me that study, but I’m still waiting.

© Howard C Wetsman MD FASAM

Jews, Genetics and Addiction

Friday, October 2nd, 2009

Growing up, I was taught that Jewish people couldn’t be alcoholics. That was a bit of wishful thinking. The people who taught me this rationalized it by saying that the Sabbath Kiddush socialized us in such a way as alcohol became something used only in a religious way. This never made sense to me as several Christian religions have sacramental use of wine and they didn’t report lower frequencies of alcoholism. So I just passed the whole thing off as a cultural myth and went about my business.

It turns out that Jews do have a lower frequency of alcoholism, but it has nothing to do with the religion or the culture. It’s in the genes.

As alcohol is processed in the body it is first turned from ethanol to ethylaldehyde on it’s way to becoming acetic acid. Ethylaldehyde, like formaldehyde, is not something the body likes, but it isn’t there long or in great quantities when the average person takes a drink. However a point mutation in the enzyme that turns ethanol into ethylaldehyde makes the enzyme run very fast and makes more ethylaldehyde than the body can process. It also gets rid of the ethanol more quickly. So someone with that mutation gets less enjoyment from alcohol and more of the aldehyde with its negative effects, it would sort of be like taking antabuse.

This point mutation is very rare in Europeans, occuring in less than 5%. In east Asians it is very common with more than 90% of Japanese and Chinese having at least one copy of the mutated gene. In Jews the prevalence is greater than 20% or more than 4 times higher than a European population. In fact more and more genetic studies are coming out showing Jews of European ancestry to be genetically more like a Middle Eastern population than a European one. (A professor from Jerusalem is hoping to ignite a grassroots peace process by showing that the Palestinian population are actually the Jews left by the Romans to man the farms in the area. It’s a fascinating topic with a lot of evidence but too much to get into here.)

So as Europeans go, a greater percentage of Ashkenazi Jews than normal “get no kick from Champagne.” This really would lower the prevelence of alcoholism in the Jewish population. However it doesn’t say much about Addiction in general.

If you look at Addiction as the addictions, depending on what drug the person uses, all you need to do is avoid the drug and you can’t get the addiction. But what if Addiction is one disease with multiple drugs? What if compulsive overeating and heroin addiction have the same common cause in the brain? That would mean that being protected from over drinking doesn’t protect someone from the illness called Addiction. This has become an important idea because recent findings at the National Institute of Drug Abuse show the same PET scan results in obese compulsive overeaters, alcoholics, cocaine addicts and heroin addicts.

There is no evidence that the disease of Addiction, taken together in all it forms, varies from population to population. The drug used does and some of that is genetic, but the genetic causes of Addiction seem to be old enough and strong enough to span across all human populations equally.

© Howard C Wetsman MD FASAM