Science of alcohol addiction
April 5, 2010 1:36 PM   Subscribe

Two questions about a theory of alcoholism: Irreversible change at the cellular level.

Here’s the theory:
At a certain point in the drinking life, a physical change can occur at the cellular level: Namely, the presence of alcohol itself begins to trigger a physical need in the cell — a need for more alcohol. (Explaining why the first drink becomes the trigger for the second, and so on.) If this physical change occurs, it is irreversible, and the person is an alcoholic; if it has not, alcoholism hasn’t yet developed. Presumably, why the cells of some people change in this way sooner than cells in other people has a strong basis in genetics.

2 separate questions: 1) Is this theory widely respected among creditable experts? 2) Is it true?
posted by LonnieK to Health & Fitness (21 answers total) 3 users marked this as a favorite
Pseudo/quasi science? William Burroughs proposed the exact same theory for heroin. He went so far as to say that if you could keep cells on the brink of heroine starvation that you could interrupt their life cycle to some degree.

I don't necessarily believe this, and I wouldn't try and pass it on to anything else, including alcohol, but I do believe that any drug, even the prescription and OTC drugs, if taken long enough, can cause changes on a cellular level.

- Sorry, anecdata
posted by TheBones at 1:42 PM on April 5, 2010

1) no. is this something you just made up?
2) no.
posted by andrewzipp at 1:43 PM on April 5, 2010 [1 favorite]

Response by poster: Nope, didn't make it up. Heard it on good authority. What if we take out "the cellular level"? Is there any irreversible physical change that occurs in alcoholism?
posted by LonnieK at 1:50 PM on April 5, 2010

Is there any irreversible physical change that occurs in alcoholism?

Apart from the cirrhosis and brain damage, probably not. Are you talking about tolerance? Because the body does adjust to being flooded with large amounts of alochol (and other drugs), but that is reversible with abstinence.
posted by dortmunder at 1:55 PM on April 5, 2010

I have read a few articles which study the effects of ethanol on mimetic cell membranes (i.e. synthetic membranes reconstituted from the component lipids). Three references:

Effects of ethanol on lipid bilayers
Direct NMR evidence for ethanol binding to the lipid-water interface of phospholipid bilayers.
Water permeability of polyunsaturated lipid membranes

From the first article: "Chronic alcohol consumption, however, was found to increase the amount of cholesterol in the outer leaflet of mouse synaptic plasma membranes by a factor of 2, to about 28 mol % of the total cholesterol (Wood & Schroeder, 1992)"

Also from the first article: "As suggested earlier by Brockerhoff (1982) and Klemm (1990), such interactions in the interfacial region of membrane lipids and/or proteins may influence neuronal membrane function, leading to some of the physiological effects of ethanol."

From the second paper: "Thereareanumberofexamplesintheliterature of altered protein function at physiological concentrations of ethanol. For instance, ethanol affects the phospholipid- dependent signal transduction mechanisms which control the activities of phospholipases C and D (Hoek & Rubin, 1990)."

So I'm not sure these point to a physical need for more alcohol in the cell, but they do show that chronic alcohol consumption can lead to fundamental changes on the cellular level, particularly for the cell membrane and membrane protein activity. Hopefully those references can point to some more in vivo studies rather than just the mimetic studies that can more fully answer your question.
posted by sararah at 1:57 PM on April 5, 2010

haha not sure why "There are a number of examples in the literature" got all smooshed together with copy and paste. whoops!
posted by sararah at 1:58 PM on April 5, 2010

Response by poster: Thanks to all for your answers. It's a complicated subject and I'm not learned in it. Let me approach it from a totally different perspective.

Jack and Jill go out with the office crowd after work. Jill has a glass of Chard and is still sipping after Jack has downed a double Martini. Jill doesn't want another drink. Jack does.

And he will want that next drink for the rest of his life. Even if he goes on the wagon, if he ever takes a drink, he'll desire another one. Physically. And not to soothe withdrawal -- that may be long over — but to soothe a demand from his (cells, brain, what?).

Repeat: Jill doesn't experience that desire. For her, a drink doesn't trigger desire for another one.

The theory was, as I recall, that the CELLS had changed. I may be wrong, or maybe the theorist was. Maybe it wasn't cells, but more like "a switch is thrown in the brain."

But 3 things were central about this "change": its physical nature, its fundamental level, and its irreversibility.
posted by LonnieK at 2:14 PM on April 5, 2010

Maybe this is along the lines of what you're looking for:

"It is suggested that alcohol-induced changes in the GABAA receptor may play a role in certain aspects of tolerance to alcohol and in altered abilities of an individual to terminate alcohol intake."

from Hoffman, PL.; Tabakoff, B. (Jul 1996). "Alcohol dependence: a commentary on mechanisms.". Alcohol

If you have access to a University library, you should be able to get a hold of the entire article.
posted by rancidchickn at 2:35 PM on April 5, 2010

I think you might be helped out by looking for information on how a craving or even a simple visual cue of an alcoholic beverage "activates the prefrontal cortex and the anterior thalamus in alcoholics but not in moderate drinkers". Maybe a search for "activated cravings center" or something of the like would yield more useful results for your purposes?

As a recovering alcoholic and a drug addict I can anecdotally confirm that FOR ME, seeing a drink triggers a craving (though it seems to lose some strength with time)-- seeing cocaine is still more triggering, and seeing meth (or even just the paraphernalia) is by far the worst.

FWIW, in the recovery community there is a saying: "you can't turn a pickle back into a cucumber".
posted by mireille at 2:37 PM on April 5, 2010 [2 favorites]

I think there are two fundamental questions here:

1. Are there changes on the cellular level due to chronic alcohol consumption,
2. Do these changes have a physiological effect on the addiction that an alcoholic suffers. i.e. does addiction stem from these cellular changes (rather than psychological addiction)

I think I sort of answered #1, although I am unclear of the reversibility of the cellular effects, and rancidchickn presented some evidence for #2.
posted by sararah at 2:39 PM on April 5, 2010

You seem to be trying to tie a macro effect ("I desire alcohol") to a micro effect ("My cells desire alcohol") but that's not how it works. In fact, most cells in your body can't use alcohol at all: it's your liver's job to metabolize alcohol into something your cells can use. So in that sense, your cells can never desire something they can't even use. And alcohol use/abuse does not fundamentally, permanently change how cell respiration happens.

As to the assertion that an addicts cells have changed... that depends on what you mean by "change". As I read information on the internet the neurons in my brain change to encode and process the information I see. So just reading MetaFilter changes my cells!

But we don't yet really understand how addiction changes our brains. People can get addicted to all sorts of things: alcohol, morphine/opiates, amphetamines, chocolate, sugar, porn/sex, video games... the list goes on and on. But does, for example, porn/sex addiction change the physical nature of our cells? I think not in the way you are looking for. But it must in some way change how our brain is wired.

You seem to want a simple explanation for how alcohol addiction occurs. But there isn't one. It's a complex set of factors including genetics, how you were raised, learned behaviors, stress coping mechanisms, social pressures...
posted by sbutler at 2:45 PM on April 5, 2010 [8 favorites]

As someone who soaked up more alcohol in college than most people do in a lifetime, then moved to being a very infrequent drinker once gainfully employed, I don't think your theory is true. I do think there could be something genetic/psychological that causes some people to be able to stop and others not though - pretty much the same way some people are obsessive-compulsive, but most are not. Maybe everyone has their kryptonite, decided at birth...
posted by meepmeow at 3:38 PM on April 5, 2010

No, this is not a theory widely respected among experts.

Alcohol can cause irreversible health problems, such as cirrhosis, but I don't think that's what you're asking about.

Addiction is never as simple as one thing. You may want to do some research on the concept of "drug, set, and setting" which says that problematic substance use is the confluence of the drug or substance, the individual's mind set or emotional state, and the setting or context in which the drug use takes place.

You may also want to learn more about the dopamine and endorphin systems in the body, as those are (some) of the places where chemical changes occur with substance use, and are part of the ways that addictive behaviors are reinforced at the cellular level, which I think is some of what you're reaching for here.

I will (again) plug In the Realm of Hungry Ghosts, by Dr. Gabor Mate, as having a comprehensive and accessible description of addiction and the neurological system. It's also just an excellent book.
posted by gingerbeer at 4:54 PM on April 5, 2010

I work for a very large study of alcoholism in a university psychiatry department, and I often try to come into threads regarding alcoholism because there is alot of popular misinformation (no offense to you OP). Here is my long, long spiel about how alcoholism happens on a biological level. The tl;dr is basically, no, individual doses of alcohol do not cause irreversible changes in cells that instantly trigger lifelong alcoholism.

The first thing many people don't realize is that there are two types of "tolerance" in the alcohol abuse and dependence literature.

"Tolerance" as most people think of it, as in building up the amount you can drink before getting drunk. This is caused by GRADUAL changes in many different cellular mechanisms in the body. Your liver cells make more alcohol dehydrogenase after repeated regular drinking, which causes you to need a higher dose of alcohol for a given level of intoxication, prompting you to drink more, and prompting the liver to make even more alcohol dehydrogenase, and so on, creating a feedback loop (at least while your liver still works).
A similar thing happens in your brain in the way the serotonin and other neurotransmitter systems respond to alcohol. Those neurotransmitters are responsible for the euphoric/relaxing effects of alcohol, and they release less neurotransmitter in response to a given dose after repeated drinking. As soon as regular drinking is ceased, these systems tend to drift back to the point they were at before drinking. How quick that happens and how complete the biological "recovery" is depends on age, duration of regular drinking, and many other factors.

Then, there is your innate biological "tolerance" that you had the very first time you had a drink. This is somewhat closer to the kind of thing you were talking about, OP. It is simply how well your body processes alcohol to begin with, without repeat dosing over time, and it varies greatly across the population. Some people are high responders- they need very little alcohol to get drunk because their livers don't break down alcohol efficiently, so it stays in the bloodstream and gets them drunk sooner and longer. These are your "Jills" and they tend not to drink alot and nurse drinks, because alcohol is technically a poison and their bodies are more vulnerable. The low responders, on the other hand, need 3 drinks to even feel a tiny buzz even the very first time they have alcohol. There is a suggestion in the literature that these are the "Jacks" you refer to. They binge drink more because their bodies can handle it, and then they develop the other kind of tolerance I discussed earlier, and that's when they get into a really powerful feedback loop of drinking more that is hard to escape.

The "Jacks" in my study also have other genetic risk factors; they are risk-seeking, or depressed, or have poor inhibition of their own impulses (yes, all these things are heritable, to some extent). Someone with poor impulse control to begin with is only going to be worse when drinking.

However, if a "Jack" has a protective environment, he may never develop alcohol abuse or dependence, despite his genetic risk factors. If he never touches alcohol because he has a religious objection to it, he won't become alcoholic. If his parents provide structure and help him control his own behavior, he's less likely to drink at a very young age. If he hangs out with the right people in college and doesn't go to parties that promote binge drinking, he won't develop the kind of tolerance that gets people into trouble over time. If on the other hand, he has an alcoholic parent, that not only suggests he inherited some genetic risk, but he will likely grow up in an environment where that risk is not blunted or managed, and once he drinks regularly and heavily, all signs point to alcoholism. If you put a "Jill" in the same home, she definitely might become alcoholic, too. You don't need the genetic risk factors to become alcoholic, and if Jill has alot of hard drinking friends and she's young, that might exert more influence than biology, but its something people grow out of. You can't grow out of your genes.

Alcoholism, like most things, is not just genes or just environment, but a complicated interaction of genes and environment. Despite what people in AA might like to believe, people do vary in their level of genetic risk, and that makes alcoholism easier to get into and harder to escape for some than others, in a way that can't be attributed to insufficient will or insufficient surrendering to a higher power, etc. That's also why there is no one behavior or set number of drinks that makes someone alcoholic, even though we use clusters of behaviors to diagnose alcohol abuse and dependence. It means very different things if our hypothetical Jill has 6 drinks in one weekend vesus Jack having 6 drinks. Just the level of drinking alone is never good enough to diagnose alcohol problems, but the frequency and quantity are usually pretty predictive of other problems.
posted by slow graffiti at 5:00 PM on April 5, 2010 [191 favorites]

You're asking about how the physical effects of alcohol translate into changes in behavior (i.e., alcoholism), and why this occurs in some people but not others.

Addictive drugs work in many different ways and have different effects on the body, but all addictive substances, including alcohol, have one thing in common: they happen to raise dopamine levels in specific parts of the brain (for our purposes, the relevant part is the nucleus accumbens, though it's not the only part involved).

The nucleus accumbens is the part of your brain dedicated to triggering pleasure-seeking behaviors based on past experiences. When you get drunk, your nucleus accumens says "FUCK MAN, THIS IS AWESOME, WE NEED TO DO THIS MORE OFTEN", and it makes a little note on its Hedonic Clipboard. When this happens, the likelihood that you will choose to drink alcohol again in a similar situation increases a tiny bit. So the next time those environmental cues start to match up again (Friday night? Check. Out with friends? Check. In a bar? Check) your nucleus accumbens will pop up and ever-so-subtly suggest, "Hey, why don't we get a drink?"

After this pattern has occurred many, many times, it starts to become a habit. You go and order that first Friday-night beer without even thinking about it. At this point, the brain is adapting to become more efficient at handling alcohol-seeking behaviors. Just like how you tie your shoes without thinking about the motions. When you do something enough times, it becomes an ingrained set of behaviors—you put on your shoes, and your hands tie your laces more or less automatically. It happens with addiction too, in part because your nucleus accumbens starts handing off its alcohol-related duties to other parts of the striatum, which are responsible for handling well-established behaviors, habits, and rituals.

The mechanics underlying these behavioral changes are still not well understood, but it's thought to be due to alterations in neuronal structure, branching, and connection. Your brain is literally rewiring itself to crave and consume alcohol. Are these changes irreversible? Not per se. But they are extremely resilient. They say you never forget how to ride a bike. Drug abuse is the same way. It becomes deeply ingrained. You can be clean for decades and still get cravings. And if you give in to those cravings, those old well-established rituals will fall right back into place.

Finally, do the neurons in your midbrain actually need alcohol? No, not at all. Physiologically, they will function perfectly well without alcohol (the exception has to do with conditions of severe withdrawal, but that's tangential to the issue of addiction). The "need" for alcohol is purely psychological, though it's no less powerful for being that.
posted by dephlogisticated at 1:25 PM on April 6, 2010 [6 favorites]

Hmm.. the literature of Alcoholics Anonymous makes it much simpler. I've read the literature quite a bit, due to having a series of alcoholic girlfriends. AA describes alcoholism as "a craving of the body, and an obsession of the mind." Alcoholics have a craving for alcohol that is activated the moment they have a drink. When they're not intoxicated, they are obsessed with finding their next drink. So when Jill gets a couple of drinks, she says, "oh I feel like I'm gonna puke, I think I'll stop drinking now." Jack gets to that same point, and says, "oh yeah, I want more of that" and he cannot stop even when he's getting intoxicated to the point of a blackout.
This was all developed as the AA theory back in a time when scientific knowledge of the physiology and psychology of alcoholism was very primitive. But it does pretty much dovetail with the modern research, if only as an empiric qualitative observation rather than a technical theory.
posted by charlie don't surf at 6:15 PM on April 6, 2010

Hmm.. the literature of Alcoholics Anonymous makes it much simpler,

Or put even more simply: "If, when you honestly want to, you find you cannot quit entirely, or if when drinking, you have little control over the amount you take, you are probably alcoholic." (p. 44)
posted by phaedon at 7:26 PM on April 6, 2010 [1 favorite]

slow graffiti, can I ask you, if you know, how Herbert Fingarette's book Heavy Drinking is regarded by contemporary alcoholism researchers? (It denies the existence of alcoholism as a disease.) I found it reasonably convincing when I read it, but it's now oldish and I wouldn't be surprised if recent studies have obsoleted it.
posted by painquale at 12:29 AM on April 8, 2010

Despite what people in AA might like to believe, people do vary in their level of genetic risk

People in AA have all sorts of opinions about all sorts of stuff, but AA as such has no opinion on this topic.
posted by shothotbot at 5:14 AM on April 9, 2010 [3 favorites]

I'm not familiar with that book, but if it says alcoholism does not exist, it flouts a major portion of the DSM and an established branch of medicine/psychiatry, so it's probably bunk. Despite controversy over individual diagnostic criteria and labels and whatnot, no disease or disorder would make it into the DSM without a majority of researchers in that subfield agreeing that they see the disorder in clinical practice and that it has certain observable characteristics that can be replicated in a majority of a sample of people with that disorder, in a controlled study. Yes, some disorders are better tested and have more consistent diagnostic criteria than others, but alcohol abuse and dependence actually do exist.
posted by slow graffiti at 10:19 AM on April 9, 2010

Perspective from a mental-health/addictions worker:

I haven't read the book either, but saying that something is probably bunk because it contradicts the DSM is a bit disingenuous (see "ego-dystonic homosexuality").

The discussion about whether alcoholism (or any other addiction) is a disease is a very interesting one that of course raises the question of the definition of disease, one which I'll not get in to in this post.

I wanted to address, from my experience, the idea of a biological imperative to continue drinking: From the majority conversations with people experiencing sobriety from addictions that I've had, I understand that the need for the immediate second drink/hit after the first is largely about reverting back to old coping mechanisms to deal with the shame and feeling of failure of having the first drink. This is of course a viscious cycle.

I'm interested in medical model analysis about addictions, but this is a complex topic that from my experience has more to do with people trying to fill an emotional hole/cover underlying trauma (we all have experienced trauma , btw). The ever present "thirst" for the drug is the body/mind's knowledge that the substance will dull the (possibly sub-conscious) emotional pain.
posted by Pertz at 9:47 AM on May 2, 2010

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