Episode 172

Social lubricant.  Addictive evil.  Between these extremes there’s a sea of alcohol.

This week’s episode features two experts in Alcohol Use Disorder.  Dr. George Koob, Director of the National Institute on Alcohol Abuse and Alcoholism, and Dr. Tom Parkman, Research Fellow at King’s College London, both join Jesse to discuss what we know, what we don’t know, and what current research is trying to find out about alcohol use and abuse.

Knowledge Gaps

Considering how common alcohol use (and abuse) is, what’s really interesting is how little we know about how alcohol acts on the brain.

In low doses, there are a number of neurotransmitter systems that alcohol affects, including GABA.

But researchers still don’t entirely understand what changes in the brain you engage in excessive alcohol consumption.  We don’t know what causes alcohol addiction, how exactly it affects the prefrontal cortex, and how it changes the adolescent brain.

Is Alcohol Healthy in Moderation?

We’ve all see the headlines that alcohol can be good for you.  But in reality the question is still somewhat unresolved.  There is good data out there suggesting the health benefits of one drink per day on including improved cardiovascular health and diabetes.

The problem is that the research is post hoc, meaning it consists of surveying people about their past alcohol use and current health status.

Dr. Koob is working on an exciting new study, the Moderate Drinking Study, that will actually follow individuals as they restrict themselves to one drink a day going forward.  Hopefully this new line of research will provide some more definitive answers on the health benefits of moderate alcohol consumption.

Alcohol and Addiction

Many people can consume alcohol moderately without any problem. Many people cannot.  Approximately 30% of people will have a problem with alcohol over the course of their lifetime, and about 6% of the population will have one at any given time.

And who becomes addicted to alcohol?  There are some predictors, including a family history of drinking or drug abuse and friend who drink heavily.  But ultimately we can’t predict who will have a problem and who won’t.

Fortunately, quite a few new therapies to treat Alcohol Use Disorder are becoming available, including psychedelics.  Unfortunately, there’s never going to be a magic pill that can completely cure alcohol addiction.

For example, one of the new prescription pills is Disulfiram, which makes you very sick if you drink alcohol while on it.  For users of the pill, it’s very effective.  Problem is, very few people actually still with taking it consistently.

When you regularly binge drink, your reward systems become desensitized, resulting in less pleasure from alcohol.  At the same time, your stress systems are overly activated when you stop drinking.  More alcohol brings temporary relief, but just perpetuates the cycle.

Dr. Koob is looking into a treatment something that would reverse the rewards deficit activation.  This may be the future of alcohol addiction therapy.

Episode Highlights

0:28Alcohol use and abuse
1:55This Week in Neuroscience: Risk-taking teens’ brains seem to disregard past bad outcomes
4:32The audience interaction section
6:33The origin of St. Patrick’s Day
7:15 Introduction to Dr. George Koob and Dr. Tom Parkman
8:39How alcohol affects the brain (and some questions that are still to be answered…)
10:44Views on alcohol in different eras and cultures
12:42Is there an upside to drinking alcohol?
15:14Are there common trends that predict who might become alcohol-dependent?
16:17What makes people more susceptible to different substances
17:30Addiction therapy
19:54Percentages of people who are affected by alcohol addiction
20:48Prescription drugs used for addiction
24:41Addiction swapping
25:34Your brain’s reward circuitry and its involvement in addiction
29:18 Wernicke-Korsakoff syndrome
30:37What will we learn about alcohol and the brain in the next 5-10 years?
32:57Why is there such a stigma around quitting drinking?
35:17What doesn’t the public know about alcohol abuse?
36:27Alcohol and the FDA
37:40Recommendations for alcohol use
41:15Ruthless Listener-Retention Gimmick: Study reveals how alcohol shifts brain into 'starvation mode'
Read Full Transcript

Dr.  George Koob: Alcohol does not bind to an actual receptor in the brain.  It doesn't bind to a dopamine transporter like cocaine.  It doesn't bind to the neuro-opioid receptor like morphine or oxycodone.  So how does it work?  We've come to realize that there are a number of neurotransmitter systems that alcohol works on it at low doses, those that would be equivalent to one or two drinks.  Some of them are ion channels.  Some of them are actually enzymes.  Drill down that question further and say well then, how does it really work?  One of the theories is that alcohol hangs out at water pockets inside the membrane and somehow in some indirect way moves the proteins around and changes how maybe ion channel work.  That's one thing we don't know a whole lot about but then we don't know a whole lot about also is what then changes in the brain when you excessively engage in alcohol.  A lot of the work we do at the institute now is directly to try and understand the nerve after processes that lead to compulsive alcohol seeking and taking.  We don't know how alcohol produces liver cirrhosis.  We don't how it damages your frontal cortex if you really get into it excessively.  We don't what it does to the adolescent brain.  We're beginning to learn some of these things but there are a lot, a lot of questions still out there.

Jesse Lawler: That's really actually amazing and surprising that in 2017 there's still neuropharmacological questions about something which humans have been using since the dawn of time.  Probably one of our best known and most widely-used psychoactive substances.

George: Right.  The standard fair is that it activates one of the major inhibitory transmitters on the brain, GABA or Gamma-Aminobutyric Acid.  There are subtypes of GABA receptors that definitely seem to be more sensitive than others but it also, alcohol suppresses glutamatergic function and that’s your excitatory transmitters.  The two together can produce kind of the numbing of neuronal activity in a way but we also know that in low doses alcohol can produce excitation and disinhibition in addition to relaxation.  It probably means that there are certain pathways that are activated in a certain ways at certain doses.  It's the fascinating area of current investigation. 

Dr.  Thomas Parkman: I think it's very much dependent on the culture as well of the time period that sort of alcohol is viewed.  If you go back to the 1930's when Alcoholic Anonymous is introduced, alcohol is very much seen as evil to the point you know, sort of an extension of the temperament movement of seeing all prohibition and all that sort of stuff.  Then, as the decade went on I think the view on alcohol has got a bit more relaxed.  There was a little bit more receptive to alcohol.  And then particularly in the UK over the last 10, 15 years has been a big push on calm reduction approaches to alcohol.  A lot of people would ask me if I've ever gotten to conversation with people that illicit drugs.  When you start talking to them about why they don't like them, it mainly comes down to the legality issues.  If you suggest to them that the harm issues by far less than alcohol, people feel uncomfortable on that sometimes.  Alcohol by far and away destroys more lives than most of the drugs probably put together, I would say.

Jesse: Is that a generational thing?  Do you think that is true when you're talking to somebody who's 20 right now as when you're talking to somebody who's 50?

Thomas: Yes.  I think it's possibly something about like that.  The thing in the UK is that the big thing that has been scaring the government I guess is binge drinking.  Young teens, early 20's going out, drinking huge amounts -- 20, 30 units plus in a sitting. 

Jesse: Wow.

Thomas: Yes, absolutely.  This is typical of Britain.  We're massively binge drinking nation.  This is the house scare of the menace.  They're trying to increase educational arrest but then on the other hand, if you talk to someone who's maybe my dad's age 50, 60, going down the bourbon, having 12 pints over 12 hours, they would see that as -- Yeah.  I’ll use the word normal I guess because that's what you did, you know work in men's clubs or all those sorts of things that was a normal thing to do.  But if you speak to them now about going on these nights out drinking vodka, drinking these sorts of alcopop-type things, I doubt they'd be able to identify.  Obviously I'm generalizing here but I doubt they'd be able to identify that a lot of the times.  Certainly, I think it's a good point you raise in terms of who you speak to, what perception of alcohol they have.  And so, most people have generally got their own opinion on that.  What's good for them?  What's bad for them type of thing.  Often they vary quite significantly. 

Jesse: There’s a lot of people out there rooting for there to be an upside drinking alcohol and you'll still here frequently maybe a glass of alcohol every couple of nights is good for the circulation or good for the cardiovascular system.  Does that bear out if somebody is eating a generally healthy diet?

George: You really hit on a very important question that's still pretty much unresolved.  There's pretty good data out there suggesting health benefits of the equivalent of one drink a day in facilitation of cardiovascular function, reduction and stroke, even benefits for diabetes.  The problem is that most of that work that's been on in this area is in a sense post-talk.  It's an analysis of different populations.  Obviously, in Mediterranean diet, beneficial with and without alcohol.  So we are actually engaged in a current study at the institute of a long-term perspective study to ask that question in individuals who will be restricted to one drink a day called the moderate drinking study.  This study is about to be launched and hopefully a lot of information will come out of it and tell us a little bit more about this exact issue.  I must add onto this that we also know that if you get involved in post more than moderate drinking, alcohol has substantial deleterious effect on the health of the body.  I don't want to make it sound like it's a monotonic dose effect function.  It's quite the opposite.  We call it a J-shape curve.  Most of the curve is on the bottom part of the J.

Jesse: I'd say it's more like a candy cane than a J because it's dipping down.

George: Exactly right.

Jesse: I was just recently reading a biography of Churchill and he was fairly famous for being a heavy drinker who would always be drinking something.  He would necessarily be drinking to the point where he's drunk but he wouldn't be fully sober either.  I just think that Tony Blair, any modern politician couldn't get away with that.  Drinking during lunch is a regular matter of course.  It just seems like some of society’s expectations have really changed.

Thomas: Absolutely.  That's a really good point actually.  I think today, when people drink, they drink to get drunk.  Whereas, I think 50 or 60 years ago, I think drinking was more of a social thing.  You go to a pub, have a few drinks.  Getting drunk was almost seen as negative in a way in terms of if you can't hold your drink type of thing.  Whereas now drinking is purely to get drunk.  And you're absolutely right.  I mean, politicians over here there’s absolutely no way they’ve come and for example go out on a pub lunch without getting absolutely hammered for it basically.  Whether that's right or wrong, personally it wouldn't bother me if I saw he was having business lunch.  I think the paparazzi generally speaking today is quite invasive but it's all that context really.  I think you're absolutely right, yeah.  Generally speaking, I think politicians will get fairly heavily criticized for it.

Jesse: As somebody who studies addiction, do you see commonalities in the personality types or other demographics?  Something that is sort of a common trend in people who wind up dealing with an addiction?

Thomas: Yes.  There's a lot of literature on predicting who might become dependent on a substance or another, and these are things like if your siblings drink, if your parents drink heavily, if there's a history of drinking or drug use for that matter in the family.  Those sorts of things are fairly possibly correlated with the impact on, if someone else will drink.  To a lesser extent, friends.  So, how much your friends drink and use drugs.  So if you're in a friendship group, you're a 17 year old guy in a friendship group and all of your friends drink, it's more likely that you will drink.  So there are certain things and sort of personality as well so if people are perhaps more extroverted, more willing to take risks, would perhaps drink more.  Again, those literature is full of that but that's not to say that people who do score highly on extraversion or who have a friendship group who would drink or have siblings that all drink, that doesn't mean that it will start drinking and become dependent on drugs or drink.  It just means that there's perhaps a slightly high correlation that they will.

Jesse: If somebody is an addictive personality type, what do you think ultimately draw somebody to alcohol versus one of the other choices of things a person could become addicted to whether that's other drugs, sex, gambling?  There’s a lot of options for addiction.

Thomas: Yes.  I think it would be very difficult to pinpoint.  First of all, an addictive personality type because there will be people who might be very addicted to one thing and have no inclination to trying any other things.  Say for example, someone might be addicted to video-gaming or something like that and the idea of drinking is absolutely abhorrent and that they would never drink.  I think it's very difficult to define an addictive personality.  Generally speaking, someone would start on alcohol because they can get a hand on mom and dad's wine or outside or whatever or they can get their older brother or sister to buy it for them.  Then they might start drinking with their friends, and then they might experiment with marijuana.  And then sort of escalate from there and that's a fairly common pathway in terms of why people start progressing and do the drug.  As to why people just stop at alcohol, I couldn't really take a good point to that as to why.  It happens a lot.  I mean, very few people actually go on to try some of the drugs especially people who then get addicted to these drugs.  A few have fallen between.

Jesse: Yes.  I've always found that interesting sort of the gateway drug mythology because there are certainly are a lot of people that never make it past that gateway.  What do you see now for people that are dealing with alcohol addiction?  It seems like there's new research going on into therapies that would’ve sounded pretty out there a couple of years ago as far as using psychedelics to try to win one's self off of other drugs in use with like a psychotherapist.  Do you have any comments or thoughts on some new therapies that are being attempted?

George: Well, we have a pretty active medications development program at the institute and the world at large is significantly interested in new medications.  Personally, I don't believe that medications alone are going to solve the problem.  There was never going to be a magic pill that cures you of alcohol use disorder but they can help you along the way much like an antidepressant can help you with someone who has a major depressive episode.

The behavioral therapies are really quite effective -- cognitive behavioral therapy in particular, motivational interviewing.  Some of the 12-steps programs, Alcoholics Anonymous itself is very effective and it's been tested.  There are counselors who are trained and certified.  They can be very helpful.  Now, addiction psychiatrist who can be board certified in addiction medicine.  There are clinical psychologists who have practices that are focused on alcohol use disorders.  There are outpatients programs where you can go in for a whole evening everyday rather than 28-day facilities.

So there's a wide range of different options for treating alcohol use disorder.  I think that's something that the public is not aware of.  There are three approved medications for the treatment of alcohol-use disorder and they are approved by the FDA and they're effective.  There's pretty good data on that.  I'm not big on psychedelics being used.  Psychedelic drugs are very, very powerful psychotropic drug.  I taught drugs at the University of California in the Psychology Department for over 30 years.

I know a lot about drugs.  There are certain individuals who are very vulnerable to psychedelic drugs.  They can precipitate invulnerable individuals to psychosis that long outlives the intoxication due to the drug.  A trade-off is just not worth it for me.  I know there are people interested in this issue.  I'm a firm believer in psychotherapy.  I'm a firm believer in mindfulness that could help facilitate some of the other behavioral treatment, but I believe that taking psychedelic drugs, they're really taking a big risk because there are untoward effects and how do you know that you are not one of those individuals who may be particularly vulnerable to the untoward effects of psychedelic drugs.  So that's where I stand on the topic.

Jesse: What percentage of people have a problem with alcohol addiction at some point during their life would you say?

George: Well, if you look at lifetime, it's over 30%.  Currently we estimate about 16 million individual with moderate to severe alcohol use disorder in this country and that works out to be somewhere between six and nine percent of the population at the given time.  It is very prevalent but the lifetime prevalence is quite high actually.  It's hard to find a family where you don't have some relative who's been inflicted.  Many of them recover blessedly so.  Now obviously, I work with people who were interested in the topic but I don't know almost anyone who works at the alcohol institute who doesn't have a relative somewhere in their family history that had an alcohol problem.

Jesse: Sure.  I think that's very safe to say.  I mean, thinking in my own family there are definitely people like you know which ones are safe to offer a beer to at Thanksgiving, and which ones aren't.

George: Exactly.

Jesse: Of the three prescription medications that there are for alcohol abuse disorder, one of them I know essentially makes you violently ill if you have both the medication and alcohol in your system at the same time.  It seems like that will be the silver bullet.  I mean, it seems like that kind of solves the problem.  But I mean, that's looking at it from the outside here and obviously there are 16 million people that are still dealing with this disorder.  So where's the disconnect there?  Why is that not the silver bullet we need?

George: It's compliance.  A physician in Scotland in the UK who has studied this extensively, Jonathan Chick, and he has shown that if he actually monitors his patients and he works with pretty severe alcoholic individuals, if he monitors his patients on disulfiram and make sure that Johnny or Sally actually take their medication, it works quite well.  The problem is getting people to take it.  I'm sure there are some side effects so if somebody relapses or has a desire to relapse, they do get sick and that puts people off taking the medication.  Interestingly enough what that drug does is it blocks an enzyme on your liver called acetaldehyde dehydrogenase.  Asian-Americans in this country about 30-40% of them are missing one of those ALDH.  So they are partially protected and if you have Asian friends who are missing this ALDH you will notice if they have like half a glass of wine, they get red nose and silly and little giddy and that's pretty much it for them because of this flush reaction that's called.  Someone on disulfiram has more or less the same phenomenon only they have the enzyme more or less completely blocked.  If people knew about it and wanted to take it and were dedicated to abstaining, it does work.  But just telling people about it then not prescribing it and then not following up with the prescription to make sure they're taking it, it becomes very difficult. 

Jesse: Are the amounts needed or the half-life in the body such that you couldn't put it into a patch where it's constantly leaking at a necessary dose into the body?

George: I think there have been attempt to that.  I'm not sure if anybody has picked it up in any marketing form and so you're right, it has to be taken orally.  There is a long acting version of one of the other medications which is known as, generic name is naltrexone, which is a drug that blunts the pleasurable effects of alcohol in simplistic way.  On naltrexone will drink one or two drinks and then say it doesn't seem to be doing much for them.  You can get that in a long acting version.  It's marketed as vivitrol and it's very effective if people want to take it.  But again that's an injection of the small tiny little polymers that contain naltrexone.  Not everybody wants to go through that and go through what’s involved in doing it but that is a long acting preparation. 

Thomas: In the UK there's three medications that one could account per say is one called disulfiram and there's another one called antabuse.  So the one that you just describe in terms of it makes you physically sick is antabuse.  For some people, it's very effective.  Essentially, it's so strong that if you use, you know when you get into like an A and E ward you have to put alcohol gel in your hands, it will react to that.  It can be that strong for certain depending on how sensitive they are to it.  So antabuse is the one that essentially is the one that makes you incredibly violently sick if you drink alcohol or consume alcohol.  For some people taking antabuse, they take antabuse and they know they can’t drink on it because it will make them incredibly ill.  Whether or not that's a good thing is to be debated but again if they're not drinking I guess you can argue that it is.

Jesse: It might not be just because it's another crutch like they might be free of alcohol but they solve a psychological issue that they're going to try to find some other outlet for.

Thomas: Yes, exactly.  I mean all to the point that if you are relying on medication for your sobriety, if that medication isn't there anymore, you can’t get your hands on that medication, you don't have the sort of the coping skills to not go back to drink, I would argue.  Because you're physically dependent and also mentally dependent on the antabuse for your sobriety.  So I would argue that whilst antabuse can be particularly useful especially in the early stages of recovery, it shouldn’t be used long-term, I would argue because you need to be able to recover psychologically and be able to stand in your own two feet without the need for medication if that make sense.

Jesse: I thought the one paper that you sent about recovering addicts essentially getting addicted to their support groups was really interesting.  It was like a meta-addiction.

Thomas: Yes, absolutely.  I mean, that's an important point I think.  Again it's similar to the antabuse.  It’s sort of swapping your addiction really for something else.  I think there's a really important place to think that self-help groups or any type or recovery paradigm whether it's a residential rehab or detoxing or anything like that, they can be incredibly important for people.  There are a couple of people I have spoken to that go to self-help groups several times a day every day.  Practically, you can't keep that up without having to then get a job or anything like that.  But psychologically, I think you really have just swapped your substance dependency for something else really.  While someone might argue that going to self-help groups may not be harmful, it's not about that.  It's about being able to psychologically stand on your own two feet without the need or the crutch for something else to support yourself with if that makes sense.

Jesse: It's interesting talking about to some of these things that would disincline somebody to enjoy alcohol.  It's probably sort of a good segue into what's going on with the reward circuitry or in this case I guess the punishment circuitry in the brain.  It explains part of why it's hard to get people to stick with these things.  Their exposure toward this is quickly followed up by retching and feeling terrible and things like that.  Can you talk about some of your work looking at the brain's reward circuitry and how that gets tied up in addiction?

George: Yes, exactly.  You've pretty much hit the nail on the head.  The reward circuitry gets engaged initially, we call this the binge intoxication where incentive salience gets activated and their transmitters like dopamine and opioid peptides or endorphins they get released and make you feel good.  That can lock you into habits of taking a lot of alcohol and going to places where alcohol is served and finding yourself at your favorite bars and so on and so forth a little more than maybe you anticipated.

But if you start drinking a lot and you start binging a lot, those transmitter systems actually become compromised and you actually loose for word function.  At the same time, you gain stress functions.  We actually have systems in our brain that are there on purpose to make us feel bad and to run from the bear and to not step out on the curb in front of the taxi in New York City.  These stress systems become activated and so you have this kind of double whammy that starts to develop where you're not feeling as much pleasure from the alcohol.  When you stop drinking your reward system is underactive.  Your stress system is overactive.

So, what do you do?  You have a drink.  There's a temporary relief from the alcohol but just drinking a lot then re-exacerbates, re-engages this dysfunction and it is one of the approaches.  But one of the approaches that we're looking at for medication is to reverse these kind of reward deficits and stress activation.  There is a drug on the market, Acamprosate.  It's called Campral, the trade name.  That actually seems to help re-establish a little bit some of these irritable, unstable, emotional feelings during withdrawals.  It's not a fantasy by any stretch but it does help people reduce their craving and it has an effectiveness out there with naltrexone which blunts the rewarding effect.  It's on the market.

The only downside to acamprosate is it’s a relatively low potency drug so you have to take three times a day.  That works for some people because they can take it with every meal but for other people that's also a nuisance.  We're working on other medications that may calibrate your stress system and that's part of ongoing research in the area.  Then, if that's not bad enough, you've wrecked your reward system, you've activated your stress system but if you really do a lot of alcohol, you impaired your executive control system which is your frontal cortex – the front end of your brain that you use for making decisions.

So, now you're making bad decisions on top of everything else.  The combination is like a triple whammy.  You got the pleasurable effects of the drug, they're diminishing, the stress systems activated and you're losing self-regulation or self-control, your ability to make proper decisions, long-term decisions about the future.  You're more likely to go for short-term rewards and not long-term rewards.  In short, you're a mess.

Jesse: And at some point in their motor control too at a certain point you're getting sloppy. 

George: Yes.  There’s all kinds of physiological additional things.  Your liver enzymes can get elevated and compromised liver doesn't make any of what I just described better so there can be muscle loss and really severe cases you end up with people with tremor and nerve damage and literally impairment in memory functions.  What I call terminal alcohol is when someone is really, really at the point where they cannot stop no matter how hard they try.  It really is devastating to almost every organ in the body.

Jesse: I'm blinking on the name of it now but there's a certain type of amnesia that I know that's really alcohol correlated and essentially sort of tabula rasa just like a blank slate after a certain point.

George: It's called Wernicke-Korsakoff syndrome mixed together now as a neurological condition which is the peripheral neuropathy and some of the other things that we're just talking about.  But can in its severest form you actually lose brain cells in your memory consolidation area.  Individuals with Wernicke-Korsakoff syndrome -- and they're fairly rare presentation these days because it's triggered by a dietary loss of thiamine and poor diet combined with high alcohol use really is a tremendous cause of Wernicke-Korsakoff.  So the tabula rasa is in fact new information.  They can remember old events that have taken place.  They often confabulate, fill up their memory with stories but they cannot remember new information. 

Jesse: So it's kind of like their personal history just stops at a certain date and after that they're living in a perpetual Groundhog Day kind of existence?

George: Exactly.  A famous researcher Larry Squire at the University of California at San Diego did some of the very early work on this.  Thiamine treatment is now a regular phenomenon in an emergency room and someone who presents with some of the Wernicke syndrome and that is irreversible but the memory deficits are not reversible.

Jesse: Some of the experiments that you're beginning now sound like there are long-term launch to an old studies that we might not have answers on for quite some time.  What do you expect that we might know in the nearer term that we don't know already?  What's coming down the pike in the next five to ten years?

George: There's a lot.  I think one of the things we're engaging in with the National Institute on Drug Abuse is a longitudinal study to understand how the adolescent brain develops just without drugs.  In that study, we will learn a lot about what drugs do to the adolescent brain but I think there's going to be unbelievable wealth of information coming from the study that we call the ABCD study, The Adolescent Brain Cognitive Development study.  We have a parallel study going on cross-sectionally in humans focused on alcohol and what it does to the developing brain.

So, these are going to be very, very exciting.  Some of the status are going to be coming very soon.  Like I said we have an active medications development program.  We have a clinical trial on a drug called Gabapentin just known as Neurontin which has been shown in single trials to be double bind placebo control trials to be effective in treating alcohol abuse disorder.

We have a multi-center trial ongoing that should be coming out some time later this year.  We're working on a brain navigator which is going to be a web-based tool.  We hope to help people find and understand what treatments are available for alcohol abuse disorder.  We're really excited about that.  90% of Americans get no medication for alcohol abuse disorder and probably close to 80% get no treatment whatsoever.  Still a lot of stigma attached to alcohol abuse disorder.  It's kind of like just backed up or just stop drinking.  Well, some people can stop drinking when they know it's harmful but many, many can't and we really would like to see in the short-term and this is in the very short-term.  It sounds very pedestrian but we really like to see the medical community engage in helping treat alcohol abuse disorder. 

On the basic research front, some of the work on what alcohol does to those areas of the brain.  I was talking about the frontal cortex that's involved in executive control that what it does to your stress system.  These are going to be exciting findings in the next few years and maybe lead to even better medications.  Maybe even lead to better understanding how the brain processes emotions.  I'm kind of the eternal optimist so a lot of the work we do in addiction and alcohol tells us a lot about how the brain works and makes us happy and what makes not happy.  You know what I mean.  The research we do at NIH which I think is in the brain areas are all going to direct itself to hopefully some of those kind of questions.

Jesse: Why do you think there's almost nothing but positive social feedback that a person gets when they say, "I'm going to quit smoking." Whereas people feel nervous when somebody talks about trying to quit alcohol like there's just more of a dark cloud around  getting alcohol out of your life than there is to getting cigarette smoke out of your life if you're doing both let's say.

George: I think it's probably the stigma moral part.  The surgeon general's report argues that alcohol-use disorder is a brain disorder.  It's a disregulation of the circuits I was telling you about and some of them are permanent.  They can be reversed and that you grow back those neurons but you can strength other neurons much like you might strengthen elements of the muscles around your knee if you have a tour name to your cruise ship.  We think that there are ways that you can change the brain back but I think getting people to understand that alcohol abuse disorders have vulnerability that it's genetic.  They have vulnerability that's history.  You could have been abused as a child.  You could have been subjected to traumatic events.   You could have been born in a war zone.  You could have both parents alcoholic.

Jesse: You could be susceptible to advertising because there's some amazing advertising for alcohol products that is pervasive too. 

George: There's many, many reasons, social reasons, peer pressure that can contribute to why you started excessive drinking and the excessive drinking itself then takes the life of its own.  If we consider it a medical problem, it is a bit ironic because when I grew up, went to high school, cigarette smoking was the cool thing to do.  But in any event we learned that smoking causes cancer and I think we learned when flight attendants for example were getting sick.  When insurance companies were giving you a break on your premium for not smoking I think that turned the corner.  Now I think Americans don't know much about alcohol to be honest with you.  I think they think of it as substance that has minimal harm when you engage in it excessively and that's not the case.  There are a lot of people in America drink.  They do fine.  They enjoy it.  It's a social lubricant.  It's used in just about every professional society I'm aware of in their cocktail party.  I'm sure a lot great business deals and creative interactions socially have occurred with people who were at the cocktail party.  I don't want to put that down but I'm just saying that the excessive use of alcohol is misunderstood in our country and I think that's part of the reason.

Jesse: What do you think the general public doesn't know about addiction that it really should?

Thomas: It's not a self-inflicted illness.  Addiction is a serious illness that people need help with.  A lot of people that you speak they don't want to take drugs anymore.  They don't want to drink anymore.  They physically need it to be able to perform normal activities.  I'll give you an example.  Some researcher did a couple of years ago, I spoke to a guy and he was an alcohol dependent.  So he has in recovery about four or five weeks and he felt really good and I said to him, "Why did you drink for so long?" And he goes, "Because I physically needed it." And I was like, "What do you mean you physically needed it?" So he would wake up in the morning and he would need to have a Colt or a bottle of vodka just to get dressed in the morning, just to have a shower in the morning because if he didn't he would be shaking.  He would be sick.  He would have unbelievable stomach pain.  He's be sweating.  He's essentially is in withdrawal.  I think there's a massive stigma against the people with addiction that massively needs to be overcome and understanding that it's not a social inflicted illness.  It's a genuine problem that people need help with.  Like I said there's a very few people that actually enjoy taking drugs or drink when they get to that stage of dependency.  They desperately want help and stigmatizing them and assuming that they are self-inflicted and they want to drink is massively incorrect in my opinion.

Jesse: It seems like with what we know about alcohol though if it hadn't been a part of human society forever and if somebody invented it in the lab and it was like, "Hey wow.  This stuff is a lot of fun.  Let's run it through the FDA or let's try to get approval for this as a food product." It wouldn't stand a snowball's chance nowadays or it would be a Schedule 1 Narcotic.

George: I don't know about a Schedule 1 Narcotic.  I think that would be carrying it a little far but i don’t think I can really say much about that because they found formulas for beer in the Egyptian tombs.  I know it's a little bit controversial but I swear to you I've seen drunk birds eating fermented mulberries in South Central Pennsylvania, okay.  Now that's the end of one.  But there are pretty good evidence that animals in certain situations can get a bit intoxicated so I'm not sure we would ever be able to do the experiment you outlined.  Should a drug come to the FDA however, there was an actual pharmaceutical agent, I'm not sure if we get through -- that much I can agree with you.  If there was a drug like an opiate that came to the FDA you were supposed to let's say put a lozenge under your tongue and it would have all this beneficial effects at low doses.  But if high doses would do your liver end, I'm not sure if the FDA would approve it. 

Jesse: So aside from your official capacity, what do you tell friends, family, loved ones about their own personal choices when it comes to alcohol use?  What are your recommendations?

George: Well, more or less what I've said so far I think drinking with moderation is fine.  The FDA has guidelines up to two drinks a day for males, one drink a day for females, seven drinks a week for females, 14 drinks a week for males, and really no untoward effects with the possible exception of a very slight five to seven percent increase in the probability of a breast cancer in females with those low doses.  But other than that, most of the deleterious effects of alcohol are minimal.  With my family, I don't have any trouble with people enjoying a glass of wine at dinner or a beer or if they want to have a cocktail before a big party or something like that.  I do have a problem.  It is a phenomenon that we've been picking up on lately of young people drinking the blackout and the legal limit for alcohol for driving is .08 gram percent.  When you drink enough alcohol to blackout that means you don't remember what took place when you were intoxicated, you doubled that amount.  That's literally about half of what will kill you.  What I would tell family members and have told family members is know your dose effect function just because two none steroidal analgesics will fix your headache, the whole bottle is going to give you a GI bleed.  I mean most Americans would not take a whole bottle and I think we have to be aware that alcohol is a drug and can act like a drug.

Jesse: I think the concept of -- I think it's called the pharmaceutical index as sort of the ratio between what would be an effective dose versus the lethal dose.  It can vary so widely with different substances and yet with alcohol it's not necessarily that wide to get a buzz versus how much will kill you is not staggeringly large difference.

George: I mean there was a time when alcohol was used as an anesthetic and it actually worked and it's actually a very good analgesic.  Just ask any older person who has their cocktail at five o'clock, ask what it does for their arthritis.  Actually alcohol is a very, very good analgesic.  But it's only a good analgesic for about 30-60 minutes on the rising phase of the blood alcohol curve and tolerance develops to it very quickly even within one evening.  Maybe one or two drinks are good relieving that pain and grandma maybe can play the piano better than she's been doing for some time.  But I can assure you that four drinks are not going to help her.  She's going to wake up in the middle of the night and not be able to sleep because of the rebound hyperexcitability and maybe not feel so hot the next day.  I think that's the part that I think is not well understood.

Written by Hannah Sabih
Hannah believes there's nothing 8 hours of sleep and some kale can't cure (yes, she's from California). She's an avid runner, reader, and traveler, who brings you the latest and greatest in neuroscience via our social media channels.
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