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What if you could Forget to Want Alcohol?

It’s that time of the year - time to welcome the new year with family, friends, good food and probably alcohol. Here in Tokyo it can be hard to keep up with the various bounenkai’s essentially “forget the year” parties throughout december. One issue I tend to run into is drinking more than I initially intended.

In college, the intention was just not to drink so much that I do anything embarrassing, but now it’s more like I’ll go out for one beer with a friend and the night ends with me drinking three. Or once in a while there’s a celebration going on so I’ll plan to have three drinks but I end up having six.

That’s not too terrible, but it’s the same issue - drinking more than I intended. So, why is it that some of us drink more than we planned on start of the night? Of course what’s going on in the brain of a social drinker versus that of an alcoholic are completely different, but the two may run into this same issue…just at drastically different degrees.

But the big question is: can we alter brain chemistry to prevent this from happening? Even if you’re totally comfortable with your alcohol consumption, finding the answer to this question can teach us some very interesting lessons about how the brain works.

The concept to explore here is called “pharmacological extinction,” but before we get into that, let’s talk about pesto. When I was a kid, everytime my Dad would go to central Texas for work, he’d come back with some fun foods from a specialty supermarket up there.

He got a couple different things but I specifically remember Orangina which I really liked, and Basil Pesto which I was sure I didn’t like. Everyone else seemed to enjoy the stuff, …but to me it looked suspiciously like mashed up oily spinach…

So after having skipped out entirely on the pesto every time my Dad brought it home, he finally convinced me to try the very last bite of of a new batch of pesto.

Based on work from people like Kent Berridge and Robert Sapolsky, I’m pretty sure this is what was going on in my head: I ended up eating the pesto, which was an unexpectedly rewarding experience. The flavor of the pesto and bread combination released some endogenous opioids telling me that this stuff is really delicious, that I like it.

My brain wanted to take a memo of this fact so we could remember how to get more later. So, dopamine was released in response to the sensation of reward provoked by the opioid system.

It is often mistakenly thought that dopamine is the neurotransmitter for liking, but as Kent Berridge and his team proved, dopamine is specifically for wanting and learning what to want, but it is not necessarily the cause of liking.

This 1993 experiment from Switzerland showed that when monkeys pressed a lever that rewarded them with apple juice, dopamine levels shot up. However, once they got the hang of the task, dopamine levels went up when the light came on.

So the shot of dopamine that came with the juice was necessary for reinforcing that behavior - for learning everything that happened to make the juice come out. After it learned this, a shot of dopamine would come in response to the light turning on as if to say “Hey that light means we can get juice.

So I know what to do: let’s press the lever!” Kind of like Pavlov’s dogs learning that bell equals food. However, what’s responsible for the actual sensation of pleasure and feeling of liking when the juice hits your tongue and goes down your throat is endogenous opioids.

These endogenous opioids would tell the monkey that drinking juice was pleasurable and rewarding, and then tell the dopamine system to take note of how to get the juice again. OK So in response to the endogenous opioids telling me I like the pesto, the dopamine system took note of how to get the pesto and taught me to want the pesto.

So how can I “forget” or “unlearn” this wanting for pesto? Let’s say my brother wanted to monopolize the pesto supply; he could sneak a bittering agent onto my slice of bread before I spread the pesto on it. Dopamine would still cue me to eat the food, but the wretched taste would blunt the rewarding endogenous opioid response.

That would cause whatever bundle of neurons that are acting as the memo for my wanting of pesto to loosen up their connections a bit. And, every time I ate the bittered pesto bread, my wanting for pesto would decrease more and more. That’s the funny thing about alcohol, or I should say ethanol, by itself it tastes - terrible.

I’m sure no one would enjoy everclear diluted in water. Beer and wine taste good, but that’s an acquired taste - no kid would think that they taste good. “It’s terrible, nobody drink the beer! The beer has gone bad!”

Alcohol is very complex, and acts on all kinds of receptors having different effects, but one source of the rewarding feeling of it is its effects on the opioid receptors in your brain, one in particular is the mu-opioid receptor.

Some research shows that the mu-opioid receptor in specific is responsible for the positive reinforcement that gets people to want and crave drugs or alcohol. So what if you could block those opioid receptors from being activated?

Your brain would never get that “reward” signal, and your brain would unlearn to want alcohol. You could go to the bar, sit down, smell the cigarette smoke, order a beer, taste it and you’d even get some of the effects of alcohol like worsening motor coordination and slurred speech, but the reward signal that your brain is expecting would never come.

Long story short, you can block opioid receptor activation with something called an opioid antagonist. On the TV show “the doctors,” they had a segment about an alcoholic person who drank a bottle of rum a day.

He received an implant of an opioid antagonist Naltrexone - which slowly releases a low dose of the medication over a period of a few months. The aim of this particular method seems to be abstinence- to keep him from drinking at all. Apparently it has done wonders for him in the first week in terms of reducing cravings.

“I haven’t had one craving, whatsoever “ This is very promising and it’s fantastic that it seems to be working for this person. But, it may not be the best approach One problem with this study trying to manage heavy drinking with Naltrexone is that the patients were encouraged to be abstinent while on the naltrexone.

“As you know, it doesn’t work with abstinence, it cannot work with abstinence.” Here is Roy Eskapa, the author of the ambitiously titled book “The Cure for Alcoholism,” in which he lays out in detail a treatment for alcoholism called the “Sinclair Method” and explains the science behind it.

However, Dr. David Sinclair, the person who this method has been credited to, refers to it as pharmacological extinction. The method is simple, you take 50mg of the opioid receptor antagonist Naltrexone one hour before drinking, and you do this every single time you expect to drink but you only take it on the days that you do drink “The medicine itself is not curative.

You have to take the medicine one hour before drinking.” As you’d expect from an opioid antagonist, Naltrexone has been used to try and treat opiate addiction. As this paper way back from 1978 found, there wasn’t too much benefit compared to placebo for those who took Naltrexone with the aim to help entirely prevent them from using heroin and getting cravings.

However, there was an improvement in people who disobeyed the instructions – those that went ahead and did heroin while on they were on the medication. Their cravings started to decrease.

Thanks to the medication, shooting up is like ringing Pavlov’s bell, but no food comes, and this brings the behavior of seeking and wanting drugs closer to extinction. Amazingly, this pharmacological extinction method has been shown to be very effective with alcohol.

Here is a graph from Dr. David Sinclair in the Roy Eskapa book showing that in rats, after only 5 “extinction sessions,” that is a naltrexone plus alcohol session, the rats were already drinking 10 times less than they normally did.

The first double blind placebo controlled clinical trial on Naltrexone and alcohol from 1992 found that Naltrexone was safe and effective with the primary benefits being seen in patients who drank alcohol while on the medication.

This clinical trial found that Naltrexone did not reduce the frequency of drinking but it significantly reduced the amount they drank. According to the earlier mentioned book, 90 out of 91 clinical trials found that opioid antagonists like Naltrexone are effective if extinction is possible, that is if a substance addicted person can use the opioid antagonist medication and use the substance.

When extinction was not possible, as in the patients had to be abstinent while taking the medication, 36 out of 37 trials found no significant benefits from the medication. According to the book, it takes on average 3 to 4 months for an alcoholic or alcohol dependent person to lose their dependence on alcohol through this pharmacological extinction method.

According to David Sinclair, the success rate in his clinics in Finland is about 78% and clinics in Florida had a success rate of 85%. If you’re curious what the experience of drinking while on Naltrexone is like, a close friend of mine from the states said: “ I’ve found that I’ve been much more picky with how things taste.

So I’ll just waste entire drinks because they don’t taste good.” And In an email she said: “it just slowly makes [drinking] less and less interesting.“ By the way, she’s not an alcoholic or alcohol dependent but sometimes simply drinks more than she intends. So what is it like for an actual alcoholic? “I’m waiting - keep waiting for the feeling and it’s not coming.

You get that first drink it’s like uaahhhh that felt good. And then it’s like give me more! But when you don’t get it… what is the point?” The Sinclair method could be a very promising route for people who are alcohol dependent considering the alternative is to essentially to go cold turkey, detox and go on to wrestle with their cravings for… who knows how long.

Considering alcohol use is the 7th leading risk factor for death and disease globally, I’m hoping this video brings more awareness to the scientifically sound, but relatively unknown Sinclair Method.

Before I close let me point out that I’m not a doctor and I’m not a pharmacologist, I don’t mean to say that social drinkers who have two extra glasses of wine at parties should just casually go out and buy this pill.

If you’re interested in this, make sure and do some more research - you can start by reading Roy Eskapa’s “The Cure for Alcoholism,” or watch the documentary produced by Claudia Cristian about Naltrexone called “One Little Pill.”