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.”
Very interesting, OP. You should cross-post this to r/stopdrinking, if you haven't already.
Thank you for this
I moved to an alcohol free farm for 6 months and I've been sober ever since. Getting separation from any addiction allows you to really get a clear birds eye view of your toxic behaviors, and having friends that don't encourage your toxic habits really is huge. We are social creatures of habit more than we realize. Sending love to all those trying to better themselves.
This is extremely interesting.
Medications that influence the state and reactions of the brain will probably become more and more important even for somewhat "mundane" things (outside of neurological disorders or psychotherapy) in the future
Wouldn't this medication stop you from enjoying other things in life, like social gatherings? Seems dangerously understudied.
/r/Alcoholism_Medication/
What’s everyone’s opinion in using this kind of method to reduce pornographic/sex addiction?
I wonder if this could help with overeating
This channel has been changing my life. I'm currently keto, meditating daily, and exercising regularly, all thanks to this Youtube channel.
I'm not sure if you'll see this WIL, but thank you for your incredible commitment to making us better :-)
While drugs like naltrexone and the "pharmacologic extenction" method might work to reduce cravings, this will not help a social or casual drinker to stop at 1 beer instead of 3. Alcoholism and drinking are complex behaviours which are driven by more than the "craving/wanting" dopamine pathway. For instance (and this is just one example), in a social setting, alcohol working on GABA receptors will reduce your resistance to social/peer pressure and loosen your resolution.