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on Gopher (inofficial)
URI Visit Hacker News on the Web
COMMENT PAGE FOR:
URI GLP-1 therapeutics: Their emerging role in alcohol and substance use disorders
jmpman wrote 4 hours 2 min ago:
Been on Mounjaro/Zepbound for the past 2 years. Lost around 80lbs, and
my brain feels like Iâm 25 again. Almost no urge for alcohol and have
an opened bag of Halloween candy in the closet which isnât calling my
name. But the most surprising part hasnât been that⦠itâs that my
no limit poker game has gotten really quite good. Iâve played for 20
years, and been well above average, but after the glp-1, something just
clicked. Maybe I no longer go on tilt or something? Played in the World
Series of poker for the first time last year and placed in the money,
in the top 10% after having not played since before Covid. I just
started playing in a house game that Iâd previously played in 10
years ago. Same people, and before Iâd never placed in the money.
Iâve now won in 3 of the last 5 games. Somethingâs different. Is
playing poker pleasurable? Not in the least, but a good friend invited
me, and played for the social aspect, but now Iâm just stunned at how
good Iâve suddenly become. Disliked the World Series so much last
year, that I opted against playing again, even though I expected to
place again. Maybe other poker players will adopt it.
TriangleEdge wrote 6 hours 27 min ago:
Why would a GLP-1 be used to dampen reward over an anti-psychotic?
neom wrote 5 hours 41 min ago:
[1] It seems it doesn't block dopamine generally, but does seem to
act on dopamine spikes?
URI [1]: https://pmc.ncbi.nlm.nih.gov/articles/PMC8820218/
jnsaff2 wrote 9 hours 42 min ago:
Just a single datapoint here. About 8 months after starting on
semaglutide I took a month off alcohol and by the time the month was
over had lost all interest for alcohol.
Almost 2 years now. I'm not religious about it and will occasionally
drink the celebratory glass of bubbles or a beer (alcohol free if
available) when it's hot outside.
Very interesting how it has worked.
WXLCKNO wrote 7 hours 12 min ago:
As someone who doesn't really drink and never has alcohol at home, is
it just that people buy beer/wine and drink on a daily basis for fun?
The wine I feel like you can pair with food and feel classy as an
excuse but beer that ain't the case.
I realize how completely dumb this question might sound.
virgildotcodes wrote 5 hours 49 min ago:
> As someone who doesn't really drink and never has alcohol at
home, is it just that people buy beer/wine and drink on a daily
basis for fun?
Yes, anything from a couple of drinks a night with dinner / tv to
getting blackout drunk multiple times a week, alone, with your
significant other, or with friends / roommates.
In the case of people in my social circle (late 30s early 40s) it's
primarily still for fun, as well as just a large amount of
momentum from your teenage years, 20s, 30s, etc. For a lot of
people I know, the association between drinking and good times /
relaxation has been deeply engrained since high school.
I've recently taken an extended break for my health, as I'm fully
aware that it takes a toll on me, but I still love grabbing some
drinks whether I'm relaxing alone in the evening or going out with
friends and family.
While it's certainly true that many people get into a dark place
with drinking and let it spiral into a self-destructive, depressive
pursuit, I don't think it's quite the rule it's made out to be.
I have a good amount of family who live idyllic, full, happy,
social lives, drinking heavily multiple times a week with their
friends and family into their 70s/80s until death.
antinomicus wrote 5 hours 52 min ago:
Basically I think âa beer would be nice right nowâ and then I
go to the store or local pub.
themafia wrote 9 hours 39 min ago:
I'm not trying to pick on you because I've seen this anecdote on many
occasions; however, it strikes me that people are quite willing to
walk past "personality changes" as a side effect of a drug.
Does anyone else feel a slight sense of worry about this?
neom wrote 5 hours 32 min ago:
I don't know much about the drug, maybe you're talking about
something else... but FWIW, I got sober from years as a practicing
alcoholic the traditional way, I had lots of personality changes,
some good some bad, but who I was when I was drinking all day every
day and who I am today are quite different people.
cheald wrote 7 hours 14 min ago:
I don't think it's a personality change, at least insofar as
personality is separate from neurochemistry. Ghrelin and dopamine
are strongly linked, and dopamine is our central reward-seeking
driver; GLP-1s generally reduce ghrelin production, which I suspect
helps remove you from a state of being constantly primed for
reward-seeking. I noticed this firsthand when I went hard keto for
the first time, and could suddently for the first time tell a
significant difference between "I want food because I'm hungry" and
"I'm not hungry but want food because it's pleasurable".
matthewdgreen wrote 7 hours 22 min ago:
I worry about it. I do tend to wonder if it can change your
relationship with addictive and maybe risky behaviors, does it also
potentially make you into a more conservative (not politically)
person? Does creativity and risk tolerance go down as well?
n8cpdx wrote 7 hours 30 min ago:
It has definitely come up in books and podcasts Iâve listened to,
but given general cultural values and biases I donât think it
gets much traction.
jnsaff2 wrote 9 hours 32 min ago:
Worry about a positive side effect? No.
jtrn wrote 9 hours 48 min ago:
I hate these articles so much. The title should be: âSpeculation on
how GLP-1a drugs could theoretically reduce alcoholism while waiting
for any real evidenceâ.
99% of promising mice studies does not result in clinical practical
application in humans. And theoretical associations and mechanisms of
action should not be promoted without huge asterisk to contextualize
how often such speculation are wrong.
If you complain about AI slop and donât see how this is just as bad
science slop, please go listen to Sabine Hossenfelder. This is just as
bad, and create just as much useless noise as AI content does on the
nett.
Mistletoe wrote 7 hours 37 min ago:
[1] Once-Weekly Semaglutide in Adults With Alcohol Use Disorder
Results
Forty-eight participants (34 [71%] female; mean [SD] age, 39.9 [10.6]
years) were randomized. Low-dose semaglutide reduced the amount of
alcohol consumed during a posttreatment laboratory
self-administration task, with evidence of medium to large effect
sizes for grams of alcohol consumed (β, â0.48; 95% CI, â0.85 to
â0.11; P = .01) and peak breath alcohol concentration (β, â0.46;
95% CI, â0.87 to â0.06; P = .03). Semaglutide treatment did not
affect average drinks per calendar day or number of drinking days,
but significantly reduced drinks per drinking day (β, â0.41; 95%
CI, â0.73 to â0.09; P = .04) and weekly alcohol craving (β,
â0.39; 95% CI, â0.73 to â0.06; P = .01), also predicting
greater reductions in heavy drinking over time relative to placebo
(β, 0.84; 95% CI, 0.71 to 0.99; P = .04). A significant
treatment-by-time interaction indicated that semaglutide treatment
predicted greater relative reductions in cigarettes per day in a
subsample of individuals with current cigarette use (β, â0.10; 95%
CI, â0.16 to â0.03; P = .005).
URI [1]: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...
lordofgibbons wrote 10 hours 34 min ago:
I've noticed that when I'm on Zepbound 2.5mg, I don't have the strong
urge to play video games and can focus on my projects. Even if I do
play video games while on it, I lose interest after a maximum of half
an hour.
hbosch wrote 10 hours 48 min ago:
Much has been said about the GLP drugs and their interactions with all
kinds of addictive disorders. Alcohol, drugs, even gambling...
Anecdotally, I "struggled" at times with gaming (not joking). I would
find myself skipping meetings at times or ducking away to play online
sometimes. It never became a real issue but I knew I did it and it was
embarrassing.
Once I started on tirzepatide, and then with retatrutide, the "urge" to
swap over to my PC between meetings and load up a game is pretty much
zeroed out.
Is this an "addiction" or a form of "abuse" similar to alcohol or other
drugs? I would have said no some time ago, but now I'm not sure. I
definitely feel like, looking back, I was more or less "addicted" to
video games. I don't want to romanticize it as some sort of "escape",
it just is what it was.
This was an unintended side effect (benefit?) of the drug for sure, in
addition to acute weight loss of course.
Unlike many others, even after titrating down and coming off the GLP's,
I have not felt the urge to binge food, video games, or anything else.
I maintain a healthy, active lifestyle and have kept my weight exactly
where I prefer it. My relationship with my body and my time has
massively improved. I feel like I am at risk of sounding like a
complete shill, obviously, but in my mind these drugs can be something
that absolutely has the potential to turn life around for many, many
people.
cm2187 wrote 44 min ago:
It could also be simply that as you lose weight, you have more tonus
(something that I experienced myself), and activities that are
inherently passive (watching TV, playing videogame) seem less
relatively compeling than more active alternatives.
andsoitis wrote 2 hours 53 min ago:
> This was an unintended side effect (benefit?) of the drug for sure,
in addition to acute weight loss of course.
Is it possible that video games were your escape from a world in
which you were obese, with all that it can entail, and losing the
weight removed the need to escape?
doctorpangloss wrote 6 hours 51 min ago:
Hard to say, youâd need a study.
League of Legends is âusedâ by a lot of people as medicine.
Nobody hides away to play Stanley Parable. Lots of games, lots of
genres, difficult to generalize.
ch4s3 wrote 5 hours 38 min ago:
I hate to imagine what LOL is used to treat, let alone the side
effects.
colonial wrote 1 hour 44 min ago:
Deficient cortisol levels, I'd think. I've seen it bring out
quite the attitude in otherwise relaxed people.
resize2996 wrote 5 hours 1 min ago:
same things as drugs and alcohol, I imagine the side effects are
different but still negative!
smiley1437 wrote 6 hours 59 min ago:
How do you just start on retatrutide? Did you sign up for a Phase 3
trial?
hbosch wrote 3 hours 47 min ago:
It's available at many clearnet peptide websites. Caveat emptor.
cj wrote 5 hours 54 min ago:
Itâs available in powder form online through âresearch
chemicalâ sites ânot for human consumptionâ.
Anyone saying theyâre taking retatrutide almost certainly
obtained it this way. Quality and purity untested.
phil21 wrote 4 hours 7 min ago:
> Quality and purity untested
Not true for everyone, or perhaps even most playing in this
space.
Every batch friends of mine have ordered has been independently
tested for purity and dosing. Random batches also tested for
sterility.
Plenty of folks yolo it, but itâs not like it was a couple
years ago. Lots of group buys being done that order a large batch
and then do random sampling for lab testing.
andsoitis wrote 2 hours 47 min ago:
> > Quality and purity untested
> Not true for everyone, or perhaps even most playing in this
space.
> Every batch friends of mine have ordered has been
independently tested for purity and dosing. Random batches also
tested for sterility.
Yes, you have to test it because the quality and purity what
you get isnât tested.
When someone sells something and they make a statement about
the product (e.g. âtestedâ), they donât mean the customer
has to test it.
aydyn wrote 2 min ago:
Not to defend buying research chemicals of unknown safety,
but that isnt what he said. Independent labs test for purity
and provide certification to the companies that sell them.
Those certifications can be verified by anyone. So its much
less trust necessary to know what you are getting.
smiley1437 wrote 5 hours 32 min ago:
I'm speechless
0cf8612b2e1e wrote 7 hours 53 min ago:
What do you now do instead of gaming? Do you find you have swapped
for a different activity or a more balanced allocation of time among
other things? Or do you still spend your off hours in the same way,
but kicked the compulsion for gaming all day?
hbosch wrote 3 hours 38 min ago:
I do the work I probably should be doing, or side projects, or
spend time with my kids, or go on a walk, or follow up on that
thing I've been putting off, or any of the other million things
that are more productive and fulfilling than video games are. It's
embarrassing to admit that I was a grown man who would put off
basic, important tasks just to play games but I did. Now I don't.
It's not even really about choosing not to, either... it really
does feel fundamentally like I cannot even derive a dopamine
response to video games at all anymore, period. Same could probably
be said about doom scrolling social media or whatever else. I just
get no false positive feedback loop from the act.
ragequittah wrote 1 hour 31 min ago:
If it works for you keep it up. As someone who finds video games
an art form I find the 'avoidance to do better things' quite
similar to someone who might avoid reading or watching movies as
a hobby.
I suppose if you just play the same game day in and day out and
it has no real substance (which admittedly is probably the
largest gaming segment) it might be a good thing to get rid of
the habit. But some games are masterpieces and they often hit
very different than other mediums because you are the protagonist
making choices. In my opinion some of the best stories come in
the form of games and I find it a real shame there's a portion of
the population who think they're a complete waste of time.
I think there's also something to be said here about being
addicted to work. I know such people and it's just as sad even if
it's what society expects of them.
hnmaniala wrote 4 hours 35 min ago:
> What do you now do instead of gaming?
Pill popping.
ImaCake wrote 5 hours 15 min ago:
Can't speak for OP but I largely spend it reading (and web). I
bought a kindle recently because I found the ipad/iphone were too
distracting to reliably avoid web surfing instead of a book. I view
the switch to long form content as a form of information dieting in
the same way as a switch to whole foods.
Rudybega wrote 9 hours 4 min ago:
I think it's probably still useful to distinguish addictions with
hardcore substance related barriers to quitting (think withdrawals)
from addictions where the barrier is a lack of dopamine or serotonin
or simple habituation.
For people with normal executive function, the second category of
problems should be fairly tractable to overcome, whereas the first is
still quite difficult.
The second only really becomes an issue when you have a bit of
executive dysfunction.
Maybe that distinction is important and one merits the term addiction
while the other doesn't? Though both categories seem to be relatively
treatable with drugs that massively improve executive function, so
the parallels are pretty glaring.
vintermann wrote 52 min ago:
Most of the addiction literature I've read says that physical
addiction is overestimated: even heroin addicts regularly go
through physical addiction, either involuntarily because they can't
get it, or voluntarily (through treatment efforts, or simply
deciding to sober up for e.g. a wedding or other important event).
What makes them addicts isn't that they can't stop, it's that they
start up again.
Conversely, people hospitalized for something acutely painful often
get addicting (or, withdrawal causing) painkillers in amounts and
at purities street users can only dream of. And once it's over,
they go through withdrawal, and it's deeply unpleasant, and they
never want to do it again. People going through something like that
aren't more likely to become opioid addicts than anyone else,
according to old study results (I may be able to dig them up if
you're interested).
It's of course different for chronic pain. But then, the reason for
people wanting to start up again is pretty obvious.
normie3000 wrote 1 hour 54 min ago:
How is a lack of dopamine different from "withdrawals"?
hyghjiyhu wrote 2 hours 46 min ago:
Idk I think the importance given to withdrawals is overrated.
Dealing with withdrawals is just matter of gradually lowering the
dose.
The lifelong craving is the bigger issue.
hamdingers wrote 8 hours 37 min ago:
The distinction you're reaching for is addiction vs dependance.
dalyons wrote 10 hours 14 min ago:
side question - has retatrutide been different enough to tirzepatide
for you that you would recommend going to the extra effort to source
it?
hbosch wrote 3 hours 48 min ago:
I think it depends. With tirzepatide (my first encounter with GLP1
meds) I got acute appetite suppression, perhaps too acute. I living
comfortably on sometimes 1500 calories or less per day, and I track
my calories religiously. We are talking maybe 1 cup of yogurt with
frozen berries in the morning, and 1 whey protein shake around 3pm
(Fairlife milk + 2 scoops whey) and I would be absolutely full
until bed. No energy deficiencies to note. I worked out regularly 5
days a week.
This caused rapid weight loss. A side effect of this rapid weight
loss and lack of food intake I also attribute to my thinning hair
and dry, splotchy skin outbreaks. Any sort of overeating on
tirzepatide (for me) caused severe sickness, or nausea.
Retatrutide, by contrast, causes far less pure appetite suppression
(my dosage is also lower) and has another mechanism which helps me
maintain leanness while also eating extra calories. I think I
prefer the reta, but if I ever felt the need to very simply destroy
my appetite again I wouldn't hesitate to use tirzepatide again.
I procured both tirzepatide and retatrutide through the peptide
"grey markets" so one was not harder to come by than the other.
georgeburdell wrote 10 hours 36 min ago:
I'm going to put on my Boomer pull-yourselves-up-by-the-bootstraps
hat, but are you concerned about the loss of grit resulting from
changing your behaviors without the drug?
hbosch wrote 3 hours 43 min ago:
What do you mean "grit"? Does doing something more efficiently mean
you lose it? What's the difference, say, between someone using an
LLM to help them code and someone else using a drug to help them
diet? Is the coder using an LLM losing their "grit"? Do you walk to
work in 30 inches of snow, uphill both ways, in the rain? Are you
concerned about your loss of "grit" by not doing so? This argument
continues to baffle me.
I didn't take the GLP to help me with addictive behavior traits
beyond my diet, but I observed tertiary benefits of the drug.
As I've titrated my dose down to zero, I've retained those habits
and my weight. I'm in the best shape of my life and mentally
healthier than I've been in over a decade.
Nursie wrote 6 hours 17 min ago:
Good god no.
If I can change my behaviour and achieve good health outcomes,
relatively painlessly, why on earth would I not?
This comes across to me like people who won't use painkillers - I
should feel the pain, masking it is fake, there is virtue in
suffering etc. Turns out those people often end up with secondary
complications to (for example) muscle damage, because they've
adapted their movements so much to avoid using the painful muscle
that now everything else is tense, strained and locked up.
Better living through chemistry, 100%.
WheatMillington wrote 6 hours 26 min ago:
The idea that some people are overweight simply because they don't
have grit, determination and self-discipline is asinine.
lurking_swe wrote 18 min ago:
_some_ of the overweight people? most certainly! Most of them? I
donât think so.
Life is more complicated than that. We all know that.
BurningFrog wrote 4 hours 30 min ago:
I'm overweight for those reasons.
smiley1437 wrote 6 hours 46 min ago:
Not the GP, but do you think Serena Williams - world number 1
womens tennis player for 319 weeks, who trained for 5 hours per day
at her peak - has insufficient grit?
Because she went on GLP-1 to lose weight.
Leherenn wrote 1 hour 28 min ago:
Grit, or willpower, or whatever you want to name it isn't a
unique, constant value. There are plenty of athletes who could
spent hours training every day but are overcome by addictions.
People who grind at work but cannot fill paperwork to save their
life. That will diligently do something for months then stops
after an unexpected interruption.
There's probably generally a bit of correlation. But just because
someone can be very focused and go to extreme lengths in one
aspect of their life doesn't mean they can consistently do it in
every aspect of their life.
justinator wrote 4 hours 40 min ago:
Was it sponsored? Did she make a considerable amount of money
doing it?
Because that has nothing to with grit, that's just business.
UniverseHacker wrote 8 hours 55 min ago:
I think this is a valid point, and the reason I havenât tried
these drugs and donât plan to. There are huge benefits to
developing the mental strength and discipline to lean into
discomfort consistently and just do what needs to be done- and all
types of addiction provide one of the hardest, and therefore most
valuable and useful obstacles here. As Marcus Aurelius said âThe
impediment to action advances action. What stands in the way
becomes the way.â
Iâve found that the general act of leaning into challenges and
mild physical discomfort has a ripple effect on my mind, and all
types of addiction and dopamine seeking behaviors become
automatically less interesting- almost exactly like what people
report on these drugs. If I take a cold shower or work out every
morning even when I donât feel like it- pretty soon Iâm eating
healthier and limiting my alcohol, caffeine, and screen time
without even really trying to.
That said, it only works if you manage to actually do it. Itâs
much better to get over addiction with a drug than to continue
suffering from the addiction, and be unable to escape, especially
something that causes as much damage as alcohol can.
One idea I had was to set a deadline for overcoming an addiction,
and to just use the drug if you reach the deadline and the mental
approach is still unsuccessful.
kiba wrote 1 hour 57 min ago:
Getting rid of an addiction also counts as strengthening your
mind in itself. A healthier mind will be in a better position to
strengthen and fortify itself.
chiefalchemist wrote 5 hours 15 min ago:
The issue with addiction is, itâs very often a symptom of other
underlying issues. Relapse are common because too often the
underlying problem isnât treated. Overcoming the addiction is
hard because it means facing the thing the addiction allows you
to avoid.
Addiction is also common(ism) amongst those who suffer from NDP.
In this case, is it truly addiction, or simply another tool in
their NPD cache of weapons.
I donât disagree with you. But itâs also important to be
aware of some of the nuances and finer points. I also recommend
reading âThe Courage to be Dislikedâ. Not that it / Adler
speak to addiction but itâs a thought provoking alternative to
the Freudian paradigm.
delis-thumbs-7e wrote 6 hours 59 min ago:
I wonder if you have more âgritâ than Sugar Ray Leonard, one
of the greatest boxers of all time. His fight with Roberto Duran
are legendary.
As so many boxers (and many athletes for that matter) he was
addicted to drugs and alcohol for many years. Probably sexual
abuse he suffered as a kid had something to do with it. He was
able to quit, but I think cold shower and a run in the morning
was not quite enough to do it.
Nobody just starts abusing their body with chemicals. It is not
difficult to quit, you can stay off your Jones for months, but if
you do nothing to the demons that made you enter the 36th chamber
in the first place, you are going to slip sooner or later. It
takes more than a splash of cold water on the face.
Marcus Aurelius was literally a god and the emperor of the world.
He prob had little bit more resources to help gim other than
stoism. Similarly if you have loving family and friends, a good
therapist and some sort of medication,you canmaybe wim the fight
with the devil that gets you to use. Training and getting used to
being uncomfortable surely helps, but you wonât kick anything
for long only with them.
Therefore these drugs wonât be a solution either. Are you going
to use them rest of your life? Whatever it is that makes you want
to drink, smoke, shoot, gamble or whatever is still going to be
there. Bit used together with therapy and loving environment
might help. Of course, most addicts have no access to any of
these resources.
UniverseHacker wrote 6 hours 53 min ago:
I agree with all of what you said, and I'd argue that the
stoics including Aurelius probably would have as well. Leaning
into discomfort is just a step that can help you actually do
things like get therapy and be present and engaged in a loving
environment. At least for me that's the case- I have seemed to
need all of those things together as a system to really thrive
in life, not just one or the other.
CBT and ACT are modern therapy methods based on stoic methods,
very widely used, and very effective for regular people that
aren't emperors.
delis-thumbs-7e wrote 6 hours 36 min ago:
They are most often effective if you can afford them was my
point. I have ADHD as well and boxing (waking up before work
to run in cold November morning, 9 rounds with a heavyweight
who had nobody his size to spar, thousand ab movements
afterwords and hey itâs only Tuesday) helped me
tremendously with focus, staying of the booze and so on, but
if I had not done years of therapy and had meds as well as
found more varing environment, I prob would no be hete. And I
was lucky to have a god job to pay for all that.
I do think you need tremendous mental effort, or grit, even
to fight serious addiction. But it is only a start.
pton_xd wrote 7 hours 31 min ago:
Anecdotally I've experienced something similar.
After I started committing, really committing to consistently
working out, a lot of other things fell into place more or less
automatically. I stopped drinking, started eating very cleanly (I
became ravenously hungry; junk food and sweets aren't appealing
anymore), and stopped spending as much time on gaming. I know
your broader point is about leaning into discomfort, but
specifically leaning into exercise seems to bring extra benefits.
Exercise is medicine, as they say.
UniverseHacker wrote 7 hours 12 min ago:
I think for this to work psychologically, it just needs to be
something difficult or uncomfortable that you can do an awful
lot of in a way that is sustainable, and doesn't actively harm
you... all the better if you actually benefit directly from it,
like with exercising, but cold showers work just as well,
simply because they're uncomfortable and take much less time
than working out- I personally do both.
ridgeguy wrote 8 hours 40 min ago:
If you're wired like Marcus Aurelius, maybe it'll work out ok.
Peoples' neurochemistry differs enormously. One person's positive
reinforcing experience is another's nociceptive hell. (source:
Ph.D. neurophysiologist here)
Arguments like yours presuppose humans have free will, that it's
widely distributed, and if $whoever would just get on it, they'd
progress.
More and more, it appears what we have is the perception of free
will, not the real thing - whatever that actually might be.
UniverseHacker wrote 8 hours 20 min ago:
Not doubting your expertise, but I am skeptical of the idea
that this method of intentionally leaning into discomfort only
works for some minuscule abnormal subset of people that are
just wired differently. Instead, I suspect it's tapping into
something deeper about how our reward system is structured,
something extremely related to how these GLP-1 agonists work,
which explains why they are both effective against a shockingly
wide array of seemingly different situations.
The basic idea seems to be at the core of both a lot of modern
self help gurus advice that seems to actually work for a huge
fraction of the people that really commit to them (David
Goggins, Wim Hof, etc.) as well as modern psychotherapy systems
like CBT and ACT that are proven clinically effective.
How many people are really trying this approach, and it not
working for them? More often, I see people saying it sounds
like it royally sucks (which is true and basically the entire
point), and never trying it- which is valid, but doesn't really
demonstrate that it wouldn't work for them.
It absolutely is a "nociceptive hell" at first for everyone
that tries it, but when you connect that with intention,
purpose, and meaning it eventually transforms into something
almost enjoyable. Becoming strong enough to meet discomfort or
pain feels amazing, especially for someone that usually
experiences the opposite of that.
I also have ADHD, which is explained in part as a developmental
disability of executive control, but I find this approach to be
extremely effective for regaining executive control, even to
levels that people without ADHD lack. Basically, I suspect ADHD
isn't a loss of executive control at all, but the executive
control is being blocked by something like the feeling of pain
or drug withdrawal, and that once you are okay with just having
that bad feeling all of the time, you get your executive
control back. I'm curious if GLP-1 drugs also help with ADHD?
My prediction is that they would.
ridgeguy wrote 5 hours 39 min ago:
This topic is a great example of how results from
down-in-the-weeds biochemistry immediately raise questions at
the top levels of consciousness and existence.
âLeaning into discomfortâ for personal change may well
work for much more than a miniscule fraction of people. It
may be that such success is made more likely by some
structural predisposition â an attenuated neuronal response
to negative reinforcement, or some other precondition that
allows its âcarrierâ to keep plugging to a successful
outcome.
But clearly, thereâs also a more than miniscule fraction of
people for whom that doesnât work. Their preconditions may
deflect them from even trying that particular path, or cause
them to give up along the way. I really donât know, but
that fraction seems at least as significant as the fraction
for whom uncomfortable personal development paths lead to
success.
Early in my career, I strongly believed in free will. I mean,
I had it, right? And I didnât regard my consciousness as
all that different from my fellow hominids, so theyâre
probably all similarly endowed, right? Except...
Over time, research with small molecules like epinephrine and
the psychedelics showed that perception/decisions/will could
be profoundly influenced by neurochemistry. Ditto for various
neuronal illnesses that are associated with profound
personality changes.
I regard the GLP-1 results as a further demonstration that
âfree willâ, whatever that is, is fundamentally
mechanistic. There are few, maybe no, organismic drives
stronger than hunger. A weekly injection of a GLP-1 agonist
turns that drive way, way down in most of those who try it.
This commonly exhibits itself in profound behavioral
modification: if you were an inveterate snacker, suddenly
youâre not interested in snacks. You pass them by in your
pantry and at the grocery store. Your cognition around
snacking changes, to the extent that not only arenât you
snacking, but you might find yourself setting a reminder that
itâs time to have lunch. Given the strength of the hunger
drive, thatâs a very big deal, and revelatory about how we
work.
I used to think I understood âfree willâ. Lately, I find
it increasingly hard to define. Iâm moving more in the
direction of Robert Sapolsky as more research results come
in. It feels to me a bit like the âGod of the gapsâ
phenomenon, in which the space available for faith in the
supernatural grows smaller with every scientific discovery.
Itâs a remarkable time to be alive and have the luxury of
considering these questions.
UniverseHacker wrote 5 hours 11 min ago:
Ah, you might have seen my reply to someone else addressing
the free will question from a philosophical angle, but
despite also being in the life sciences, I never expected
you were thinking about it biochemically.
I think it's obvious that we don't have "free will" in that
sense, it had never really occurred to me to consider
otherwise- people are definitely quite driven by instincts,
neurochemicals, etc. they they can't consciously choose.
However, I think my comment in the other thread still
applies- that for an individual, it doesn't really matter
one way or another- your firsthand experience is still
going to be one of exercising your will to increase the
odds of getting outcomes you want in life, or choosing not
to, and definitely not getting them.
But there is some biological clue here about who we are,
and how our brains work that is fascinating, when you
consider the breadth of human health problems and
challenges that these GLP-1 agonists influence. I can't
wait to see what more is learned about this in the future.
pseudalopex wrote 5 hours 48 min ago:
Nothing they wrote implied minuscule or abnormal.
Can you define huge fraction and really commit? And cite
evidence?
I disagree the basic idea of CBT or ACT is leaning into
discomfort. In the senses articles suggest David Goggins and
Wim Hof advise even less.
CBT and ACT work for many patients and don't work for many
patients.
Some people liked intense exercise their whole lives. Some
people hated it when they started but liked it eventually.
Some people exercised daily since decades and hated every
minute. Do you not believe the 1st and 3rd groups?
Pushing through bad feelings is a form of executive control.
And ADHD impairments are not limited to impulse control.
People who have ADHD who do not take medication have
significantly higher rates of driving accidents than people
who do not have ADHD or take ADHD medication. Proprioception,
internal time perception, and working memory impairments are
common.
UniverseHacker wrote 4 hours 21 min ago:
> I disagree the basic idea of CBT or ACT is leaning into
discomfort. In the senses articles suggest David Goggins
and Wim Hof advise even less.
I am somewhat baffled by your statement, as I feel it is
largely self evident being familiar with, and having tried
both therapy methods with professional therapists, and both
Goggins and Hof's advice for years. I think a simple
wikipedia level explanation of what those things actually
are would suffice to answer your question, so I have
nothing major to add, unless I am misunderstanding you.
Goggins whole shtick in particular is just this one basic
point, make yourself as mentally tough as possible by
intentionally always doing whatever is difficult. Hof is
also just literally getting into very cold water
consistently, which is really not easy- and he has no real
philosophy or theory, he just has you do it and see what
happens.
Perhaps the therapy methods are less clear, but reframing
things or deciding on clear values and purpose, are in my
view, psychological tools to make the difficult endurable,
or in some cases even enjoyable. This makes more sense if
you're seeing the methods in the context of how the ancient
stoics used the same techniques that inspired those
therapies- especially Epictetus.
> Can you define huge fraction and really commit? And cite
evidence?
Not really, it's just firsthand experience from doing them,
and having widely sought out and read the experiences of
others that did online.
ineedasername wrote 7 hours 30 min ago:
âI am skeptical of the idea that this method of
intentionally leaning into discomfort only works for some
minuscule abnormal subset of people that are just wired
differentlyâ
That may be the aspect of this line of thinking thatâs not
clear then: it doesnât work for anyone. At least, in so far
as the free will is illusory, it is a hallucination that such
people have that they made such decisions, and stuck to them.
Itâs the demon hand syndrome, the person hallucinating a
rationale for its motion.
UniverseHacker wrote 7 hours 22 min ago:
The free will question seems to be a red herring-
philosophers and physicists can argue all they want about
if something like free will is physically possible or not,
but for all intents and purposes, even without free will,
the path of someone overcoming, e.g. alcoholism after using
these methods requires using them in a way that is
challenging, and if you decide on the nihilistic stance
that there is no free will so there is no point in ever
trying to do anything, then you are guaranteed an
undesirable outcome.
Perhaps beforehand it was somehow "pre-determined" which of
these attitudes and paths you would take, but that is
completely irrelevant for the individual just living life,
they have no way to know that one way or another, or any
reason to actually care, as they still need to act exactly
like they have free will and made the right choice to
actually play out a future as the type of person
pre-determined to have a desirable outcome.
It doesn't actually feel any easier or less painful to
accomplish something difficult, even if free will is some
sort of illusion when looked at from the outside
perspective. You still experience, e.g. trying and failing
over and over and never giving up until you succeed.
I can buy that, for example perhaps there is something
outside our control that decides if you are capable of
never giving up, but you still cannot know until you decide
to never give up and try it- so it literally does not
matter except as a philosophical curiosity.
I think a more interesting biological (and philosophical)
question is why and how exactly do these GLP-1 drugs work,
and why exactly are they so shockingly effective? Maybe
they do somehow act on the brain to offer exactly the same
psychological benefits as the stoic approach I am talking
about, by the same or related underlying mechanism, and
they're essentially interchangeable but work more often?
hiddencost wrote 9 hours 9 min ago:
wet farting noise
inopinatus wrote 9 hours 52 min ago:
Turns out that this attitude was bullgrit all along.
afthonos wrote 10 hours 15 min ago:
Definitely not GP, but I think itâs pretty clear that whatever
grit there was to have, GP did not have it. âDie an early death
due to being overweight or build the gritâ is strictly worse than
âlose the weight without building the grit, or build the gritâ,
and itâs even more so when you realize that âor build the
gritâ was never in the cards. Because then the choice becomes
âdie an early death or donâtâ. Building the grit can be done
on other, hopefully less lethal, projects.
dynm wrote 10 hours 53 min ago:
> A more recent RCT showed that low-dose semaglutide reduced laboratory
alcohol self-administration, as well as drinks per drinking days and
craving, in people with AUD [72].
I think this quote is... wrong? Or at least extremely misleading? Here,
citation 72 refers to a paper by Henderson et al. That paper did
(sorta) reduced laboratory alcohol self-administration, but did not
find any reduction in the amount that people drank.
URI [1]: https://dynomight.net/glp-1/
dynm wrote 10 hours 49 min ago:
OK looking at the original abstract:
> Semaglutide treatment did not affect average drinks per calendar
day or number of drinking days, but significantly reduced drinks per
drinking day (β, â0.41; 95% CI, â0.73 to â0.09; P = .04)
So they didn't find any reduction in (1) drinking, or (2) in the
number of days that people drank, but they did technically find (3) a
reduction in the number of drinks that people consumed on the days
that they drank. So I guess what they said is technically correct...
but I still think it's very odd not to mention the headline result
that there was no actual reduction in drinking!
wrs wrote 10 hours 16 min ago:
I donât understand the math here. The average per calendar day
didnât go down, so the total drinking is the same. That total is
distributed among the drinking days, which are also the same. So
how can the drinks per drinking day have changed?
dynm wrote 8 hours 11 min ago:
Strange, right? Take a look at figure 4 here: [1] This is as in
the abstract:
1. drinks/day declined in both groups and somewhat more in the
treatment group but wasn't statistically significant
2. number of drinks/day basically wasn't different at all
3. drinks/drinking day didn't change in the placebo group but did
decline in the treatment group
(These are all actually regression coefficients computed on
non-random samples but nevermind.) Somehow it seems like what's
happening is that 3 rises to statistical significance even though
1 doesn't.
URI [1]: https://jamanetwork.com/journals/jamapsychiatry/fullarti...
sghiassy wrote 11 hours 6 min ago:
As an alcohol enthusiast on 12.5mg of Zepbound for the last several
months, my ethanol consumption hasnât diminished much
not_a_bot_4sho wrote 5 hours 36 min ago:
Interesting. I'm at zepbound 5mg and noticed that alcohol brings me
no joy.
It used to be the case that 1-2 drinks would make me feel good, and
introduce a craving for more (a "just one more will get me right"
feeling).
But that's gone now. It's an amazing side effect.
anonu wrote 7 hours 30 min ago:
have you lost weight?
sghiassy wrote 6 hours 35 min ago:
Yup, 20lbs effortlessly. But Iâve plateaued despite going up in
dosage. So still stuck at 200lbs
not_a_bot_4sho wrote 1 hour 46 min ago:
20lbs is still a fantastic achievement!
bluescrn wrote 10 hours 47 min ago:
As a beer enthusiast drinking unhealthy amounts rather too
frequently, my drinking went way down when on Mounjaro.
(Maybe it wouldn't have made the same difference if I was into whisky
instead of beer - with beer, I suspect it's the relatively large
volume of drink involved that may have made it less appealing?)
Recently switched to Wegovy since the big Mounjaro price hikes here
in the UK, and it seems rather less effective overall. Both beer and
snacks are somewhat more appealing again :(
sghiassy wrote 11 hours 5 min ago:
I can also add I have little to zero side effects from Zepboubd if
that adds anything
stavros wrote 7 hours 58 min ago:
Side effects are generally rare, but it really depends on the
person. I tried to start five times, and got massive side effects
each time. The last time I started, I did my own protocol (started
at 0.5mg every three days and increased a bit on every injection).
Now I'm up to 6mg and I'm not getting any side effects, but it also
doesn't work for me! I lost 6kg at one point but the effects wore
off and I gained the weight again.
None of my friends had this experience, for everyone else it's
worked with no side effects. I really am cursed.
n8cpdx wrote 7 hours 35 min ago:
Be on the look out, I had really bad semaglutide side effects and
had to stop. Thought microdosing would help, but the side effects
just ramped up more slowly, culminating in what I assume was
gastroparesis (my food just stopped digesting for over a day and
I couldnât eat despite being hungry and depleted, not to speak
of the rest of the digestive process).
I also had drastically degraded (increased) resting heart rate,
(decreased) heart rate variability, and exercise intolerance - a
normal easy run started to make it feel like my heart would
explode and gave me palpitations. Off it, I can run a 5K and
beyond no problem, if my knees cooperate.
Food noise came into the picture much worse than baseline after I
stopped, although it did eventually come down and Iâve been
able to start losing weight again after a few months off.
Berberine seems to help, at the expense of giving me nausea like
semaglutide, but no other side effects.
tracker1 wrote 1 day ago:
All I will say, is if/when you start noticing digestive issues, it's
probably the GLP-1 even if it's after a year of taking the stuff... and
woah boy, coming off the stuff is anything but fun.
titanomachy wrote 10 hours 12 min ago:
What was your comedown like? After 6 months of taking subcutaneous
semaglutide, I just stopped taking it one day and it was fine. Need a
bit more effort to be mindful of snacking now, though.
EDIT: saw your other comment that you felt you were starving. that
sucks. the whole thing experience sounds awful.
tanvach wrote 22 hours 1 min ago:
How so? Can you describe more of your experience if you don't mind
sharing?
tracker1 wrote 16 hours 10 min ago:
Started developing gastroparesis issues after about a year on
Trulicity... over the pandemic, due to shortages I was switched to
Ozempic for a few months which was less effective with my diabetes
mgt. I didn't actually lose weight on the medication(s).
After seeing several doctors about the issue including a couple
specialists, only one of about half a dozen medications tried
actually worked to help the gastro issues, which included fecal
vomiting, rotted fermented food coming up, both regularly. No
actual blockages. The medication that did work wasn't covered by
my insurance. After a couple years of suffering, I saw a news
report about the Trulicity lawsuit related to gastroparesis issues.
Over the same period, I started to develop retina issues, several
retina bleeds and regular injections to treat it.
When I found out about the lawsuit, I stopped taking the medication
going back to straight insulin injections (long and short)
currently Lantis and Novalog. For close to a year after coming
off, I experienced a feeling of starvation 24/8... didn't matter if
I was physically full up to my throat, the ravenous feeling of
hunger would not subside. I gained about 80# during this time
(again, didn't lose weight on the meds).
I'm a few years off and my digestion is inconsistent and
unpredictable... sometimes I'll have a few days where things flow
normally... others I'll be backed up for close to a week and have
to take a heavy magnesium laxative to get things going again. I
stay pretty close to carnivore as just about anything else can
range from discomfort to pain. Not to mention legume allergies and
really sensitive to wheat... I still cheat about once every other
week, and I pay for it physically.
Because I was on more than the one medication, I cannot participate
in either the Trulicity or the Ozempic class action lawsuits.
These medications have kind of ruined my life. I'm now about half
blind and using 45" monitors to work, and even then have to zoom
text and lean in to be able to function.
Over the years, I've been on several drugs for diabetes that I'd
built up a quick tolerance to, that may have had other negative
effects... Byetta, Victoza and others... I've always had digestion
sensitivities, these just turned it up to 11. When I started
Trulicity, my insulin use was pretty minimal and I was already on a
Keto diet and had been losing weight... I wish I'd stuck with that
and never even heard of the stuff.
Some of the recollections are a bit jumbled, apologies for that,
I'm just kind of writing as it comes to mind.
Aside: along with the medical issues has been some employment
inconsistencies the past few years with a few contract roles spread
a few months apart. I had hoped to maintain my income level as
many available jobs were lower pay. Currently, my insurance is
"emergency" coverage based, and doesn't even cover the 3 doctors
I'm seeing regularly and doesn't help much with the medications I
am still taking. Let alone the eye injections I haven't been able
to get for about a year now ($7k/eye/injection). Tried working 2
jobs for a while, but couldn't keep up with the load after a few
months. I'm depressed and angry. Prior to about 8 years ago, I
never carried debt... now I'm maxed out and staring at bankruptcy.
ArnoVW wrote 10 hours 54 min ago:
That sounds pretty awful. Hang in there. Hope you have a support
network of sorts and find a way out.
t-writescode wrote 1 day ago:
Technology and discovery are so cool.
One breakthrough and then a WHOLE BUNCH OF NEW STUFF happens all at
once now that this new idea or new pathway is created.
mRNA vaccines break away and now they're testing them in everything.
GLP-1 showing signs of use in obesity and now it's being tested for a
whole gamut of other things. All very exciting!
fullshark wrote 11 hours 8 min ago:
This was the framing behind James Burke's Connections if I recall, a
wonderful documentary series.
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