GLP-1 therapeutics: Their emerging role in alcohol and substance use disorders
53 comments
·October 28, 2025hbosch
0cf8612b2e1e
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?
Rudybega
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.
hamdingers
The distinction you're reaching for is addiction vs dependance.
smiley1437
How do you just start on retatrutide? Did you sign up for a Phase 3 trial?
doctorpangloss
Hard to say, you’d need a study.
League of Legends is “used” by a lot of people as medicine. Nobody hides away to play Stanley Parable. Lots of games, lots of genres, difficult to generalize.
dalyons
side question - has retatrutide been different enough to tirzepatide for you that you would recommend going to the extra effort to source it?
georgeburdell
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?
afthonos
Definitely not GP, but I think it’s pretty clear that whatever grit there was to have, GP did not have it. “Die an early death due to being overweight or build the grit” is strictly worse than “lose the weight without building the grit, or build the grit”, and it’s even more so when you realize that “or build the grit” was never in the cards. Because then the choice becomes “die an early death or don’t“. Building the grit can be done on other, hopefully less lethal, projects.
UniverseHacker
I think this is a valid point, and the reason I haven’t tried these drugs and don’t 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 “The impediment to action advances action. What stands in the way becomes the way.”
I’ve 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 don’t feel like it- pretty soon I’m 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. It’s 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.
ridgeguy
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.
delis-thumbs-7e
I wonder if you have more ”grit” 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 won’t kick anything for long only with them.
Therefore these drugs won’t 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.
pton_xd
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.
smiley1437
Not the GP, but do you think Serena Williams - world number 1 tennis 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.
WheatMillington
The idea that some people are overweight simply because they don't have grit, determination and self-discipline is asinine.
inopinatus
Turns out that this attitude was bullgrit all along.
hiddencost
wet farting noise
TriangleEdge
Why would a GLP-1 be used to dampen reward over an anti-psychotic?
tracker1
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
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
How so? Can you describe more of your experience if you don't mind sharing?
tracker1
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
That sounds pretty awful. Hang in there. Hope you have a support network of sorts and find a way out.
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sghiassy
As an alcohol enthusiast on 12.5mg of Zepbound for the last several months, my ethanol consumption hasn’t diminished much
bluescrn
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
I can also add I have little to zero side effects from Zepboubd if that adds anything
stavros
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
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 couldn’t 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 I’ve 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.
dynm
> 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. https://dynomight.net/glp-1/
dynm
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, −0.41; 95% CI, −0.73 to −0.09; 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
I don’t understand the math here. The average per calendar day didn’t 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
Strange, right? Take a look at figure 4 here: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...
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.
lordofgibbons
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.
jtrn
I hate these articles so much. The title should be: “Speculation on how GLP-1a drugs could theoretically reduce alcoholism while waiting for any real evidence”.
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 don’t 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
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...
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, −0.48; 95% CI, −0.85 to −0.11; P = .01) and peak breath alcohol concentration (β, −0.46; 95% CI, −0.87 to −0.06; 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, −0.41; 95% CI, −0.73 to −0.09; P = .04) and weekly alcohol craving (β, −0.39; 95% CI, −0.73 to −0.06; 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, −0.10; 95% CI, −0.16 to −0.03; P = .005).
jnsaff2
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
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.
themafia
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?
cheald
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
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
It has definitely come up in books and podcasts I’ve listened to, but given general cultural values and biases I don’t think it gets much traction.
jnsaff2
Worry about a positive side effect? No.
t-writescode
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
This was the framing behind James Burke's Connections if I recall, a wonderful documentary series.
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.