GLP-1 therapeutics: Their emerging role in alcohol and substance use disorders

Posted by PaulHoule 10/28/2025

GLP-1 therapeutics: Their emerging role in alcohol and substance use disorders(academic.oup.com)

254 points | 198 commentspage 2

testaburger 10/30/2025|

One thing i noticed being on ozempic at first and then mounjaro after, while mounjaro is better for weight loss in general, ozempic was better at tampering my desire to drink throughout the week (although i wouldn't say i had AUD on either). I think the reason for this is the half life: ozempic is 7 days, (enough to get you until the next once a week dose), while mounjaro is only 5 days (which means by day 6/7 less than half the dose your took at the beginning of the week is still in your system). This also applies to food as well: my craving were less for sweets etc by the end of the week before the next dose on ozempic vs now on mounjaro. Although I think because mounjaro has 2 mechanisms of action vs just 1 for ozempic, I still end up losing more weight. But this is subjective based on my experience.

However, Ozempic will be generic early 2026 in Canada, and there's no way in hell I would pay 4-5x the difference (I'm guessing) for mounjaro as the benefit is relatively minor already given the half life difference (right now the price is almost the same).

I’m not diabetic, so my insurance doesn’t cover it, meaning I have to pay full price, which only went up after Eli Lilly switched from vials to pens in Canada. I genuinely hate Eli Lilly for : 1) their pricing, 2) for eliminating vials in favor of pens, and 3) for how they handled my situation. I reached out to their customer service honestly, admitting I wouldn’t qualify for a discount (even though I’d seen countless Reddit posts from people lying on the form and getting approved anyway and told them this). I reached out and requested in good faith and was flat-out denied, basically brushed off by their support team. This destroyed a lot of goodwill i had initially towards them because of better results and any future brand loyalty I might have had.

baq 10/30/2025|

buy a share of LLY every time you buy a pen, you'll be selling the stuff to yourself soon.

teitoklien 10/30/2025||

i doubt it would help, their stock will probably go down as glp lose their patents globally in most countries and become generics

elric 10/30/2025||

So how does this work? Does it somehow boost "willpower" so we can rationally decide which substances we want to consume? Does it somehow smooth out the negative moods that lead us to snack/drink/sleep around/inhale/..? Does it mess with "desire" in general?

DuckConference 10/30/2025||

On possibility I've seen raised is that slower GI movement -> slower alcohol uptake -> not getting as much of a "hit" from drinking as the effects come on more slowly.

next_xibalba 10/30/2025|||

In my personal experience, I do still get the same hit from drinking–I feel a buzz almost immediately, same as before. Rather, I just don't feel the "urge". I've never been a heavy drinker, but I would occasionally crave a beer or two, particularly at the end of a work week. Also, drinking on a GLP1 (I've been on both Tirzepatide and Semaglutide) absolutely wrecks my GI tract for 24-48 hours. Usually with an onset of maybe 8 hours, I get horrible heartburn, moderate to severe nausea, and even mild diarrhea.

fragmede 10/31/2025|||

I don't think it's any one thing. People like different kinds of alcohol, for different reasons. For someone who's alcohol cravings are based on the sugar in their preferred alcoholic drink, it isn't surprising then, that a medication that lowers their desire to ingest sugar lowers their desire to drink (their chosen sugary drink). Naturally this doesn't cover all alcohol drinkers, but it can't also be none of them.

ceejayoz 10/30/2025|||

My understanding is it essentially tamps down cravings.

andy_ppp 10/30/2025||

From my experience, yes, these things as well as making you feel sick and full quicker illicit the same feeling for me as building consistency and routine and grinding it out and a sense of self pride - you know that feeling when you are heading in the right direction and are able to take the harder rather than the easy option deliberately. It's pretty strange that a drug does this and I wonder if coming off them you then find making difficult decisions harder than before because you were faking a muscle normally built through hard work, one of the reasons I decided to stop taking them.

lordofgibbons 10/29/2025||

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.

SubiculumCode 10/30/2025|

I know this is late to this topic, but I was wondering. You say you have more time for your projects, but do you ALSO lose motivation to do your projects too?

I am in a career that I really enjoy, but which requires high motivation and productivity. I don't want to lose that along with the pounds.

lordofgibbons 10/31/2025||

Not really. It lets me focus on what I want to focus on without losing motivation. Gaming is just an addictive behavior which is why it works against it, but not real work that I actually want to do.

FrustratedMonky 10/30/2025||

What if work is the addiction? Or Solving Puzzles?

Does GPL-1 also dampen those? How much does it dampen just any fixed behavior?

next_xibalba 10/30/2025||

GLP1s seem like the closest thing we’ve had to miracle drugs in years if not decades.

TriangleEdge 10/30/2025||

Why would a GLP-1 be used to dampen reward over an anti-psychotic?

neom 10/30/2025|

https://pmc.ncbi.nlm.nih.gov/articles/PMC8820218/

It seems it doesn't block dopamine generally, but does seem to act on dopamine spikes?

joeel84 10/30/2025||

It also affects mood - basically removing desire for anything.

monitron 10/30/2025||

I'm sorry if it has that effect on you. Personally I've been on tirzepatide for about a year now and have not experienced anything like that.

It seems to reduce my impulsivity, but I still enjoy things very much. I am just able to stop when I "should," or wait for delayed gratification, when previously I had trouble doing so.

I'd say my mood has been higher overall. Feeling like I am in control is an everyday boost.

ramoz 10/30/2025||

is this anecdotal?

president_zippy 10/30/2025||

Maybe this explains why another company just entered into a bidding war with Pfizer to acquire Metsera (MTSR).

Thank God, because my $60 strike call options just turned from a $55k loss to a $180k gain overnight. I shoulda read the CVRs BEFORE buying calls, but I was so blinded by the prospect of easy M&A arbitrage gains I couldn't risk missing out by taking 30 minutes to read the terms of the acquisition.

Glad I have the chance to quit while I'm ahead! Last time I ever fuck around with options trading!

t-writescode 10/28/2025||

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 10/29/2025|

This was the framing behind James Burke's Connections if I recall, a wonderful documentary series.

jtrn 10/29/2025|

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 10/30/2025|

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).