This actually makes me a bit concerned about long term, general Ozempic use.
This to me at least makes one suspicious that this pathway is very deep in the reward subsystems of the brain, and is not just specific to say appetite and food.
What are the long-term effects of Ozempic use on these pathways? I am not sure we know?
For example, will people who have taken long-term Ozempic be less likely to do startups because their reward seeking behavior is altered?
It will take many years (decades?) before we get a complete picture of all the downstream effects of this.
Now, if someone is morbidly obese, severely diabetic, has heart disease, etc, I think it is pretty obvious that the benefits outweigh the risks. However, if it is used as an "easy" way for weight-control, especially long-term, I think there are still questions.
If you look back at the history of medicines, we do have a history of "wonder drugs" - see for example Heroin or even the COX-2 inhibitors (Vioxx) that later in retrospect had some major caveats.
We also have a history of vaccines and antibiotics, so I don't think we should automatically assume there's some deep risk. These have been on the market for over a decade now and used by tens of millions of people.
We know it's generally safe for diabetic people because that's what it was originally for. No one tested long term for the last decade of other potential psychological effects like altered reward seeking behavior.
Can confirm! Started Rybelsus (pill form of Ozempic/semaglutide) early last year. Within a month I quit cold turkey on whiskey and other hard liquors at home. Wish I could say the same for wine, but just cutting out the whiskey I was drinking was huge. I'm down ~50lbs since then.
Just stopped having the cravings for whiskey (and I forgot beer too) at home. I still partake in an old fashioned or a pint of beer when I'm out for dinner and drinks. But for me at home the whiskey was a different "addiction" than wine. I really do wish I could drop the wine, but it just feels different than the whiskey and beer did.
I’ve been on Zepbound since January and my craving/desire for any alcohol basically is gone. I have gone periods without drinking before while trying to lose weight but I always felt like I was missing out because I was only not drinking to help lose weight, I would avoid some social gatherings just because it wasn’t fun to be there and not “socialize”. Now I just don’t want to and I don’t care about saying no thanks or even think about it. And if I do have a drink it’s usually literally just a drink and even then I might not even finish it.
The AA industrial complex has such a hold on this part of our medical system, I doubt you'll see doctors prescribing it to reduce drinking. I was drinking too much, told my doctor, got the usual crap about going to AA. I asked for a naltrexone prescription. He hadn't heard of it, said it wouldn't work, but did give it to me. Alcoholism cured. We already know how to fix it, there's just a lot of people making money off selling the ineffective program from 100 years ago.
I was lucky in that my doc has been very open to treatments for alcholism and obesity. She prescribed me Nal but it made me very nauseous, worse than Semaglutide. Tried to do the Sinclair Method but just couldn't do it. Then it was the actual diabetic A1C diagnosis that got her to prescribe the Rybelsus. And she was very supportive of me moving to Mounjaro (tirzepitide) when I plateaued in my weight loss.
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Have Ehlers Danlos and another thing, with quite a few effects I get ongoing, it's actually why I try experimenting with drugs in general. I wasn't much overweight but gave it a shot since it seemed like a fascinating drug, and the results were shocking to me.
Perennial light sleeper, couldn't drink caffeine either due to extreme long half life and sleep issues. On it, fall asleep at night like a "normal" person for the first time. Able to drink coffee too. I chalked that up to the fact it does have a bit of a drowsiness effect, but... then I noticed I was just having a bit less back pain. Noticed my tingling in feet and muscle fasciculation was down.
I've been on and off it now ever since, but I take lower doses/breaks since I don't need it for weight. But I was getting "attacks" of inflammation every ~6 months, since doing it for 1.5 years not a single attack (knock on wood).
My thought there is - yes fasting is great for a lot of things and maybe helped, but I can't help but think it's other effect. I've tried a lot of things, even other peptides that supposedly work and had 0 effects across hundreds of supplements. This stuff had huge effects.
The friend I can't speak to much, simply that they told me they started it and without my prompting told me a couple months later about the allergy thing.
I'm still waiting to see if really does have all of the reported positive effects, but if holds up, then this suggests to me that the negative effects must have a common cause. There's some aspect of modern life that causes compulsive self-medicating behaviors, and we've stumbled on a treatment for it.
Have you got a citation for that? I've not seen anything that indicates the drug itself is addictive, though there's ample evidence that its effects wane quickly after discontinuation of therapy.
This is what worries me. I have devised a law of absolutes that is, "Nothing is all upside" or "Everything has unintended negative consequences". And the more something appears to be all upside, the more devastating the downside usually turns out to be.
While simple heuristics like that can get you quite far in life, it doesn't mean that they are laws of nature. I suppose time will ultimately tell, but these drugs are super widely used and apparently the class (GLP1 agonists) is not as novel as you might think; the blockbusters we see today are improved versions of drugs that have existed for awhile. If there was some horrible, monkey's paw catch, we'd likely have seen it by now.
I suppose the biggest example of such a faustian weight-loss drug would be Fen-Phen, and it's issues were discovered within a few years of its rise to prominence.
History of medicine is full of incredible breakthroughs that are mostly upsides, like antibiotics, vaccines, new cancer immune therapies, etc. It happens!
The problem is also that this class of drugs (modified peptides) is produced in a very different way from most drugs (small molecules). When small molecule GLP-1 receptor agonists hit the market the shortage will be over very quickly. There is a lot of capacity to produce small molecules in place already. Many companies are currently racing to bring small molecules to market.
Novo Nordisk is running their lines at max capacity and cutting production of some other drugs. I think the last number I saw was new weekly prescriptions are up 3x from Dec 2023.
Unlike Eli Lilly (who use chemical synthesis for Zepbound) they use yeast for synthesis and have decided not to contract out production to protect manufacturing trade secrets which makes ramping up slower, have to wait for their Denmark plant upgrade to come online.
When there are drug shortages, you can have a compounding pharmacy mix up proprietary drugs. I'm not endorsing this in any way, that's between you and your doctor, but bringing it up in case you didn't know of it.
That's useless if you need a specific, very new, and patent protected ingredient. For Ozempic generics, that's at least until 2026 until you can go to Brazil or 2031 if you're in the US [1].
The problem at the core is not like the shortages we have in Germany for basic stuff like general fever and pain medication, that's usually due to other countries just bidding more... for Ozempic, it's that virtually every single person gets blasted with joyful weight loss stories by influencers, demand for it is insane, and Novo Nordisk can't keep up with manufacturing despite the growth of the company being enough to account for the economic growth of the entire country of Denmark [2].
> One of the conditions of section 503A restricts compounded drugs that are essentially copies of commercially available drugs, but FDA does not consider a drug to be commercially available when it appears on FDA’s drug shortages list.
I know for a fact you can obtain compounded semaglutide.
It is actually very easy to obtain compounded semaglutide or tirzepatide right now if you qualify for a prescription and can pay a few hundred dollars a month.
For many, yes. Due to my high medical expenses and having great insurance, I meet my deductibles and out-of-pocket early each year, so most of my medication has a $0 cost.
Ten bucks says hunger and reward center actuation are deeply intertwined, and these interesting outcomes of GLP-1 agonists are how we're figuring that out.
Yeah, other GLP-1 receptor agonists are expected to have similar effects. One of the effects of GLP-1 receptor activation is a reduction in the rate of gastric emptying. So it slows down digestion and gives you a full, satiated feeling. Guess the urge for some drugs is related to the urge for food and that's how it supresses drug use. But the last bit is speculation on my part.
I am curious if the benefits for alcohol addiction are from the reduction in appetite or reducing the actual dependence on alcohol. Either way still good to have another relative safe way to treat alcohol addiction.
I'm certainly not qualified to speak on this but I heard this story recently about an effective treatment for alcoholism that's been available for decades but for complicated reasons hasn't been widely accessible: https://www.reflector.show/p/how-to-listen-to-episode-1-the-...
Honest question, how does one perform a study on "non-treatment seeking participants"? Were these people who signed up and assumed they were part of a weight-loss study but were actually chosen due to drinking habits?
Seeing the types of things this helps with, I wonder if there is any effect on impulse control issues for people with ADHD in general. Would love to see some studies done on this.
This to me at least makes one suspicious that this pathway is very deep in the reward subsystems of the brain, and is not just specific to say appetite and food.
What are the long-term effects of Ozempic use on these pathways? I am not sure we know?
For example, will people who have taken long-term Ozempic be less likely to do startups because their reward seeking behavior is altered?
It will take many years (decades?) before we get a complete picture of all the downstream effects of this.
Now, if someone is morbidly obese, severely diabetic, has heart disease, etc, I think it is pretty obvious that the benefits outweigh the risks. However, if it is used as an "easy" way for weight-control, especially long-term, I think there are still questions.
If you look back at the history of medicines, we do have a history of "wonder drugs" - see for example Heroin or even the COX-2 inhibitors (Vioxx) that later in retrospect had some major caveats.