GLP-1 effects on dopamine
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This topic was touched on months ago here and people shared how they now drank less alcohol or it cured their shopping addiction. I wanted to bring it up again to see if any longer term RUO researches are experiencing the same blunting of dopamine as myself, or if they are still just experiencing less dopamine like at the beginning of research.
Not everyone will experience anhedonia but some will, and some will only with higher doses.
I’m looking for longer term researchers to share their experiences.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12632335/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12155186/
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I got an email from the VA recently saying that they are starting to open trials using GLP-1’s for alcohol and drug addiction, which means we will likely see a lot more on this in coming years. They are also starting to investigate psychedelics for TBI and PTSD.
Given the VA’s historical reputation, I see these as good both as a peptide researcher and as a veteran, since these are relatively cutting edge treatments.
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As far as psychedelics go, I hope they use the more predictable oral (sublingual) administration. If the subject is on a glp-1 it will still blunt the effects, though. I’m glad they are finally researching it because there are so many people out in the wild the treatments have been successful for.
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Oh yes, has absolutely smacked the hell out of my rat. No interest in psychedelics whatsoever; I grew up in the 1970's with no need to put rat through that part of history.
Working strictly on intuition, I think this might not have become a major problem if rat had begun using strictly Semi, instead of starting with Tirz. I work with, and often talk with others outside of work whose rats are on Semi only, they've lost weight and don't have 'the dump' that others on Tirz and Reta seem to have. I've yet to find anyone who started exclusively with Cagri or Survo, or others without GIP.
Which is my next rat experiment. I wonder...?
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Its real, so I guess it depends on how much it effects the individual. Me for example I have no desire to drink or smoke weed, I may have an occasional one and done, but I find myself to be way more productive and sleep is better. I think the whole picture needs to be looked at from 30,000 ft view. For many people if the pleasure of food was a hidden addiction you may need to re calibrate your system. The things that may have brought pleasure before like alcohol or sweet fatty foods for example will be affected by the dopamine recalibration. For me all the healthy changes and challenges have made me feel better and my dopamine is balanced and I now look forward to healthy routine changes like scheduled stretching, breathwork, cardio, healthy meal prep, my only addiction is shopping for peptides and researching healthy lifestyle changes. It all compounds and maybe some struggle with the change more than others but I'm not sure zooming in and looking only at the compound itself as the culprit is the answer. For most people is the caveat, of course there will probably extreme cases out there who just can't take it becasue of some obscure reason genetically. I would say its not a silver bullet but it is a really powerful tool, the work still needs to be done. You may find new pleasures over time and maybe your energy systems or something else needs to be reviewed and supported and the Reta is only making this obvious now as your dopamine system is operating without the huge spike and dips like it did before.
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This topic was touched on months ago here and people shared how they now drank less alcohol or it cured their shopping addiction. I wanted to bring it up again to see if any longer term RUO researches are experiencing the same blunting of dopamine as myself, or if they are still just experiencing less dopamine like at the beginning of research.
Not everyone will experience anhedonia but some will, and some will only with higher doses.
I’m looking for longer term researchers to share their experiences.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12632335/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12155186/
@MyB couple things to be aware of with Reta or GLP's that can effect how you "feel" like well being wich can effect moods or emotions.
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If you are losing weight at a more rapid weight the body tends to stopre toxins in fat. With your reved up metabolic rate you mmay be detoxifying at a higher rate and this can effect the well being feeling. so hydration and antioxident support like Glysine, NAC, Glutothione, liposal Vitamin C, melationin before bed. Also polyphenol rich foods in the day, berries etc.
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The brain demands a lot of ATP and energy, with your new metabiolic rate you will want to support your mitochondria - Co q10 ubiquinol, Alpha Lipoic Acid, NAD+ SS-31, virgin Cod Liver oil (Rosita) unfortified nutritional yeast ( Bvitamins) or a B complex, aqua greens spirulina and chlorella, Urolithin A, An Amino complex with B12 and MIC (Flawless compounds or Glow Aminos has one named AM Shred) Methelene Blue low dose, Ketone Salts (Keto Base is a good brand) or Ketone Esters (Kinetik is really good) All these things support the mitochondria as Reta revs up the demand to burn energy they will make sure or support the fuel in the tank - basically energy. I don't know too many people who say they are full of energy that aren't in a good mood.
Not sayinjg you need to do it all or you may already be doing some of this I'm just giving you some ideas in case you haven't explored these supports or coinsidered the down stream effects and demands Reta or GLP's will have on your system.
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This may be a Captin Obvious statement but a long term calorie restriction from GLP's can leave one feeling glum. Getting enough calories and the right macros should be the first step along with sunlight in the morning and a good sleep. the basics, and then look into supplementing if the symptoms are still there.
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This is 1000% real. Tirz and Reta should be a standard for every kind of addiction disorder (and possibly other issues).
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I think some may of missed the point of GLP-1 can chemically shunt dopamine.
After two years of use:
98% increased risk of any psychiatric disorders
195% higher risk of major depression
108% increased risk for anxiety
106% elevated risk for suicidal behavior -
I use retatrutide, and yes, it blunts dopamine signaling in the brain’s reward pathways by activating GLP-1 receptors, which dampens the pleasure and motivation tied to food and other rewards (anhedonia). Dopamine is a chemical messenger in the brain that controls pleasure, desire, and motivation.
American corporations spend billions of dollars to exploit the brain’s dopamine reward system through social media, online apps, porn, and processed foods to keep people hooked. Most major addictive drugs of abuse activate the brain’s dopamine reward pathway. The effects of alcohol and THC are driven in part by the brain’s dopamine system, which controls reward and motivation as well.
It is weakening the "Thinking Brain". The prefrontal cortex is the part of the brain responsible for self-control and stopping impulsive urges. Chronic addiction and constant bursts of dopamine can weaken this area, making it harder to resist sudden temptations. So a degree of anhedonia is welcome at times like these. To many it is a blessing. That's why I keep saying reta is more than just a fat loss drug.
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I think some may of missed the point of GLP-1 can chemically shunt dopamine.
After two years of use:
98% increased risk of any psychiatric disorders
195% higher risk of major depression
108% increased risk for anxiety
106% elevated risk for suicidal behaviorI think some may of missed the point of GLP-1 can chemically shunt dopamine.
After two years of use:
98% increased risk of any psychiatric disorders
195% higher risk of major depression
108% increased risk for anxiety
106% elevated risk for suicidal behaviorAs long as we are using AI.
Those exact percentages come directly from an observational study published in late 2024 using electronic health record database data (TriNetX).
While the numbers themselves are real quotes from that paper, the conclusion that GLP-1s "chemically shunt dopamine" to cause severe depression is an oversimplification and clinically misleading. Large-scale evaluations by regulatory agencies like the FDA, as well as broader clinical trial analyses, do not support a direct causal link.Loss of Dopaminergic Coping Mechanisms: For many individuals, eating functions as a primary, immediate mechanism for emotional regulation and dopamine stimulation. When a medication blunts that reward response, a patient loses a core coping mechanism without an immediate replacement, which can manifest clinically as temporary mood disruption, emotional flatness, or heightened anxiety.
I dont even doubt those percntages but numbers can always be misleading without context.
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You want to know what else is just as bad as an overly expressed dopamine? Fear. Fear is just as disruptive as dopamine because both override your logical brain, though they push your behavior in completely opposite directions. While dopamine drives you to seek rewards impulsively, fear drives you to avoid threats reactively. Both disrupt normal decision-making by hijacking the prefrontal cortex—the brain's command center for self-control and logic. That's why many seek distractions and *self medicate (dopamine).
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I think some may of missed the point of GLP-1 can chemically shunt dopamine.
After two years of use:
98% increased risk of any psychiatric disorders
195% higher risk of major depression
108% increased risk for anxiety
106% elevated risk for suicidal behaviorAs long as we are using AI.
Those exact percentages come directly from an observational study published in late 2024 using electronic health record database data (TriNetX).
While the numbers themselves are real quotes from that paper, the conclusion that GLP-1s "chemically shunt dopamine" to cause severe depression is an oversimplification and clinically misleading. Large-scale evaluations by regulatory agencies like the FDA, as well as broader clinical trial analyses, do not support a direct causal link.Loss of Dopaminergic Coping Mechanisms: For many individuals, eating functions as a primary, immediate mechanism for emotional regulation and dopamine stimulation. When a medication blunts that reward response, a patient loses a core coping mechanism without an immediate replacement, which can manifest clinically as temporary mood disruption, emotional flatness, or heightened anxiety.
I dont even doubt those percntages but numbers can always be misleading without context.
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I got an email from the VA recently saying that they are starting to open trials using GLP-1’s for alcohol and drug addiction, which means we will likely see a lot more on this in coming years. They are also starting to investigate psychedelics for TBI and PTSD.
Given the VA’s historical reputation, I see these as good both as a peptide researcher and as a veteran, since these are relatively cutting edge treatments.
@ResearchCat The problem here is that the effect only lasts as long as the person takes the drug. It also only stems the physical urge. It does nothing to help the mental issue behind what's causing the alcoholic to drink in the first place. GLP-1 would be a fabulous tool for alcoholism IF, and only IF, the alcoholic proceeded to get the mental help they needed through therapy, rehabilitation, and/or AA meetings. They would need to address the root cause of their problem. Otherwise, the relapse if they ever had to go off the drug would be detrimental. Just like the drug only fixes your metabolic issues while you take it, the same holds true for addiction.
Thank you for your service.
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Its real, so I guess it depends on how much it effects the individual. Me for example I have no desire to drink or smoke weed, I may have an occasional one and done, but I find myself to be way more productive and sleep is better. I think the whole picture needs to be looked at from 30,000 ft view. For many people if the pleasure of food was a hidden addiction you may need to re calibrate your system. The things that may have brought pleasure before like alcohol or sweet fatty foods for example will be affected by the dopamine recalibration. For me all the healthy changes and challenges have made me feel better and my dopamine is balanced and I now look forward to healthy routine changes like scheduled stretching, breathwork, cardio, healthy meal prep, my only addiction is shopping for peptides and researching healthy lifestyle changes. It all compounds and maybe some struggle with the change more than others but I'm not sure zooming in and looking only at the compound itself as the culprit is the answer. For most people is the caveat, of course there will probably extreme cases out there who just can't take it becasue of some obscure reason genetically. I would say its not a silver bullet but it is a really powerful tool, the work still needs to be done. You may find new pleasures over time and maybe your energy systems or something else needs to be reviewed and supported and the Reta is only making this obvious now as your dopamine system is operating without the huge spike and dips like it did before.
my only addiction is shopping for peptides
Funny how that works...
If you are losing weight at a more rapid weight the body tends to stopre toxins in fat. With your reved up metabolic rate you mmay be detoxifying at a higher rate
Big time fatty detox, and lots of B vitamins and others will further detox, making one feel like crap. B vits should be methylated only and don't OD yourself on them. My main problem is fatigue.
Everyone knows these peps only work as long as you're taking them. I know 2 people who've made the cut after a year off them, but those are paltry numbers. It is what it is. Given these FACTS, I'd still poke.
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@ResearchCat The problem here is that the effect only lasts as long as the person takes the drug. It also only stems the physical urge. It does nothing to help the mental issue behind what's causing the alcoholic to drink in the first place. GLP-1 would be a fabulous tool for alcoholism IF, and only IF, the alcoholic proceeded to get the mental help they needed through therapy, rehabilitation, and/or AA meetings. They would need to address the root cause of their problem. Otherwise, the relapse if they ever had to go off the drug would be detrimental. Just like the drug only fixes your metabolic issues while you take it, the same holds true for addiction.
Thank you for your service.
@kerryh It’s a fair point, but that is the same as with people using GLP-1’s for weight loss. Presumably - even if we know it isn’t true - people using these things are taking a holistic approach.
It’s actually well established that many GLP-1 users experience depression after losing weight because the problems driving them to eat didn’t go away with the weight. But it is still a powerful tool. And having experience with alcoholics, I can say that while the underlying issues remain, a few less lost jobs, car wrecks, and cocaine charges would make addressing the underlying issues more approachable.
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In regards to addiction, a GLP might provide a window. That's all any intervention provides, same as with Rehab. What's most important is that the person is truly sick and tired of where they are. If they want to change their life then they have to use all available resources to chase that new life with the same intensity they chased their addiction.
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@ResearchCat The problem here is that the effect only lasts as long as the person takes the drug. It also only stems the physical urge. It does nothing to help the mental issue behind what's causing the alcoholic to drink in the first place. GLP-1 would be a fabulous tool for alcoholism IF, and only IF, the alcoholic proceeded to get the mental help they needed through therapy, rehabilitation, and/or AA meetings. They would need to address the root cause of their problem. Otherwise, the relapse if they ever had to go off the drug would be detrimental. Just like the drug only fixes your metabolic issues while you take it, the same holds true for addiction.
Thank you for your service.
@kerryh I believe if you use it long enough you'll rewire new habits to maintain your new body and mind composition (epigenetics). If you pay attention you will learn your biology, diet, physic, learning what it takes to be in a healthy state. Mind, body and soul. If you have to microdose .5mg of reta for the rest of my life now in then I will, considering the consequences in the state of health most are in. I am out of this system of manage decline slowly killing you and bleeding your wealth.
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@kerryh I believe if you use it long enough you'll rewire new habits to maintain your new body and mind composition (epigenetics). If you pay attention you will learn your biology, diet, physic, learning what it takes to be in a healthy state. Mind, body and soul. If you have to microdose .5mg of reta for the rest of my life now in then I will, considering the consequences in the state of health most are in. I am out of this system of manage decline slowly killing you and bleeding your wealth.
@EXTROPIAN I’m listening to a longevity researcher who is talking about GLP-1’s as a lifelong thing along with metformin and rapamycin. I am not a big fan of taking meds, or taking anything for life, but if we are talking about living past 100 (150 is what he is talking about) and being mentally and physically capable, I am willing to negotiate.
I am playing the longest game.
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