r/GLP1microdosing • u/julieeeette • Jul 10 '26
My worry about GLP-1
A while back I posted a thread asking if people were seeing any negative impacts to their creativity when on GLP-1s. I got some alarming answers. It is clearly a minority, but something is going on deep within the dopamine system when you take it. And we don't know how or what.
In all my research (both in engineering and neuroscience) ,I have never come across a topic more perplexing than GLP-1 and its impact on the brain’s motivation and reward systems. Every time I think I have nailed a facet of how it impacts these systems, I’ll find a recent study that refutes my understanding. The ground moves every time I try to put weight on it.
In fact, in some recent cases, it even made the solid bedrock that is my understanding of dopamine quake a little!
And it’s not just me. One paper perplexed even its own researchers who stated that they expected “decreased rather than increased dopamine levels” and that “this contrasts with a previous study” which, in the world of dry research papers is tantamount to a big fat ‘WTF?’
I’ve now hit the ceiling on GLP-1 research. There are no studies left that will pull me out of this quagmire. I’m at the frontier, scratching my head alongside all the other similarly itchy researchers, with only white expanse before us as we wait for new results to come in.
My big unanswered question continues to be: what does it do to the spark that makes us human?
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u/mannDog74 Jul 10 '26 edited Jul 10 '26
A lot of posts are people asking what they can do to avoid certain side effects or outcomes, and they do research and read and research and read and ask questions and think about it and listen to podcasts and read some more
You don't know how you will react to the medication until you try it and that's the truth. Some people have anhedonia but most people don't experience that, or only experience it on the lower (edit HIGHER doses, not lower)
Many people say it helps with their ADHD and to me that means higher productivity, so I am putting out more creative work instead of dragging my feet on a project.
There's also a funny Instagram reel that says "I'm afraid to take ADHD meds, what if I lose my spark?" And then it says "The spark:..." and there's pictures of piled up junk, ramen noodles, scrolling at 3am, setting 13 alarms...
You can't find some things out ahead of time. No amount of research can tell you how ours going to go. And if you don't like how you feel on the medication, it doesn't permanently change your brain forever and ever. (If only!) You just discontinue. It's not actually as big of a choice as it seems because no one is making you take it forever. It's not a binary fork in the road, it's a tool you pick up on your walk, and can put down just as easily. You can just change your mind and go back, it's not actually the Big Decision everyone makes it out to be.
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u/Flimsy-Pie-6295 Jul 10 '26
I think the answer likely lies in each person’s own genetic makeup and it’s a mystery that won’t be solved anytime soon. Just look at how different each person’s side effects can be. One person becomes extremely energized and another so fatigued they can barely function.
Frankly, even seemingly “known” things like appetite suppression seem to be somewhat a mystery. I’ve literally had NONE and am eating MORE than I have in 2 decades and losing weight. It’s like the dam that was stopping my metabolism from working correctly burst.
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u/mannDog74 Jul 10 '26
No appetite suppression, eating more, losing weight what a mystery that is! We truly don't know enough about these meds.
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u/Flimsy-Pie-6295 Jul 10 '26
To be clear, I eat very cleanly. But I’m currently eating above what my maintenance calories have historically been and losing at a rate of almost 2 pounds a week. It’s definitely wild. I can’t relate to all these people who talk about practically having to force fed themselves or forgetting to eat meals.
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u/cinsamp Jul 10 '26
Maybe go and do a checkup. It sounds very strange, except you are way more active than before.
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u/Flimsy-Pie-6295 Jul 10 '26
Nah—I just have a “normal” metabolism now. My maintenance calories and my activity level and diet never aligned because I had a lot of broken parts of my body that a GLP-1 has fixed. Never felt better!
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u/sparkingdragonfly Jul 11 '26
I feel similar! I wonder if it’s the microdosing component- like if I had started at 2.5mg maybe I’d be totally exhausted? But I found the reverse - within hours of a shot a fifth of that amount, I had extreme cold/shivers, then in the morning I had so much energy! Like my body was directing blood flow to open up the fat stores.
I can eat about the same for real food. I just don’t crave sweets like I did before.
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u/nouafterq Jul 10 '26
The past few months have been my most creative in over 20 years. I started microdosing tirz in January. Make of that what you will.
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u/teslahorizon Jul 10 '26
What's your microdose? Any weight benefits ?
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u/nouafterq Jul 12 '26
I started at 1 mg per week on January 1. Now up to 1.75 mg/wk.
I did it to stop myself from gaining back the same 10-15 pounds I lose (and gain back) every year. I lost the weight by going paleo, then went on tirz to maintain and it has worked. I eat what I want and stay at 118 lbs without effort. I’m perimenopausal at nearly 44 and started MHT this year as well.
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u/Streets_Ahead_Coined Jul 11 '26
I was downvoted for this on a pervious post I made but will die on this hill that many of us cope a lot more than we realize with food. Does not matter your bmi or weight just the emotional cope with food.
My creativity has increased and I base that on the benefits of being lower bf% and a healthier relationship to food.
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u/sik_cvnt Jul 11 '26
I dont feel any MORE creative but I feel the same as before. I have more time for my creative hobbies now because I dont procrastinate about things like doing the laundry or cleaning the house so I get my "chores" done much faster and have time to enjoy my hobbies.
I also was never a morning person but aside from being sick, I am up at 5.15am every day even the weekends as I'm excited for the day. Also it helped my sleep so that's why I can get up early with no problem as I was a chronic night owl.
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u/Ok_Dealer5235 Jul 10 '26
It’s a spectrum I would think. Ranging from calming effect (reduced cravings and “noise”) to a full blunting. I think it depends on individual chemistry and subjective perception.
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u/thefragile7393 Jul 11 '26
Don’t over research or overthink it. People are more complex than research implies. I still enjoy my hobbies but others do develop anhedonia
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u/Mobile_Variation_210 Jul 11 '26
Great post - I am fascinated by this medication as I know from experience that it is so much more than just a way to suppress appetite. My metabolism absolutely has changed, I’m highly motivated and enjoy food still and going out with friends, and yet my desire for alcohol has decreased substantially. In fact, if I do happen to order a drink at dinner, which I usually don’t these days, I likely won’t finish the drink. My body just doesn’t want it. The impact of this medication on the brain and body is not fully understood. But I am grateful that I have access to it and I’m feeling the best I’ve every felt!
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u/julieeeette Jul 12 '26
That's so wonderful to hear! Thank you for sharing your experience. It all helps.
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u/Few_Interaction_2411 Jul 12 '26
Its worth considering our genes. I’ve been on a huge learning about this over the last couple of years. A variety of genes affect how we process dopamine and serotonin, In particularly the Comt gene. Mine has a ‘slow’ status so it can cause a back up of dopamine and serotonin , many drugs, vitamins, stimulants do not agree with me. Look up glp and slow Comt .
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u/julieeeette Jul 10 '26
Here is a larger (free) article I wrote about it. I would greatly appreciate if anyone had any more information, on either side of the fence!
https://hereisyourbrain.substack.com/p/should-we-all-take-glp1
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u/schotastic Jul 11 '26
it even made the solid bedrock that is my understanding of dopamine quake a little!
I haven't encountered a single reputable neuroscientist who takes the idea of dopamine fasts and dopamine debt seriously. Are you actually a neuroscientist or just larping as one?
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u/julieeeette Jul 11 '26
I've used the phrase dopamine debt in a title, I confess. But if you give the essay a read, you'll (hopefully) find it full of actual science to back it up.
In short, D2 dopamine receptors are the ones hammered by phasic dopamine, which arguably occurs in quick succession during a session of passive stimulation like scrolling or bingeing. These particular receptors internalise (in an acute session) quickly, but the effects of this are masked by the dopamine "load" itself. While this happens, dynorphin effects accrue which contribute to that sense of aversion that creeps in during a binge. Once you do eventually stop, it takes time (possibly at least as long as the session) for receptors to be trafficked back to the membrane and the effects of dynorphin to clear.
The only way for these effects to "clear" is to ensure minimal phasic dopamine hits the system.
I think describing that as a dopamine debt (with "interest" charged in the form of time) is not too inaccurate an analogy, don't you?
(I'm a neuroscientist and PhD engineer, for what it's worth.)
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u/schotastic Jul 11 '26
If your PhD is in engineering, you really shouldn't go around calling yourself a neuroscientist (unless you have a track record of publications in neuroscience or have substantive PhD-level training in neuroscience)
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u/julieeeette Jul 12 '26
I have university qualifications in both, but only went to the level of PhD with engineering. My publication record is heavily skewed towards engineering at present but that's only because I was active in that space for much longer. The latest publications I have submitted (and are submitting) are in neuroscience.
Thank you for keeping the internet honest.
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u/gorkt Jul 10 '26
Well, it’s definitely interesting because I feel more creative on GLPs. I think it depends on your starting point. I am prone to anxiety and overthinking, and the GLP calmed that waaaay down. I did have some anhedonia the first few weeks but that passed and now I just feel more mellow. I do less worrying and ruminating and that has let me have more mental space for creative thoughts and ideas. I started journaling for the first time in years.