Subject: GLP-1 Mental Flatness & Anhedonia — Peptides Worth Researching
From: Derek from Peptide Price <[email-masked]>
To: [email-masked]
Date: Sun, 5 Apr 2026 00:24:03 +0000
List-Id: <derekpruski.substack.com>

View this post on the web at https://derekpruski.substack.com/p/glp-1-mental-flatness-and-anhedonia

For research purposes only. Not for human consumption.
Earlier today I put out a post in the community about anhedonia and the mental flatness some RS subjects experience while on GLP-1 compounds. One thing was apparent from the responses: a lot of researchers are noticing their RS losing motivation to do things throughout the day — on top of the food noise reduction. Getting work done, daily tasks, things they used to enjoy. All of it feels like it requires more effort than it should.
This piece breaks down what’s actually happening and walks through five compounds currently being explored in the research community as potential tools to address it.
What Is Anhedonia?
Anhedonia is the reduced ability to feel pleasure or reward from things that normally produce it. This isn’t clinical depression — at least not in the way most people think about it. It’s subtler than that. A flattening. A dimming that makes everything feel a little more effortful and a little less worthwhile.
In the context of GLP-1 research, it tends to surface like this: the RS has no interest in hobbies it previously enjoyed. Work feels hollow, even when the RS is competent and experienced at it. Social interactions feel transactional. Morning motivation is low — not “tired” low, but “why bother” low. Emotional intimacy and connection feel muted in a way that’s hard to articulate.
The food noise goes quiet, which is the intended effect. But for some subjects, so does everything else.
This is not a character flaw or a motivation problem. The brain’s reward circuitry is genuinely dampened, and there’s a real reason for it.
Why Do GLP-1 Compounds Do This?
Most people assume GLP-1 compounds work purely in the gut — suppressing appetite and slowing digestion. That’s part of it. But GLP-1 receptors also exist in the brain, including in areas that control how motivated we feel, how much pleasure we get from things, and how emotionally engaged we are day to day.
Think of dopamine as the brain’s “drive” chemical. It’s what makes you want to start a task, finish a project, or feel rewarded after doing something. GLP-1 compounds can dial down dopamine activity in these areas — not dramatically, but enough that some RS subjects notice a consistent low-grade flatness that doesn’t go away on its own.
The same mechanism making the compounds so effective at reducing compulsive eating can also reduce the brain’s general sense of reward and motivation. This is why some RS subjects report feeling “fine” but flat. Functional but muted. No real highs, no real lows.
The Five Compounds Being Researched
Adamax
Adamax is a more advanced version of a well-known research peptide called Semax, designed to work more effectively in the brain. Its primary mechanism involves something called BDNF — think of this as a protein that acts like fertilizer for brain cells. It helps keep the parts of the brain responsible for motivation and mood healthy and responsive.
When BDNF activity is low, motivation drops, mood flattens, and the brain’s reward system becomes less responsive. This may be part of what’s happening with GLP-1-induced flatness, which is why Adamax has become a point of interest for researchers dealing with this specific issue.
Research is exploring its potential to support motivation and cognitive drive, improve mood and emotional responsiveness, and produce a mild calming effect without making the RS feel sedated or foggy.
Dosing being explored in the community runs 300–500 mcg administered intranasally or subcutaneously, either 1–3x per week or daily for structured cycles of 4–6 weeks on followed by 4–6 weeks off. Weekend-only protocols are also being used by researchers who want to limit exposure while still observing its effects.
Adamax is a subtle compound. Effects tend to build gradually rather than being immediately noticeable after a single administration.
Bromantane
Bromantane is a compound originally developed in Russia, sitting somewhere between an adaptogen and a performance enhancer. What makes it interesting in this context is that it doesn’t work like a stimulant — it doesn’t spike dopamine artificially. Instead, research suggests it helps the brain produce more of its own dopamine by supporting the enzymes responsible for making it.
For GLP-1 anhedonia, where the problem is the brain’s reward output being turned down, this is a potentially meaningful distinction. Rather than forcing a dopamine spike, Bromantane may help restore the brain’s natural capacity to generate it.
Research is also exploring its potential to reduce fatigue without overstimulation, support motivation in subjects with flat baseline affect, and provide a calming effect that doesn’t interfere with mental output.
Dosing being explored runs 50–100 mg, 1–3x per week. Community guidance leans toward the lower end of that frequency range. It is not intended for indefinite daily use — structured time off is recommended. Many researchers are using it situationally on days that require higher output rather than as a daily compound.
Bromantane has a long half-life, meaning it stays active in the system for an extended period. Daily stacking is not what the research community is generally exploring here. Effects are consistently described as clean and grounded rather than stimulating.
PE-22-28
PE-22-28 is a synthetic peptide built from a naturally occurring protein fragment in the body. Its mechanism centers on serotonin — specifically on removing a brake that prevents the brain from using serotonin effectively.
Here’s a simple way to think about it: there’s a switch in the brain that, when stuck in the “on” position, blocks serotonin from doing its job. PE-22-28 is being researched for its ability to flip that switch off, allowing serotonin signaling to function more normally. This is different from how antidepressants work — it’s not increasing serotonin production, it’s improving how well the brain can actually use what it has.
For GLP-1 flatness that has a mood and emotional component alongside the motivation issues, this makes PE-22-28 a relevant compound to understand.
Research is exploring its potential for restoring emotional responsiveness, supporting motivation without stimulant activity, and rapidly improving hedonic tone — the baseline sense that things are worth engaging with.
Dosing being explored runs 300 mcg daily via intranasal administration, for active cycles of 6–8 weeks followed by a 4-week washout before resuming.
Effects are described as subtle — more like a ceiling being lifted than a noticeable acute change. Research in this area is still relatively early but the underlying mechanism is well-supported in the preclinical literature.
Oxytocin
Most people know oxytocin as the “bonding hormone” — associated with trust, connection, and intimacy. But its role in the brain’s reward system is broader than that. It’s deeply tied to how rewarding social interactions feel, how emotionally present we are with the people around us, and how much we actually enjoy connection rather than just going through the motions of it.
GLP-1 flatness frequently hits this territory specifically. RS subjects in the community consistently report that intimacy and emotional connection feel muted — not absent, but thinner than it used to be. Oxytocin is being researched as a potential tool to restore that layer of reward.
Research is exploring its potential to bring back the emotional richness associated with social connection, improve the subjective experience of intimacy, reduce emotional blunting, and enhance the rewarding feeling tied to being around other people.
Dosing being explored:
Weeks 1–8: 120–240 mcg daily
Weeks 9–12 (Washout): No dosing
Effects are described as enhancing the emotional coloring of experiences that are already happening rather than producing a standalone noticeable effect. Community reports suggest it is most impactful in subjects experiencing significant emotional blunting rather than mild flatness.
PT-141 (Bremelanotide)
PT-141 works through a completely different pathway than the other compounds in this post. Rather than targeting dopamine or serotonin directly, it works on a system in the brain that governs desire, motivation toward intimacy, and anticipatory reward — the feeling of actually wanting something before you have it.
That anticipatory component is worth paying attention to. One of the hallmarks of anhedonia is the loss of wanting. Things don’t sound appealing before you do them, even if you know logically they should. PT-141’s mechanism may be relevant here specifically because it targets that “wanting” signal rather than the downstream experience of pleasure itself.
Research is exploring its potential to restore sexual motivation and desire, reactivate the anticipatory reward response, support emotional engagement in intimate contexts, and produce mood-adjacent effects through its central mechanism.
Dosing being explored runs 500 mcg – 2 mg per research administration, administered 1–2 hours before the relevant observation window. Most community research starts at the lower end — 500 mcg to 1 mg — to assess tolerance before titrating up. Frequency is kept to a maximum of 2–3x per week to avoid the receptors becoming desensitized over time.
Nausea is the most commonly reported side effect, particularly at higher doses. Starting low significantly reduces this. PT-141 is situational by design — not a daily compound. Its mechanism is distinct enough from the others in this post that it functions as a complement rather than an overlap for subjects dealing specifically with the intimacy and desire component of GLP-1 flatness.
A Few General Research Notes
These compounds are not validated treatments for GLP-1 side effects. This is exploratory territory based on mechanism and community-reported observations. No compound in this post should be combined without first running each one individually to understand how the RS responds. The washout periods listed matter — don’t skip them.
It’s also worth noting that anhedonia from GLP-1 compounds often improves or resolves after the GLP-1 is discontinued. The compounds covered here are being explored for subjects who are continuing their GLP-1 research and want to address quality of life in the interim. Bloodwork baselines before introducing any new compound into a protocol are always worth doing.
Mental flatness from GLP-1s is real, it’s mechanism-driven, and it’s talked about far less than it should be. Hopefully this gives researchers a clearer starting point for understanding what’s happening and what’s being explored.
For research purposes only. Not for human consumption.

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