Happy Tuesday!
I dropped a new episode on Spotify today all about GLP-1 agonists and anhedonia aka the reduced ability to feel pleasure.
This has come onto my radar hard over the last 12–18 months.
At first, it sounded like internet noise. Then I started seeing it show up more and more in real people, real coaching situations, and live Q&As.
Interestingly, reports have found psychiatric adverse events made up 1.2% of total reports for semaglutide, liraglutide, and tirzepatide.
And a large observational cohort study reported a 195% higher risk of major depression among GLP-1 RA users (association, not proof).
So today, let’s dig deeper into why this may be happening.
Anhedonia
Most people think depression means crying in bed, hopelessness, and existential dread. That can be depression, sure.
But anhedonia is more of an inability to feel joy or pleasure.
It’s when you take the thing you love most (golf, lifting, music, sex, your business, cooking, being around your people), and suddenly it feels empty.
And that distinction matters because when anhedonia is medication-induced, it can show up in someone whose life is objectively going well.
Great relationships. Great work. Great momentum. And then they start a GLP-1, and within weeks, they are completely numb.
The Paradox
I’ve never personally had GLP-1s make me feel emotionally flat. If anything, they’ve made me happier because they give me mental clarity.
Some people feel freed from cravings and compulsive habits (overeating, alcohol, dopamine chasing).
Other people feel like that same “freedom” from compulsive behavior spills over into everything, where motivation, joy, and excitement suddenly vanish from their lives.
For many people, this blunting can be a miracle to break bad habits.
But for others, this blunting can leave their life devoid of joy and happiness.
The Mechanism and Dopamine
GLP-1 receptors exist in brain regions tied to reward and motivation, especially the ventral tegmental area (VTA) and the nucleus accumbens (NAc).
Dopamine bursts in these pathways drive our desire to seek food, excitement, novelty, and reward.
GLP-1 activation can reduce these reward pathways, which is why these drugs work so well for appetite and cravings.
Now, does that mean everyone loses dopamine and becomes flat? No. Biology is individualized.
But when you see anhedonia, this is the pathway that makes the most sense.
Reward signaling gets turned down. And for some people, it turns down too far.
More Than the Drug
I think there are multiple causes here, and this is where we need to zoom out.
Yes, there’s the direct neurochemical effect. But then you have the downstream cascade:
Rapid weight loss can shift hormones fast. Leptin drops. Thyroid output can adapt downward. Sex hormones can get disrupted.
Caloric deficit itself can create fatigue and emotional flattening. These are the most powerful appetite suppressants we’ve ever had.
Carb restriction can lower serotonin in certain people, and that can affect mood and sleep.
Lifestyle changes matter more than people want to admit. If food and alcohol were major social hubs, you could create a behavioral void without realizing it.
And then there’s mental health history. Some people are simply more sensitive to shifts in reward circuitry.
This is why I keep saying these drugs are powerful. With power comes responsibility.
Comparisons of GLP-1s
Based on current evidence and mechanism, here’s how I see it playing out:
Semaglutide seems to have the most reports tied to mood issues. There’s even a published case report of two patients who developed depressive symptoms about a month after starting semaglutide, which improved after discontinuation.
Tirzepatide appears (so far) to have a weaker psychiatric signal, with psychiatric events still possible but relatively uncommon.
Retatrutide is newer and we simply don’t have the same volume of formal post-marketing-style data yet. But anecdotally, people can still experience blunting, likely driven by the GLP-1 side of the molecule.
Cagrilintide isn’t a GLP-1 (it’s an amylin analog), but I’ve seen similar reports of “flatness.” Mechanistically, it still intersects with reward circuitry, and stacked with GLP-1s, it may raise the odds of anhedonia for certain people.
Fixing It
If you’re experiencing this, first, you’re not crazy. Second, don’t let anybody gaslight you into thinking it’s purely psychological.
Here are strategies that actually make sense:
Track it. Journal. Rate mood and motivation daily. Patterns matter.
Adjust dosing strategy. Often, the issue is the speed of dose escalation or large weekly spikes. Splitting doses can help some people smooth CNS impact.
Don’t starve yourself. Protein. Hydration. Micronutrients. Some healthy carbs if you’re feeling flat.
Protect hormones. Rapid fat loss can downshift sex hormones and thyroid signaling in some people. If your hormones crash, your mood usually follows.
Behavioral activation. Schedule joy on purpose.
Stay social. Don’t accidentally delete your social life because you’re not hungry.
If needed, switch compounds. Sometimes moving from semaglutide to tirzepatide (or stepping down dose) changes everything.
Final Thoughts
If you listened to the episode on Spotify, leave a comment and tell me what you think.
And if you’ve experienced this, or someone you love has, share this with them.
Oftentimes, anhedonia is driven by neurochemical changes from drugs in tandem with lifestyle issues.
As always, thank you from the bottom of my heart for being here, supporting the work, and letting me keep showing up and making this content.
Without you, I don’t exist!
Best,
Hunter Williams