Brain Regions Affected by GLP-1s

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In this episode, I dive deep into a topic that’s been coming up more and more over the last 12–18 months: anhedonia and motivational blunting in people using GLP-1 agonist peptides. While GLP-1s like semaglutide, tirzepatide, and retatrutide have been absolute game-changers for weight loss, metabolic health, and even addictive behaviors, there’s a smaller—but very real—subset of people who experience something unexpected: a reduced ability to feel pleasure.

Personally, I’ve never experienced this side effect. In fact, GLP-1s have done the opposite for me by giving me more mental clarity and freedom from compulsive behaviors. But enough people have reported feeling emotionally flat, unmotivated, or disconnected from things they used to enjoy that it deserves a serious, evidence-based conversation.

In this episode, I break down what anhedonia actually is, how it differs from depression, and why it can happen with GLP-1s from a neurochemical standpoint—specifically dopamine signaling and reward circuitry in the brain. We’ll look at the clinical data, real-world reports, differences between GLP-1 compounds, and why dose, speed of titration, weight loss, hormones, and lifestyle factors all matter.

Most importantly, I share practical strategies for mitigating these effects so you can still harness the benefits of GLP-1s without sacrificing joy, motivation, or quality of life.