What the FDA Says vs. What Patients Are Reporting
“If you take this shot, you could lose 30 pounds. If you take this pill, you can lose this. But what are the long-term effects? What will it do to your body? Your mind? What will it do to us five years from now? Ten years from now?”
Those were the words of Academy Award–winning actress Mo’Nique, who recently raised concerns about glucagon-like peptide-1 receptor agonist medications (GLP-1 drugs).
Her questions are not dramatic.
They are rational.
GLP-1 drugs such as Ozempic, Wegovy, Mounjaro, and Zepbound are widely promoted for weight loss. Many patients report something powerful after starting them:
“The food noise is gone.”
But if a drug can quiet your mind about food, how exactly is it working in your brain?
Because GLP-1 drugs do not just affect your stomach.
They bind to receptors in your brain.
And as prescriptions increase, reports of anxiety, depression, emotional dullness, mental fog, and in rare cases, suicidal thoughts have also surfaced (1, 2).
Yes, weight loss may occur.
But Mo’Nique’s question remains:
What happens to your mind over time?
What Is Glucagon-Like Peptide-1 (GLP-1)?
Glucagon-like peptide-1 (GLP-1) is a hormone made in the gut when you eat.
It helps regulate blood sugar and insulin. It also signals fullness.
GLP-1 receptor agonist drugs are medications engineered to mimic this hormone.
They slow digestion, increase satiety, and reduce appetite.
That is how they support weight loss.
But GLP-1 receptors are not only found in the digestive system.
They are located in the brain (3, 4).
And that matters.
What Is a Receptor – And Why Should You Care?
If you are going to take a drug that interacts with your brain, you deserve to understand what a receptor is.
A receptor is like a docking station on a cell.
Hormones are chemical messengers.
Receptors are the receivers.
Think of insulin.
Insulin is often described as a “key.”
Cells have insulin receptors that act like “locks.”
When insulin binds to its receptor, like a key fitting into a lock, the door opens and glucose enters the cell.
No receptor. No signal.
Wrong key. No response.
Right key. The cell changes behavior.
You can also think of receptors like:
- A light switch
- A mailbox receiving a message
- A volume knob controlling intensity
GLP-1 drugs bind to GLP-1 receptors.
Those receptors are found in the brainstem, hypothalamus, and reward pathways (3, 4).
When they are activated, brain cells change how they signal.
That includes areas that regulate stress, appetite, and emotional tone.
Natural GLP-1 vs. Drug GLP-1: Why Duration Matters
Here is something most people are not told.
Natural GLP-1 only circulates in the body for about one to two minutes (5).
It is rapidly broken down by an enzyme called dipeptidyl peptidase-4 (DPP-4) (5).
Short pulse.
Signal delivered.
Cleared away.
That is normal physiology.
GLP-1 drugs are engineered to resist DPP-4-mediated breakdown (6, 7).
Instead of lasting minutes, they remain active for hours or days.
That means receptors in your brain are exposed to prolonged stimulation.
Your brain evolved under brief hormonal pulses, not continuous pharmacologic activation.
That does not prove harm.
But it is biologically different from natural exposure.
And researchers are still studying what sustained receptor activation means in the long term.
The Brain’s Reward System
GLP-1 receptors are located in the brainstem and hypothalamus (3, 4).
They are also present in the mesolimbic reward system, which regulates dopamine signaling (3, 4).
The reward system influences:
- Motivation
- Pleasure
- Drive
- Emotional reinforcement
GLP-1 activation reduces the rewarding value of food (3, 4).
That may explain appetite suppression.
But dopamine pathways do not regulate food alone.
They influence emotional tone.
Some patients report:
- Emotional flattening
- Reduced excitement
- Mental fog
- Loss of pleasure
These symptoms are consistent with alterations in the reward system.
This is biologically plausible.
It does not mean everyone experiences it.
But it explains why some might.
What Patients Are Reporting
Post-marketing surveillance has identified reports of suicidal ideation and psychiatric adverse events associated with GLP-1 receptor agonists (1, 2).
A VigiBase pharmacovigilance analysis identified suicidal ideation reports (1).
An analysis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System also identified psychiatric adverse event signals (2).
A population-based cohort study from Chung Shan Medical University reported increased relative risks of depression, anxiety, and suicidal behavior among GLP-1 users compared to non-users (8).
At the same time, the FDA reviewed clinical trial data and stated they did not find a statistically significant increase in suicidal thoughts at the population level (9).
Both observations can coexist.
If most individuals improve emotionally after weight loss, but a smaller subgroup worsens, the average may appear unchanged.
That does not erase the subgroup.
Where This Can Lead – The Medication Cascade
Consider a scenario.
A person begins a GLP-1 medication.
Within weeks, they feel more anxious or emotionally flat.
They report this to their doctor.
If the medication is not suspected, they may be referred to a psychiatrist.
They are prescribed a selective serotonin reuptake inhibitor (SSRI).
Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and anxiety. Early pivotal trials evaluating SSRIs for acute depression commonly lasted 6 to 12 weeks (10).
Today, antidepressant use is widespread. National data indicate that approximately 13–20% of U.S. adults report using antidepressant medications (11).
This does not mean antidepressants are never helpful.
But if a GLP-1 medication contributes to mood changes in a subset of users, and that possibility is not explored, a person may enter long-term psychiatric treatment for what could be a pharmacologic effect.
Medication A → symptom → Medication B.
That cascade deserves awareness.
What Researchers Are Still Studying
Natural GLP-1 exposure lasts minutes (5).
Drug exposure lasts hours or days (6, 7).
In neuroscience, prolonged receptor activation in some systems can lead to receptor adaptation.
GLP-1 receptor agonists are relatively new in the treatment of widespread obesity.
Long-term data on brain receptor exposure are still evolving.
This is not panic.
It is scientific caution.
A Balanced Perspective
GLP-1 drugs have helped many individuals lose weight and improve metabolic markers.
That benefit is real.
But weight loss and brain health should not be separated.
If anxiety, depression, emotional dullness, or mental fog appear after starting a GLP-1 drug, the timing deserves attention.
Your waistline matters.
But so does your mind.
Bottom Line
The concerns Mo’Nique has expressed are real.
And I agree with her central question:
No one truly knows what the long-term effects of continuous GLP-1 receptor stimulation in the brain five or ten years from now will be.
These drugs are powerful.
They change their appetite.
They change reward signaling.
They interact with brain receptors.
That matters.
Right now, GLP-1 drugs are the shining object. They are heavily marketed. They are endorsed by celebrities. They are discussed everywhere.
But history teaches us something important.
What looks like a breakthrough today can reveal unintended consequences tomorrow.
People are often influenced – sometimes unknowingly – into believing that if something is popular, it must be fully understood and fully safe.
That is not always true.
GLP-1 drugs may help with weight loss.
But they may also carry unknown risks for both the body and the mind.
And when it comes to your brain, “unknown” deserves caution.
If you are currently taking a GLP-1 drug and want to transition off safely, we have a program designed to support that process.
If you want to lose weight without GLP-1 medications, we have a program for you as well.
You do not have to choose between your waistline and your mind.
Email your questions to robert@dietfreelife.com
Or schedule a free consultation to learn about our programs and services.
Your health deserves more than a trend.
It deserves understanding.
References
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- Montastruc, F., Palmaro, A., Bagheri, H., & Montastruc, J. L. (2023). Reporting of suicidal ideation with GLP-1 receptor agonists: Analysis in VigiBase. Drug Safety, 46(9), 1055–1063.
- Cheng, Y., et al. (2023). Psychiatric adverse events associated with GLP-1 receptor agonists: FAERS analysis. Frontiers in Pharmacology, 14.
- Alhadeff, A. L., Rupprecht, L. E., & Hayes, M. R. (2012). GLP-1 neurons project to reward centers to control food intake. Endocrinology, 153(2), 647–658.
- Dickson, S. L., et al. (2012). GLP-1 analogue decreases reward value of food via mesolimbic pathways. Journal of Neuroscience, 32(14), 4812–4820.
- Holst, J. J. (2007). The physiology of glucagon-like peptide-1. Physiological Reviews, 87(4), 1409–1439.
- Knudsen, L. B., & Lau, J. (2019). The discovery and development of liraglutide and semaglutide. Frontiers in Endocrinology, 10, 155.
- Drucker, D. J. (2018). Mechanisms of action and therapeutic application of GLP-1. Cell Metabolism, 27(4), 740–756.
- Chung Shan Medical University. (2023). Association between GLP-1 receptor agonists and psychiatric outcomes: Population-based cohort study.
- S. Food and Drug Administration. (2024). Drug safety communication on GLP-1 receptor agonists and suicidal ideation.
- Geddes, J. R., et al. (2003). Relapse prevention with antidepressant drug treatment in depressive disorders: A systematic review. Lancet, 361(9358), 653–661.
- Centers for Disease Control and Prevention. (2020). Antidepressant use among adults: United States, 2015–2018. NCHS Data Brief.
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Robert Ferguson is a California- and Florida-based single father of two daughters, clinical nutritionist, Omega Balancing Coach™, researcher, best-selling author, speaker, podcast and television host, health advisor, NAACP Image Award Nominee, creator of the Diet Free Life methodology, and Chief Nutrition Officer for iCoura Health. He also serves on the Presidential Task Force on Obesity for the National Medical Association and the Health and Product Advisory Board for Zinzino, Inc.
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