GLP-1 drugs have transformed the conversation around weight loss. Medications such as semaglutide and tirzepatide can produce substantial weight reduction and have demonstrated important metabolic and cardiovascular benefits. But as their popularity continues to grow, another question deserves equal attention: how much do we actually understand about the long-term effects of manipulating these powerful biological pathways?
The answer is more complicated than the increasingly casual way these drugs are discussed online.
GLP-1 receptors are found not only in the digestive system but also in the brain. GLP-1 signalling influences appetite, satiety, reward and energy regulation. This does not mean that GLP-1 drugs are inherently harmful to mental health. In fact, in January 2026, the US Food and Drug Administration said its review of 91 clinical trials involving more than 107,000 people found no increased risk of suicidal thoughts or behaviour, depression, anxiety, irritability or psychosis among GLP-1 receptor agonist users. (fda.gov)
That finding is important. But it doesn’t mean that every individual’s experience will be identical, nor that every possible neurological consequence of long-term use has been resolved.
There are already well-established physical adverse effects. Gastrointestinal symptoms—including nausea, vomiting, diarrhoea and constipation—are common. Other recognised risks include gallbladder disease and pancreatitis, while delayed gastric emptying can have implications for anaesthesia and aspiration. These are not hypothetical concerns; they are reflected in regulatory safety information. (FDA Access Data)
Then there are the newer drugs.
Retatrutide is not simply another GLP-1. It is an investigational drug that simultaneously activates three receptors: GIP, GLP-1 and glucagon. In clinical trials, gastrointestinal side effects were common, and dose-dependent increases in heart rate were observed. Because retatrutide remains investigational, there is considerably less long-term safety data than exists for established GLP-1 medications.
This distinction matters.
There is currently no good clinical evidence proving that retatrutide “destroys” the thyroid, permanently changes personality, eliminates creativity or causes cognitive decline. Claims like these should not be presented as established fact.
But individual experiences still deserve to be heard.
I took retatrutide for approximately six months. During that period, I experienced what felt like profound anhedonia, cognitive dulling and a dramatic change in my ability to think creatively. Writing—which had always felt natural to me—became extraordinarily difficult. Most disturbingly, I experienced intrusive thoughts about harming myself that felt completely alien and appeared without an obvious reason.
I cannot prove that retatrutide caused those experiences. Correlation is not causation, and an individual experience cannot substitute for controlled research. But neither should an experience like that simply be dismissed because it isn’t yet explained by the literature.
I have now been off peptides for several months. More recently, after taking a dose of thymosin alpha-1, I experienced what felt like another period of cognitive and emotional disruption. Again, that does not establish causation. It does, however, reinforce my personal belief that we should be cautious about treating powerful peptide drugs as though we already understand every consequence of manipulating these signalling systems.
The lesson isn’t that GLP-1 drugs are “bad”.
It is that effective does not mean fully understood.
These medications are changing fundamental systems involved in appetite, metabolism and brain signalling. As millions more people use them—often for years rather than months—we need long-term research that looks beyond weight on the scales and examines cognition, mood, motivation, reward, endocrine function and quality of life.
Patients deserve the benefits of medical innovation. They also deserve honesty about uncertainty.
And if someone experiences a profound or unexpected change in mood, cognition or behaviour while taking a GLP-1 or an investigational peptide, that experience should be taken seriously and discussed with a qualified healthcare professional.
The question isn’t whether we should stop researching these drugs. It’s whether we’re willing to keep asking difficult questions while the research catches up with their rapidly expanding use.