This story covers a personal reaction to an investigational weight-loss drug, expert cautions about off-trial use, clinical trial results and the possible links between these medicines and mood changes.
Bunnie XO, who is married to country singer Jelly Roll, has opened up about a severe depressive episode she believes followed taking retatrutide, an experimental medication still in trials. She said she received the medication from a wellness center in Nashville and felt physically ill in the first week, then noticed rapid slimming within two weeks. In the fourth week she increased her dose by one unit and began to experience profound mental numbness and mood changes.
“I literally got sent into the worst suicidal depression that I’ve had since 2020,” she said. “I’m talking like it scared me so bad. I didn’t think I was going to make it through the two weeks. Like I was praying to God.”
The podcaster also described losing the ability to enjoy things that once mattered. “You could see like my eyes were black,” she said. “I just drove in silence because I just couldn’t handle anything.
“It was either overstimulating or it was to the point where it just stole my joy. I had no joy, like nothing to live for. It was so dark.”
Lilly, the maker of retatrutide, noted the molecule is investigational and legally available only to clinical trial participants. “No one should consider taking anything claiming to be retatrutide outside of a Lilly-sponsored clinical trial,” the spokesperson wrote. “This was not a Lilly product, and the company continues to warn the public about the potential dangers of fake medicines.”
After stopping the medication for about 20 days, Bunnie reported that her joy began to return and called the experience a battle. “My story is not what’s going to happen to you,” she shared. “There’s so many people who are taking reta and love it and all that. But something happened with me.”
Dr. Marc Siegel, a senior medical analyst, warned that retatrutide is a new triple agonist targeting GLP-1, GIP and glucagon receptors and that these agents have been linked in some cases to psychiatric symptoms. “[It] has been linked potentially to depression and suicidal thoughts, as have the GLP-1 drugs, where some studies have shown increased psychiatric risks, so there is a potential link here.” He also highlighted that impacts on the brain’s reward system can be unpredictable.
Early phase 3 results showed striking weight loss in some trial groups, with participants on a 12-mg dose reporting dramatic reductions. A company statement touted that retatrutide could be an important option for patients with substantial weight loss needs and complications like knee osteoarthritis. Seven additional phase 3 trials are ongoing and regulatory review could lie years ahead.
Experts caution the effects are not fully mapped and the side effect profile overlaps with other drugs in this family, especially gastrointestinal symptoms and some rare but serious reactions. “Dopamine, serotonin and norepinephrine affect mood and appetite, reduce cravings and can have a positive effect on mood, but also can be negative,” he said. “Somewhat unpredictable.”
Clinicians stress careful evaluation before assigning causality for major depressive episodes. “It is essential to understand the patient’s complete medical and psychiatric history, including other medical conditions, precise weight change dynamics, concomitant medications and psychosocial stressors,” he said. Philip Rabito has warned these agents may “approach bariatric surgery level outcomes” while also bringing less-understood long-term risks.
Hormonal context matters, too: Bunnie’s age places her in an age range when reproductive hormone fluctuations can influence mood. “Estrogen has well-documented neuroprotective and mood-stabilizing effects,” he said. “Until a protocol is established, patients outside clinical trials should not inject these medications,” he cautioned, and anyone experiencing severe mood changes should “seek immediate professional help.”
