FAPESP-supported research shows that small doses of the antibiotic minocycline may be helpful in treating panic disorder. Experiments conducted in mice at the State University of São Paulo (UNESP) and in humans at the Federal University of Rio de Janeiro (UFRJ) showed that minocycline is as effective as clonazepam, the most commonly prescribed anti-panic drug and best known by its brand name Rivotril.
The study was published in the journal translational psychiatry.
The doses of antibiotics needed to treat panic attacks in this study were lower than those used to treat bacterial infections, reducing the chance of bacterial resistance developing.
“In our experimental model, we use carbon dioxide (CO₂) When inhaled to induce a panic attack, mice treated with minocycline for 14 days before the experiment showed a reduction in one of their panic-inducing responses. “In humans, this treatment reduced the intensity of panic attacks induced by CO₂ inhalation,” said Beatriz de Oliveira, lead author of the study. Oliveira conducted this research during his undergraduate studies on a FAPESP scholarship at the UNESCO Faculty of Agriculture and Veterinary Medicine (FCAV) in Jabotívar.
This study is part of the project “Physiopathology of CO₂ sensitivity: the role of the locus coeruleus”, supported by FAPESP and coordinated by FCAV-UNESP Professor Luciane Gargaglioni.
It is well known that some mental illnesses are caused by inflammation of nerve cells. Although minocycline has anti-inflammatory effects at low doses, it does not necessarily have antibiotic effects, so improvement in symptoms is thought to occur by reducing inflammation. This is different from the mechanism used by clonazepam, which works by inhibiting specific receptors in the brain. ”
Mr. Lucien Gargaglioni, Professor FCAV-UNESP
Although some responses to antibiotic treatment differ from those to clonazepam, which was used as a control in human studies, minocycline may be an alternative for patients who do not respond to psychiatric medications. These drugs account for approximately 50% of cases.
“Clonazepam enhances the action of GABA (Gamma-aminobutyric acid, neurotransmitter) by binding to receptors of the same name. These receptors are located throughout the brain. Therefore, clonazepam is a controlled substance because its use slows heart and breathing rates, impairs decision-making ability, and causes other side effects such as dependence,” Gargaglioni explains.
Minocycline is safe for humans because it is already used for other purposes. Therefore, clinical trials may proceed directly to Phase 2. Phase 2 includes increasing the number of patients, testing different doses, and evaluating possible side effects, among other evaluations performed in this type of study.
This study also paves the way for the search for other drugs with anti-inflammatory effects on microglia that may be as effective or even more satisfying than minocycline in the treatment of panic disorder.
experiment
Researchers observed that patients who took minocycline had decreased levels of pro-inflammatory cytokines, such as interleukin (IL)-2sRα and IL-6, and increased levels of IL-10, which promotes anti-inflammatory responses. Additionally, TNFα, a cytokine associated with various inflammatory processes, was also reduced.
A total of 49 patients diagnosed with panic disorder were analyzed. At the beginning of the study and again after taking clonazepam or minocycline for seven days, they breathed in air enriched with 35% carbon dioxide. In both cases, anxiety symptoms were measured by trained psychiatrists using standard methods for this type of research.
“Neither that concentration of carbon dioxide, nor the 20% concentration used in the mice, exists in nature. However, excess carbon dioxide causes a feeling of suffocation similar to a panic attack. It’s a very unpleasant feeling, so we gave the control group clonazepam. In this case, it would not be ethical to have one group take a placebo,” Gargaglioni says.
Although the scientific literature has reported differences in cytokine levels in mice receiving various treatments, these differences were not detected in the present study, likely due to methodological limitations.
However, after treatment with minocycline, we observed significant behavioral responses in the animals, including a decrease in jumping, one of the responses after inducing a panic attack by enriching the air with 20% carbon dioxide.
Analysis of the locus coeruleus, a CO2-sensitive region of the brain, showed that the mice had reduced microglial density 6 hours after gas exposure. This finding strengthens the role of this part of the brain in panic attacks.
“After testing different intervals at which brain changes are observed, we concluded that 6 hours after a 15-minute CO₂ exposure is ideal. This is an important finding for future research,” Oliveira said.
Further research is needed before minocycline can be employed for this purpose. The study opens the door to new ways to treat this and other psychiatric disorders associated with increased inflammation in nerve cells.
sauce:
São Paulo Research Foundation (FAPESP)
Reference magazines:
de Oliveira, BFG; Others. (2026). Minocycline reduces panic responses in a CO2-induced panic attack model: a translational approach. Translational psychiatry. DOI: 10.1038/s41398-026-03836-7. https://www.nature.com/articles/s41398-026-03836-7
