The neurobiology of anxiolytic placebo effects

• Applicant: Dr. Benjamin Meyer
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 506717928

A professional clinical environment, comprehensive information on the efficacy of a therapy and a positive doctor-patient relationship can have a decisive influence on patients' expectations of a therapeutic intervention. This alone can lead to symptom relief, commonly referred to as the placebo effect. Although placebo effects occur in a variety of clinical conditions, major advances have been made primarily in studying the neurophysiology of the pain-reducing placebo effect (placebo analgesia or placebo hypoalgesia). Surveys of clinical staff and evaluations of clinical trials show that, in addition to the hypoalgesic placebo effect, the much less researched fear-/anxiety-reducing placebo effect (placebo anxiolysis) is also of high clinical relevance. In two previous studies, we have established a task design in our laboratory to test placebo anxiolysis in healthy participants. Using functional magnetic resonance imaging (fMRI), we have shown that similar neural structures are modulated during placebo hypoalgesia and placebo anxiolysis, suggesting commonalities in neurochemical control. In this project, we first aim to investigate the role of endogenous opioids (which have a key function in placebo hypoalgesia) in the placebo-induced reduction of experimental fear in healthy subjects. For this purpose, we want to combine our previously established task design with the administration of the drug naloxone to block opioid receptors throughout the experiment. In a second study, the task design will then be modified to specifically investigate the placebo effect on more persistent anxiety symptoms. This adjustment is important, first, to reduce the discrepancy between experimentally induced and clinical symptoms (which usually extend over a longer period of time) and, second, to account for differences in the neurophysiology underlying phasic fear and sustained states of anxiety. The findings of this project can make an important contribution to better understanding the functional and neurochemical basis of placebo effects on both fear and anxiety. They can also provide initial indications of suitable biomarkers to identify patients who respond particularly strongly to placebos. In the future, this may help to optimize therapeutic strategies and improve test sensitivity in clinical trials investigating anxiolytic drugs.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Raffael Kalisch; Professor Dr. Oliver Tüscher