The placebo effect is a learning phenomenon strongly associated with cognitive mechanisms. Placebo conditioning, particularly, combines threat learning with verbal instructions and expectations....Show moreThe placebo effect is a learning phenomenon strongly associated with cognitive mechanisms. Placebo conditioning, particularly, combines threat learning with verbal instructions and expectations. These processes are central in shaping subjective pain experience and threat-related episodic memory. However, the specific influence of placebo conditioning on episodic memory accuracy and generalization is not yet known. It is hypothesized that threat associations enhance memory recognition and generalization by increasing arousal; thus, introducing a placebo manipulation in a threat conditioning paradigm might impair memory recognition by decreasing arousal. This can offer insights into the broader clinical implications of placebo, as threat-related responses and memory bias are hallmarks of anxiety disorders. This study used a within subjects experimental design with 72 healthy participants undergoing a pain calibration/placebo conditioning procedure, a Pavlovian threat conditioning paradigm with a placebo manipulation using pictures, and a memory test. Participants completed pain, mnemonic, and confidence ratings. We predicted that the placebo condition would correlate with lower subjective pain experience, and the CS+ condition with increased recognition memory and generalization compared to the CS+ placebo and CS- conditions. Although the placebo manipulation was successful, it did not significantly affect memory recognition, generalization or discrimination. There were indications that the CS+ condition correlated with higher recognition compared to the CS- condition, but these should be interpreted with caution. We conclude that the placebo manipulation’s subtle effects may not have reached the necessary threshold of arousal and motivational engagement required to alter memory processes. Limitations and suggestions for future research are discussed.Show less