Results from clinical trials show that serotonergic psychedelics have efficacy in treating psychiatric disorders, where currently approved pharmacotherapies are inadequate. Developing psychedelic medicines, however, comes with unique challenges, such as tempering heightened anxiety associated with the psychedelic experience. We conceived a new strategy to potentially mitigate psychedelic effects with defined electromagnetic signals (ES). We recorded the electromagnetic fields emitted by the serotonin 2 receptor (5-HT2R) agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) and converted them to a playable WAV file. We then exposed the DOI WAV ES to mice to assess its effects on the DOI-elicited, 5-HT2AR dependent head-twitch response (HTR). The DOI WAV signal significantly attenuated the HTR in mice elicited by 0.1 and 0.3 mg/kg subcutaneous DOI (p < 0.05 and p < 0.01, respectively). A scrambled WAV signal did not affect the DOI-elicited HTR, suggesting specificity of the DOI WAV signal. These results provide evidence that defined ES could modulate the psychoactive effects of serotonergic psychedelics. We discuss putative explanations for the distinct effects of the DOI WAV signal in the context of previous studies that demonstrate ES's efficacy for treating other conditions, including pain and cancer.