Abstract Introduction Unexpected enhancement of sexual arousal, desire, and orgasm following diphenhydramine (DPH) ingestion has emerged in anecdotal reports across online platforms. Aims To examine whether there are common effects of DPH on the sexual responses of women and men who respond to DPH with excitation rather than sedation. Methods Qualitative case data were gathered from surveys of men and women on a DPH Reddit site to examine the consistency, intensity, and subjective nature of DPH effects on sexual arousal, desire, and orgasm. Results Participants described enhanced sexual arousal, orgasm, increased stimulation sensitivity, and profound emotional release from DPH. Some found the effects stronger than those of prescription medications for sexual arousal disorders. Conclusion These observations suggest a paradoxical pharmacological action of DPH, potentially involving dopaminergic and/or histaminergic pathways. While DPH itself is not a recognized therapeutic agent for the treatment of sexual dysfunctions, these unexpected effects may point toward a novel neurochemical mechanism of sexual excitation in some individuals that warrants further investigation.
Regis et al. (Mon,) studied this question.