(579) Exploratory Case Studies of Enhanced Sexual Arousal in Men and Women Taking Diphenhydramine Hydrochloride

Introduction Antihistamines are widely believed to induce unwanted sexual side-effects. Because histamine relaxes smooth muscles allowing for genital blood flow during sexual arousal, antihistamines can disrupt this process leading to sexual arousal problems like erectile dysfunction. Antihistamines also reduce mucous secretion that can lead to vaginal dryness. Many first generation H1 receptor antagonists also induce drowsiness, which can decrease sexual desire and blunt genitosensory stimulation. However, some individuals show a paradoxical increase in excitement and arousal in response to some H1 antihistamines like diphenhydramine (DPH). Unexpected enhancement of sexual arousal, desire, and orgasm following DPH ingestion has emerged in anecdotal reports across online platforms. Objective To examine whether there are common effects of DPH on the sexual responses of women and men. Methods Qualitative case data were gathered with permission from individuals on a Reddit site devoted to DPH excitation to examine the consistency, intensity, and subjective nature of DPH effects on sexual arousal, desire, and orgasm. Results Men and women described enhanced orgasm, increased genital sensitivity, and profound emotional release. Some found the effects stronger than those of prescription medications for sexual arousal disorders, such as PDE-5 inhibitors. Conclusions 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 that warrants further clinical investigation. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: J.G.P. is a consultant to FirmTech Inc., Kanna Health Ltd., Ovoca Bio/IVIX Corp., Reunion Neuroscience Inc., SmartBod/Lioness, Inc., and Vella Bioscience. However, there are no conflicts of interest regarding the present case study. M.P.R. has no conflicts to report.