AUTHOR=Platteau Tom , Schrooten Jochen , Herrijgers Corinne , den Daas Chantal , Ventura Mireia , Strong Carol , de Wit John TITLE=Polydrug use during chemsex: single and intersecting sexual effects of commonly used drugs JOURNAL=Frontiers in Public Health VOLUME=Volume 13 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1618070 DOI=10.3389/fpubh.2025.1618070 ISSN=2296-2565 ABSTRACT=Chemsex refers to the intentional use of psychoactive substances to enhance, explore, or alter sexual experiences. The use of geolocation apps, and its link with physical, psychological, and social harms for the individual as well as society has been described ‘Polydrug use’—combining multiple substances to amplify or diversify effects—is frequently reported across these groups. This article provides a comprehensive overview of the sexual effects of substances commonly used in chemsex contexts. We introduce the Pharmacosex Wheel, a visual tool that categorizes drugs based on their pharmacological properties and their specific effects on sexual experience. Substances are grouped into seven classes: stimulants, empathogens, psychedelics, dissociatives, depressants, opioids, and cannabinoids. Each class is discussed in relation to its typical impact on sexual behavior, desire, sensation, and connection. To further illuminate the dynamics of polydrug use, we present a layered model that maps core and intersecting effects of combined substances. Core effects include stimulation (e.g., from stimulants), disinhibition (e.g., from depressants and dissociatives), and altered sensory perception (e.g., from empathogens, cannabinoids, and psychedelics). When substances with different core effects are combined, intersecting effects emerge—such as euphoria, empathy, or chill—which often result in rich and multifaceted sexual experiences. This model also incorporates user motivations, acknowledging that the choice of substances often aligns with specific desires or anticipated outcomes. Finally, we position the most commonly used substances within this framework, grouping them according to their chemical structure, pharmacological action, and the experiential reports of users. By approaching chemsex from a drug-positive perspective, without neglecting potential negative impacts, this article aims to foster a nuanced understanding of substance use in sexual contexts. Our goal is to support more informed research, destigmatize user experiences, and contribute to the development of tailored care within drug and sexual health services.