(107) Chemsex: The Neuropharmacology of Pleasure and Risk

Chemsex—the intentional use of psychoactive drugs to enhance or prolong sex—has grown from a niche practice in late-1990s club scenes into a global public health concern, especially among men who have sex with men (MSM). Common substances include methamphetamine, mephedrone, synthetic cathinones, GHB/GBL, MDMA, and sildenafil, often used in polydrug patterns. These drugs act on dopamine, serotonin, and GABA systems to boost arousal, endurance, and emotional connection, but also raise risks of infectious disease, cardiovascular strain, psychiatric problems, and dependence. Among MSM in Western Europe, chemsex prevalence ranges from 5–15%, with emerging reports in heterosexual and digital networks. The review calls for integrated harm-reduction, digital outreach, and culturally competent care.

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Abstract

Abstract Introduction Emerging in the late 1990s within sexualized contexts, chemsex-the intentional use of psychoactive substances to enhance or prolong sexual activity-has evolved from a niche practice to a globally recognized public health concern, particularly among LGBTQ populations and men who have sex with men (MSM). Early accounts involved 3,4-methylenedioxymethamphetamine (MDMA) and gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL) in club and party settings. Over time, methamphetamine, mephedrone, and other synthetic cathinones-particularly pyrovalerone derivatives-became dominant, especially across Europe, Australia, and North America. Beyond its sociocultural origins, chemsex now represents a complex intersection of neuropharmacology, sexual behavior, and cardiovascular and infectious disease epidemiology. Understanding its historical trajectory, neurochemical mechanisms, and the consequences of polydrug use is crucial to designing effective harm-reduction and clinical interventions. Objective To provide a comprehensive narrative review of the evolution of chemsex practices, focusing on the main psychoactive agents, their neurobiological mechanisms and clinical effects, and current epidemiological patterns and health outcomes. Methods A narrative review was conducted through PubMed, Scopus, and Web of Science (2010–2025). Eligible studies described pharmacodynamics, patterns of use, and clinical outcomes. Grey literature and public health reports were included to contextualize the historical development of chemsex practices. Results Chemsex commonly involves methamphetamine, mephedrone, synthetic cathinones (especially pyrovalerone derivatives), GHB/GBL, MDMA, and phosphodiesterase type 5 inhibitors (e.g., sildenafil), frequently combined in dynamic patterns of polydrug use. Among MSM, chemsex prevalence ranges from 5–15% in Western Europe, with emerging reports in heterosexual and digitally mediated sexual networks. Polydrug use-particularly when involving injection-is associated with elevated risks of infectious disease transmission, cardiovascular strain, psychiatric comorbidities (depression, anxiety, psychosis), and dependence. Methamphetamine and mephedrone stimulate dopaminergic and noradrenergic pathways, enhancing sexual arousal, impulsivity, and endurance. MDMA increases serotonergic and oxytocinergic activity, fostering emotional connection and sensory amplification. GHB, a GABA-B receptor agonist, produces euphoria, relaxation, and muscle disinhibition but can cause profound CNS depression at higher doses. Sildenafil, often used to counteract stimulant-induced erectile dysfunction, further elevates cardiovascular load. Combined use of stimulants, empathogens, and sedatives creates synergistic yet unstable neurochemical effects, heightening risks of arrhythmia, hyperthermia, hyponatremia, dehydration, and serotonin toxicity. Polydrug patterns alter metabolism, prolong exposure, and unpredictably intensify toxicity. Conclusions Once confined to underground sexual subcultures, chemsex has transitioned into a mainstream concern in sexual medicine, demanding multidisciplinary attention. Advances in understanding its neurochemical underpinnings reveal potent reinforcement mechanisms but also highlight the urgent need for integrated responses addressing addiction, mental health, and infectious disease prevention. Future priorities include tailored harm-reduction strategies, digital outreach, and culturally competent clinical care to mitigate the evolving impact of chemsex on global sexual health. Disclosure No