ChemSex and Sexualized Substance Use

"The term 'chemsex', coming from the contraction of 'chemical sex' was coined to indicate the voluntary intake of certain psychoactive and non psychoactive drugs in the context of sex parties and sexual intercourses with the intention of facilitating and/or enhancing the sexual encounter mostly among men who have sex with other men (MSM) [1].

"According to different studies, mainly homosexual and bisexual male partygoers use one or more drugs in combination to facilitate prolonged sexual sessions possibly with multiple sexual partners [2], although MSM are more prone to use sex enhancer drugs in comparison to non-MSM. A serious harmful behaviour related to this latter evidence is that those MSM, who are aware of being HIV positive and take anti HIV medication (e.g. Highly Active Anti-Retroviral Therapy, HAART) more commonly use 'chemsex' drugs than the ones who are HIV negative or with an unknown status [3-5]. This is mainly done to potentiate physical performance impaired by the disease and to counteract the effects of consequent pharmacological treatment [6].

"Whereas in the nineties of the last century the most common abused drugs in the 'party and sex' contest were: cannabis, ecstasy, amphetamine and cocaine, more recently 'chemsex' has been associated to new psychoactive drugs and sex enhancers such as, γ-hydroxybutyric acid (GHB) and congeners, mephedrone, methamphetamine (commonly called crystal methamphetamine or chrystal [sic] meth), erectile dysfunction agents and alkyl nitrites (or poppers) [5, 6]."

"'Chemsex' has been defined as a voluntary intake of certain psychoactive and non-psychoactive drugs in the context of sex parties and sexual intercourse with the intention of enhancing, prolonging, and sustaining sexual experiences, hence facilitating the sexual encounter [1]. These sessions are mostly among men who have sex with men [2,3,4,5,6,7,8,9,10,11,12,13,14]. Conversely, one could argue that the use of drugs whilst being involved in intimate, sexual behavior may relate to a vast range of populations. From this point of view, similar concepts have been proposed, including perisexual drug use [15], sexualized drug behavior [16], 'Sex on Chems' (Wilson and Williamson, 2024) [17], 'Party-n-Play' [18], wired sex [19], and 'Pampalibog' (in the Filipino language; [20]). Chemsex practices are becoming increasingly popular. Data from 55, 446 MSM subjects living in 44 urban centers were made available by Schmidt et al. [21]. In the European region, the past 4 weeks’ chemsex involvement was highest in Brighton (16.3%), Manchester (15.5%), London (13.2%), Amsterdam (11.2%), and Barcelona (7.9%). In 2018, 785 MSM were recruited at nine Dutch clinics, and 511 (65%) completed the online questionnaire. Chemsex, which was defined as using cocaine, crystal meth, designer drugs, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, 'speed' and/or 3,4-methylenedioxymethamphetamine (XTC; MDMA), was reported by 41% of interviewees during the previous 6 months [22].

"At times, to enhance libido, potency, and sexual pleasure, a range of aphrodisiacs, which are often naturally occurring and traditionally used, are self-administered [23]; moreover, aphrodisiacs’ intake is frequently rooted in cultural beliefs and superstitions. The U.S. Food and Drug Administration (FDA) defines an aphrodisiac drug product as 'any product that bears labeling claims that it will arouse or increase sexual desire, or that it will improve sexual performance'. Conversely, the European Medicines Agency (EMA) does not have specific definitions for aphrodisiac products but regulates drugs for sexual dysfunction [24]. As a result, a range of over-the-counter (OTC) herbal products and approved prescription drugs (for example, for erectile dysfunction) are legally available. From an anthropological perspective, chemsex cultures are multifaceted and shaped by a wide range of social and psychological factors [25], for example, geographical location, the use of apps and online platforms, and the availability of specific substances. Indeed, there is a lack of research as well on how sexual experience affects drug reward in animals [26]. Mating is clearly regarded as a basic reward activity. In fact, conventional reinforcers (e.g., food, sex) stimulate dopamine (DA) transmission in the nucleus accumbens shell [27]. Addictive drugs share with conventional reinforcers the property of stimulating DA transmission in the nucleus accumbens shell. This response, however, undergoes one-trial habituation in the case of conventional reinforcers. Resistance to habituation allows drugs to repetitively activate DA transmission in the shell upon repeated self-administration [27]. In sober sex, a clear post-ejaculation refractory time (PERT), e.g., the period after a single ejaculation when further erections and ejaculations are inhibited, has been documented [28]. Conversely, Schreck et al. [29] documented a 40-hour-long chemsex session. Further, a recent UK-based, mixed methods study surveyed some 123 subjects; 86% of respondents engaged in riskier sex during sessions and 35% no longer enjoyed sober sex [17]. Hence, one could argue that chemsex may respond to the perceived need to use a range of drugs to overcome resistance to habituation, synergistically increase sex-derived physiological pleasure, and facilitate voluntary self-exposure to idiosyncratic practices. To experience a more intense rush and longer sex, some drugs are being injected so that much higher bioavailability levels are being attained [30,31]."

"The most commonly reported desired effects of sex under the influence of drugs include enhanced emotional connection, intense bodily sensations, disinhibition, and increased lust (1). The most studied form of sexualized drug use is chemsex, a term specifically describing the intentional use of particular drugs to intensify sexual experiences, primarily among gay, bisexual, and other men who have sex with men (gbMSM). Additional characteristics of chemsex include the use of geolocation apps, and its link with a range of physical, psychological, and social harms from both individual and societal perspectives (2). Chemsex has become a significant public health issue that warrants attention (3). Initially, the term chemsex was defined by the use of mephedrone (4-MMC), methamphetamine (crystal meth), γ-hydroxybutyrate (GHB), and γ-butyrolactone (GBL) (4). However, more recent studies have suggested a broader understanding of chemsex, with modified definitions and revised categorizations of substances (2, 5) based on regional differences (6, 7) and variations in user populations (8). To capture this variation, the term ‘pharmacosex’ was coined as a way to describe how wider populations experiment with a range of illicit substances that modify and enhance their sex lives (1).

"As prevalence of chemsex differs depending on the used definition, it is hard to assess a reliable prevalence. Data from the EMIS-study in 2017 revealed lifetime prevalence of 15, and 10% in the past 12 months (9). A recent meta-analysis and review article estimates the prevalence of chemsex among gbMSM in Europe at 16% (95% CI: 11–21%) (5). However, higher prevalence rates have been observed in specific subpopulations. For example, 39.8 and 63% of gbMSM using pre-exposure prophylaxis (PrEP) for HIV prevention in France (10) and Spain (11) respectively reported engaging in chemsex. Additionally, 30.6% of users of gay dating platforms (12), 41% of men who have sex with men (MSM) attending sexually transmitted infection (STI) clinics (13), 36.1% of HIV-negative MSM (14), and 48.5% of gbMSM living with HIV (15) reported similar behaviors.

"The most recent Drug Report by the European Monitoring Center for Drugs and Drug Addiction highlights an increase in polydrug use (16). Polydrug use refers to the simultaneous or sequential use of two or more psychoactive substances, either by deliberately combining different drugs or by using substances that contain multiple active ingredients (16). A specific increase in polydrug use for sexual purposes has been observed among gbMSM engaging in chemsex (17–20). Individuals often combine various substances either to mitigate negative side effects or to enhance their sexual experience through synergistic effects. Therefore, polydrug use in a sexual context is conceptually part of chemsex."

"In recent years, the development of new substances, collectively referred to as New Psychoactive Substances (NPS), has surged (28). This term encompasses a broad range of synthetic and plant-derived psychoactive substances that have gained prominence since 2008 (27). NPS include newly designed synthetic drugs, plant-based compounds or their extracts, previously existing substances that have recently entered the market, and certain pharmaceuticals or medications. The number of identified NPS has risen dramatically, growing from 236 in 2012 (29) to 930 in 2023 (30). A specific category of NPS, known as cathinones (e.g., mephedrone (4-MMC), metaphedrone (3-MMC), and others), is commonly used in sexual contexts (2).

"To capture the diverse effects of newly developed substances, a new categorization was deemed necessary. Building on the work of Leonard (31), Adley and colleagues (27) developed the Drugs Wheel, a taxonomy that includes both established drugs and NPS. The primary goal of the Drugs Wheel is to offer a comprehensive framework, integrating information on the effects of individual drugs, their actions on receptor pathways, and harm reduction strategies for each of its seven categories (27).

"This Drugs Wheel, created in collaboration with stakeholders and end-users (27), organizes substances into seven categories: stimulants, empathogens, psychedelics, dissociatives, depressants, opioids, and cannabinoids. With the approval of the original developers, Schrooten and colleagues adapted this taxonomy into the Pharmacosex Wheel, published in Dutch (32). Figure 1 below presents a translation of this Pharmacosex Wheel (32) and provides an overview of the sexual effects of individual drugs, including their impact on sexual desire, arousal, and orgasm, within each of the seven categories outlined in the Drugs Wheel (27)."

"Amphetamine-type substances include oral ('meth'), smokable ('crystal meth') and injectable/rectally administered methamphetamine, together with a vast range of other substances, including PMA (4-methoxyamphetamine, 'Dr. Death'), PMMA (4-methoxymethamphetamine), 4-MTA (4-methylthioamphetamine, 'flatliners'), DMA (2,5-dimethoxyamphetamine), MPA (methiopropamine), etc. [32]. Meth is the default substance associated with chemsex among MSM subjects in Asia, followed by GHB/GBL and ketamine [33]. Furthermore, Schecke et al. [34] carried out an online survey with some 1050 German-speaking participants who provided information on substance use. They found that 27% used crystal meth in the last 12 months. Some 89% of those subjects used methamphetamine in a sexual setting, and 50% reported injecting this molecule.

"Meth acts on DA neuron terminals projecting from the ventral tegmental area to the nucleus accumbens, representing the reward system in the brain [35]. Indeed, there are differences in bioavailability levels between the different methamphetamine formulations; when injecting the molecule, the bioavailability (BA) levels will equal to 100%; with the smokable formulation, the BA levels exceed 90%, and with the oral meth-related BA levels may be of around 60% [36]."

"MDMA (3,4-methylenedioxymethamphetamine; ‘ecstasy’; 'Molly', etc.) use is not uncommon in sexualized drug use [41,42].

"MDMA is not the only psychedelic phenethylamine (PIAs) molecule; others include products such as the 'fly' drugs, the toxic N-methoxybenzyl (NBOMe) compounds, indanes, and benzofurans. Recent and popular appearances in the drug scenario include several 2C-molecules, such as 2,5-dimethoxy-4-bromophenethylamine (2-CB, 'Nexus'), 2,5-dimethoxy-4-iodophenethylamine (2C-I), and 2,5-dimethoxy-4-ethylphenethylamine (2C-E). Overall, the range of MDMA-like compounds, including the NBOMes, may be purposefully or unintentionally ingested as MDMA substitutes. Most MDMA-like molecules show agonism at 5-HT2A receptors, whilst some of them also inhibit the dopamine/noradrenaline/serotonin reuptake (for an overview, see [43])."

"Alkyl nitrites are a chemical class of substances colloquially known as 'poppers' (Rush, Bolt, Locker Room, Bullet, Aroma of Men, Dr. Bananas, Cum, Heart-On), whose basic pharmacological action of the nitrites is relaxation of vascular smooth muscles [39]. The route of administration is inhalation of the vapour of the volatilized organic liquid. Indeed, for their rapid onset, short-acting potent vasodilators, disinhibiting effect, poppers have been consumed in recreational and sexual settings since the 1970s [40].

"In the 1990s the popularity of alkyl nitrites significantly increased for both heterosexual and homosexual sexual intercourses. Interestingly, among the 'chemsex' drugs, these ones are frequently used by youngsters too, for the misperception of the products harmlessness. Nitrites have been reported by many women to be useful for abandonment to a full sexual experience. Furthermore, anal penetration becomes easier, probably from a combination of nitrites actions on the anal sphincter and decreased pain perception [40]. These two actions plus mild hallucinatory sensations (e.g. 'visions of bright colours, often containing symbolic representations of the sexual moment') made the products highly popular in gay discos to enjoy at most music, lights, other drugs and social-sexual excitement [40].

"Among poppers, the most common sold are: amyl nitrite (isoamyl nitrite, isopentyl nitrite), but also cyclohexyl nitrite, isobutyl nitrite (2-methylpropyl nitrite), isopropyl nitrite (2-propyl nitrite), and less frequently butyl nitrite.

"Pharmacologically, alkyl nitrites act inducing relaxation of vascular smooth muscles, with an indirect effect on heart, by systemic arterioles relaxation resulting in a decrease of blood pressure, reflex tachycardia and a drop in the activity of the left ventricle. The peak action in blood pressure occurs in 30 seconds, with an average increase of 30 mm of systolic pressure, returning to normal within two minutes. When using these substances individuals feel different sensations like warmth, dizziness and an altered heartbeat and facial blush. This response can range from high pleasure to moderate nausea and headaches according to the scenario and the expectations [40]."

"The most used PS are synthetic cathinones, the leader of which being mephedrone or 4 MMC (4-methylmetcathinone). Their development was inspired by the Khat plant (Catha edulis) that is considered as a natural amphetamine and is used in certain countries of East Africa and the Arabian Peninsula (Kalix, 1990). These new designer substances are sold as bath salts 'not for human consumption' to circumvent the legislation (Coppola and Mondola, 2012). They belong to the phenylethylamine family (Petit et al., 2013) and are psychostimulants with an amphetamine- or cocaine-like effect. They generate agitation, euphoria, and empathy in users and increase libido and sexual performance.

"These PS have a strong addictogenic effect with dependence levels of 30% according to DSM-IV criteria (Dargan et al., 2011; Winstock et al., 2011). The main acute complications are cardiac, psychiatric, and neurological, and they can be fatal (Busardo et al., 2015; Ezaki et al., 2016; Sande, 2016; Kronstrand et al., 2018; Riley et al., 2019; Table 3).

"Blood levels in case of lethal intoxication are higher than in cases of non-lethal poisoning, and lethal situations arise from the combining of several drugs (Papaseit et al., 2017). These substances have been classified as narcotics in Europe since 2010 (Forsyth, 2012) and it is currently illegal to purchase or possess them, but they are usually obtained on the Internet or directly during party and play. Cathinones take the form of a white powder or small crystals. They are taken orally, by snorting, intrarectally (booty bump), or by injection (slamming).

"In the study of Spiller et al. (2011) the main clinical effects (>10%) related to cathinones consumption were agitation (82%), combative violent behavior (57%), tachycardia (56%), hallucinations (40%), paranoia (36%), confusion (34%), myoclonus (19%), hypertension (17%), chest pain (17%), and mydriasis (13%).

"In another serie, main complications of cathinones related to chemsex were psychotic symptoms, agitation, anxiety, suicidal ideation, or suicide attempt (Batisse et al., 2014). More recently, severe psychiatric symptoms have been observed with ephylone, a recent available synthetic cathinones, in a context of chemsex (Serre et al., 2019)."