1. IntroductionChemsex, defined at the European Chemsex Forum in Paris 2019 [1] as “the use of specific drugs in sexual contexts by gay men, bisexuals, men who have sex with men (MSM) and trans* people”, is a major international public health challenge [2]. Although there are reports of chemsex use in groups such as trans people, the profile of chemsex users tends to be that of a single gay man, aged 25–45, highly educated, and employed [3].Mephedrone, γ-hydroxybutyric acid/γ-butyrolactone (GHB/GBL) and methamphetamine are very characteristic drugs in chemsex sessions [3]. However, polydrug use is common [4]. The key element of these sessions is their duration, which can last for days, and in which it is common to have sex with multiple partners and to engage in risky behavior such as intravenous drug use (known as slamsex) [5].The growth of this phenomenon has been closely linked to the proliferation of geosocial networking dating apps, which facilitate both contact with potential sexual partners and the acquisition of substances [6,7]. Following Stuart (2019), engagement in chemsex is not necessarily problematic nor addictive, being important in promoting a person’s agency and autonomy to make choices based on their own assessment of the consequences [8]. Chemsex can enhance men’s capability to have the sex they want by increasing libido, sexual arousal and performance, pleasure, facilitation of sexual relations, euphoria, empathy, socialization, self-esteem, confidence, and disinhibition [4,9].However, the practice of chemsex has been associated with legal problems; family, social, and emotional deterioration; medical risks such as overdose, interactions with other treatments and non-adherence; as well as increased incidence of infections such as HCV, HIV, syphilis, and gonorrhea, among other complications [10]. A progressive increase in the number of psychiatric consultations and admissions related to chemsex practice has also been described, with substance abuse disorders, depression, and anxiety as the most prevalent diagnoses [11].Several risk factors associated in the scientific literature with the development of psychotic disorders are found in the practice of chemsex: drug use [4], sexually transmitted infections [12,13], stressful events and circumstances [14,15], experiences of trauma and post-traumatic stress [16,17,18,19], and loneliness [20], among others. Nevertheless, the relationship between psychosis and chemsex has been poorly investigated. To the best of our knowledge, no systematic review on the matter has been carried out to date. Aims

The present research aims to analyze the relationship between the practice of chemsex and the development of psychotic symptoms and disorders. The secondary objectives are to study the incidence of psychotic symptoms and disorders in people who practice chemsex and the risk factors associated with their development.

4. Discussion

The purpose of this review was to investigate the association between chemsex and psychotic symptomatology/disorders. Beyond confirming a relationship between the two, the results of the present review also allow us to describe, following a biopsychosocial perspective, a series of risk factors for psychosis associated with the chemsex phenomenon.

In our review, we found percentages of psychotic phenomenology related to chemsex ranging from 6.7% to 37.2% (Table 4), which are higher than the 5% usually observed in the general adult population [39]. We also observed that psychotic disorders were the most frequent diagnoses together with substance use disorders, depressive disorders, and anxiety disorders. Symptomatology described included delusions of paranoid [29,30,36,38], reference, and prejudice [31] types, as well as hallucinations [35] of visual [30,31,37], auditory [31,36], tactile [31], and kinesthetic [30] types. Discontinuation of consumption and the use of antipsychotics and other adjuvant drugs were effective, requiring hospital admission in 37.5% of cases [31].A variety of drugs were used in the studies (Table 2). There are several hypotheses about the pathophysiological mechanisms by which the use of these drugs could generate psychotic symptomatology. Some hypotheses are imbalance in dopamine levels in the prefrontal cortex with cannabis, genetic variants in the dopamine transporter and in catechol-O-methyltransferase for cocaine, dysregulation in glutamate transmission pathways through the thalamocortical system with methamphetamine, action on 5-HT2A receptors with LSD, long-term neurotoxicity with MDMA, and D2 receptor affinity and inhibition of GABAergic activity in the prefrontal cortex with ketamine [40]. Among the studies providing data on the possible drug associated with the psychotic episode, we find methamphetamine [37] and mephedrone in slamsex [30]. On the other hand, the study by Dolengevich et al. (2019) [38] found a significant relationship between the use of smoked methamphetamine and the presence of psychosis (OR = 3.15, p = 0.007). Polydrug use (45.4–100%) and slamsex (15.7–50.8%) showed high frequency data in our review, which found a relationship between slamsex (OR = 3.37, p = 0.006) and polydrug use (OR = 2.64, p = 0.031) with the presence of psychotic symptoms [38]. In addition, polydrug use was more frequent among those who practiced slamsex [35,38], as well as booty bumping, which could have kinetics similar to those of slamming [34]. The temporal and contextual circumstances in which the psychotic symptomatology occurred, during the sessions or in the days following them, is evidence of the close relationship between drug taking and the presentation of psychotic phenomenology. The evolution was variable; 66% had a duration of less than one month, although 20% of those affected had a duration of psychotic symptomatology of more than six months, usually due to persistent drug use [31]. A frequent history of substance abuse prior to chemsex has also been observed, with figures ranging from 27–69% in our review [31,34,35].Age is a risk factor for psychosis, with higher rates of psychotic disorders observed among young males, which is consistent with much of the population described in this review, even though the mean age in our review (36–40.2 years) (Table 2) is slightly higher than the commonly observed higher incidence for psychosis, which is around 18–24 years [41]. Another factor that has been related to the occurrence of psychotic disorders is foreign/ethnic minority status, which generates a greater number of adverse circumstances and stressors that increase the risk of psychosis [42]. In our review we observed that 17.6–69.8% of the samples (Table 3) belonged to a minority population group or were foreigners, remarkable figures to take into consideration. In relation to the results of work activity, academic studies, and economic level, these factors do not seem to be relevant in the psychosis–chemsex interaction, since most of the samples were under employment, had salaries >1000 euros per month, and had higher education (Table 3). On the other hand, the relationship between urbanicity and psychosis [43] does seem to play a relevant role in the chemsex phenomenon; most of the studies reflected in this review focused on large cities, where the chemsex phenomenon has developed the most [44].It is difficult to differentiate the relationship between chemsex and psychosis and the well-known association between non-sexualized drug use and psychosis. Previous research has shown that men engaged in chemsex might have suffered early adverse events and might have an avoidant–insecure attachment style [45], having had previous low sexual wellbeing and mental health. Much research shows that gay and bisexual men face a multitude of distal and proximal stressors (violence, discrimination, expectations of rejection, internalized homophobia, concealment of their sexuality) across the life course, which can heighten the risk of mental health problems. This is known as the minority stress theory [46,47,48]. Moreover, it has been scientifically reported that the homosexual population is up to two times more likely to suffer from psychotic symptoms than the heterosexual population [49]. The use of chemsex has been reported as a coping mechanism for the stressors that MSM experience on a daily basis [14]. In our review we have found escape and disinhibition as reasons to practice chemsex, as well as to increase self-esteem and self-confidence [34,35,37]. However, the practice of chemsex can lead to highly stressful circumstances such as work, social, and emotional problems: -Bohn et al. (2020) [36] identified that 33.6% of those who used chemsex had missed work or had worked while still under the influence of drugs.-Schreck et al. (2020) [35] described that 55% of men had social problems, with 44% experiencing separation and 24% missing work.-In the study by Dolengevich et al. (2019) [38], up to 31.5% of men reported interference with work, social, or family life, with a greater impact on the slamsex group (64.7%) compared to the chemsex group without slamsex (25.3%).The prevalence of anxiety disorders found among the samples was 3.5–26.9% (Table 4) while that found in the general male population does not reach 3% [50]. In the study by Dolengevich et al. (2019) [38], anxiety was shown to be a predictor of the association between psychosis and chemsex (OR = 2.70, p = 0.042); however, the study by Bohn et al. (2020) [36] found no significant differences in anxiety, although it did show that chemsex users had higher scores on the GAD-7 scale than non-chemsex users.Another line of research in psychosis is linked to trauma (16). In the study by Bohn et al. (2020) [36], up to 76.8% of the sample reported a traumatic history, with a mean number of traumatic events experienced per person of 2:1 between chemsex and non-chemsex users. However, no significant predictive association was found between post-traumatic stress and psychotic symptoms in the chemsex group. These findings could be related to the mediating role of chemsex in coping with trauma [17]. On the other hand, this review also reflects the situations of sexual abuse that can occur in chemsex sessions, especially in situations of overdose, a factor that has been related to the development of psychosis through the trauma generated [19].Recently, a polygenic association between isolation and subjective loneliness and psychosis has been demonstrated [51]. Along these lines, the results found in the present review show a high percentage of men who lived alone (53.33%) [33], and loneliness and the search for socialization as reasons for attending chemsex sessions [37]; these factors could play a role in the development of psychotic phenomenology.In relation to STIs and infections due to intravenous drug use, we found high figures in our review, especially for HIV. The risk behaviors associated with chemsex and reflected in our review, such as having multiple sexual partners, sex without condoms, fisting, and sharing injecting equipment, among others, justify the infection figures. In the study by Hibbert et al. (2021) [37], patients reported adequate adherence to PrEP, although this measure only reduces the risk of HIV infection and not against other STIs. It is also noted that slamsex practice conferred a higher risk of infections than those who practiced chemsex without slamsex [38]. At the neuropsychiatric level, some of these infections are associated with the development of psychosis; for example, opportunistic infections of the central nervous system, brain lymphomas, and encephalitis can occur in HIV and lead to secondary psychosis [52]. However, the studies in our review reported high adherence to antiretroviral therapy and undetectable viral load, although these results were lower among those who practiced slamsex [38]. Psychotic symptoms can also be found as a manifestation of neurosyphilis [8] or as a consequence of hepatitis treatment [53].Taking all of the above into consideration, Figure 2 provides a diagram showing the factors that could favor the development of psychosis associated with the practice of chemsex.

Figure 2. Diagram of the relationship between chemsex and psychosis.

Figure 2. Diagram of the relationship between chemsex and psychosis.

Some of these risk factors have a cultural and social basis, which opens the door to social changes with a potential preventive effect. For example, belonging to an ethnic minority seems to be an individual risk factor for chemsex and psychosis, but the combined effect of homonegativity and racism can critically contribute to this relation; therefore, societal and psychotherapeutic interventions for enhancing psychological well-being among gay and bisexual men should focus on building feelings of identity resilience [46]. Potential preventive interventions include a person-centered therapeutic approach that can enable the individual to focus on positive aspects of their lives that generate feelings of self-esteem, self-efficacy, continuity, and positive distinctiveness. Prevention and awareness should be promoted without leading to greater stigma. At a clinical level, it also seems important to address abstinence among those who present a related psychotic episode, given the high rate of continued use. Chemsex is a modifiable risk factor for psychosis (and many other mental and physical pathologies) and we must understand the motivations and set of psychosocial circumstances that lead our patients to practice it, approaching via active listening and looking for a reduction and alternative projection of internal discomfort. 4.1. Limitations and StrengthsThe number of studies that analyzed psychotic symptoms and disorders related to chemsex use was small. Of the included studies, six collected psychotic symptomatology in the form of self-reports [29,36,37,38] so biases such as recall and the non-medical judgement of participants may have interfered. Moreover, in four of the studies, the samples were ≤30 subjects (Table 2), including one case report, which limits the generalizability of the results. An added limitation was the heterogeneity in collecting and reflecting the findings in the studies, as well as the presence of four articles that sampled more specific subpopulations than the one in this review, which made it difficult to unify and synthesize the information. As previously mentioned, only one study included a trans population [36]; furthermore, the fact that it did so by self-identification with male sex left out trans women, a part of the group in which a large amount of sexualized drug use is being found [54]. However, as we explained, the role of this minority group has yet to be studied, with MSM being the clear demographic that defines chemsex. Moreover, only one study included a comparative non-chemsex group [36], and another established comparative slamsex and non-slamsex chemsex groups [38], leading to less specificity in our research. Finally, the use of a mixed form of systematic review allowed us to combine quantitative and qualitative contributions, which added to the integration of biological, psychological, and social perspectives carried out in this work and allows for a more complete approach to the phenomenon. 4.2. Future Lines of Research

Future lines of research should better define the role of the different risk factors for psychosis within chemsex in order to understand how, beyond the action of drugs, the phenomenon with all its integrated aspects would place chemsex as a risk factor for the development of psychotic symptoms and disorders. Future research should also investigate in greater depth what motivations these subjects have for engaging in chemsex despite knowing physical and psychological consequences, as well as what preventive interventions could be effective in this field.