Lethal lust: suicidal behavior and chemsex — a narrative review of the literature

Chemsex is described as the use of certain drugs—commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone—before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical harm, such as sexually transmittable infections (STIs), and are more likely to experience mental health symptoms. To further assess this, we reviewed the recent literature to evaluate whether the psychological impact of chemsex behavior includes suicidal ideation and suicidal attempts. Pubmed/MEDLINE was searched for articles reporting suicidal ideation and behavior among chemsex users with the terms “chemsex”, “sexualized drug use”, “suicide”, and “mental health”. Twelve articles (three case reports and nine cross-sectional studies) were included in the final narrative review. Overall, we retrieved mixed results regarding the relationship between chemsex practice and suicidality outcomes. Considering the inhomogeneous nature of the studies, the findings indicate that suicidality could be an issue of concern among MSM in general but among chemsex users in particular. Possible risk factors for suicidality among chemsex participants may include adversities experienced due to one’s sexual orientation and an increased risk for HIV and other STI infections and the resulting negative impact on mental well-being. These aspects warrant further investigations

Glutaryl-CoA dehydrogenase misfolding in glutaric acidemia type 1

Glutaric acidemia type 1 (GA1) is a neurotoxic metabolic disorder due to glutaryl-CoA dehydrogenase (GCDH) deficiency. The high number of missense variants associated with the disease and their impact on GCDH activity suggest that disturbed protein conformation can affect the biochemical phenotype. We aimed to elucidate the molecular basis of protein loss of function in GA1 by performing a parallel analysis in a large panel of GCDH missense variants using different biochemical and biophysical methodologies. Thirteen GCDH variants were investigated in regard to protein stability, hydrophobicity, oligomerization, aggregation, and activity. An altered oligomerization, loss of protein stability and solubility, as well as an augmented susceptibility to aggregation were observed. GA1 variants led to a loss of enzymatic activity, particularly when present at the N-terminal domain. The reduced cellular activity was associated with loss of tetramerization. Our results also suggest a correlation between variant sequence location and cellular protein stability (p < 0.05), with a more pronounced loss of protein observed with variant proximity to the N-terminus. The broad panel of variant-mediated conformational changes of the GCDH protein supports the classification of GA1 as a protein-misfolding disorder. This work supports research toward new therapeutic strategies that target this molecular disease phenotype

We have a lot to do: lack of sexual protection and information - results of the German-language online survey “let's talk about chemsex”

Background: The prevalence of chemsex and sexualized substance use is increasing in several European countries, particularly among men who have sex with men. In this subgroup, illegal substance use is associated with increased sexual risk behavior, which can result in severe physical and psychological impairments. The present study examined the incidence and prevalence of chemsex in German-speaking countries. Methods: To further describe the high-risk group of Chemsex users, participants (N = 429) were asked about their psychotropic substance use, sexual and health-related behavior, health status, and socio-demographic information by using an online questionnaire. Whether Chemsex has negative effects on well-being was measured with the WHO well-being index. Of additional interest was how informed Chemsex users are about the topic and what needs are placed on the practitioners. The online questionnaire consisted of 105 items, and data was collected from March to May 2019. Thousand forty seven datasets were saved with a dropout rate of 59%, 123 completed questionnaires fulfilled the criteria for chemsex users (n =123). Results: There were no significant differences in well-being between chemsex users and non-users. All participants protected themselves against sexually transmitted diseases irregularly or not at all. The majority of chemsex users reported intermittently using illegal substances (ketamine, methamphetamine, mephedrone, γ-butyrolactone/γ-hydroxy butyric acid). They viewed their sexual and substance use behavior as problematic, but few showed motivation for behavior change. Chemsex users clearly expressed a need for more information and advice centers. Conclusion: The results provide information on chemsex users that can be used for the future development of a therapy manual and thus contribute to improving health care for this group. The prevalence of chemsex is increasing and urgently needs more research to protect clients from health impairments and stigmatization