Search Results (108)

Background/Objectives: Chemsex is defined as the intentional use of psychoactive substances to enhance or prolong sexual activity, predominantly observed among men who have sex with men. It has emerged as a notable behavioral and public health concern due to its association with high-risk sexual practices, psychiatric morbidity, and somatic complications. Despite increasing recognition, global prevalence estimates vary widely (3–52.5%) due to differences in study populations and methodology. Commonly used substances include synthetic cathinones, amphetamines/methamphetamines, MDMA, GHB/GBL, ketamine, alkyl nitrites, and PDE-5 inhibitors. Methods: A narrative review was conducted using PubMed through 11 December 2025. Search terms combined chemsex-related terminology, substance names, and health outcomes. Recent English-language publications (2020–2025) were prioritized. Evidence was synthesized thematically across epidemiology, health complications, motivations, and interventions. Results: Chemsex is strongly associated with unprotected sex, multipartner encounters, and prolonged intercourse, leading to significantly increased rates of HIV, syphilis, gonorrhoea, and chlamydia. Psychiatric complications include depression, anxiety, compulsive sexual behavior, and psychosis, with higher risks in individuals engaging in slamming or polysubstance use. Somatic complications vary by substance and include cardiovascular disease, hyponatremia, rhabdomyolysis, ulcerative cystitis, methemoglobinemia, and overdose. Motivational factors extend beyond sexual enhancement and include minority stress, internalized and externalized stigma, and maladaptive coping mechanisms. Integrated interventions combining harm reduction, cognitive–behavioral therapy, peer-led services, and pharmacotherapy, alongside digital health tools to support PrEP adherence and risk reduction, show promise in mitigating these harms. Conclusions: Chemsex represents a complex interplay of biological, psychological, and sociocultural factors that contribute to elevated STI risk and psychiatric and somatic morbidity. Addressing chemsex requires destigmatized, multidisciplinary approaches that integrate behavioral, pharmacological, and community-based interventions. Digital health innovations can further enhance engagement, risk reduction, and access to timely care. Full article

Background/Objectives: MDMA and MDA are among the stimulant drugs most frequently encountered in forensic casework, and oral fluid represents a practical biological matrix for their detection. However, liquid oral fluid requires refrigeration, is susceptible to degradation, and can be logistically demanding for routine laboratories. Dried Oral Fluid Spots (DOFS) offer a low-cost and stable alternative. This study aimed to develop and validate a DOFS-based analytical workflow for quantifying MDMA and MDA using liquid chromatography and a diode-array detector. Methods: Watercolor paper was selected as the substrate and pretreated with diluted nitric acid to improve analyte desorption. DOFS were prepared using 150 µL of pooled oral fluid, dried for 4 h, and extracted with methanol. Chromatographic separation was performed on a phenyl column using aqueous TFA and acetonitrile mobile phase. Method validation followed the ICH M10 criteria. Results: The method showed linear responses between 12.5 and 5000 ng mL⁻¹, with LOD and LLOQ of 6 and 12 ng mL⁻¹ for both analytes, respectively. Precision and accuracy met acceptance criteria across all QC levels. Recoveries ranged from 84% to98%. DOFS samples demonstrated adequate stability under multiple storage and handling conditions. Conclusions: The optimized DOFS–LC–DAD workflow offers a robust, low-cost, and flexible approach for the analysis of MDMA and MDA in oral fluid for laboratory-based or semi-controlled collection environments. Its compatibility with both LC- and GC-based detectors enhances applicability in diverse forensic laboratory settings. Full article

Aim: There is an urgent need for systematic and well-designed studies to clarify the role of systemic inflammatory parameters, especially the neutrophil–lymphocyte-ratio (NLR), in the pathophysiology and clinical management of unregulated substance addiction. This review aims to synthesize current evidence on the relationship between unregulated substance addiction and systemic inflammatory parameters, focusing specifically on the NLR as a potential biomarker. Methods: To ensure a transparent approach in the collection of evidence, this review was carried out following the recommendations of the PRISMA 2020 guidelines and registered in PROSPERO (CRD420251151136). We searched the PubMed and Scopus databases in July2025 using combinations of MeSH terms and keywords related to unregulated substance use and inflammatory biomarkers. The strategy included terms such as “cocaine,” “cannabis,” “opioids,” “heroin,” “fentanyl,” “methadone,” “buprenorphine” “nitazene”, “MDMA”, and “methamphetamine,” combined with “neutrophil-to-lymphocyte ratio.” Filters were applied to limit results to human studies published between 2015 and 2025 in English. The methodological quality of the studies included was assessed using the STROBE 22-item checklist. Results: Fifteen studies were included in this review. Methamphetamine and opioid users showed higher NLR and MLR values. For cocaine abuse, although the evidence is limited to a single population-based study, a significant increase in NLR was reported. Controversial results were observed for cannabis use. Conclusions: Systemic inflammation markers are related to unregulated substance abuse disorders; however, the sparse available evidence encourages the need for well-designed large, prospective clinical trials. Full article

Synthetic cathinones are cathinone analogues that humans have artificially created. The first compounds appeared on the European market in 2005. They belong to a class of drugs called stimulants, classified as new psychoactive substances. Synthetic cathinones are very popular; people use these drugs because they are cheaper “substitutes” for other stimulants. They produce psychostimulant and hallucinogenic effects similar to cocaine, amphetamine, and MDMA, among others. Despite their presence on the market for several years, the precise toxicological impacts of these compounds on the human body remain unknown. Studies were conducted on the effects of selected cathinones (mephedrone, clephedrone) on blood cells: erythrocytes and platelets. The effect of cathinones was determined by measuring the surface density of biological membranes using microelectrophoresis. The continued popularity of these compounds, coupled with limited knowledge of their precise effects on the human body, makes the problem significant and requires ongoing research. Based on the results obtained for mephedrone and clephedrone, it can be concluded that at the tested concentrations (170 ng/mL and 2700 ng/mL), they alter the surface charge density of the biological membranes of red blood cells and platelets. Full article

Background: Psychedelic-assisted therapy is gaining renewed attention as a potential treatment for various mental disorders. Despite increasing numbers of randomized controlled trials (RCTs) and meta-analyses, a comprehensive synthesis of the evidence across different substances and indications is lacking. This umbrella review aims to evaluate the effectiveness and safety of psychedelic-assisted therapy—primarily psilocybin, MDMA, and LSD—across major psychiatric disorders, including depression, post-traumatic stress disorder (PTSD), and substance use disorders. Methods: We systematically identified and synthesized data from 23 meta-analyses encompassing over 100 primary studies. Outcomes were standardized and re-expressed as Hedges’ g to enable cross-study comparisons. Study quality was assessed using AMSTAR2, and certainty of evidence was evaluated via the GRADE framework. Results: The number of identified meta-analyses differed markedly depending on the substance and clinical indication: psilocybin for depression (n = 9) and MDMA for PTSD (n = 10) had the strongest evidence base, while fewer meta-analyses were available for LSD in alcohol use disorder (n = 2) and depression (n = 2), ayahuasca in depression (n = 2), and MDMA in autism spectrum disorder (n = 2). Psilocybin demonstrated large effect sizes in major depression (Hedges’ g ≈ 1.05), with some evidence of sustained benefits up to six months. MDMA showed very large effects in reducing PTSD symptoms (Hedges’ g ≈ 1.24), often after 2–3 sessions. LSD yielded short-term benefits for alcohol use disorder (OR ≈ 2.0), though effects declined over time. Across studies, adverse events were generally mild and transient, with no consistent signal for serious harm. Considerable methodological variability was observed, including small and sometimes overlapping samples, heterogeneity, risk of bias, and limited long-term data. These constraints should be taken into account when interpreting the overall findings. Conclusions: Current evidence supports the short-term efficacy and safety of psychedelic-assisted therapy for selected psychiatric disorders, particularly depression and PTSD. However, the low methodological quality of studies and most meta-analyses, as well gaps in long-term safety data highlight the need for high-quality studies. Full article

Music festivals have emerged as venues for the consumption of recreational drugs and novel psychoactive substances. This systematic review provides the first critical evaluation and synthesis of published wastewater analyses for detecting recreational drug use at music festivals worldwide. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we systematically searched PubMed, Embase, MEDLINE, and SCOPUS databases using terms combining music festivals, drugs, and wastewater analysis. Twenty-three studies were included, spanning festivals with 6200 to 600,000 attendees. Two primary sampling approaches emerged: wastewater sampling (16 studies) and pooled urine sampling (7 studies), using Liquid Chromatography–Tandem Mass Spectrometry or Liquid Chromatography–High-Resolution Mass Spectrometry for chemical analysis. 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) emerged as the most consistently detected substance. Regional variations included a dominance of methamphetamine in Eastern Europe, MDMA use in Western Europe, and a high prevalence of cocaine use in South America. Regarding the music genre, electronic dance music events showed markedly higher MDMA rates. Limitations include geographic underrepresentation of African and Asian countries and a gender bias in pooled urine sampling. Future research should work on enhancing sampling infrastructure, analytical capabilities, public health surveillance, and harm reduction strategies. Full article

In recent years, the issue of drivers under the influence of medications and psychoactive substances as a cause of road accidents has gained increasing importance. This study aimed to assess the prevalence and blood concentration ranges of alcohol and psychoactive substances among drivers in northeastern Poland between 2013 and 2024. To determine the prevalence of medications and psychoactive substances in drivers’ blood, data were collected from 266 blood samples obtained from drivers (251 men and 15 women). Among these, 79 drivers died immediately, 61 drivers survived the accident, and 126 drivers were stopped for roadside checks. The presence of the studied substances was confirmed using gas chromatography combined with mass spectrometry detection (GC-MS) and liquid chromatography combined with mass spectrometry detection (LC-MS). Blood alcohol content was measured using headspace gas chromatography with a flame ionisation detector (HS-GC-FID). Psychoactive substances were detected in 152 of the 266 samples. Drivers testing positive for medications and psychoactive substances were most frequently stopped during roadside controls—67.46%. Among the total positive cases, psychoactive substances used alone or in combination included THC—46.3% (range 0.2–20 ng/mL), alcohol—26.8% (range 0.1–4.1‰), amphetamines—20.7% (range 15–2997 ng/mL), opiates—4.3% (morphine 66.0 ng/mL; methadone 174.0 ng/mL; ranges: tramadol 15.0–600.0 ng/mL; fentanyl 45.0–100.0 ng/mL), benzodiazepines—9.8% (ranges: diazepam 55.0–480.0 ng/mL; midazolam 17.0–1200.0 ng/mL; clonazepam 21.0–36.0 ng/mL), stimulants—6.10% (ranges: amphetamine 15.0–2997.0 ng/mL; cocaine 4.0–30.0 ng/mL; benzoylecgonine 38.0–602.0 ng/mL; PMMA 45.0–360.0 ng/mL; MDMA 20.0–75.0 ng/mL; mephedrone 37.5 ng/mL; alfa-PVP 120 ng/mL), psychotropic drugs—3.1% (carbamazepine 8.0–2100.0 ng/mL; zolpidem 233.0 ng/mL; citalopram 320.0 ng/mL; opipramol 220 ng/mL). The most commonly used substance among car and motorcycle drivers was THC (37.7% of car drivers and 60% of motorcyclists). Among operators of other types of vehicles, alcohol was the most frequently detected substance, present in 35% of cases. The majority of drivers (81.1%) were under the influence of a single substance. Among the drivers, 7.3% consumed alcohol in combination with at least one other substance, and 11.6% used two or more substances excluding alcohol. Among the psychoactive substances most frequently used alone or in combination with others, THC was predominant. Roadside testing, based on effects similar to alcohol intoxication, was mainly conducted on male drivers. Full article

Background: Youth and young adults with early psychosis frequently use cannabis, yet the reliability of self-reported use is uncertain in clinical practice. We examined the concordance between self-reported cannabis use and urine toxicology among patients enrolled in an Early Psychosis Intervention (EPI) program in Southeast Ontario, Canada. Methods: We conducted a cross-sectional chart review of 116 EPI patients (2016–2019). Demographics, self-reported cannabis use (yes/no), concurrent substance use, and urine toxicology results from the initial clinical assessment were extracted. Diagnostic indices (sensitivity, specificity, positive/negative predictive values, and accuracy) were calculated using urine toxicology as the reference. The clinical panel used a 50 ng/mL threshold for THC-COOH; the specific assay platform (immunoassay vs. confirmatory GC-/LC-MS) was not specified in records and is noted as a limitation. Results: Overall, 82.8% (96/116) self-reported cannabis use. Self-report showed high sensitivity (88.4%) but very low specificity (20.3%), with PPV 39.2%, NPV 75.0%, and accuracy 45.30%, indicating limited concordance with urine toxicology. Self-reported cannabis use was significantly associated with self-reported cocaine and MDMA use, while associations with methamphetamine, opioids, and benzodiazepines were not significant. Conclusions: In this EPI cohort, self-reports overestimated cannabis use relative to urine toxicology (high sensitivity, low specificity, and accuracy <50%). These findings support cautious clinical interpretation of self-report and the complementary value of biological verification, especially when use is infrequent or the testing window/threshold may miss exposure. Future work should incorporate use frequency, potency, and timing relative to testing, and clearly specify toxicology assay methods. Full article

Background: Driving is a coordinated psychomotor activity that involves reaction time, attention, and decision-making. Psychoactive substances such as 2-phenylethylamine (PEA) derivatives and opioids may affect these functions and contribute to traffic safety. This systematic review revealed the effects of the selected PEA derivatives and opioids on psychomotor performance among drivers and potential road safety outcomes. Methods: The review followed PRISMA 2020 standards. Using the PICO method, we conducted a systematic search in Embase, PubMed, and Web of Science (2000–2025). Included studies involved adult participants and quantified the effect of PEA derivatives or opioids on driving-related psychomotor function. Thirty-one articles, such as randomized controlled trials, crossover studies, observational studies, and simulator-based studies, were examined. Risk of bias was evaluated using the RoB2 tool. Results: Evidence indicates therapeutic amphetamine and methylphenidate doses can enhance psychomotor function and safety in patients with ADHD. Recreational or high-dose use of methamphetamine and MDMA is associated with impaired coordination, variable speed, and increased impulsivity. Opioid effects are tolerance- and dose-dependent. Small therapeutic doses of fentanyl in chronically treated patients do not notably impair driving. On the other hand, methadone and tramadol commonly cause somnolence, retardation of reaction, and increased accident risk. Conclusions: The impact of opioids and PEA derivatives on psychomotor function is multifactorial, depending on dose, time, route of administration, and patient status. These substances can either improve or impair driving safety. The findings confirm the need for individual-specific pharmacotherapy treatment. They also highlight the importance of further studies to formulate evidence-based clinical and legislative guidelines. Full article

States like Hawai‘i are decriminalizing psychedelics based on emerging evidence linking their use to improved psychological well-being. Yet, in many cultural contexts, stigma surrounding mental illness may lead individuals to pursue non-traditional forms of healing, including psychedelics, in place of formal care. This study examines how psychedelic use relates to mental health treatment-seeking behaviors among Asians and Native Hawaiians and Other Pacific Islanders (NHOPIs). Using the National Survey of Drug Use and Health (NSDUH) data from 2008 to 2019 (n = 458,372), the analysis compares Non-Hispanic Whites with Asian and NHOPI respondents to assess associations between MDMA and lifetime classic psychedelic use, psychological distress (K6 scale), and formal mental health service utilization. Nested logistic regression models conducted in Stata 18 indicate that psychedelic use among White individuals is associated with a lower likelihood of seeking formal treatment. In contrast, among NHOPI individuals, psychedelic use is associated with increased odds of accessing mental health care. These findings suggest that psychedelic use may serve culturally distinct roles in coping with distress, shaped by structural stigma and the perceived trustworthiness of formal treatment systems. Full article

Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics—particularly 5-HT₂A receptor agonists such as psilocybin—in the treatment of eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). The paper contextualizes these interventions within the broader serotonin hypothesis of EDs, emphasizing serotonergic dysregulation and impaired cognitive flexibility as central features of these conditions. Drawing from animal models, human neuroimaging studies, and emerging clinical trials, the authors outline how psychedelics may promote neuroplasticity and psychological insight through modulation of 5-HT₂A signaling. Preliminary evidence from open-label studies suggests psilocybin may improve ED symptoms and quality of life, though findings are early and methodologically limited. The paper also reviews data on ayahuasca, MDMA, and non-psychedelic serotonergic agents, highlighting both the promise and complexity of psychedelic-assisted therapy in EDs. The authors conclude that while further controlled trials are needed to clarify efficacy, safety, and optimal treatment parameters, psychedelics offer a novel, mechanistically distinct avenue for addressing entrenched ED psychopathology. Full article

New psychoactive substances (NPSs) are emerging narcotics or psychotropics that pose a public health risk. The most commonly reported NPSs are synthetic cannabinoids and synthetic cathinones. Synthetic cannabinoids mimic the effects of Δ9-tetrahydrocannabinol (Δ9-THC), often with greater potency, while synthetic cathinones act as stimulants, frequently serving as cheaper alternatives to amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. While some synthetic cannabinoids exhibit chirality depending on their synthesis precursors, synthetic cathinones are intrinsically chiral. Biotargets can recognize and differentiate between enantiomers, leading to distinct biological responses (enantioselectivity). Understanding these differences is crucial; therefore, the development of enantioresolution methods to assess the biological and toxicological effects of enantiomer is necessary. This work systematically compiles enantioselectivity studies and enantioresolution methods of synthetic cannabinoids and synthetic cathinones, following PRISMA guidelines. The main aim of this review is to explore the impact of chirality on these NPSs, improving our understanding of their toxicological behavior and evaluating advances in analytical techniques for their enantioseparation. Key examples from both groups are presented. This review highlights the importance of continuing research in this field, as demonstrated by the differing properties of synthetic cannabinoid and synthetic cathinone enantiomers, which are closely linked to variations in biological and toxicological outcomes. Full article

This systematic review and meta-analysis evaluates (1) the effectiveness of psychedelic-assisted therapy (PAT) using psilocybin and ketamine for psychosocial symptoms in adults with cancer, (2) contextualizes findings with non-randomized and exploratory studies of other psychedelics, and (3) examines the role of therapeutic frameworks in shaping outcomes. We searched PubMed, Cochrane Library, PsycINFO, and EMBASE (2000–2024) for randomized controlled trials (RCTs) and non-randomized studies investigating psychedelic agents in cancer populations. Meta-analyses pooled RCTs of psilocybin or ketamine using random-effects models. Non-randomized studies were synthesized narratively. Risk of bias and evidence certainty were assessed via Cochrane ROB 2.0, NIH Before–After tool, and GRADE. Eleven placebo-controlled RCTs and four single open-label studies were included. Meta-analysis of four ketamine RCTs (n = 354) showed large, rapid effects on depression/anxiety (Hedges’ g = −1.37, 95% CI: −2.66 to −0.08; I² = 92%). Three psilocybin RCTs (n = 101) showed a large effect of psilocybin on alleviating depression (Hedges’ g = −3.13, 95% CI: −10.04 to 3.77; I² = 95%). MDMA and LSD trials suggested promise but lacked rigor. PAT may offer meaningful relief for cancer-related distress, though effects vary by therapeutic model and context. Oncology-specific trials are needed to standardize and scale for implementation. Full article

With rapid societal changes and increasing stress levels, the abuse of psychoactive substances has emerged as a global health crisis. Studies indicate that the mitochondrial calcium uniporter (MCU) plays a pivotal role in neurotoxic damage induced by psychoactive substances. As the primary channel for mitochondrial Ca²⁺ uptake, MCU dysfunction can lead to Ca²⁺ overload, oxidative stress, and apoptosis, representing a crucial mechanism underlying neurotoxic damage. Psychoactive substances such as 3,4-Methylenedioxymethamphetamine (MDMA), cocaine, and morphine influence MCU function through multiple pathways, resulting in excessive Ca²⁺ accumulation and mitochondrial dysfunction, ultimately leading to neuronal injury. Although MCU inhibitors have demonstrated potential in alleviating Ca²⁺ overload and improving neural function in preliminary studies, their selectivity and long-term safety require further evaluation. Future research should explore the precise regulatory mechanisms of MCU in neurotoxic damage induced by psychoactive substances and develop more effective targeted therapeutic strategies. Full article

Psychedelic substances have recently emerged as a promising method for treating mental health conditions, despite a history of stigmatization and restriction in use. The present review synthesizes existing literature on the therapeutic potential of psychedelics such as LSD, psilocybin, and MDMA in addressing specific mental health conditions like depression, anxiety, and addiction. On reviewing the existing literature, it became apparent that when administered in controlled settings with psychological support, psychedelics can induce profound psychological insights, leading to long-lasting and positive changes in mood, cognition, and behaviour. This review discusses the ethical, social, and regulatory challenges linked to using psychedelics within the mental health sector across different countries, and how these might influence societal beliefs towards their efficacy and use. Further research would be beneficial for eliciting a deeper understanding of the use of psychedelics in the field of mental health, leading to the development of standardized administration protocols and a thorough appreciation of societal implications and long-term outcomes. This review discusses the potential for psychedelics to revolutionize mental health treatment while underlining the urgent need for rigorous scientific inquiry on this topic and the ethical considerations surrounding the use of psychedelics for therapeutic purposes. Full article