Search Results (68)

Background: Polysubstance use, particularly the combination of opioids and stimulants, represents a growing public health concern due to its high risk of severe multisystem complications and mortality. Here, we present a case illustrating the lethal synergy of opioid–stimulant co-use. Methods: A 37-year-old male with chronic Hepatitis C and documented polysubstance use reported recent use of fentanyl, cocaine, methamphetamine, and cannabis. He presented with generalized weakness, left lower limb pain, tense edema, and anuria. Clinical assessment included monitoring of vital signs, physical examination, capillary blood gas analysis, extended laboratory panels (muscle and cardiac enzymes, electrolytes, and coagulation parameters), urinalysis, and Doppler imaging. Management over five days included intravenous hydration, diuretics, urinary alkalinization, electrolyte correction, anticoagulation, metabolic and vitamin therapy, hemodialysis, and comprehensive supportive care. Results: Laboratory evaluation revealed massive rhabdomyolysis (peak CK 161,050 U/L), severe hyperkalemia (K⁺ 8.4 mmol/L), metabolic acidosis, acute kidney injury with oligoanuria, and left-sided deep vein thrombosis. Despite intensive multidisciplinary interventions, the patient’s repeated refusal of ongoing treatment critically contributed to a fatal outcome. Conclusions: This case underscores the high mortality risk associated with opioid–stimulant co-use and the crucial impact of treatment refusal. Clinicians and public health stakeholders should recognize the rapid progression of multisystem dysfunction in polysubstance users and prioritize early, aggressive interventions combined with patient engagement strategies to mitigate fatal outcomes. Full article

Background: Mitragynine pseudoindoxyl (MP) is a semi-synthetic kratom metabolite increasingly sold online and over-the-counter, marketed misleadingly as “kratom” or “7-OH,” despite lacking FDA approval and safety data in humans. Methods: This case report describes a 44-year-old male with polysubstance use history who developed opioid withdrawal symptoms after regular MP use (400 mg daily for pain management following neck injury). Vital signs, alcohol and opioid withdrawal scores and clinical outcomes were recorded. Results: The patient presented exhibiting symptoms of moderate opioid withdrawal in the absence of other opioid use. A buprenorphine macro-induction protocol was initiated. Following pre-treatment using chlorpromazine as an anti-emetic and diazepam to treat concomitant alcohol withdrawal, 32 mg buprenorphine were provided (16 mg × 2) on day one, with subsequent maintenance dosing and adjunctive medications. The patient demonstrated significant symptomatic improvement with decreased COWS scores and expressed interest in long-acting injectable buprenorphine maintenance therapy. Discussion: This represents the first documented case of suspected MP withdrawal successfully managed with buprenorphine macro-induction, demonstrating the potential efficacy of this approach for novel semi-synthetic kratom metabolites when standard withdrawal management protocols are insufficient. Further studies should evaluate long term outcomes and validate findings. Full article

Background: Chronic cocaine exposure is increasingly associated with persistent brain alterations, yet it remains unclear whether these changes reflect reversible neuroadaptation, accelerated brain ageing, or a degeneration-like trajectory in a vulnerable subgroup. This Perspective proposes a neuroprogressive vulnerability framework—referred to as cocaine-specific encephalopathy/cerebropathy only in a heuristic sense—to organise heterogeneous evidence without implying a distinct neurodegenerative disease entity. Methods: We conducted a structured, critical synthesis of peer-reviewed human and preclinical literature (PubMed, Scopus, Web of Science; inception to December 2025), integrating neuroimaging (MRI/DTI/fMRI/PET/SPECT), neuropathology/post-mortem findings, neurochemical and molecular mechanisms, and neuropsychological outcomes, with explicit attention to confounders (polysubstance use, psychiatric and medical comorbidity, HIV, vascular risk, abstinence duration). Results: Convergent evidence supports a multi-hit vulnerability model in which chronic stimulant exposure may weaken neural resilience through dopaminergic dysregulation, oxidative stress, mitochondrial dysfunction, neuroinflammatory signalling, and putative α-synuclein–related mechanisms. Human imaging studies consistently implicate fronto–striato–limbic circuits and suggest possible cerebellar involvement, but findings are heterogeneous and often cross-sectional; direct evidence of progressive neuronal loss or disease-defining proteinopathies attributable to cocaine remains limited. Conclusions: Rather than asserting cocaine-induced classic neurodegeneration, we outline an exploratory framework in which chronic cocaine exposure may increase susceptibility to neuroprogressive impairment in a subset of biologically vulnerable individuals. Longitudinal multimodal studies combining advanced imaging, biomarkers, and phenotypic stratification are needed to clarify causality, temporal progression, and reversibility with sustained abstinence. Full article

Background: Medical students often face substantial psychological stress, which can increase the risk of substance use, professional detriment, and insufficient patient care. However, substance use in medical students remains understudied in Iraq. This study highlights the prevalence, patterns, risk factors, and negative effects of substance use among medical students at the University of Baghdad. A cross-sectional study involving 414 medical students at the University of Baghdad was conducted. The questionnaire included sociodemographic variables and the Alcohol, Smoking, and Substance Involvement Screening Test to screen for psychoactive substance use. The lifetime prevalence of substance use was 38.9%. Among substance users, 42.8% used nicotine, 22.3% used sedatives, 4.3% used inhalants, and 3.1% used amphetamines, with only 27.3% reporting polysubstance use. Through multivariate logistic regression, it was identified that males are approximately 2.8 times more likely to use substances compared to females (OR: 2.8, 95% CI: 2.1–5.2, p-value < 0.001), and students with a positive family history of substance use are approximately 3.1 times more likely to use substances compared to those without (OR: 3.1, 95% CI: 2.8–7.5, p-value < 0.001). These findings underscore the importance of implementing early preventive strategies, targeted mental health interventions, and substance use awareness programs within Iraqi medical institutions. Full article

Background: Methamphetamine (MA) use in people living with HIV (PLWH) has been linked to neurocognitive and behavioral dysregulation. We hypothesized that PLWH with active MA use (MAHIV) would show poorer cognitive performance, greater emotional and sleep burden, higher behavioral risk, and alterations in circulating biomarkers of immune activation and neuronal injury, relative to PLWH without MA use and HIV-negative Controls. Methods: Cross-sectional analytic study of 121 adults: PLWH with MA use (MAHIV, n = 40), PLWH without use (n = 42), and HIV-negative Controls (n = 39). Outcomes were ART discontinuation, physical activity, neurocognition (MoCA), depression (BDI), anxiety (GAD-7), sleep (PSQI), and substance use (ASSIST). Circulating biomarkers measured by ELISA: sCD14, neuron-specific enolase (NSE), S100B, and neurofilament light chain (NfL). Results: MAHIV participants had more frequent ART discontinuation than PLWH and the lowest physical activity. Chemsex with polysubstance use, condomless sex, and multiple partners were most prevalent in MAHIV. This group showed the highest anxiety and depressive burdens, and the greatest sleep disturbances. Global cognition (MoCA) was lowest in MAHIV, with significant deficits in executive function, memory, attention, and language; 82.5% had at least mild cognitive impairment. sCD14 was significantly higher in MAHIV than in PLWH and Controls, and NSE was elevated in both MAHIV and PLWH versus Controls. sCD14 correlated inversely with MoCA and positively with GAD-7 and BDI-II. Conclusions: Among PLWH, MA use is associated with greater ART nonadherence, syndemic mental-health and sleep disturbances, broader neurocognitive deficits, and elevations in circulating sCD14 and NSE. The sCD14–cognition and sCD14–mood relationships highlight chronic immune activation as a candidate pathway for neurocognitive and affective impairment and support sCD14 and NSE as potential stratification and monitoring biomarkers in MA-using PLWH. Full article

In recent years, xylazine has emerged as a cutting agent combined with illicit drugs to extend their effects. The present study aimed to discover drug use patterns associated with xylazine-positive and -negative urine toxicology drug screens and to assess whether xylazine can be used as a marker for exposure to designer drugs/new psychoactive substances in our study population. This is a retrospective analysis of urine toxicology results from two different analytical platforms: a targeted, structurally confirmatory, high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay that quantifies 136 drugs and metabolites including xylazine; and a non-targeted ThermoFisher Orbitrap Tribrid mass spectrometry system (Thermo Scientific^TM, Bremen, Germany) in combination with database searches for the identification of drugs not captured by the targeted assay. All participants were patients receiving care through the Addiction Research and Treatment Services (ARTS), with documented substance misuse, undergoing routine urine drug toxicology testing at the iC42 Clinical Toxicology. Data analysis was performed using Sciex OS version 2.2.0.5738 after extraction using the targeted, structurally confirmatory and quantitative LC-MS/MS platform (SCIEX, Framingham, MA, USA). The drug patterns found in xylazine-positive and -negative urine samples were statistically significantly different (p < 0.001), indicating different consumption patterns associated with xylazine. Moreover, the overall concentrations of drugs (normalized to creatinine) were also statistically significantly different with higher concentrations in the urine samples that tested negative for xylazine. In contrast, samples that were positive for xylazine contained significantly higher concentrations of various designer drugs/new psychoactive substances as detected by the untargeted platform (p < 0.0001). The results indicated that xylazine has become increasingly common in Denver’s drug circulation and that xylazine may be used as a marker to prompt reflex testing with non-targeted high-resolution mass spectrometry assays in combination with database searches to test for the exposure to designer drugs/new psychoactive substances in our patient population. Full article

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: This study aimed to compare clinical and psychosocial characteristics of substance-using adolescents in Türkiye with and without a history of suicide attempts to identify distinguishing risk factors. Methods: A retrospective analysis was conducted using medical records from 140 adolescents (aged 13–18) treated at a specialized Child and Adolescent Substance Use Center in Türkiye between March 2023 and February 2025. Sociodemographic, clinical, and substance use data were collected. Group comparisons were performed using chi-square and t-tests. Logistic regression was used to identify predictors of suicide attempt history. Results: Among the sample, 52 adolescents (37.1%) had a history of suicide attempts. Compared to their counterparts, the substance-using adolescents were more likely to be female (73.1%) and have histories of psychiatric hospitalization, institutional care, criminal behavior, and polysubstance use (p < 0.05). High-frequency use (≥3 days/week) of methamphetamine, stimulants, cannabinoids, and alcohol was significantly more common in this group (all p < 0.01). The Addiction Profile Index–Adolescent form (API-A) scores indicated more severe addiction profiles. Using cross-validated LASSO and confirmatory logistic regression, female gender emerged as the only robust independent predictor of suicide attempt history (OR = 6.84). Conclusions: Adolescents with a history of suicide attempts exhibit more severe substance use, particularly involving cannabinoids, and greater psychosocial adversity. This distinct risk profile underscores the need for early, gender-sensitive, and multidimensional interventions. Full article

Background: This review examines the prevalence of substance abuse and related disorders in South Pacific nations. Methods: The review focused on data included in reports published since 2000 from countries like Samoa, Papua New Guinea, Fiji, and French Polynesia, excluding Hawaii, New Zealand, Australia, and American Samoa. Prevalence studies indexed in Medline, CINAHL, PsycInfo, Embase, and Cochrane were screened and retrieved. Joanna Briggs Institute critical appraisal tools were used to assess included studies. Results: Ten studies with diverse methods, such as national surveys, were analysed. Results show high variability in prevalence across countries, sexes, and ethnicities. Notably, tobacco and betel nut use are prevalent. Indigenous populations and men face higher SUD burdens. Discussion: inconsistencies in study methods and reliance on self-reporting limit direct comparison. Data on co-occurring disorders and polysubstance use are limited, highlighting research gaps. The review emphasises the need for culturally sensitive, standardised research to monitor emerging trends like synthetic drug use. Policy suggestions call for targeted interventions and improved surveillance to reduce disparities and support vulnerable populations in Pacific Island communities. Full article

Background/Objectives: Nitrous oxide (N₂O), commonly known as laughing gas, is increasingly being used recreationally. While neurological risks are recognized, psychiatric effects remain underexplored. This study investigates neuropsychiatric presentations among patients referred to the Emergency Mental Health (EMH) team at Sunshine Hospital, Melbourne, Australia, associated with recreational N₂O use. Methods: We conducted a retrospective observational review of EMH referrals between August 2020 and July 2024. Inclusion criteria were patients with documented recreational N₂O use within the preceding 12 months. Cases were operationally defined as presenting with either predominantly psychiatric features (psychosis or suicidal ideation/self-harm documented by clinician) or predominantly neurological features (ataxia, paresthesia, pyramidal signs, or other focal deficits). Primary outcomes included type and severity of neuropsychiatric presentation, concurrent substance use, and disposition from the Emergency Department. Results: Of 25 identified patients, 23 met inclusion criteria (12 males, 11 females; mean age 29.3 ± 8.3 years). Psychotic symptoms were reported in 11/23 (47.8%, 95% CI 27.3–69.0) and suicidal ideation or self-harm in 8/23 (34.8%, 95% CI 17.2–55.7). Neurological symptoms, including paraesthesia and ataxia, occurred in 5/23 (21.7%, 95% CI 7.5–43.7). Concurrent substance use was documented in 19/23 (82.6%, 95% CI 61.2–95.0), most frequently cannabis, alcohol, and tobacco. Over half of patients (12/23; 52.2%, 95% CI 30.6–73.2) identified as culturally and linguistically diverse (CALD). Conclusions: Among EMH-referred ED patients, recreational N₂O use is associated with a spectrum of neuropsychiatric presentations, including psychosis, suicidality, and neurological symptoms. These findings reflect clinical associations rather than causal relationships and highlight the need for early recognition, targeted assessment, and appropriate follow-up in high-risk patients. Full article

Stigmatized views of emotionality form within familial, cultural, and societal contexts and serve as a mechanism impacting youth mental health and substance misuse with notable ties to health equity. Yet critical questions remain regarding the impact of racial identity on emotionality stigma in urban groups and the moderating relationship between race and emotionality stigma on youth mental health and substance misuse. The current study aimed to investigate emotionality stigma as a mechanism of health inequity by exploring the relationships between racial identity, emotionality stigma, and adolescent mental health and substance misuse. Urban adolescents (n = 85) recruited from a combined mental health and substance use treatment program reported on their stigmatized views of emotionality, mental health, and substance use. Participants primarily identified as multicultural (60.3%) and socioeconomically disadvantaged, with 55.2% requiring transportation assistance and 63.8% being either insured through Medicaid or uninsured. Findings suggest a link between racial identity and emotionality stigma that was associated with attachment (β = −3.43, p < 0.001) as well as substance misuse type (β = 5.36, p < 0.001) and polysubstance use (β = −6.53, p < 0.001) for urban adolescents in combined treatment. This study is the first to provide empirical support for the interconnected role of sociocultural factors and emotionality stigma and calls for systems-level change to address emotionality stigma individually, communally, and socially. Full article

Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, methamphetamines, and other synthetic drugs. All major psychoactive substances readily cross the placenta and can remain detectable in breast milk, leading to a shared cascade of obstetric complications (hypertensive disorders, placental abruption, pre-term labor), fetal consequences (growth restriction, structural malformations), and neonatal morbidities such as neonatal abstinence syndrome and sudden infant death. Mechanistically, trans-placental diffusion, oxidative stress, inflammatory signaling, and placental vascular dysfunction converge to disrupt critical neuro- and cardiovascular developmental windows. Early identification hinges on the combined use of validated screening questionnaires (4 P’s Plus, CRAFFT, T-ACE, AUDIT-C, TWEAK) and matrix-specific biomarkers (PEth, EtG, FAEE, CDT), while effective treatment requires integrated obstetric, addiction, and mental health services. Medication for opioid use disorders, particularly buprenorphine, alone or with naloxone, confers superior neonatal outcomes compared to methadone and underscores the value of harm-reducing non-punitive care models. Public-health strategies, such as Mexico’s “first 1 000 days” framework, wrap-around clinics, and home-visiting programs, demonstrate the potential of multisectoral interventions, but are hampered by structural inequities and punitive legislation that deter care-seeking. Research gaps persist in polysubstance exposure, culturally tailored therapies, and long-term neurodevelopmental trajectories. Multigenerational, omics-enabled cohorts, and digital longitudinal-care platforms represent promising avenues for closing these gaps and informing truly preventive perinatal health policies. Full article

Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions are limited. We examined potentially interacting associations of lifetime methamphetamine use disorder (MUD), recent cannabis use, and HIV with four plasma markers of immune and inflammatory functions. Method: Participants with HIV (PWH, n = 86) and without HIV (PWoH, n = 148) provided urine and blood samples and completed neuromedical, psychiatric, and substance use assessments. Generalized linear models examined main and conditional associations of lifetime MUD, past-month cannabis use, and HIV with plasma concentrations of CXCL10/IP-10, CCL2/MCP-1, ICAM-1, and VCAM-1. Results: PWH displayed higher CXCL10/IP-10 than PWoH. Past-month cannabis use was independently associated with lower CXCL10/IP-10 levels and conditionally lower CCL2/MCP-1, ICAM-1, and VCAM-1 levels among people with lifetime MUD, but only PWoH displayed cannabis-associated lower VCAM-1 levels. Conclusions: Human plasma sample evidence suggests that cannabis use is associated with lower levels of immune and inflammatory molecules in the context of MUD or HIV. Cannabinoid pathways may be worthwhile clinical targets for treating sequelae of chronic inflammatory conditions. Full article

Substance-induced psychosis is a recognized clinical entity, commonly linked to cannabinoids, stimulants, hallucinogens, alcohol, and polysubstance use. These agents may provoke transient or persistent psychotic symptoms during intoxication or withdrawal. Opioids, however, constitute a noteworthy exception: psychosis is rarely observed during opioid intoxication, and emerging data suggest that opioid agonists might even exert antipsychotic-like effects. This article examines the paradoxical interaction between opioids and psychosis, with attention to clinical reports of psychotic symptoms arising following abrupt discontinuation of methadone or buprenorphine. In numerous cases, symptoms resolved swiftly after reintroduction of the opioid agonist, implying a neuromodulatory role. Opioids, unlike other substances of abuse, seem to lack intrinsic psychotogenic effects and may influence dopaminergic activity via kappa-opioid receptor antagonism and endorphinergic mechanisms. This challenges standard models of substance-induced psychosis and calls for a refined understanding of opioid pharmacodynamics in psychiatric contexts. In psychotic presentations among polysubstance users who also use opioids, restoring opioid agonist therapy should be prioritized, with antipsychotics reserved as second-line options—preferably agents with favorable receptor profiles. Where opioids are not involved, antipsychotics remain first-line, but should be applied judiciously, with efforts to taper when clinically appropriate. Full article

Background: Polysubstance use, particularly combining opioids with stimulants such as cocaine, is rising among individuals with substance use disorders. This practice aims to balance cocaine’s stimulant effects with opioids’ sedative effect, potentially decreasing adverse outcomes. We hypothesized that concurrent exposure to cocaine and opioids would reduce the risk of neonatal opioid withdrawal syndrome (NOWS) compared to opioid use alone. Methods: This analysis draws from an ongoing prospective study of maternal substance use (SUD) at Regional One Health’s perinatal center in Memphis, TN, and included mothers and their infants born between 2018 and 2022. Maternal SUD was identified via screening questionnaires, urine toxicology, or umbilical cord tissue analysis. Participants were grouped into using (a) opioids with cocaine (OwC) and (b) opioids without cocaine (OwoC). Univariate and regression analyses were conducted to assess the risk of NOWS. Results: A total of 353 infants were born to 342 mothers, with 31% (110/353) of the infants born to women who used cocaine along with opioids. While maternal demographics were similar, the OwC group had significantly lower rates of prenatal care, chronic pain history, and MOUD enrollment (p = 0.03). Infants in the OwC group had significantly higher rates of NOWS (p < 0.01), longer hospital stays (p < 0.01), and 6.5 times greater odds of developing NOWS (p < 0.001). NOWS was associated with an average 15-day increase in the length of stay for term infants (95% CI: 11.2, 18.8; p < 0.001). Conclusions: Contrary to our hypothesis, our study highlights the significant impact of maternal cocaine use on the increased likelihood of NOWS and extended hospital stays for affected infants. Full article