Trace amine associated receptor 1: predicted effects of single nucleotide variants on structure-function in geographically diverse populations.

Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmaceutical target under investigation for the treatment of several neuropsychiatric conditions. TAAR1 single nucleotide variants (SNV) have been found in patients with schizophrenia and metabolic disorders. However, the frequency of variants in geographically diverse populations and the functional effects of such variants are unknown. In this study, we aimed to characterise the distribution of TAAR1 SNVs in five different WHO regions using the Database of Genotypes and Phenotypes (dbGaP) and conducted a critical computational analysis using available TAAR1 structural data to identify SNVs affecting ligand binding and/or functional regions. Our analysis shows 19 orthosteric, 9 signalling and 16 micro-switch SNVs hypothesised to critically influence the agonist induced TAAR1 activation. These SNVs may non-proportionally influence populations from discrete regions and differentially influence the activity of TAAR1-targeting therapeutics in genetically and geographically diverse populations. Notably, our dataset presented with orthosteric SNVs D1033.32N (found only in the South-East Asian Region and Western Pacific Region) and T1945.42A (found only in South-East Asian Region), and 2 signalling SNVs (V1253.54A/T2526.36A, found in African Region and commonly, respectively), all of which have previously demonstrated to influence ligand induced functions of TAAR1. Furthermore, bioinformatics analysis using SIFT4G, MutationTaster 2, PROVEAN and MutationAssessor predicted all 16 micro-switch SNVs are damaging and may further influence the agonist activation of TAAR1, thereby possibly impacting upon clinical outcomes. Understanding the genetic basis of TAAR1 function and the impact of common mutations within clinical populations is important for the safe and effective utilisation of novel and existing pharmacotherapies.

Amphetamines Improve the Motivation to Invest Effort in Attention-Deficit/Hyperactivity Disorder.

Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the willingness to engage in cognitively or physically effortful behavior. However, the degree to which effort sensitivity is impaired in ADHD has rarely been tested, and the efficacy of stimulant medication in ameliorating any such impairments is unclear. Here, we tested 20 individuals with ADHD (11 males, 9 females) who were managed with amphetamine-based medication (dexamfetamine, lisdexamfetamine), and 24 controls (8 males, 16 females). Individuals with ADHD were tested over two counterbalanced sessions, ON and OFF their usual amphetamine-based medication. In each session, participants performed an effort-based decision-making task, in which they were required to choose how much cognitive or physical effort they were willing to engage in return for reward. Our results revealed three main findings. First, individuals with ADHD had lower motivation relative to controls to invest effort in both the cognitive and physical domains. Second, amphetamine increased motivation uniformly across both domains. Finally, the net effect of amphetamine treatment was to mostly restore motivation across both domains of effort relative to healthy controls. These data provide clear evidence for a heightened sensitivity to both cognitive and physical effort in ADHD, and reveal the efficacy of amphetamine-based drugs in restoring effort sensitivity to levels similar to controls. These findings confirm the existence of reduced motivational drive in ADHD, and more broadly provide direct causal evidence for a domain-general role of catecholamines in motivating effortful behavior.SIGNIFICANCE STATEMENT A core feature of attention-deficit/hyperactivity disorder (ADHD) is thought to be a heightened aversion to effort. Surprisingly, however, the degree to which effort sensitivity is impaired in ADHD has rarely been tested. More broadly, the relative efficacy of catecholamines in motivating the investment of cognitive and physical effort is unclear. We tested 20 individuals with ADHD ON and OFF amphetamines, and compared their behavior on an effort-based decision-making task to 24 controls. When tested OFF medication, the ADHD group was less cognitively and physically motivated than controls. However, amphetamines led to a comparable increase in motivation across both domains. This demonstrates the efficacy of catecholamines in facilitating domain-general effort, and highlights the broader potential of such drugs to treat disorders of motivation.

Lisdexamfetamine dimesylate-exposition in male rats during the peripubertal period impairs inflammatory mechanisms, antioxidant activity, and apoptosis process in kidneys of male pubertal rats.

Lisdexamfetamine dimesylate (LDX) is a prodrug of dextroamphetamine, which has been widely recommended for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). There are still no data in the literature relating the possible toxic effects of LDX in the kidney. Therefore, the present study aims to evaluate the effects of LDX exposure on morphological, oxidative stress, cell death and inflammation parameters in the kidneys of male pubertal Wistar rats, since the kidneys are organs related to the excretion of most drugs. For this, twenty male Wistar rats were distributed randomly into two experimental groups: LDX group-received 11,3 mg/kg/day of LDX; and Control group-received tap water. Animals were treated by gavage from postnatal day (PND) 25 to 65. At PND 66, plasma was collected to the biochemical dosage, and the kidneys were collected for determinations of the inflammatory profile, oxidative status, cell death, and for histochemical, and morphometric analyses. Our results show that there was an increase in the number of cells marked for cell death, and a reduction of proximal and distal convoluted tubules mean diameter in the group that received LDX. In addition, our results also showed an increase in MPO and NAG activity, indicating an inflammatory response. The oxidative status showed that the antioxidant system is working undisrupted and avoiding oxidative stress. Therefore, LDX-exposition in male rats during the peripubertal period causes renal changes in pubertal age involving inflammatory mechanisms, antioxidant activity and apoptosis process.

A retrospective review of methylamphetamine detected in child deaths reported to the Victorian Coroner, Australia.

This study investigated methylamphetamine (MA) exposures in the deaths of children (≤ 12 years old) reported to the Coroner in the state of Victoria, Australia, between 2011 and 2020. Demographics, autopsy findings including the cause of death, self-reported prenatal or caregiver drug use, child protection services information, and toxicological findings were summarized by descriptive statistics. Validated methods of liquid chromatography-tandem mass spectrometry were used in the analysis of drugs. There were 50 child deaths with MA detected in blood, urine, and/or hair with 64% (n = 32) identified in 2018-2020. Most children were 1-365 days old (66%, n = 33) and the cause of death was unascertained in 62% (n = 31) of cases. MA was toxicologically confirmed in hair (94%, n = 47) significantly more than blood (18%, n = 9). Prenatal or caregiver drug use was self-reported in 44% (n = 22) and 42% (n = 21) of cases, respectively. Moreover, only 54% (n = 27) of deceased children were a child protection client at their time of death. These findings suggest the number of deceased children exposed to MA has increased over the past 10 years, which is consistent with the greater supply of crystal MA in the Australian community. Hair analysis provided additional means to identify cases that were unknown to child protection services and may have implications for other children in the same drug exposure environment.

Amphetamine use and its associations with antiretroviral adherence and viral load among sexual minority men and transgender women living with HIV.

Substance use has complex associations to HIV disease progression. The current study tested the associations between several substances and HIV viral load while accounting for confounders relevant to HIV disease progression and substance use. Young sexual minority men and transgender women living with HIV (LWH) in Georgia (N = 385) completed measures and biological tests for HIV viral load and substance use. Multivariable regression models tested the role of specific drugs (i.e., alcohol, cannabis/THC, cocaine, and combined amphetamine and methamphetamine) directly on viral load and indirectly through antiretroviral (ART) adherence. ART adherence and HIV care self-efficacy were consistently associated with greater HIV suppression. Alcohol and cocaine were not associated with ART adherence or viral load. Cannabis was negatively associated with ART adherence (B = -.053, p = .037) but not viral load. Amphetamine/methamphetamine demonstrated significant direct effects on higher viral load (B = .708, p = .010) while indirectly influencing viral load through a negative association with ART adherence. Our findings support previous research demonstrating amphetamine/methamphetamine use impacts viral load both directly and indirectly through ART adherence. Interventions addressing amphetamine/methamphetamine use by young sexual minority men and transgender women LWH are urgently needed, and future research should focus on determining the mechanisms by which formulations of amphetamine impact HIV replication.Trial registration: ClinicalTrials.gov identifier: NCT03665532.

Prescription psychostimulants for cocaine use disorder: A review from molecular basis to clinical approach.

Cocaine use is a public health concern in many countries worldwide, particularly in the Americas and Oceania. Overdose deaths involving stimulants, such as cocaine, have been increasing markedly in North America, especially with concurrent opioid involvement. To date, no pharmacological treatment is available to treat stimulant (including cocaine) use disorders. Prescription psychostimulants (PPs) could be useful to treat cocaine use disorder (CUD) as they share the pharmacological effects with cocaine, as evidenced by a recent meta-analysis that assessed 38 randomized clinical trials (RCTs). PPs were found to promote sustained abstinence and reduce drug use in patients with CUD. The aim of this paper is to provide a narrative review of the clinical pharmacology of PPs and comment on the current stage of evidence supporting PPs to treat CUD. We also propose a model of care that integrates PPs with evidence-based psychosocial interventions (such as cognitive-behavioural therapy [CBT] and contingency management [CM]), a harm reduction approach and case management with social support.

Amphetamine-Related Emergency Department Visits in Ontario, Canada, 2003-2020.

OBJECTIVES: Despite unregulated amphetamine use increasing, there are limited data on related emergency department (ED) visits in Canada. Our primary objective was to examine trends in amphetamine-related ED visits over time in Ontario, including by age and sex. Secondary objectives were to examine whether patient characteristics were associated with ED revisit within 6 months. METHODS: Using administrative claims and census data, we calculated annual patient- and encounter-based rates of amphetamine-related ED visits from 2003 to 2020 among individuals 18+ years of age. We also performed a retrospective cohort study of individuals with amphetamine-related ED visits between 2019 and 2020 to determine whether select factors were associated with ED revisit within 6 months. Multivariable logistic regression modelling was used to measure associations. RESULTS: The population-based rate of amphetamine-related ED visits increased nearly 15-fold between 2003 (1.9/100,000 Ontarians) and 2020 (27.9/100,000 Ontarians). Seventy-five percent of individuals returned to the ED for any reason within 6 months. Psychosis and use of other substances were both independently associated with ED revisit for any reason within 6 months (psychosis: AOR = 1.54, 95% CI = 1.30-1.83; other substances: AOR = 1.84, 95% CI = 1.57-2.15), whereas having a primary care physician was negatively associated with ED revisit (AOR = 0.77, 95% CI = 0.60-0.98). CONCLUSIONS: Increasing rates of amphetamine-related ED visits in Ontario are cause for concern. Diagnoses of psychosis and the use of other substances may serve to identify individuals who are most likely to benefit from both primary and substance-specific care.

Understanding the Mechanisms of Action and Effects of Drugs of Abuse.

AIM: Drug abuse and addiction are major public health concerns, with millions of people worldwide affected by the negative consequences of drug use. To better understand this complex issue, a review was conducted to examine the mechanisms of action and effects of drugs of abuse, including their acute and chronic effects, the symptoms of abstinence syndrome, as well as their cardiovascular impacts. METHODS: The analyzed data were obtained after surveying an electronic database, namely PubMed, with no time limit, grey literature sources, and reference lists of relevant articles. RESULTS: The review highlights the different categories of drugs of abuse, such as opioids, stimulants, depressants, hallucinogens, and cannabis, and discusses the specific ways that each drug affects the brain and body. Additionally, the review explores the short-term and long-term effects of drug abuse on the body and mind, including changes in brain structure and function, physical health problems, and mental health issues, such as depression and anxiety. In addition, the review explores the effects of drug abuse on cardiovascular health, focusing on electrocardiogram changes. Moreover, the analysis of relevant literature also highlighted possible genetic susceptibility in various addictions. Furthermore, the review delves into the withdrawal symptoms that occur when someone stops using drugs of abuse after a period of chronic use. CONCLUSION: Overall, this review provides a comprehensive overview of the current state of knowledge on drug abuse and addiction. The findings of this review can inform the development of evidence-based prevention and intervention strategies to address this critical public health issue.

Methylamphetamine toxicity and its involvement in death: A retrospective observational study of deaths reported to the Victorian Coroner, Australia.

A retrospective observational study of Victorian deaths involving MA between 2010 and 2019 was conducted to determine the prevalence and contribution of methylamphetamine (MA) toxicity to death in the absence of other factors. Demographics, autopsy findings, toxicology, and the cause of death were reviewed. Coronial cases were categorized into five groups: deaths due to MA toxicity in the absence of other factors (Group A1); deaths due to MA toxicity in the setting of other potentially contributing factors (Group A2); deaths due to MA toxicity in the setting of significant natural disease (Group B); deaths primarily due to multiple-drug toxicity (Group C); and deaths primarily due to natural causes (Group D). There were 506 deaths involving MA categorized into Group A1 (n = 1, 0.6%), Group A2 (n = 8, 1.6%), Group B (n = 28, 5.5%), Group C (n = 229, 45%), and Group D (n = 240, 47%). Significant natural disease was prevalent among deaths involving MA and mainly concerned forms of cardiovascular disease (n = 277, 55%). The MA concentration in the one death included in Group A1 was 2.1 mg/L. The median MA concentrations of Group A2 (1.6 mg/L) and Group B (0.5 mg/L) were significantly higher than Group C (0.2 mg/L) and Group D (0.2 mg/L). Additionally, many other toxicologically significant drugs were detected and mostly comprised of central nervous system depressants. Deaths due to MA toxicity in the absence of other factors were rare despite the greater availability of crystal MA in the Australian community. The study highlights the interpretative challenges of MA blood concentrations and the continuing harms of this drug in Australia.

Concentrations of psychoactive substances in blood samples from non-fatal and fatal opioid overdoses.

AIM: The primary aim was to compare concentrations of psychoactive substances in blood in non-fatal and fatal opioid overdoses. The secondary aim was to assess the concentration levels of naloxone in blood in non-fatal overdoses and the association between naloxone findings and concomitantly detected drugs. METHOD DESIGN: Case-control study. SETTING: Norway. Fatal overdoses from 2017 and non-fatal overdoses from February 2018 to September 2019. CASES: Thirty-one non-fatal and 160 fatal opioid overdose cases. Data from the non-fatal overdoses were collected from hospital records and blood samples, and data from the fatal overdoses were collected from autopsy reports. Concentrations of psychoactive substances (including ethanol) in blood samples were collected at the time of hospital admission for the non-fatal overdoses and during autopsy for the fatal overdoses. RESULTS: The median number of different substances detected was four for fatal and five for non-fatal overdoses. The fatal overdoses had higher pooled concentrations of opioids (188 vs 57.2 ng/mL, P < .001), benzodiazepines (5467 vs 2051 ng/mL, P = .005) and amphetamines (581 vs 121 ng/mL, P < .001) than the non-fatal overdoses. A linear relationship between naloxone and concomitant pooled opioid concentrations was found (95% confidence interval = 0.002-0.135, P < .05). CONCLUSION: The total load of drug concentrations was associated with the fatal outcome of an overdose, while the number of drugs used, to a lesser extent, differentiated between those who survived and those who died from an overdose. Higher opioid concentrations were associated with treatment with higher naloxone doses.

Key Interpretation Challenges for Wastewater-Based Epidemiology of Illicit Drugs: A Norwegian Three-City Case Study.

INTRODUCTION: Wastewater-based epidemiology (WBE) has emerged as a timely, non-invasive, and cost-effective indicator of illicit drug consumption. It is increasingly used by international organizations as a proxy measure for estimates of drug prevalence and related trends. Nevertheless, the literature exploring the limitations of WBE remains limited. This paper aims to shed further light on important shortcomings of WBE with recommendations on moving forward. METHOD: Utilizing case study and statistical analysis, the paper critically reviews methodological challenges associated with WBE results related to (i) levels, (ii) trends, and (iii) between-city comparisons of drug use. Data from raw influent wastewater samples from wastewater plants in the cities of Oslo, Bergen and Stavanger/Sandnes were analysed for amphetamine, methamphetamine, MDMA, and cocaine (benzoylecgonine) over a 3-year period. Normalized population loads were calculated and variation in daily loads analysed with plots and estimation of means, confidence intervals, and coefficient of variation. Linear regression models examined trends and between-city differences. RESULTS: Plots and statistical analyses revealed extensive variation in daily loads, with min/max values of 6.1/453.9 mg/day per 1,000 inhabitants 15-64 years for amphetamine and correspondingly 9.4/675.9 mg for methamphetamine. Substantial differences in load levels and patterns across time and plants were also observed. A carefully designed sampling procedure and a relatively large number of daily samples are required to obtain estimates of sufficient precision for determining trends in space or time. Cross-referencing with alternative trend variables can improve the interpretation of WBE trend indicators. Finally, when using mean load levels for different wastewater-treatment plants to assess spatial variation in drug use, the representativeness of the catchment area should be evaluated before interpreting observed changes as city differences. CONCLUSION: Although WBE is a useful supplementary indicator of illicit drug consumption, important methodological issues and potential shortcomings should be taken into account when designing sampling procedures and interpreting the analytical results.

Amphetamine-Type Stimulant Dependence and Association with Concurrent Use of Cocaine, Alcohol, and Cannabis: A Cross-Sectional Study.

INTRODUCTION: Amphetamine-type stimulants (ATSs) are the second most commonly used class of illegal substances in Europe. Although concurrent substance use has been subject to research, little is known about associations between concurrent use of cocaine, alcohol, or cannabis and ATS dependence. We expect that the concurrent use of any of the substance, especially cannabis and cocaine, is associated with ATS dependence. METHODS: Cross-sectional data were gathered within the European ATTUNE study in 2018/2019. Participants (N = 721) were asked about their consumption patterns and social, psychological, and economic situation. Multivariate logistic regressions were carried out for associations between ATS dependence and use combinations of frequent cocaine, alcohol, or cannabis, with the reference group of no frequent concurrent use (model 1). Model 2 calculated associations for ATS dependence with lifetime methamphetamine use for respective use combinations. RESULTS: The study population was on average 28.9 years old (SD = 7.7), with the majority being male (63.5%). In model 1, the adjusted odds ratio (aOR) for frequent alcohol use was 0.70 (confidence interval [CI] 0.41-1.20). Similar results were shown for model 2 (aOR 0.82, CI 0.42-1.62). Frequent cannabis use significantly reduced the chance for ATS dependence by 50% in adjusted model 1 (aOR 0.50, CI 0.28-0.89) and by 62% in model 2 (aOR 0.38, CI 0.18-0.82). For frequent cocaine use, models 1 and 2 report an aOR at 1.37 (CI 0.58-3.25) and 2.39 (CI 0.77-7.43), although not statistically significant. Frequent users of all 3 substances had a significant 3-fold chance for ATS dependence (model 1: aOR 2.98, CI 1.16-7.63; model 2: aOR 2.95, CI 1.02-8.58). DISCUSSION: Against initial hypotheses, frequent concurrent use of alcohol or cannabis generally decreased chances for ATS dependence. An explanation could be the study population, which consists of many irregular users of ATS, who mainly consume alcohol or cannabis. Cocaine generally increased chances, although results were not significant. The frequent use of all 3 substances together with ATS in the last year was significantly associated with dependence, thus reporting important information for treatment services. Further research is needed for disentangling causal relationships underlying these associations and for pinpointing consequences for relapse prevention and retention success.

Emergency department visits and trends related to cocaine, psychostimulants, and opioids in the United States, 2008-2018.

BACKGROUND: Drug-related emergency department (ED) visits are escalating, especially for stimulant use (i.e., cocaine and psychostimulants such as methamphetamine). We sought to characterize rates, presentation, and management of ED visits related to cocaine and psychostimulant use, compared to opioid use, in the United States (US). METHODS: We used 2008-2018 National Hospital Ambulatory Medical Care Survey data to identify a nationally representative sample of ED visits related to cocaine and psychostimulant use, with opioids as the comparator. To make visits mutually exclusive for analysis, we excluded visits related to 2 or more of the three possible drug categories. We estimated annual rate trends using unadjusted Poisson regression; described demographics, presenting concerns, and management; and determined associations between drug-type and presenting concerns (categorized as psychiatric, neurologic, cardiopulmonary, and drug toxicity/withdrawal) using logistic regression, adjusting for age, sex, race/ethnicity, and homelessness. RESULTS: Cocaine-related ED visits did not significantly increase, while psychostimulant-related ED visits increased from 2008 to 2018 (2.2 visits per 10,000 population to 12.9 visits per 10,000 population; p < 0.001). Cocaine-related ED visits had higher usage of cardiac testing, while psychostimulant-related ED visits had higher usage of chemical restraints than opioid-related ED visits. Cocaine- and psychostimulant-related ED visits had greater odds of presenting with cardiopulmonary concerns (cocaine adjusted odds ratio [aOR] 2.95, 95% CI 1.70-5.13; psychostimulant aOR 2.46, 95% CI 1.42-4.26), while psychostimulant-related visits had greater odds of presenting with psychiatric concerns (aOR 2.69, 95% CI 1.83-3.95) and lower odds of presenting with drug toxicity/withdrawal concerns (aOR 0.47, 95%CI 0.30-0.73) compared to opioid-related ED visits. CONCLUSION: Presentations for stimulant-related ED visits differ from opioid-related ED visits: compared to opioids, ED presentations related to cocaine and psychostimulants are less often identified as related to drug toxicity/withdrawal and more often require interventions to address acute cardiopulmonary and psychiatric complications.

Substance use disorders and chronic itch.

Chronic pruritus is one dermatologic manifestation of an underlying substance use disorder. Recent literature has uncovered similarities between the general neurologic mechanisms of addiction and chronic itch, largely involving activation of the dopaminergic reward circuits within the brain and imbalances between mu and kappa opioid receptor activation. It is likely that the use of specific drugs, like central nervous system stimulants and opioids, results in further activation and imbalances within these pathways, perpetuating both addiction and pruritus simultaneously. Opioid users often present to dermatology clinics with a generalized pruritus, whereas individuals using central nervous system stimulants like cocaine and methylenedioxymethamphetamine (MDMA), as well as legally prescribed drugs like treatments for attention deficit hyperactivity disorder, frequently complain of crawling, delusional infestation-like sensations underneath the skin. Because of these overlapping mechanisms and similar clinical presentations to many other chronically itchy conditions, it is necessary for dermatologists to consider and investigate an underlying substance use disorder to effectively treat these patients.

Open-label pilot study of lisdexamfetamine for cocaine use disorder.

Background: Cocaine use disorder (CUD) is a substantial public health problem with no FDA-approved medication treatments. Psychostimulants have shown promise as pharmacotherapy for CUD. Lisdexamfetamine, a novel prodrug psychostimulant, is roughly 40-50% as potent as dextroamphetamine.Objectives: To evaluate the safety, tolerability, and optimal dosing of lisdexamfetamine for treating CUD.Methods: Open-label, 8-week trial of 17 CUD adults. Participants were titrated to the maximum tolerated dose of 140 mg over 2-week period and maintained for 4 weeks, followed by a two-week taper period. The primary outcome measures were the maximum daily dose achieved during the study period and tolerability as measured by medication-related study drop-out.Results: Among the 16 participants with post-enrollment data, the mean dose of lisdexamfetamine achieved was 118.1 mg (standard deviation (SD) = 40.4), mean retention was 6.5 weeks (SD = 2.0), and no participants discontinued study medication due to adverse effects. Four participants had dose reductions due to adverse effects and continued in the trial. Six participants (37.5%) were abstinent for the last 3 weeks of their study participation. Mean dollars of cocaine spent per day significantly decreased from $19.72 at baseline to $7.57 during the last 3 weeks of study participation (t15 = 3.60, p = .003). The mean percent of using days significantly decreased from 25% at baseline to 12% during the last 3 weeks of study participation (t15 = 3.33, p = .005).Conclusion: The use of lisdexamfetamine for CUD in doses ranging to 140 mg daily was safe and generally well tolerated.

Drug and alcohol positivity of traumatically injured patients related to COVID-19 stay-at-home orders.

Background: COVID-19 related stay-at-home (SAH) orders created many economic and social stressors, possibly increasing the risk of drug/alcohol abuse in the community and trauma population.Objectives: Describe changes in alcohol/drug use in traumatically injured patients after SAH orders in California and evaluate demographic or injury pattern changes in alcohol or drug-positive patients.Methods: A retrospective analysis of 11 trauma centers in Southern California (1/1/2020-6/30/2020) was performed. Blood alcohol concentration, urine toxicology results, demographics, and injury characteristics were collected. Patients were grouped based on injury date - before SAH (PRE-SAH), immediately after SAH (POST-SAH), and a historical comparison (3/19/2019-6/30/2019) (CONTROL) - and compared in separate analyses. Groups were compared using chi-square tests for categorical variables and Mann-Whitney U tests for continuous variables.Results: 20,448 trauma patients (13,634 male, 6,814 female) were identified across three time-periods. The POST-SAH group had higher rates of any drug (26.2% vs. 21.6% and 24.7%, OR = 1.26 and 1.08, p < .001 and p = .035), amphetamine (10.4% vs. 7.5% and 9.3%, OR = 1.43 and 1.14, p < .001 and p = .023), tetrahydrocannabinol (THC) (13.8% vs. 11.0% and 11.4%, OR = 1.30 and 1.25, p < .001 and p < .001), and 3,4-methylenedioxy methamphetamine (MDMA) (0.8% vs. 0.4% and 0.2%, OR = 2.02 and 4.97, p = .003 and p < .001) positivity compared to PRE-SAH and CONTROL groups. Alcohol concentration and positivity were similar between groups (p > .05).Conclusion: This Southern California multicenter study demonstrated increased amphetamine, MDMA, and THC positivity in trauma patients after SAH, but no difference in alcohol positivity or blood concentration. Drug prevention strategies should continue to be adapted within and outside of hospitals during a pandemic.

Application of Microextraction-Based Techniques for Screening-Controlled Drugs in Forensic Context-A Review.

The analysis of controlled drugs in forensic matrices, i.e., urine, blood, plasma, saliva, and hair, is one of the current hot topics in the clinical and toxicological context. The use of microextraction-based approaches has gained considerable notoriety, mainly due to the great simplicity, cost-benefit, and environmental sustainability. For this reason, the application of these innovative techniques has become more relevant than ever in programs for monitoring priority substances such as the main illicit drugs, e.g., opioids, stimulants, cannabinoids, hallucinogens, dissociative drugs, and related compounds. The present contribution aims to make a comprehensive review on the state-of-the art advantages and future trends on the application of microextraction-based techniques for screening-controlled drugs in the forensic context.

Prevalence of Non-medical Amphetamine Use Among Men with Diagnosed HIV Infection Who Have Sex with Men in the United States, 2015-2016.

Amphetamine use is higher among men who have sex with men (MSM) compared with other men, and is associated with sexual behavior linked to HIV transmission. No national estimates of amphetamine use among MSM with HIV have been published. We used data from the Medical Monitoring Project, a nationally representative sample of persons with diagnosed HIV, to describe patterns in amphetamine use in the past 12 months among MSM during 2015-2016 (N = 3796). Prevalence of amphetamine use in this population was 9.6% (95% CI 7.6, 11.6%) in the past 12 months. MSM who used amphetamines were more likely to have condomless sex with partners without HIV or of unknown serostatus (PR 1.87; 95% CI 1.62, 2.16) and less likely to be durably virally suppressed (PR 0.81; 95% CI 0.71, 0.91). Interventions to address amphetamine use and associated transmission risk behaviors among MSM living with HIV may decrease transmission.

Clinical Trials for Stimulant Use Disorders: Addressing Heterogeneities That May Undermine Treatment Outcomes.

In recent years, use of cocaine and amphetamines and deaths associated with stimulants have been on the rise, and there are still no FDA-approved medications for stimulant use disorders. One contributing factor may involve heterogeneity. At the neurobiological level, dual dopamine dysfunction may be undermining medication efficacy, suggesting a need for combination pharmacotherapies. At the population level, individual variability is expressed in a number of ways and, if left unaddressed, may interfere with medication efficacy. This chapter reviews studies investigating medications to address dopamine dysfunction, and it also identifies several prominent heterogeneities associated with stimulant (and other substance) use disorders. The chapter has implications for improving interventions to treat stimulant use disorders, and the theme of individual heterogeneity may have broader application across substance use disorders.

The use of stimulants in depression: Results from a self-controlled register study.

OBJECTIVE: To investigate the effectiveness of stimulants in patients with depression, by using naturalistic outcome measures, such as psychiatric admissions, psychiatric bed-days and incidents of intentional self-harm or suicide attempts. METHODS: Via linkage of the Danish nationwide health registers, we identified all patients with a diagnosis of depression initiating stimulants, including methylphenidate, modafinil, amphetamine, dexamphetamine or lisdexamphetamine, from 1995 to 2012. We used a mirror-image model to test whether redemption of a stimulant prescription was associated with a reduction in psychiatric admissions, inpatient days and incidents of intentional self-harm or suicide attempts. Specifically, the number of these outcomes in the 2 years leading up to redemption of a stimulant prescription was compared to the two subsequent years. Similar outcomes were used in a reverse mirror-image model to investigate the effect of stimulant termination. RESULTS: A total of 3354, 935 and 105 patients diagnosed with depression redeemed prescriptions for methylphenidate, modafinil or amphetamine/dexamphetamine/lisdexamphetamine, respectively. Initiation of methylphenidate was not associated with a significant change in psychiatric admissions (mean: -0.02 admissions, p = 0.11) or inpatient days (mean: 0.13 days, p = 0.74). Similar findings were made for modafinil and the amphetamines. In addition, no clinically relevant change in psychiatric admissions or inpatient days was found after termination of a stimulant. After initiation of methylphenidate, the incidents of self-harm or suicide attempts were reduced by 54%, from 68 to 31 events (p = 0.004). No significant change in incidents of self-harm or suicide attempts were found for modafinil or the amphetamines. CONCLUSION: This nationwide study, using naturalistic outcomes, does not support the use of stimulants in patients with depression. However, the use of methylphenidate was associated with a 54% reduction in incidents of self-harm or suicide attempts, indicating that methylphenidate may potentially be useful in patients with depression with suicidal- or self-harming behaviour. However, further studies are needed, before any firm conclusions can be made.