Amphetamine exposure during embryogenesis changes expression and function of the dopamine transporter in Caenorhabditis elegans offspring.

The dopamine transporter (DAT) is a transmembrane protein that regulates dopamine (DA) neurotransmission by binding to and moving DA from the synaptic cleft back into the neurons. Besides moving DA and other endogenous monoamines, DAT is also a neuronal carrier for exogenous compounds such as the psychostimulant amphetamine (Amph), and several studies have shown that Amph-induced behaviors require a functional DAT. Here, we demonstrate that exposure to Amph during early development causes behavioral, functional, and epigenetic modifications at the Caenorhabditis elegans DAT gene homolog, dat-1, in C. elegans offspring. Specifically, we show that, while embryos exposed to Amph generate adults that produce offspring with no obvious behavioral alterations, both adults and offspring exhibit an increased behavioral response when challenged with Amph. Our functional studies suggest that a decrease in DAT-1 expression underlies the increased behavioral response to Amph seen in offspring. Moreover, our epigenetic data suggest that histone methylation is a mechanism utilized by Amph to maintain changes in DAT-1 expression in offspring. Taken together, our data reveal that Amph, by altering the epigenetic landscape of DAT, propagates long-lasting functional and behavioral changes in offspring.

CREB-Binding Protein Regulates Cocaine- and Amphetamine-Regulated Transcript Peptide Expression in the Lateral Hypothalamus: Implication in Reward and Reinforcement.

Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) is known to play an important role in reward processing. The rats conditioned to intra-cranial self-stimulation (ICSS) showed massive upregulation of CART protein and mRNA in the vicinity of the electrode implanted to deliver the electric current directly at the lateral hypothalamus (LH)-medial forebrain bundle (MFB) area. However, the underlying mechanisms leading to the upregulation of CART in ICSS animals remain elusive. We tested the putative role of CREB-binding protein (CBP), an epigenetic enzyme with intrinsic histone acetyltransferase (HAT) activity, in regulating CART expression during ICSS. An electrode was implanted in LH-MFB and the rats were conditioned to self-stimulation in an operant chamber. CBP siRNA was delivered ipsilaterally in the LH-MFB to knock-down CBP and the effects on lever press activity were monitored. While ICSS-conditioned rats showed distinct increase in CART, CBP and pCREB levels, enhanced CBP binding and histone acetylation (H3K9ac) were noticed on the CART promoter in chromatin immunoprecipitation assay. Direct infusion of CBP siRNA in the LH-MFB lowered lever press activity, CBP levels, histone acetylation at the CART promoter, and CART mRNA and peptide expression. Co-infusion of CARTp in LH-MFB rescued the waning effects of CBP siRNA on self-stimulation. We suggest that CBP-mediated histone acetylation may play a causal role in CART expression in LH, which in turn may drive the positive reinforcement of lever press activity.

Compulsive Biting and Chewing with Mixed Amphetamine Salts: A Case Report.

Stimulants are the first-line pharmacological treatment for attention deficit hyperactivity disorder (ADHD). We present the unique case of a patient who developed a chewing compulsion when taking mixed amphetamine salts (MAS). A 32-year-old female patient with a past medical history of gastroesophageal reflux disease (GERD), gastroparesis, and migraines was seen for initial psychiatric assessment due to concerns for irritability. She was diagnosed with post-traumatic stress disorder (PTSD); generalized anxiety disorder; ADHD, inattentive type; and unspecified bipolar disorder. Lamotrigine was started and titrated to 25mg twice per day, with improved mood stability. MAS immediate-release (IR) was started at 2.5mg and titrated to 5mg daily for ADHD. She then experienced an uncontrollable urge to chew, finding relief when chewing on a child's teething necklace, which provided satisfaction and a reduction in anxiety. She denied jaw tightness or teeth grinding. The dose of MAS IR was reduced to 2.5mg daily with improvement in symptoms and later increased again to 5mg daily, which she was then able to tolerate. Stereotyped biting behaviors have been observed in rats with the use of amphetamines, and the onset of compulsive behavior has emerged in children with the use of dextroamphetamine. However, this is the first known case of compulsive chewing or biting movements reported in humans with MAS use. This case highlights the need to assess patients for adverse events, such as compulsive biting and chewing movements or other oral facial stereotypies, after commencement of stimulants, including MAS.

Are all ADHD medications created equal? Exploring the differences that enable evening dosing.

With more than 30 available stimulant medications, choosing among therapeutic options for attention-deficit/hyperactivity disorder (ADHD) has become increasingly complex and patient specific. All ADHD stimulants owe their action to variants of either amphetamine or methylphenidate, yet formulation and delivery system differences create unique pharmacokinetic and clinical profiles for each medication. A benefit of the diversity within ADHD pharmacotherapy is that it facilitates tailoring treatment to meet patient needs. Historically, there has been a constant among long-acting stimulant options, regardless of formulation, which was morning dosing. The introduction of delayed-release and extended-release methylphenidate (DR/ER-MPH) is the first long-acting stimulant that patients take in the evening, with the clinical effect delayed until awakening in the morning. This paradigm shift has generated questions among clinicians and continued interest in real-world experience and data. This review used available clinical data, real-world evidence, emerging analyses, and clinical experience to evaluate the characteristics of DR/ER-MPH and its clinical utility within the greater context of ADHD medications and to provide clinicians with practical guidance on the use of DR/ER-MPH in children, adolescents, and adults with ADHD.

Magnetic surface-imprinted polymer microspheres coupled with HPLC-MS/MS for sensitive detection of amphetamine-type drugs in water.

Magnetic surface imprinted polymer microspheres (Fe3O4@MIPs) were successfully synthesized via Pickering emulsion polymerization, utilizing N-Methylphenethylamine as a surrogate template for amphetamine-type drugs. Fe3O4@MIPs not only possessed excellent dispersibility and enough magnetic properties in aqueous solutions, but also displayed good selectivity towards six amphetamines, with an imprinting factor ranging from 1.8 to 2.6. The adsorption kinetics closely aligned with the pseudo-second-order model, and the adsorption efficiency exceeds 80 % for each amphetamine at equilibrium. Fe3O4@MIPs were then employed as the efficient adsorbents for the extraction of amphetamine drugs. Extraction parameters, including sample pH, the mass of adsorbent, and the type and volume of eluting solvent, were carefully optimized. In combination with the high performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-MS/MS), a selective magnetic solid-phase extraction (MISPE) method utilizing Fe3O4@MIPs was developed for the detection of six amphetamines in water samples. The limits of detection and limits of quantitation were determined to be 5.2∼23 ng L-1 and 17∼77 ng L-1, respectively. Recoveries for the six target drugs from lake water and sewage samples fell within the range of 87.2∼110 %. Additionally, the MISPE-HPLC-MS/MS method exhibited excellent repeatability, with a precision below 8.5 % at two spiking levels. The prepared Fe3O4@MIPs possessed the advantages of high selectivity, straightforward preparation, facile separation and good reusability, and was highly suitable for the efficient extraction of amphetamine-type substances in complex environmental water.

Adolescent stress differentially modifies dopamine and norepinephrine release in the medial prefrontal cortex of adult rats.

Adolescent stress (AS) has been associated with higher vulnerability to psychiatric disorders such as schizophrenia, depression, or drug dependence. Moreover, the alteration of brain catecholamine (CAT) transmission in the medial prefrontal cortex (mPFC) has been found to play a major role in the etiology of psychiatric disturbances. We investigated the effect of adolescent stress on CAT transmission in the mPFC of freely moving adult rats because of the importance of this area in the etiology of psychiatric disorders, and because CAT transmission is the target of a relevant group of drugs used in the therapy of depression and psychosis. We assessed basal dopamine (DA) and norepinephrine (NE) extracellular concentrations (output) by brain microdialysis in in the mPFC of adult rats that were exposed to chronic mild stress in adolescence. To ascertain the role of an altered release or reuptake, we stimulated DA and NE output by administering either different doses of amphetamine (0.5 and 1.0 mg / kg s.c.), which by a complex mechanism determines a dose dependent increase in the CAT output, or reboxetine (10 mg/kg i.p.), a selective NE reuptake inhibitor. The results showed the following: (i) basal DA output in AS rats was lower than in controls, while no difference in basal NE output was observed; (ii) amphetamine, dose dependently, stimulated DA and NE output to a greater extent in AS rats than in controls; (iii) reboxetine stimulated NE output to a greater extent in AS rats than in controls, while no difference in stimulated DA output was observed between the two groups. These results show that AS determines enduring effects on DA and NE transmission in the mPFC and might lead to the occurrence of psychiatric disorders or increase the vulnerability to drug addiction.

Substance Use Disorder Admission Rates Before and After the Lockdown in a Large Addiction Center in Saudi Arabia: A Retrospective Cohort Study.

Objective: This study aimed to examine the potential changes in substance use disorder (SUD) admission rates before and after the lockdown in a major addiction center in Saudi Arabia. Method: This retrospective cohort study extracted data from Al-Amal Hospital Electronic Health Record in the city of Dammam, Eastern region of Saudi Arabia. A total of 2,426 cases included in the analysis for patients who received services from the SUD treatment programs from 1/1/2015 to 31/12/2021. Results: Before the pandemic, there was a consistent increase in the admission rates for patients with substance use disorder. The highest proportion of increase were among unemployed, young, newly admitted patients. During lockdown, there was nearly a 70% reduction in SUDs-related admission rate. The age group 18-25 was seven-times more likely to be admitted for SUD after the lockdown. Amphetamine-related admissions were two times more likely to be admitted after the lockdown (Odds ratio (OR) 2.04; confidence interval (CI) 95%[1.64, 2.54]). Conclusions: There was nearly 70% reduction in SUDs admission rates during the lockdown. After the lockdown, a significant proportional increase in amphetamine use disorder admissions was observed mostly among the patients age group 18-24 with a history of a previous admissions. Determining populations at risk for high health care utilization is crucial in building a comprehensive and effective prevention strategy. Therefore, the need to adopt coordinated strategies and innovative, comprehensive approaches to benefit individuals with SUD is imperative to face the increased rate of SUD related admissions.

Amphetamine and methylphenidate potential on the recovery from stroke and traumatic brain injury: a review.

The prevalence of stroke and traumatic brain injury is increasing worldwide. However, current treatments do not fully cure or stop their progression, acting mostly on symptoms. Amphetamine and methylphenidate are stimulants already approved for attention deficit hyperactivity disorder and narcolepsy treatment, with neuroprotective potential and benefits when used in appropriate doses. This review aimed to summarize pre-clinical and clinical trials testing either amphetamine or methylphenidate for the treatment of stroke and traumatic brain injury. We used PubMed as a database and included the following keywords ((methylphenidate) OR (Ritalin) OR (Concerta) OR (Biphentin) OR (amphetamine) OR (Adderall)) AND ((stroke) OR (brain injury) OR (neuroplasticity)). Overall, studies provided inconsistent results regarding cognitive and motor function. Neurite outgrowth, synaptic proteins, dendritic complexity, and synaptic plasticity increases were reported in pre-clinical studies along with function improvement. Clinical trials have demonstrated that, depending on the brain region, there is an increase in motor activity, attention, and memory due to the stimulation of the functionally depressed catecholamine system and the activation of neuronal remodeling proteins. Nevertheless, more clinical trials and pre-clinical studies are needed to understand the drugs' full potential for their use in these brain diseases namely, to ascertain the treatment time window, ideal dosage, long-term effects, and mechanisms, while avoiding their addictive potential.

Branch retinal artery occlusion in a 49-year-Old woman taking phentermine.

Purpose: This report describes the presentation of a 49-year-old woman with a branch retinal artery occlusion of the right eye in the setting of taking phentermine, a commonly used weight loss medication. Observations: A 49-year-old woman presented with acute painless vision loss in her right eye and was found to have a branch retinal artery occlusion after taking prescribed dosages of phentermine for weight loss therapy. Fundus examination revealed retinal whitening in the distribution of the superior temporal branch retinal artery, and spectral domain optical coherence tomography demonstrated macular edema. Systemic evaluation was negative for cardiovascular, infectious, or autoimmune etiologies. Based on the retinal findings, the patient was diagnosed with phentermine associated branch retinal artery occlusion. She was followed for nine years with no further complications and her vision remained stable in the right eye. Conclusions and Importance: This case highlights that phentermine, a commonly used weight loss medication, could be associated with ischemic retinopathies. Thus, clinicians should be aware that retinal vascular occlusions may not only occur in those who use recreational amphetamines but also in patients taking the prescribed dosages of a weight loss medication like phentermine.

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder.

Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms.Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY).Methods: At postnatal day 32, parallel groups of 12-24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior.Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832).Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

Association between socioeconomic and motherhood characteristics with receiving community-based treatment services among justice-involved young female drug users: a retrospective cohort study in Taiwan.

BACKGROUND: Drug-involved individuals who contact treatment services in Taiwan are mostly driven by criminal justice systems either as an alternative or adjunct to criminal sanctions for a drug offence. With a focus on justice-involved young female drug users, the present study examines the extent to which socioeconomic and motherhood characteristics are associated with receiving deferred prosecution, a scheme diverting drug offenders to community-based addiction treatment. METHODS: We identified a cohort of 5869 women under the age of 30 arrested for using Schedule II drugs (primarily amphetamine-like stimulants) from the 2011-2017 National Police Criminal Records in Taiwan. Information concerning socioeconomic characteristics, pregnancy and live birth history, and deferred prosecution was obtained through linkage with the 2006-2019 National Health Insurance, birth registration, and deferred prosecution datasets. Multinomial logistic regression was used to evaluate the association with stratification by recidivism status. RESULTS: Within six months of arrest, 21% of first-time offenders (n = 2645) received deferred prosecution and 23% received correction-based rehabilitation; the corresponding estimates for recidivists (n = 3224) were 6% and 15%, respectively. Among first-time offenders, low/unstable income was associated with lower odds of deferred prosecution (adjusted odds ratio [aOR] = 0.71; 95% CI: 0.58, 0.88). For recidivists, those with low/unstable income (aOR = 1.58) or unemployment (aOR = 1.58) had higher odds of correction-based rehabilitation; being pregnant at arrest was linked with reduced odds of deferred prosecution (aOR = 0.31, 95% CI: 0.13, 0.71) and correction-based rehabilitation (aOR = 0.50, 95% CI: 0.32, 0.77). CONCLUSIONS: For the young women arrested for drug offences, disadvantaged socioeconomic conditions were generally unfavored by the diversion to treatment in the community. Childbearing upon arrest may lower not only the odds of receiving medical treatment but also correctional intervention. The criminal prosecution policy and process should be informed by female drug offenders' need for treatment and recovery.

Effect of Amphetamine Dependence on Redox State via Alteration of Urinary Levels of Major and Trace Elements: A Case-Control Study in the Saudi Population.

Background Drug and substance abuse remains a major medical problem worldwide. Amphetamines are potent stimulants of the central nervous system. Amphetamine abuse is highly prevalent among drug-dependents. This study was conducted in Qassim, Saudi Arabia, to evaluate amphetamine's toxic effects on major and trace elements and their correlation with redox status. Methods The study involved amphetamine-only patients admitted to the Erada Rehabilitation Centre from March to October 2023. Urine samples were analysed from both normal subjects and amphetamine-dependent groups. Results Urinary sodium and chloride levels were significantly higher in the amphetamine-dependent group than in the control group, while their calcium levels decreased. Lipid peroxidase levels significantly increased in people with a substance use disorder (SUD), indicating oxidative stress. Together, their total antioxidant capacity decreased. Zinc (Zn), copper (Cu), lead (Pb), cadmium (Cd), sodium (Na), and total antioxidant capacity levels were positively correlated with lipid peroxidase. Conclusions Amphetamine-dependent people are more likely to experience a variety of health problems. This study found a direct correlation between an imbalance in major and trace elements and the redox status.

Adolescent chemogenetic activation of dopaminergic neurons leads to reversible decreases in amphetamine-induced stereotypic behavior.

Chronic perturbations of neuronal activity can evoke homeostatic and new setpoints for neurotransmission. Using chemogenetics to probe the relationship between neuronal cell types and behavior, we recently found reversible decreases in dopamine (DA) transmission, basal behavior, and amphetamine (AMPH) response following repeated stimulation of DA neurons in adult mice. It is unclear, however, whether altering DA neuronal activity via chemogenetics early in development leads to behavioral phenotypes that are reversible, as alterations of neuronal activity during developmentally sensitive periods might be expected to induce persistent effects on behavior. To examine the impact of developmental perturbation of DA neuron activity on basal and AMPH behavior, we expressed excitatory hM3D(Gq) in postnatal DA neurons in TH-Cre and WT mice. Basal and CNO- or AMPH-induced locomotion and stereotypy was evaluated in a longitudinal design, with clozapine N-oxide (CNO, 1.0 mg/kg) administered across adolescence (postnatal days 15-47). Repeated CNO administration did not impact basal behavior and only minimally reduced AMPH-induced hyperlocomotor response in adolescent TH-CrehM3Dq mice relative to WThM3Dq littermate controls. Following repeated CNO administration, however, AMPH-induced stereotypic behavior robustly decreased in adolescent TH-CrehM3Dq mice relative to controls. A two-month CNO washout period rescued the diminished AMPH-induced stereotypic behavior. Our findings indicate that the homeostatic compensations that take place in response to chronic hM3D(Gq) stimulation during adolescence are temporary and are dependent on ongoing chemogenetic stimulation.

[Stimulants : Current insights into the principles, diagnostics and treatment]. / Stimulanzien : Aktuelle Erkenntnisse zu Grundlagen, Diagnostik und Therapie.

BACKGROUND: Consumption of stimulant drugs, a heterogeneous group of addictive substances, has significantly increased in recent years with rising numbers of stimulant-associated intoxication and deaths. OBJECTIVE: To provide an overview of recent scientific evidence of the diagnosis and treatment of stimulant use disorders. MATERIAL AND METHODS: A literature review of the neuropathology, clinical presentation, diagnostic criteria and evidence-based treatment for stimulant use disorders. RESULTS: The chronic use of stimulant drugs is associated with significant physical (e.g., hypertension, tachycardia and dyspnoea) and psychological harm (e.g., dependence, psychotic disorders and affective disorders). Despite major advances in the research of the neuropathology of stimulant use disorder and the refinement of diagnostic criteria, the disorder still presents a challenge, not least because of the lack of effective treatments. There are currently no approved pharmacotherapeutic interventions for stimulant use disorder and meta-analyses show that the efficacy of behavioural interventions is low to moderate, similar to cognitive behavioural treatment. CONCLUSION: Despite growing insights into the neuropathology associated with stimulant use disorder, treatment remains a challenge. The lack of effective interventions makes it difficult to give clear recommendations for the clinical practice. Further scientific research is thus warranted.

Enantiomeric profile of amphetamines in seized drug samples and in blood of impaired drivers in Iceland: the rise of (R)-methamphetamine?

Amphetamine (AMP) and methamphetamine (METH) use is increasing globally. Illegal AMP is generally a racemic mixture, whereas AMP-containing attention-deficit hyperactivity disorder drugs prescribed in Iceland consist of S-AMP. AMP is also a main metabolite of interest after METH intake. Distinguishing between legal and illegal AMP intake is vital in forensic toxicology. A chiral UPLC-MS/MS method was used to determine the enantiomeric profile of AMP and METH in circulation in Iceland by analysing blood samples from drivers suspected of driving under the influence of drugs (DUID) and seized drug samples from 2021 and 2022. All seized AMP samples (n = 48) were racemic, whereas all but one seized METH sample (n = 26) were enantiopure. Surprisingly, a large portion of the enantiopure METH samples was R-METH. DUID blood samples positive for AMP (n = 564) had a median blood concentration of 180 ng/mL (range 20-2770 ng/mL) and a median enantiomeric fraction (EFR) of 0.54 (range 0-0.73), whereas samples positive for METH (n = 236) had a median blood concentration of 185 ng/mL (range 20-2300 ng/mL) and a median EFR of 0.23 (range 0-1). The findings of this study show a significantly lower blood concentration in drivers with only S-AMP detected compared with when the R-isomer is also detected. No significant difference in blood concentration was detected between the sample groups containing S-METH, R-METH, or both enantiomers. The occurrence of R-METH in both seized drug samples and DUID cases indicates a change in drug supply and a need for better scientific knowledge on R-METH abuse.

Mortality, morbidity, and predictors of death among amphetamine-type stimulant users - a longitudinal, nationwide register study.

Introduction: Use of amphetamine-type stimulants (ATS) contributes substantially to the global burden of disease. Large-scale follow-up studies of morbidity and mortality in ATS users are few. This study analysed morbidity, mortality, and potential predictors of all-cause mortality in a nationwide cohort of patients with ATS use disorder. Methods: Data was acquired from national Swedish registers. All Swedish residents 18 years or older, with a registered ATS use diagnosis in 2013-2014 were included (N = 5,018) and followed until December 31, 2017. Comorbid diagnoses and causes of death were assessed and potential predictors of all-cause mortality were examined through Cox regression. Results: Median age at inclusion was 36.6 years (interquartile range 27.4---48.1) and 70.5 % were men. The crude mortality rate was 24.6 per 1,000 person-years. The adjusted all-cause standardized mortality ratio was 12.4 (95 % CI [11.34-13.55]). The most common cause of death was overdose (28.9 %). Multiple drug use (hazard ratio 1.39, 95 % CI [1.14-1.70], p = 0.004), anxiety (hazard ratio 1.39, 95 % CI [1.11-1.72], p = 0.014), viral hepatitis (hazard ratio 1.85, 95 % CI [1.50-2.29], p = 0.004), and liver disease (hazard ratio 2.41, 95 % CI [1.55-3.74], p = 0.004) were predictors of all-cause mortality. Conclusions: Multiple drug use, anxiety disorders, viral hepatitis and liver diseases were identified as risk factors for death. Our findings call for better screening, prevention, and treatment of somatic and psychiatric comorbidity among ATS users to reduce mortality.

Characterising methamphetamine/amphetamine use among opioid agonist therapy-seeking adults with prescription-type opioid use disorder in Canada.

INTRODUCTION: There has been a significant increase in methamphetamine/amphetamine use in North America, particularly among people who use opioids. Despite its association with several negative health consequences, the population of people who use methamphetamine/amphetamine with opioids is not well characterised. The aim of this study was to investigate correlates of methamphetamine/amphetamine use among adults with prescription-type opioid use disorder (POUD) starting methadone or buprenorphine/naloxone as part of a pragmatic randomised treatment trial in Canada. METHODS: Multivariable logistic regression analyses were used to determine factors associated with baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) among participants of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care in people with POUD (e.g., licit or illicit, including fentanyl, prescribed or not). RESULTS: The sample included 269 participants, of which 142 (52.8%) had positive baseline methamphetamine/amphetamine UDT. In the multivariable model, positive fentanyl UDT (adjusted odds ratio [AOR] 13.21, 95% confidence interval [CI] 6.45, 28.30), non-fatal overdose in the last 6 months (AOR 2.26, CI 1.01, 5.17) and a lifetime history of opioid agonist therapy exposure prior to study entry (AOR 2.30, CI 1.09, 4.87) remained positively associated with baseline methamphetamine/amphetamine use. DISCUSSION AND CONCLUSIONS: In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including overdose risk. This suggests the need for targeted interventions to optimise treatment outcomes and prevent future overdoses in this population. CLINICAL TRIAL REGISTRATION: Available at: ClinicalTrials.gov NCT03033732.

The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Evaluation of the immune system status and hematological dyscrasias, among amphetamine and cannabis abusers at Eradah Hospital in Qassim, Saudi Arabia.

This cross-sectional study aims to evaluate the immune system status and hematological disturbances among individuals who abuse amphetamines and cannabis. Substance abuse, particularly of amphetamines and cannabis, has been associated with various adverse effects on the body, including potential impacts on the immune system and hematological parameters. However, limited research has been conducted to comprehensively assess these effects in a cross-sectional design. Additionally, fungal infections are on the rise internationally, and immune-compromised people are particularly susceptible. The study will recruit a sample of amphetamine and cannabis abusers (n = 50) at the Eradah Hospital in the Qassim Region of Buraydah and assess their sociodemographic and biochemical variables, including blood indices and differential WBC indices, liver, and kidney profiles. Additionally, 50 sputum samples in total were cultured for testing for fungus infections. To obtain the descriptive statistics, the data was imported into Microsoft Excel and subjected to statistical analysis using SPSS 22.0. Amphetamine and cannabis abuser's sociodemographic variables analysis observed that the majority (52%) were aged 18-30, with 56% in secondary school. Unemployment was a significant issue, and most had no other health issues. The majority (50%) had 5-10 years of abuse, while 32% had less than 5 years, and only 18% had been drug abusers for more than 10 years. There were significant changes (p < 0.001) in all different leukocyte blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Furthermore, a microscopic examination of blood films from individuals who misuse the combination of the medications "amphetamine and cannabis" reveals hazardous alterations in Neutrophils. Out of 50, 35 sputum samples showed positive growth on Sabouraud dextrose agar (SDA) with chloramphenicol antibiotic, indicating a unicellular fungal growth. The present study explores the immune system and hematological disturbances linked to amphetamine and cannabis abuse, providing insights into health risks and targeted interventions. The findings complement previous research on drug users' hematological abnormalities, particularly in white blood cells. Routine hematological tests help identify alterations in homeostatic conditions, improving patient knowledge and preventing major issues. Further research is needed on multi-drug abuse prevention, early detection, and intervention. The cross-sectional design allows for a snapshot of the immune system and hematological status among abusers, laying the groundwork for future longitudinal studies. Key Words: Drug Effect, Immunity, Epidemiology, Oxidative Stress, Inflammation.

Psychostimulants and social behaviors.

Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that the neural circuits underlying the regulation and expression of social behaviors are highly overlapped with those targeted by psychostimulants, which in most cases have strong rewarding and, consequently, addictive properties. In the present work, we provide an overview regarding the effects of illicit and prescription psychostimulants, such as cocaine, amphetamine-type stimulants, methylphenidate or modafinil, upon social behaviors such as social play, maternal behavior, aggression, pair bonding and social cognition and how psychostimulants in both animals and humans alter them. Finally, we discuss why these effects can vary depending on numerous variables such as the type of drug considered, acute versus long-term use, clinical versus recreational consumption, or the presence or absence of concomitant risk factors.