Association Between Inflammatory Cytokines, Executive Function, and Substance Use in Patients With Opioid Use Disorder and Amphetamine-Type Stimulants Use Disorder.

BACKGROUND: Long-term opioid and amphetamine-type stimulants (ATS) abuse may affect immunological function and impair executive function. We aimed to determine whether biomarkers of inflammation and executive function were associated with substance use in individuals with opioid use disorder (OUD) and ATS use disorder (ATSUD). The interactions between these biomarkers were also explored. METHODS: We assessed plasma cytokines [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-8, IL-6, transforming growth factor (TGF)-ß1, brain-derived neurotrophic factor (BDNF), and executive function in terms of the Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) in OUD and ATSUD patients and healthy controls (HC). OUD and ATSUD patients were followed for 12 weeks, and their urine morphine and amphetamine tests, cytokine levels, and executive function were repeatedly measured. RESULTS: We enrolled 483 patients and 145 HC. Plasma TNF-α, CRP, IL-8, IL-6, and BDNF levels and most subscale scores on the WCST and CPT significantly differed between OUD and ATSUD patients and HC. Increased TNF-α levels and more perseveration error on the WCST were significantly associated with more urine drug-positive results and less abstinence. Plasma IL-6 and CRP levels were significantly negatively correlated with WCST and CPT performance. CONCLUSION: OUD and ATSUD patients had more inflammation and worse executive function than HC. Inflammatory markers and WCST performance were associated with their urinary drug results, and higher inflammation was associated with poor executive function. Studies on regulating the inflammatory process and enhancing executive function in OUD and ATSUD are warranted.

Amphetamine-Related Fatalities and Altered Brain Chemicals: A Preliminary Investigation Using the Comparative Toxicogenomic Database.

Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0-0.5 g/mL), medium (>0.5 to 1.5 g/mL), and high (>1.5 g/mL), based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid (AA), docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical-disease associations using the CTD tools and predicted an association between DHA, AA and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer's disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, a supplement therapy may be needed to prevent omega-3 fatty acid deficiency.

Mucocutaneous alterations and complications in amphetamine abusers: a narrative review.

Amphetamines are the second most commonly used illicit drug worldwide. Amphetamine use can result in significant cutaneous morbidity. This review highlights the dermatological manifestations of amphetamine abuse.

Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns.

This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.

Psychosis with Methylphenidate or Amphetamine in Patients with ADHD.

BACKGROUND: The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied. METHODS: We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases. RESULTS: We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09). CONCLUSIONS: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.).

Use of Amphetamine-Type Stimulants Among Emergency Department Patients With Untreated Opioid Use Disorder.

STUDY OBJECTIVE: Concurrent use of amphetamine-type stimulants among individuals with opioid use disorder can exacerbate social and medical harms, including overdose risk. The study evaluated rates of amphetamine-type stimulant use among patients with untreated opioid use disorder presenting at emergency departments in Baltimore, MD; New York, NY; Cincinnati, OH; and Seattle, WA. METHODS: Emergency department (ED) patients with untreated opioid use disorder (N=396) and enrolled between February 2017 and January 2019 in a multisite hybrid type III implementation science study were evaluated for concurrent amphetamine-type stimulant use. Individuals with urine tests positive for methamphetamine, amphetamine, or both were compared with amphetamine-type stimulant-negative patients. RESULTS: Overall, 38% of patients (150/396) were amphetamine-type stimulant positive; none reported receiving prescribed amphetamine or methamphetamine medications. Amphetamine-type stimulant-positive versus -negative patients were younger: mean age was 36 years (SD 10 years) versus 40 years (SD 12 years), 69% (104/150) versus 46% (114/246) were white, 65% (98/150) versus 54% (132/246) were unemployed, 67% (101/150) versus 49 (121/246) had unstable housing, 47% (71/150) versus 25% (61/245) reported an incarceration during 1 year before study admission, 60% (77/128) versus 45% (87/195) were hepatitis C positive, 79% (118/150) versus 47% (115/245) reported drug injection during 1 month before the study admission, and 42% (62/149) versus 29% (70/244) presented to the ED for an injury. Lower proportions of amphetamine-type stimulant-positive patients had cocaine-positive urine test results (33% [50/150] versus 52% [129/246]) and reported seeking treatment for substance use problems as a reason for their ED visit (10% [14/148] versus 19% [46/246]). All comparisons were statistically significant at P<.05 with the false discovery rate correction. CONCLUSION: Amphetamine-type stimulant use among ED patients with untreated opioid use disorder was associated with distinct sociodemographic, social, and health factors. Improved ED-based screening, intervention, and referral protocols for patients with opioid use disorder and amphetamine-type stimulant use are needed.

Use Motives of Patients with Amphetamine-Type Stimulants Use Disorder and Attention-Deficit/Hyperactivity Disorder.

INTRODUCTION: There is a frequent comorbidity of amphetamine-type stimulants (ATS) use disorders and attention-deficit/hyperactivity disorder (ADHD). The assumption that this patient group "self-medicate" suggests that there are different use motives for ATS addicted patients with and without ADHD. OBJECTIVE: Our study investigates these potential differences in use motives. METHODS: Within a mixed-method approach, we examined the use motives of adults with ATS use disorder with and without ADHD in the first and latest month of their use. For this purpose, we used the 12-item Amphetamine-Type Stimulants Motive Questionnaire (AMQ) and a mind mapping technique after verifying that these tools are applicable to adults with ADHD. RESULTS: The mixed-method approach showed that enhancement motives were the most important motives in the first month of use (e.g., fun/kick/rush/desire, and curiosity/interest in the drug/appeal), and over time, the incidence of coping motives increased (e.g., repression and freeing the mind/not having to think/switching off). There were no differences between adults with and without ADHD in the AMQ data, while the qualitative data showed that adults with ADHD used ATS less often out of social motives. In particular, the results showed no differences in the coping dimension and, thus, did not suggest that self-medication is an important factor for patients with ADHD. CONCLUSIONS: Patients with and without ADHD show very similar motive patterns for ATS use. This indicates that ATS treatment programs addressing use motives do not necessarily have to be different for patients with and without ADHD.

No Fever, No Murmur, No Problem? A Concealed Case of Infective Endocarditis.

BACKGROUND: Infective endocarditis is associated with significant morbidity and mortality, despite advances in diagnosis and treatment strategies. Injecting drug users are particularly at risk of endovascular infections, especially with multi-resistant and virulent microorganisms. Typically, patients with endocarditis present with constitutional symptoms, such as high fever and malaise combined with cardiorespiratory symptoms of valvular failure or emboli, such as septic pulmonary embolism. CASE REPORT: A 33-year-old female with a history of peptic ulcer disease presented to the emergency department with 3 days of increasing unilateral calf pain and swelling. There was no history of trauma or immobilization, no fever or clinical signs of sepsis or cardiopulmonary symptoms. A history of recent i.v. amphetamine injection in the forearm was elicited and empiric treatment for endovascular infection was commenced. Workup revealed methicillin-resistant Staphylococcus aureus mitral papillary endocarditis with gastrocnemius pyomyositis, multi-joint septic arthritis, and brain abscesses. After a 60-day inpatient stay, including intensive care admission for septic shock, the patient made a good recovery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The incidence of injecting drug use is increasing, and these patients are at risk of severe invasive infections with multi-resistant organisms. The emergency physician is most often responsible for the initial workup and treatment of patients with suspected infective endocarditis, with timely collection of blood cultures and appropriate antibiotics being essential interventions. This case highlights that even without fever, murmurs, or constitutional symptoms, severe multisystem infections from endocarditis can occur.

Amphetamine-type-substance-related presentations to the Emergency Department Mental Health Team of a local health district in Australia.

OBJECTIVES: To identify the prevalence and profile of amphetamine-type-substance-related presentations to the Emergency Department Mental Health Team of a local health district in Australia. METHODS: Data was collected from medical records of all amphetamine-type-substance presentations to the Emergency Department Mental Health Team over a 1-year period, between 1 January 2015 and 31 December 2015. RESULTS: Of all presentations referred to the Emergency Department Mental Health Team, 0.15% (N = 189) were amphetamine-type-substance related. Of these, the majority were male, the average age was 32, 19.0% engaged in intravenous drug use, some were aggressive and 15.9% required tranquilisation. The most common presenting issues were psychosis and suicidal threats, intent and behaviour (including intentional overdose). Multiple comorbid conditions were identified. On discharge, 34.4% were admitted into a psychiatric hospital and 32.8% were referred to Community Mental health teams. CONCLUSIONS: Amphetamine-type-substance users suffer from multiple comorbidities and pose a significant burden on emergency services.

[Series: Medicaments and oral healthcare. Medicaments and addictive substances, potentially inducing or ameliorating bruxism]. / Serie: Medicamenten en mondzorg. Medicamenten en verslavende middelen die potentieel bruxisme induceren of dempen.

Bruxism is described as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. This article provides an inventory of medications registered in the Netherlands and of addictive substances reported to potentially induce or aggravate bruxism as an adverse effect, and of medications registered in the Netherlands reported to potentially ameliorate existing bruxism. Groups of medications known as having the potential adverse effect of bruxism are amphetamines, anticonvulsants and selective serotonin reuptake inhibitors. Separate medicaments found in the scientific literature, having this potential are aripiprazole, atomoxetine, duloxetine, flecainide, ketotifen and methadone. Addictive substances with bruxism as potential adverse effect are alcohol, heroin, methamphetamine, methylenedioxymethamphetamine, nicotine and piperazines. Medications with the potential to ameliorate existing bruxism are botulinum toxin A, bromocriptine, buspirone, clonazepam, clonidine, gabapentin and levodopa.

Amphetamine availability predicts amphetamine-related mental health admissions: A time series analysis.

OBJECTIVE: Amphetamine use and availability have increased in Australia and there are concerns that this has led to more frequent hospital admissions with amphetamine-related psychosis. This study examines whether amphetamine-related admissions to mental health units are more common at times of greater amphetamine availability. METHODS: We conducted an ecological study using aggregate crime and health service data for NSW, Australia, from January 2000 to March 2015. Amphetamine-related criminal incidents (arrests or cautions for possession or use) were used as an indirect measure of amphetamine availability. Semiparametric time series analysis was used to compare monthly arrest rates to monthly hospitalisation rates for (1) amphetamine abuse or dependence, (2) amphetamine-related psychosis and (3) any psychosis. RESULTS: Amphetamine-related admissions to NSW mental health units have increased four- to fivefold since 2009 and comprised approximately 10% of all admissions to these units in early 2015. There was a significant association between arrests and amphetamine-related admissions. After adjustment for seasonal variation, this effect demonstrated a time lag of 1-2 months. There was no relationship between amphetamine arrests and overall admissions for psychosis. CONCLUSION: Greater amphetamine availability significantly predicts admissions for amphetamine use disorders and amphetamine-related psychosis. Better treatment strategies are needed to break the nexus between drug availability and drug-related harm.

Psychosis associated with acute recreational drug toxicity: a European case series.

BACKGROUND: Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs. METHODS: The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset. RESULTS: Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations. CONCLUSION: The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators.

Stimulants for depression: On the up and up?

The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression--specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants. More importantly, there is little evidence from randomised controlled trials supporting their efficacy in treating depression, although modafinil has been shown to be effective in reducing prominent depressive symptoms, such as fatigue. Research is urgently required to clarify psychostimulants' mechanisms of action and to evaluate their long-term benefits and risks in the treatment of major and bipolar depression. Ultimately, specificity of action needs to be determined to inform the sophisticated clinical use of psychostimulants in the management of depression. Until then they should only be prescribed if absolutely necessary, and even then their prescription should be facilitatory and time limited unless it is for investigational purposes.

Intravenous Use of Prescription Psychostimulants; A Comparison of the Pattern and Subjective Experience between Different Methylphenidate Preparations, Amphetamine and Cocaine.

BACKGROUND/AIMS: Methylphenidate (MPH) has been the most commonly used intravenous (i.v.) substance in Iceland in recent years. In Iceland, MPH is available in 3 forms: immediate-release (IR) tablets (MPH IR, short-acting), sustainable-release (SR) capsules (MPH SR, long-acting) and osmotic-release (OROS) tablets (MPH OROS, long-acting). The aims of the study were to compare the pattern and subjective effects of i.v. MPH use to other i.v. psychostimulants and examine whether the pattern of use differs among MPH preparations. METHODS: This is a nationwide descriptive study. Information was collected from 95 i.v. substance users undergoing inpatient detoxification and reporting i.v. MPH use in the last 30 days using a semi-structured interview. RESULTS: MPH SR was both the most commonly used (96%) and preferred i.v. psychostimulant (57%). The intensity and duration of 'euphoria' did not differ between cocaine and MPH SR. No participant reported MPH OROS as their preferred substance even though a third had used it in the past month. CONCLUSIONS: The pattern of i.v. MPH use is similar to other psychostimulants among treatment seeking patients. MPH OROS was the least preferred i.v. psychostimulant, despite having the largest market share in Iceland. The results indicate that MPH OROS has less abuse potential than other MPH preparations.

Clinical Characteristics and Outcomes of Patients with Amphetamine-Associated Cardiomyopathy in South Auckland, New Zealand.

BACKGROUND: Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood. METHODS: Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified. RESULTS: Mean age at presentation was 40±10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end-diastolic dimension 6.8±1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22±8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure. CONCLUSION: Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high.

The Impact of Illicit Use of Amphetamine on Male Sexual Functions.

INTRODUCTION: Data concerning the impact of amphetamine on male sexual functions are limited, although amphetamine has been used as an aphrodisiac. AIMS: This cross-sectional study was to assess the impact of illicit use of amphetamine on male sexual functions. METHODS: Male illicit drug users in a Drug Abstention and Treatment Center were recruited to complete a self-administered questionnaire, and data were compared with age-matched controls. MAIN OUTCOME MEASURES: The International Index of Erectile Function (IIEF) and global assessment questions were used to assess sexual functions. RESULTS: Of 1,159 amphetamine mono-illicit drug users, the mean age was 31.9 ± 7.5 (18-57) years, and mean duration of drug use was 30.7 ± 52.2 (median 9, range 0.1-252) months. Half of them reported that drug use had no impact on their sexual functions. The other half reported drug impacts as reduced erectile rigidity and sexual life satisfaction, enhanced orgasmic intensity, and prolonged ejaculation latency time more often than the opposite effects, while they reported enhanced or reduced effect equally on sexual desire. Dosing frequency of amphetamine was associated with its impact on sexual functions, but duration of its use had little association with that. Compared with 211 age-matched controls, the amphetamine mono-illicit drug users had lower IIEF scores in the domains of erectile function, orgasmic function, and overall satisfaction, but there are no significant differences in intercourse satisfaction and sexual desire scores. The prevalence of erectile dysfunction (ED) was significantly higher in the drug users than in the controls (29.3% vs. 11.9%). The odds ratio of ED for amphetamine use was 2.1 (95% confidence interval 1.2-3.6) after adjustment for other risk factors. CONCLUSIONS: The impact of illicit use of amphetamine on male sexual functions varied among users, and their ED prevalence was higher than the controls.