Search

Caffeine is regularly used by college students to enhance mood and academic performance. Although high doses confer risk for negative consequences, moderate doses of caffeine may lead to acute improvements in mood and cognitive functioning. Notably, the pharmacological effects of caffeine may be enhanced by expectancy effects. College students may also engage in nonmedical prescription stimulant use for similar purposes, as students expect strong cognitive enhancement from prescription stimulants and consider them to be more efficacious than caffeine. The purpose of the current study was to examine whether the pharmacological effects of caffeine on mood/drug effects and cognitive performance are enhanced when expecting a conceivably stronger stimulant (i.e., Adderall) compared to when expecting caffeine. Sixty-five undergraduate students were randomized to condition across two variables: drug ingested (placebo or 200 mg caffeine) and drug expected (caffeine or Adderall). Participants completed self-report measures of mood and drug effects pre- and post-drug, as well as cognitive assessments post-drug. There were significant main effects of drug ingested and drug expected on several post-drug measures. Subjects receiving caffeine reported feeling more high, stimulated, anxious, and motivated than subjects receiving placebo. Further, subjects expecting Adderall reported stronger amphetamine effects and feeling more high, and performed better on a working memory test, than those expecting caffeine. Effects tended to be strongest in participants receiving caffeine and expecting Adderall. Modifying expectancies, in conjunction with the pharmacological properties of caffeine at moderate doses, may be one mechanism by which college students may experience differential effects of caffeine. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Recent advances in diagnostic research identified that individuals with higher impulsivity and sensation-seeking scores tend to report more positive subjective responses to stimulant drugs such as amphetamine. The current exploratory study hypothesized that differences in underlying mesocorticolimbic circuitry may mediate the relationship between personality and responses to stimulants due to its previously established implication in reward processes as well as the overlap between its dopaminergic projections and the pharmacodynamics of many stimulants. Forty participants (20 female) were recruited with relatively high- and low-impulsivity and sensation-seeking scores as defined by the Zuckerman-Kuhlman Personality Questionnaire (Form IIIR; Zuckerman, Kuhlman, Joireman, Teta, & Kraft, 1993) for a double-blind, placebo-controlled, intranasal amphetamine administration study conducted within an MRI scanner. Active state seed-to-voxel connectivity analyses assessed the effects of amphetamine, personality, subjective responses to amphetamine, and their interactions with mesocorticolimbic seeds on data collected during monetary incentive delay and go/no-go task performance. Results indicated that amphetamine administration largely disrupted brain activity as evidenced by connectivity values shifting toward no correlation among brain stem, striatal, and frontal cortex regions. Additionally, associations of impulsivity and connectivity between ventral tegmental and medial orbitofrontal as well as lateral orbitofrontal and putamen regions were inverted from negative to positive during the placebo and amphetamine conditions, respectively. Personality was unrelated to subjective responses to amphetamine. Results are interpreted as providing evidence of underlying differences in mesocorticolimbic circuitry being a potential target for requisite diagnostic and treatment strategies implicated with stimulant use disorders, but further research is needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Correlational evidence has linked methamphetamine use and HIV sexual risk behavior, but the direct effects of methamphetamine on sexual desire and sexual decision making in humans have not been tested. This study was designed to test the effect of methamphetamine administration on sexual desire and hypothetical condom-use decisions as measured by the Sexual Delay Discounting Task. Recreational stimulant users (n = 19) participated in this within-subject, placebo-controlled study comparing the effects of 0 mg, 20 mg, and 40 mg of oral methamphetamine. Compared to placebo, methamphetamine caused dose-related and time-related increases in a single-item sexual desire rating and some standard stimulant abuse liability ratings, as well as dose-related increases in the Sexual Arousal and Desire Inventory (SADI; a multidimensional scale capturing positive and negative aspects of desire/arousal). However, methamphetamine caused no significant mean differences in likelihood of condom use within the Sexual Delay Discounting Task or the Monetary Discounting Task. SADI scores were negatively correlated with change from placebo in condom use likelihood in the Sexual Delay Discounting Task for some partner conditions (i.e., decreased reported likelihood of condom use in participants who experienced increased desire/arousal and vice versa). These mixed results may be consistent with methamphetamine's role as both a treatment for attention-deficit/hyperactivity disorder and as a drug of abuse associated with increased delay discounting, and they suggest that methamphetamine's effects on discounting may be modulated by the reinforcing properties of what is being discounted. Delay discounting may be an understudied element of risky sexual decision making, particularly among individuals who use methamphetamine. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

To investigate long-term (12-month) safety and symptom control of extended-release methylphenidate (MPH-MLR) in children aged 4 to6 years after treatment optimization.A total of 90 children aged 4 to6 years with attention-deficit/hyperactivity disorder (ADHD) were enrolled from 2 MPH-MLR studies. Treatment-emergent adverse events (TEAEs) and ADHD symptom control were assessed in the safety population (n = 89) and modeled with mixed model analyses.Most TEAEs (89.9%) were rated by investigators as of mild or moderate severity. One serious AE was reported (unrelated to study drug). Ten children discontinued because of TEAEs. Two discontinued because of weight loss; no significant increase in the rate of underweight children from baseline to endpoint was observed. Overall, 18% lost weight and 18% reported decreased appetite. Weight and height z scores and obesity rates decreased significantly from baseline to endpoint. Insomnia was reported (9%); none of these children discontinued. Sleep quality did not change significantly. Hypertension was reported (6.7%); none of these children dropped out. Diastolic, but not systolic, blood pressure increased significantly during the follow-up. Control of ADHD symptoms was maintained throughout follow-up.These data contribute to the understanding of the long-term safety of an extended-release stimulant in children 4 to6 years of age. The observed risk of a TEAE-related discontinuation was ∼11%. TEAEs were not dose related, and most were of mild to moderate severity. Symptom control was maintained through the year-long study.A 12-Month Open Label Safety Study of Aptensio XR® in Children Ages 4-5 Years Diagnosed With ADHD (EF004); https://clinicaltrials.gov; NCT02677519.

BACKGROUND AND AIMS This study aimed to (1) describe trends in stimulant-alone and stimulant and other substance use overdose deaths from 2012 to 2018 and (2) measure patient and service use characteristics across stimulant-related overdose death profiles. DESIGN Retrospective cohort study of patients who died from stimulant-involved overdose between annual years 2012 and 2018. SETTING United States Veterans Health Administration (VHA). A total of 3631 patients died from stimulant-involved overdose, as identified through the National Death Index. MEASUREMENTS Stimulant-involved overdose deaths were categorized by stimulant type (cocaine or methamphetamine/other) and other substance co-involvement. Cause of death data were linked to patient characteristics, including demographic and treatment use preceding overdose from VHA administrative data. We examined trends over time and compared treatment use factors between the following mutually exclusive overdose profiles: cocaine alone, methamphetamine alone, cocaine + opioid, methamphetamine + opioid, any stimulant + other substance and cocaine + methamphetamine. FINDINGS The rate of overdose death was 3.06 times higher in 2018 than 2012, with increases across all toxicology profiles. Compared with cocaine-involved overdoses, methamphetamine-involved overdoses were less likely in people who were older [adjusted odds ratio (aOR) = 0.22, 95% confidence interval (CI) = 0.06-0.87 aged 65+ versus 18-29] and more likely among those who lived in rural areas (aOR = 2.73, 95% CI = 1.43-5.23). People who died from stimulant + opioid overdoses had lower odds of a stimulant use disorder diagnosis compared with stimulant alone deaths (cocaine: aOR = 0.55, 95% CI = 0.41-0.75, methamphetamine: aOR = 0.44, 95% CI = 0.29-0.68). CONCLUSIONS The rate of deaths among US Veterans from stimulant-related overdose was three times higher in 2018 than 2012. Key differences in characteristics of patients across overdose toxicology profiles, such as geographic location and health-care use, point to distinct treatment needs based on stimulant use type.

Objectives: To study the safety and efficacy of the long-acting methylphenidate formulation PRC-063 in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Adolescents 12 to ≤...

Stimulant use disorder (SUD) is a public health problem in the United States that is associated with increased morbidity and mortality. Psychosocial interventions, such as cognitive behavioral therapy and contingency management, are the main treatment modality for SUDs and no pharmacotherapy is currently FDA approved for this indication. Although some medications show promising data for the treatment of SUD, the evidence remains inconsistent, and the clinical application is limited due to the heterogenicity of the population and the lack of studies in patients with various comorbidities. Selection of pharmacotherapy treatment for methamphetamine intoxication, persistent methamphetamine-associated psychosis with methamphetamine use disorder, and cocaine use disorder in patients with co-occurring OUD are discussed in 3 patient cases.

Background and purpose Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to date. Experimental approach Pharmacokinetics, acute effects, and addictive potential in a series of behavioural tests in Wistar rats were performed following subcutaneous (s.c.) administration of DCK (5, 10, and 30 mg·kg-1 ) and its enantiomers S-DCK (10 mg·kg-1 ) and R-DCK (10 mg·kg-1 ). Additionally, activity at human N-methyl-d-aspartate (NMDA) receptors was also evaluated. Key results DCK rapidly crossed the blood brain barrier, with maximum brain levels achieved at 30 min and remaining high at 2 h after administration. Its antagonist activity at NMDA receptors is comparable to that of ketamine with S-DCK being more potent. DCK had stimulatory effects on locomotion, induced place preference, and robustly disrupted PPI. Locomotor stimulant effects tended to disappear more quickly than disruptive effects on PPI. S-DCK had more pronounced stimulatory properties than its R-enantiomer. However, the potency in disrupting PPI was comparable in both enantiomers. Conclusion and implications DCK showed similar behavioural and addictive profiles and pharmacodynamics to ketamine, with S-DCK being in general more active. It has a slightly slower pharmacokinetic profile than ketamine, which is consistent with its reported longer duration of action. These findings have implications and significance for understanding the risks associated with illicit use of DCK.

Methamphetamine is a highly addictive central stimulant with extensive and strong neurotoxicity. The neurotoxicity of methamphetamine is closely related to the imbalance of dopamine levels and the destruction of the blood-brain barrier. An increase in dopamine may induce adverse effects such as behavioral sensitization and excessive locomotion. Damage to the blood-brain barrier can cause toxic or harmful substances to leak to the central nervous system, leading to neurotoxicity. The renin-angiotensin system is essential for the regulation of dopamine levels in the brain. Matrix metalloproteinase-9 causes reward effects and behavioral sensitization by inducing dopamine release. Prolactin has been shown to be involved in the regulation of tight junction proteins and the integrity of the blood-brain barrier. At present, the treatment of methamphetamine detoxification is still based on psychotherapy, and there is no specific medicine. With the rapid increase in global seizures of methamphetamine, the treatment of its toxicity has attracted more and more attention. This review intends to summarize the therapeutic mechanisms of renin-angiotensin inhibitors, matrix metalloproteinase-9 inhibitors and protein hormones (prolactin) on methamphetamine neurotoxicity. The repair effects of these three on methamphetamine may be related to the maintenance of brain dopamine balance and the integrity of the blood-brain barrier. This review is expected to provide the new therapeutic strategy of methamphetamine toxicity.

Objective To evaluate the frequency and correlates of needing to switch the initial treatment with a stimulant medication to the alternative family in newly referred, untreated adults with ADHD initiating treatment. Methods Subjects were consecutively referred unmedicated adults with DSM-5 ADHD who initiated stimulant treatment. Before assessment with an expert clinician, participants completed a battery of self-report measures to assess psychopathology, executive functioning, emotional dysregulation, and mind wandering. The rate of switching was examined using information from electronic medical records for up to three clinical follow-up visits. Those who did and did not need to switch were compared on baseline demographic and clinical characteristics. Results Twenty-four percent (N = 21/86) of ADHD patients needed to switch from their initially prescribed stimulant family within 60 days of initiating treatment due to poor tolerability. While the rate of switching was significantly higher in those initially prescribed MPH, the rate of patients requiring changes in formulation or additional antianxiety or antidepressant treatment was higher in those taking AMPH. There were some hints about predictive risk factors for switching by the presence of emotional dysregulation and depressive symptoms, depending on age and sex. Conclusions These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying safe and effective treatments for these patients.

The pathophysiology of saccular aneurysm rupture (berry aneurysm) secondary to cocaine and methamphetamine use has been classically attributed to their effects on cerebrovasculature. We conducted a literature review to determine the contribution of cocaine and methamphetamines to aneurysm formation and subarachnoid hemorrhage (SAH). Our literature search revealed the contribution to berry aneurysm by both cocaine and methamphetamines is multifactorial and includes: hemodynamic compromise, hypertensive effects, inflammation, wall stress and hypoperfusion of cerebral vasculature. The pathophysiological mechanisms by which these drugs contribute to saccular aneurysm and SAH is reviewed. We further discuss current grading scales used to measure the severity and extent of SAH in cocaine and methamphetamine users. Additionally, conflicting data regarding the specific role of cocaine and methamphetamines was retrieved. Although questions remain regarding the exact role of cocaine and methamphetamines, the evidence suggests that they do increase the probability of saccular aneurysm formation, rupture and poor patient prognosis.

Background Stimulant use has increased across the US, with concomitant opioid and methamphetamine use doubling between 2011 and 2017. Shifting patterns of polysubstance use have led to rising psychostimulant-involved deaths. While it is known that individuals who use methamphetamine require greater access to treatment, there is still little known about methamphetamine use and treatment among individuals who are already engaged in outpatient substance use treatment. Objectives To characterize care-engaged individuals who use methamphetamine to guide harm reduction and treatment strategies. Methods Retrospective cohort study of individuals at a large academic medical center in Massachusetts with ≥ 2 positive methamphetamine oral fluid toxicology tests between August 2019 and January 2020. We performed descriptive analysis of sociodemographic, medical, and drug use characteristics and a comparative analysis of injection methamphetamine use versus other routes of use. Results Included were 71 individuals [56 male (80%), 66 non-Hispanic white (94%), median age 36 (IQR 30–42)]. Nearly all had opioid (94%) and stimulant use disorder (92%). Most had (93%) or were (83%) being treated with medications for opioid use disorder, but few received pharmacologic treatment for methamphetamine use disorder (24%). None received contingency management treatment. People who inject methamphetamine (68%) were more likely to have a history of overdose (91% vs. 70%; p = 0.02), have HCV (94% vs. 52%; p Conclusions Individuals in our study had high prevalence of polysubstance use, particularly concomitant methamphetamine and opioid use. Individuals who were well connected to substance use treatment for their opioid use were still likely to be undertreated for their methamphetamine use disorder and would benefit from greater access to contingency management treatment, harm reduction resources, and resources to address adverse social determinants of health.

We investigated the association of 90-day opioid and stimulant co-use and HIV risk behaviors in a cross-sectional analysis of hospitalized HIV-negative people who inject drugs (PWID). We compared those injecting opioids alone to two sub-groups who co-used opioids with (1) cocaine, (2) amphetamine-type stimulants (ATS), on sex and injection drug risk behaviors assessed via the Risk Assessment Battery (RAB), where a higher score indicates a higher risk. Of 197 participants who injected opioids, 53% co-used cocaine only, 5% co-used ATS only, 18% co-used both cocaine and ATS, 24% co-used neither stimulant. PWID who injected opioids alone had a mean RAB drug risk score of 5.98 points and sex risk score of 2.16 points. Compared to PWID who injected opioids alone, PWID who co-used stimulants had higher mean drug risk RAB scores: cocaine, b = 2.84 points [95% confidence interval (CI) 1.01; 4.67]; ATS, b = 3.43 points (95% CI 1.29; 5.57). Compared to PWID who injected opioids alone, cocaine co-use was associated with higher sex RAB scores b = 1.06 points (95% CI 0.32; 1.79). Overall, we found a significant association between stimulant co-use and higher HIV sex and drug risk scores.Investigamos la asociación entre el uso conjunto de opioides y estimulantes durante 90 días y las conductas de riesgo frente al VIH en un análisis transversal de personas hospitalizadas que se inyectan drogas y que son VIH negativas (“PWID” en lo sucesivo). Se comparó a los que consumían únicamente opioides con dos subgrupos que consumían opioides junto con (1) cocaína, (2) estimulantes de tipo anfetamínico (“ATS” en lo sucesivo), en relación con las conductas de riesgo evaluadas mediante la Serie de Pruebas de Evaluación de Riesgos (“RAB” en lo sucesivo). De los 197 participantes, el 53% sólo consumía cocaína, el 5% sólo ATS y el 18% cocaína y ATS; el 24% restante únicamente se inyectaba opiáceos. En comparación con las PWID que únicamente se inyectaban opioides, las PWID que consumían paralelamente estimulantes tenían puntuaciones medias más altas en el RAB de riesgo de drogas: cocaína, b = 2.84 puntos (intervalo de confianza [IC] del 95% 1.01; 4.67); ATS, b = 3.43 puntos (IC del 95% 1.29; 5.57). En comparación con las PWID que únicamente se inyectaban opioides, el co-consumo de cocaína se relacionó con puntuaciones más altas en la RAB en el sexo (1.06 puntos, IC del 95% 0.32; 1.79). En general, se encontró una asociación significativa entre el co-consumo de estimulantes y las puntuaciones más altas de riesgo sexual y de drogas frente al VIH.

Background Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation strategies are often helpful at reducing the severity of depression. While there are many potential adjunctive medication choices, psychostimulants are among the more controversial options. Objectives The present review sought to clarify the comparative efficacy and safety of different stimulant-like medications to treat depression. Methods We conducted a systematic review and network meta-analysis of randomized, controlled trials (RCTs) using psychostimulant medications to treat adults with depression. Outcomes were pooled using rate ratios (RRs) for dichotomous outcomes (e.g., response, adverse events) and standardized mean differences (SMDs) for continuous outcomes (e.g., change in depression scores). Results We identified 37 eligible studies (ranging from 1958 to 2016). We assessed nine psychostimulants: methylphenidate (n=14), dextroamphetamine (n=9), modafinil (n=6), lisdexamphetamine (n=3), methylamphetamine (n=3), pemoline (n=2), atomoxetine (n=1), desipramine (n=1), and imipramine (n=1). Overall, psychostimulants demonstrated efficacy for depression, reduced fatigue and sleepiness, and appeared well-tolerated. However, there was inconsistent evidence across particular psychostimulants. For example, the only psychostimulant which demonstrated efficacy for depression—in terms of both symptom severity and response rates—was methylphenidate. Conclusions While our review suggests that some psychostimulants—particularly methylphenidate—appear well-tolerated and demonstrate some efficacy for depression, as well as fatigue and sleepiness, the strength of evidence in our estimates was low to very low for most agents given the small sample sizes, few RCTs, and imprecision in most estimates. A lack of consistent evidence precludes a definitive hierarchy of treatments and points to a need for additional, high-quality RCTs.

In the United States, men who have sex with men (MSM) remain as the demographic group with the highest HIV incidence rates and account for 53% of new HIV infections in 2006 (Rajasingham, Mimiaga, White, Pinkston, Baden, & Mitty, 2012). One of the reasons accounting for such high rates of HIV transmission between gay, bisexual and MSM (GBM) can be attributed to poly-substance use and the use of crystal methamphetamine (Solomon, Halkitis, Moeller, & Pappas, 2012; Rajasingham et al., 2012). The U.S. Centre for Disease Control and Prevention (2007) reported methamphetamine use in the MSM community is of particular concern due to the high prevalence of HIV and the use of the stimulant. Meanwhile, researchers have found methamphetamine use is closely corrleated to sexual risk taking among GBM and such intimate link between risky sexual behaviour and methamphetamine use have led to a possible double epidemic (Halkitis, Green, & Carragher, 2006). In particular, the use of methamphetamine has been found to be correlated to the frequency of unprotected insertive anal intercourse (UIAI) and unprotected receptive anal intercourse (URAI) among HIV positive and persons with unknown serostatus causal partners over time (Halkitis, Mukherjee, & Palamar, 2009). As an effort to better understand this social pheonemon, this paper focuses on the exploration and identification of the psycho-social and socio-cultural factors of crystal methamphetamine use among the GBM population.

Objective Substance use rates have increased in adults 50 years and older, and substance use in this population is associated with significant consequences. Given that little is known about their underlying substance use patterns, the objective was to identify latent classes of adults 50 years and older by past-year substance use, past-month substance use, and past-year substance use disorder (SUD) diagnosis. Methods The National Survey on Drug Use and Health is an annual nationwide cross-sectional U.S. survey. Participants were 35,229 civilian, non-institutionalized U.S. residents, 50 years and older. Past-year and past-month alcohol, tobacco, marijuana, heroin, cocaine, methamphetamine use, and opioid, stimulant, and tranquilizer/sedative prescription drug misuse (PDM) were captured, as was past-year DSM-IV SUD from these substances. Correlates included mental health, physical health, and healthcare utilization variables. Results Latent class analysis indicated four past-year or past-month substance use subgroups (Alcohol-Only, Alcohol-Tobacco-Marijuana, Cocaine-Polydrug, PDM-Polydrug), with SUD prevalence rising from 3.2% to 17.3%, 68.8%, and 78.5% by past-year subgroup; similarly, rates of past-year suicidal ideation increased from 2.1%, to 4.8%, 12.0%, and 20.4% by past-year subgroup. For SUD, there were three subgroups (Low Nicotine Dependence [ND], High Alcohol Use Disorder, Multiple SUDs). Over 90% of adults were in a low-risk subgroup (i.e., Alcohol-Only and Low ND), but members of Cocaine-Polydrug, PDM-Polydrug, or Multiple SUDs latent classes had high rates of mental and physical health concerns. Conclusions Most adults 50 and older have lower risk profiles, but those engaged in PDM or cocaine use are heavily substance-involved and need screening and likely multi-disciplinary intervention.

Attention-deficit/hyperactivity disorder is associated with impaired cognitive functioning and increased delay discounting (i.e., a stronger preference for immediate reward). At the group level, stimulant medication improves cognition and delay discounting, yet not all children exhibit problems in these domains, and previous work has not examined whether stimulant-induced improvements are moderated by baseline performance. To address this question in the current study, 82 children with attention-deficit/hyperactivity disorder (9-12 years old) attended a week-long research camp. On the baseline day (Monday), participants completed tasks of inhibitory control, visuospatial working memory, reaction time variability, and delay discounting. Children then completed a 3-day, randomized, double-blind, placebo-controlled trial of ∼1 mg/kg and 2 mg/kg long-acting methylphenidate (mean doses = 39.1 and 74.3 mg, respectively), during which they were readministered the battery of tasks. Cognitive composites (mean of inhibitory control, working memory, and reaction time variability performance) were created for the baseline and medication evaluation phases. As predicted, the extent to which cognition was improved with medication compared with placebo and with 2 mg/kg compared with 1 mg/kg was greatest among children with poorer baseline cognitive function. Children with stronger baseline cognition exhibited less improvement with methylphenidate compared with placebo and did not benefit from the 2 compared with the 1 mg/kg dose. In contrast, medication-related improvement in delay discounting was unrelated to baseline discounting. Given that improving cognitive function is one potential mechanisms by which stimulants exert their therapeutic effects, this study has significant implications for understanding how and for whom stimulant medication works. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Antonio Pardo, Thomas R King, Eman Rafla, Judith C Kando Tris Pharma, Inc. Clinical and Medical Affairs, Monmouth Junction, NJ, USAAntonio PardoTris Pharma, Inc., 2031 US Route 130, Monmouth Junction, NJ, 08852, USATel +1 (732) 940-2800Email apardo@trispharma.comIntroduction/Objective: ADHD is, for many people, a lifelong disease that requires chronic medication use. Stimulant therapy is often recommended as first-line treatment for ADHD. Adherence to stimulant treatment among patients diagnosed with ADHD is poor. Major regulatory agencies have recommended measurement of palatability for new tablet formulations. A new amphetamine extended-release tablet (AMPH ER TAB) for the treatment of attention-deficit/hyperactivity disorder (ADHD) was developed. The AMPH ER TAB has a bubblegum flavor and can be chewed or swallowed whole. In 2016, the FDA developed a draft guidance document on the topic of chewable drug tablet formulation palatability.Methods: A palatability study of the AMPH ER TAB using the 2016 FDA guidance was conducted. Subjects were asked to assess the taste, aftertaste, and mouthfeel of the tablet formulation using a short questionnaire. Scores from the questionnaire were rated and presented.Results: The substudy assessed 35 subjects with a mean age of 38 (± 11) years. Subjects were predominantly male, non-Hispanic, and White. Most subjects rated the oral sensation/mouth feel and taste of the tablet as positive (pleasant to very pleasant) (70.1% and 83.6%, respectively). Additionally, 86.6% of the subjects rated the strength of the taste as neutral (moderate taste) or positive (mild to no taste). Finally, 82.1% of all subjects rated the aftertaste as positive (pleasant to very pleasant) and 92.5% of subjects rated the strength of the aftertaste as neutral or positive (mild to no taste). The trends in evaluation scores for each question were similar regardless of whether the ER chewable tablet was administered under fasted or fed conditions.Conclusion: The positive palatability data presented here will be useful for future “real-world” assessments of adherence to treatment with the AMPH ER TAB. Enhanced adherence may bolster the argument that taste, mouthfeel, and aftertaste are critical determinants of treatment adherence.Keywords: ADHD, palatability, tablet, stimulant, amphetamine

Misuse of dextroamphetamine occurs in work and recreational contexts. While acute drug effects broadly predict abuse liability, few studies have considered the relationship between acute effects and context. This study examined how individual differences in acute effects of dextroamphetamine relate to desire to take dextroamphetamine again in different contexts. This secondary analysis used data from healthy adults with no history of moderate-to-severe substance use disorder, who received oral doses of placebo and dextroamphetamine (10 and 20 mg) over 3 sessions under double-blind, randomized conditions. Subjects rated subjective effects and completed reward-related behavioral tasks. Subjects rated their desire to take dextroamphetamine again in hypothetical work and recreational contexts. Multilevel models examined within-subjects change scores (10 mg-placebo; 20 mg-placebo) to determine how subjective effects and behavioral outcomes predicted desire to take dextroamphetamine again for work versus recreation. Subjects reported more desire to take 20 mg dextroamphetamine again for work than for recreation. At 20 mg, there was an interaction between context and liking/wanting, such that liking/wanting predicted desire to use dextroamphetamine for work only. There was also an interaction at 20 mg between context and psychomotor speed, such that psychomotor speed predicted interest in using dextroamphetamine for recreation only. We found that positive subjective effects predicted desire to use dextroamphetamine again for work, while increased motor effects predicted desire to use dextroamphetamine recreationally. Hedonic effects may be perceived as advantageous when working, while increased physical energy may be preferred during recreation, suggesting that context of intended use is important when examining abuse liability.

College students’ prescription stimulant and opioid misuse (PSM and POM) share psychosocial risks with other substance use. We sought to extend a prior study of these issues. Methods: National Coll...

Dopamine system deficiencies and associated behavioral phenotypes may be a critical barrier to success in treating stimulant use disorders. Similarities in dopamine dysfunction between cocaine and methamphetamine use disorder but also key differences may impact treatment efficacy and outcome. This review will first compare the epidemiology of cocaine and methamphetamine use disorder. A detailed account of the pharmacokinetic and pharmacodynamic properties associated with each drug will then be discussed, with an emphasis on effects on the dopamine system and associated signaling pathways. Lastly, treatment results from pharmacological clinical trials will be summarized along with a more comprehensive review of the involvement of the trace amine-associated receptor on dopamine signaling dysfunction among stimulants and its potential as a therapeutic target.

Cathinone, the main psychoactive compound found in the plant Catha edulis Forsk. (khat), is a β-keto analogue of amphetamine, sharing not only the phenethylamine structure, but also the amphetamine-like stimulant effects. Synthetic cathinones are derivatives of the naturally occurring cathinone that largely entered the recreational drug market at the end of 2000s. The former “legal status”, impressive marketing strategies and their commercial availability, either in the so-called “smartshops” or via the Internet, prompted their large spread, contributing to their increasing popularity in the following years. As their popularity increased, the risks posed for public health became clear, with several reports of intoxications and deaths involving these substances appearing both in the social media and scientific literature. The regulatory measures introduced thereafter to halt these trending drugs of abuse have proved to be of low impact, as a continuous emergence of new non-controlled derivatives keep appearing to replace those prohibited. Users resort to synthetic cathinones due to their psychostimulant properties but are often unaware of the dangers they may incur when using these substances. Therefore, studies aimed at unveiling the pharmacological and toxicological properties of these substances are imperative, as they will provide increased expertise to the clinicians that face this problem on a daily basis. The present work provides a comprehensive review on history and legal status, chemistry, pharmacokinetics, pharmacodynamics, adverse effects and lethality in humans, as well as on the current knowledge of the neurotoxic mechanisms of synthetic cathinones.

Background and Objective Pedestrian crashes represent a leading cause of pediatric injury. Children have particular risk due to underdeveloped cognitive and executive function skills. Given children with excessive daytime sleepiness (EDS) face deficiencies in executive function and cognitive skill that impact cognitive functions necessary for safe pedestrian engagement, this study examined whether treatment with the stimulant medication modafinil might improve both cognitive functioning and pedestrian safety among children with EDS. Methods Twelve children aged 8–16 years diagnosed with EDS participated in a within-subjects experiment. Children completed two laboratory visits, one while treated with modafinil and one untreated. During each visit, children completed two self-report sleepiness inventories, two cognitive tests [psychomotor vigilance test (PVT) and Conners’ continuous performance task (CPT; version 3.0, Multi-Health Systems, Inc.)], and 20 virtual pedestrian environment street-crossings. Parents completed a sleepiness survey about children. Results Related samples t-tests found consistent patterns of reduced sleepiness, improved cognitive functioning, and safer pedestrian behavior while children were medicated with modafinil compared to unmedicated. Statistically significant differences emerged for parent-reported child sleepiness (p < 0.01); PVT false starts, indicating improved attention, vigilance and alertness (p < 0.10); CPT omissions, signifying failure to respond to stimuli (p < 0.05); and shortest time-to-contact with oncoming virtual traffic (p < 0.05). Chi-square demonstrated children had fewer collisions with oncoming virtual traffic while medicated than unmedicated (p < 0.05). Conclusions Medication with the stimulant modafinil improved multiple aspects of cognitive functioning and pedestrian safety among children with EDS. The greatest benefits emerged on measures of alertness, attention, and response latency. Results suggest modafinil may improve real-world functioning in tasks like crossing streets.

Background Drug checking is a harm reduction intervention aiming to reduce substance use-related risks by improving drug user knowledge of the composition of unregulated drugs. With increasing fears of fentanyl adulteration in unregulated drugs, this study sought to examine whether the expected type of drug checked (stimulant vs. opioid) was associated with timing of drug checking service utilization (pre-consumption vs. post-consumption). Methods Data were derived from drug checking sites in British Columbia between October 31, 2017 and December 31, 2019. Pearson’s Chi-square test was used to examine the relationship between expected sample type (stimulant vs. opioid) and timing of service utilization. Odds ratios (OR) were calculated to assess the strength of this relationship. The Mantel–Haenszel (MH) test was used to adjust for service location. Results A total of 3561 unique stimulant and opioid samples were eligible for inclusion, including 691 (19.40%) stimulant samples; and 2222 (62.40%) samples that were tested pre-consumption. Results indicated a positive association between testing stimulant samples and testing pre-consumption (OR = 1.45; 95% CI 1.21–1.73). Regions outside of the epicenter of the province’s drug scene showed a stronger association with testing pre-consumption (ORMH = 2.33; 95% CI 1.51–3.56) than inside the epicenter (ORMH = 1.33; 95% CI 1.09–1.63). Conclusion Stimulant samples were more likely to be checked pre-consumption as compared with opioid samples, and stimulant samples were more likely to be tested pre-consumption in regions outside the epicenter of the province’s drug scene. This pattern may reflect a concern for fentanyl-adulterated stimulant drugs.

Purpose Opioid overdose deaths involving stimulants are on the rise. Demographic characteristics for these deaths to be used in prevention efforts have not been established. Methods We conducted a statewide retrospective study to evaluate the characteristics of fatal opioid overdoses with stimulant involvement using 2018 Tennessee State Unintentional Drug Overdose Reporting System data. Data sources included death certificates, autopsy reports, toxicology, and prescription drug monitoring program data. Frequencies were generated to compare demographics, circumstances, opioid history, death scene information, bystander intervention, and toxicology between fatal opioid overdoses with and without stimulant involvement. Results A total of 1183 SUDORS opioid overdose deaths occurred in Tennessee in 2018 of which 434 (36.7%) involved a stimulant. Fatal opioid overdoses involving stimulants had higher frequencies of illicit drugs on toxicology specifically marijuana, fentanyl, and heroin compared to fatal opioid overdoses without stimulants. Fatal opioid overdoses involving stimulants had higher frequencies of scene indications of injection drug use compared to fatal opioid overdoses without stimulant involvement. Conclusions Fatal overdoses are shifting from mainly opioid to multidrug involvement and over one-third include use of stimulants. This analysis can help public health practitioners understand the circumstances around fatal opioid overdoses involving stimulants to inform tailored prevention strategies.

Introduction Initiation of tobacco products typically occurs in adolescence. Adolescence is a critical period in development where the maturation of brain neurocircuitry is vulnerable to nicotine. Nicotine-containing products and psychostimulants, such as methamphetamine (METH), are often coabused. Rodent studies have shown that nicotine exposure in early adolescence increases subsequent drug intake and reward. Given the exponential increase in e-cigarette use among adolescents, there is a pressing need to understand whether adolescent nicotine exposure impacts concurrent increased METH use. The objective of this study is to evaluate age, sex, and longitudinal effects of nicotine pretreatment on METH reinforcement. Aims and Methods Male and female Sprague-Dawley rats were pretreated with a subchronic, low-dose nicotine (2×, 30 µg/kg/0.1 mL, intravenous) or saline during early adolescence (postnatal days [PN] 28–31) or adulthood (PN 86–89). Following nicotine pretreatment, on PN 32 or PN 90, animals underwent operant intravenous self-administration for METH (20 µg/kg/inf) over a 2-hour period for five consecutive days. Results Early adolescent nicotine exposure enhances intravenous METH self-administration in male, but not female adolescents. Male adult rats self-administer METH over the 5-day testing period, independent of nicotine exposure. In contrast, nicotine exposure increases METH self-administration in female adults during the later sessions of the 5-day testing period. Conclusions Taken together, our data highlight age- and sex-dependent effects of low dose, subchronic nicotine pretreatment on subsequent intravenous METH self-administration. Implications A majority of polysubstance users begin smoking before the age of 18. Mounting evidence highlights adolescent susceptibility to nicotine exposure on brain and behavior. With the escalation in nicotine-containing products and stimulant use among adolescents, it is important to identify the consequences from adolescent nicotine use, including polysubstance use. Our study provides evidence that adolescent nicotine exposure enhances subsequent METH use, with important sex- and age-dependent effects.

Monoamine releasers such as d-methamphetamine (d-MA) can reduce cocaine use in laboratory studies and have been forwarded for the management of cocaine use disorder (CUD). However, the proven abuse liability of d-MA has limited enthusiasm for clinical use. The levorotatory isomer of MA, l-MA, appears to have lesser stimulant effects, possibly due to its preferential norepinephrine-releasing properties compared with dopamine. The present study evaluated the abuse potential of l-MA by comparing its reinforcing effects with known stimulant drugs of abuse in nonhuman primates. Adult rhesus macaques (N = 4) responded for intravenous injections of cocaine, d-MA, methcathinone (MCAT), or l-MA under a fixed-ratio (FR) schedule of reinforcement; reinforcing effectiveness was evaluated using behavioral economic demand procedures. In a separate cohort (N = 9), daily activity and food-reinforced responding were assessed during 100 days of treatment with daily dosages of l-MA (2.3 mg/kg per day, i.v.) or d-MA (0.74 mg/kg per day, i.v.) previously shown to decrease cocaine self-administration. Results show that all drugs maintained self-administration, with peak injections reaching ∼100 inj per session for cocaine, MCAT, and d-MA and ∼50 inj per session for l-MA . In demand studies, self-administration of each drug gradually decreased as FR size increased. The exponential model of demand indicated that the reinforcing effectiveness of l-MA was significantly less than the other drugs studied. Chronic l-MA treatment did not appreciably alter daily activity and only transiently suppressed food-reinforced responding. These data, coupled with previous findings that l-MA effectively reduces stimulant self-administration, suggest that l-MA, or other norepinephrine-preferring releasers, may serve as agonist medication for CUD with lesser abuse liability than common psychostimulants. SIGNIFICANCE STATEMENT: Development of pharmacotherapies for cocaine use disorder remains a formidable challenge. Agonist-based therapies show promise, but enthusiasm is tempered by the abuse liability of previously proposed medications. This study evaluated the abuse liability and chronic treatment effects of methamphetamine’s levorotatory isomer (l-MA). l-MA demonstrated lower abuse liability compared with commonly abused stimulants and produced few untoward effects. In the context of recent studies demonstrating that l-MA attenuates stimulant self-administration, these findings support l-MA’s potential as a pharmacotherapy for stimulant addiction.

The production and use of the highly addictive stimulant methamphetamine are a serious public health problem in the USA and globally. Because of its increased popularity with recreational drug users, accidental or intentional poisoning incidents in companion animals have become an unavoidable scenario in veterinary medicine. We describe a case of methamphetamine poisoning in a 4-year-old female German Shepherd, with postmortem analytical quantitation of methamphetamine and its metabolite, amphetamine, in bodily tissues and fluids. Many tissues and bodily fluids can be tested to confirm methamphetamine exposure. More importantly, the higher concentrations found in stomach contents and liver, kidney and heart tissues suggest these are the most useful diagnostic specimens for postmortem confirmation of toxicosis in pets, especially in cases in which the source material is not available for testing or in cases with no postmortem evaluation.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into adulthood. However, it remains unclear how maternal ADHD could affect pregnancy and birth as well as early mother-(father)-child interaction. There are several studies investigating the effect of depressed or anxious parents on parent-child-interactions in early infancy, but data about the influence of parental ADHD is lacking although it is a common mental disorder in parents. Additionally, the prescription of stimulant and other ADHD medication for adult ADHD patients is rising due to improved diagnostic procedures and a greater awareness of this disorder in adulthood among psychiatrists and psychologists. However, this leads to increased numbers of treated ADHD women that wish to have children or experience unplanned pregnancies while taking stimulant medication. In our systematic review we aimed at analysing the current evidence for the association of maternal ADHD with pregnancy and birth outcomes, pregnancy risks and health behaviour in pregnancy, as well as the association of parental ADHD with early parent-child interaction and early child development in the first 3 years. Furthermore, we reviewed recent evidence on the risks of stimulant and non-stimulant treatment for ADHD in pregnancy and lactation.

Methamphetamine is the most commonly seized amphetamine-type stimulant (ATS) worldwide. Chemical residues associated with the use or manufacture of methamphetamine can persist in the air and surfaces in a property for over 5 years and potentially pose risks to the health and safety of the public. When a house is tested for contamination, the test focuses on the presence of surface methamphetamine residue; however, other hazardous chemicals may also be present, including methamphetamine precursors and reaction products. As little has been reported about the ageing of the methamphetamine inside dwellings, there is currently large uncertainty regarding its fate and/or degradation products in such environments. If the indoor reactivity of methamphetamine is similar to that of nicotine-derived third-hand smoke, the production of a carcinogenic nitrosamine is an expected result. Thus, this proof-of-concept study investigated the reaction of methamphetamine with the common gaseous indoor oxidant nitrous acid (HONO) and monitored the fate of the resulting reaction products in simulated laboratory experiments to further understand the potential health risks associated with contaminated properties. Surface methamphetamine residue was observed to decrease with an exponential decay with an upper limit of 2.38 ± 0.5 × 10-3 min-1 upon exposure to HONO gas (5.7 ppmv, 0.25 L min-1 ). N-nitrosomethamphetamine (NMA), a suspected human mutagen and carcinogen, was detected to have a steady-state formation over the sampling time frame, with a surface area concentration of 0.87 μg/100 cm2 , suggesting that the risks to public health for properties contaminated with methamphetamine may be currently underestimated.

Chronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetam...

Background: Coffee is one of the most consumed drinks in the world and has become a routine part of everyday life. Coffee is known to be a stimulant because of its high caffeine content. Parkinson's disease is the second most common neurodegenerative disorder characterized by the clinical presentation of motor and non-motor disorders. Neuroinflammation plays a major role in the pathogenesis of Parkinson's disease which is regulated by reactive microglia and causes neurodegeneration of dopaminergic neurons. Consumption of caffeine can exert anti-inflammatory effects on nerves in a variety of pathological conditions. Method: The method used is a literature study from various national and international journals. This method is used with the aim of summarizing a current topic in order to increase an understanding. The literature study restates previously published material and reports new facts or analyzes from relevant literature studies and then compares the results in the article. Results: Caffeine can act as a neuroprotective against the development of Parkinson's disease by keeping the blood-brain barrier intact so that the function of the central nervous system remains stable. Caffeine can improve motor function in Parkinson's disease patients by modulating adenosine A2AR receptors at different doses. Caffeine as an adjuvant drug in the treatment of Parkinson's disease is given together with Trihexyphenidyl (THP) which is an anti-Parkinson's agent that has been used clinically to treat Parkinson's disease. Conclusion: Caffeine is a neuroprotective agent that is widely available and can be used in the treatment of Parkinson's disease with current therapies. However, the correct dosage and safety of caffeine are of particular concern, especially when given at high doses for a period of time and concurrently with other Parkinson's drugs.

Supplemental digital content is available in the text., Background Viloxazine extended-release is a novel nonstimulant under investigation as a potential treatment for attention-deficit/hyperactivity disorder (ADHD). Given the potential for viloxazine extended-release to be co-administered with stimulant ADHD pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine extended-release + lisdexamfetamine dimesylate (lisdexamfetamine) versus viloxazine extended-release and lisdexamfetamine alone. Methods In this single-center, cross-over, open-label trial, healthy, non-ADHD adults received single oral doses of 700 mg viloxazine extended-release alone, 50 mg lisdexamfetamine alone, and a combination of viloxazine extended-release (700 mg) + lisdexamfetamine (50 mg), with blood samples collected over 4 days postadministration. The active drug in viloxazine extended-release (viloxazine) and primary metabolite of lisdexamfetamine (d-amphetamine) were measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events, vital signs, echocardiograms, and clinical laboratory evaluations. Results Thirty-six adults were enrolled, and 34 completed the trial. The least squares geometric mean ratios are reported as [combination / single drug (90% confidence intervals)]. Viloxazine extended-release: Cmax = 95.96% (91.33–100.82), area under the concentration–time curve from 0 to the last measurable time (AUC0-t) = 99.19% (96.53–101.91), and area under the concentration–time curve from 0 to infinity (AUCinf) = 99.23% (96.61–101.93). Lisdexamfetamine: Cmax = 112.78% (109.93–115.71), AUC0-t = 109.64% (105.25–114.22), and AUCinf = 109.52% (105.19–114.03). All reported adverse events, except 1 (moderate vomiting), were mild in severity. Conclusions Co-administration of viloxazine extended-release and lisdexamfetamine did not impact the pharmacokinetics of viloxazine or d-amphetamine relative to administration of either drug alone. After single dose administration, the combination appeared to be safe and well tolerated.

Synthetic cathinones are among the most popular new psychoactive substances, being abused for their stimulant properties, which are similar to those of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Considering that the liver is a likely target for cathinones-induced toxicity, and for their metabolic activation/detoxification, we aimed to determine the hepatotoxicity of three commonly abused synthetic cathinones: butylone, α-methylamino-butyrophenone (buphedrone) and 3,4-dimethylmethcathinone (3,4-DMMC). We characterized their cytotoxic profile in primary rat hepatocytes (PRH) and in the HepaRG and HepG2 cell lines. PRH was the most sensitive cell model, showing the lowest EC50 values for all three substances (0.158 mM for 3,4-DMMC; 1.21 mM for butylone; 1.57 mM for buphedrone). Co-exposure of PRH to the synthetic cathinones and CYP450 inhibitors (selective and non-selective) proved that hepatic metabolism reduced the toxicity of buphedrone but increased that of butylone and 3,4-DMMC. All compounds were able to increase oxidative stress, disrupting mitochondrial homeostasis and inducing apoptotic and necrotic features, while also increasing the occurrence of acidic vesicular organelles in PRH, compatible with autophagic activation. In conclusion, butylone, buphedrone and 3,4-DMMC have hepatotoxic potential, and their toxicity lies in the interference with a number of homeostatic processes, while being influenced by their metabolic fate.

Background: Aspects of the canonical stress response differ in stimulant, opioid, and alcohol users relative to controls, and dysregulated responses to stress may contribute to continued use of these drugs. Little prior research has focused on stress responses in regular cannabis smokers. We assessed responses to a standardized laboratory social stress assay (the Trier Social Stress Task; TSST) in regular cannabis smokers (CANs) compared with controls (CONs). Methods: Healthy, non-treatment-seeking adult CANs (⩾4×/week; smoking cannabis as usual) and demographically matched CONs completed the TSST. Outcome measures were subjective mood, heart rate, and salivary cortisol. Results: Nineteen CANs (1 female) and 20 CONs (2 female) participated; groups were matched on trauma exposure, sex, race, and age. CANs smoked cannabis 6.4 ± 1.1 days/week. Eight CANs and one CON smoked tobacco cigarettes daily. Overall, the TSST produced expected increases in anxiety, negative mood states, cortisol, and heart rate. CANs had blunted subjective response to stress relative to CONs, but they did not differ in physiological (cortisol and cardiovascular) stress responding. Conclusion: These results indicate that CANs have blunted mood responses to social stress, but normative physiological stress responding. Observed differences could be due to residual effects of cannabis, reluctance to endorse negative mood states, or to issues related to identifying (i.e., emotional identification) or feeling (i.e., interoception) stress-related affective states. Further research is warranted to characterize the mechanisms of these differences and assess implications for daily functioning and treatment outcomes.

This longitudinal study with 76 sexual minority men living with HIV who use methamphetamine examined whether dysregulation of essential amino acid precursors for neurotransmitters at baseline predicted positive and negative affect at 15 months. After controlling for covariates including baseline positive affect, a higher baseline kynurenine/tryptophan (K/T) ratio independently predicted lower positive affect at 15 months (β = - 18.31; 95% CI = - 35.35, - 1.27; p = 0.036). Future clinical research should examine whether bio-behavioral interventions targeting tryptophan degradation could optimize treatments for people living with co-occurring HIV and stimulant use disorders.

BackgroundDrug classes are grouped based on their chemical and pharmacological properties, but prescription and illicit drugs differ in other important ways. Potential differences in genetic and environmental influences on the (mis)use of prescription and illicit drugs that are subsumed under the same class should be examined. Opioid and stimulant classes contain prescription and illicit forms differentially associated with salient risk factors (common route of administration, legality), making them useful comparators for addressing this etiological issue.MethodsA total of 2410 individual Australian twins [Mage = 31.77 (s.d. = 2.48); 67% women] were interviewed about prescription misuse and illicit use of opioids and stimulants. Univariate and bivariate biometric models partitioned variances and covariances into additive genetic, shared environmental, and unique environmental influences across drug types.ResultsVariation in the propensity to misuse prescription opioids was attributable to genes (41%) and unique environment (59%). Illicit opioid use was attributable to shared (71%) and unique (29%) environment. Prescription stimulant misuse was attributable to genes (79%) and unique environment (21%). Illicit stimulant use was attributable to genes (48%), shared environment (29%), and unique environment (23%). There was evidence for genetic influence common to both stimulant types, but limited evidence for genetic influence common to both opioid types. Bivariate correlations suggested that prescription opioid use may be more genetically similar to prescription stimulant use than to illicit opioid use.ConclusionsPrescription opioid misuse may share little genetic influence with illicit opioid use. Future research may consider avoiding unitary drug classifications, particularly when examining genetic influences.

Ibogaine is a psychotropic indole alkaloid extracted from the roots of the Tabernanthe iboga shrub from the Apocynaceae family. Depending on the taken dose, it can lead to stimulant effects, euphoria, visual and auditory hallucinations, along with auditory, olfactory, and gustatory synesthesia. In addition to its historical usage in spiritual rituals of African tribes, these days iboga extract presents a prohibited, alternative drug widely used as a part of addiction treatment. Ibogaine used in opioid withdrawal is associated with serious side effects and sudden deaths. Besides its main use as an anti-addiction medication in alternative medicine, in moderate doses (from 100mg to 1g) ibogaine most commonly causes a "trance-like state".In this paper, we report the case of a heroin addict who died suddenly 5-12 hours after oral ingestion of powder labeled Tabernanthe iboga which had been bought online and used in the process of detoxification during an addiction treatment. The man was found dead in a rented apartment, where he was undergoing the addiction treatment.External examination revealed no lesions other than nonspecific injuries on the legs. The autopsy showed congestion of internal organs and pulmonary edema. Histopathological analysis of the heart showed neither macroscopic nor microscopic abnormalities. The concentration of ibogaine was 3.26mg/L. Moreover, systematic toxicological analyses of biological samples showed the presence of morphine and codeine. These data suggest that death, which occurred unnaturally after initiation of the "treatment", was probably the result of the cardiovascular effects caused by the ibogaine powder.The presented case highlights the worldwide problem of various products being widely available over the internet and the danger associated with consumption thereof.

People with stimulant use disorders are usually underweight. Current accepted knowledge is that they are skinny because stimulants suppress appetite - they eat less. But is it that simple? Here we review the relationship between stimulant use, food intake, metabolism and body weight, and highlight key points that may challenge current knowledge: 1) Stimulants interact with the hormonal signals that regulate appetite including ghrelin and leptin, and can produce long-term alterations in the ability to monitor and compensate energy deficits. 2) The diet of people with stimulant use disorders might be characterised by altered nutritional geometry, rather than overall reduction of food intake. 3) Long-term changes in homeostatic signals and nutrient intake can produce metabolic deficits that contribute to unhealthy low weight. Based on this knowledge we advocate for increasing awareness about the nuances of stimulant-related nutritional and metabolic deficits among addiction clinicians, and increased research on the interaction between stimulant use, appetite signaling, and metabolic deficits.

Analeptics are the classes of stimulant drugs which are generally used to treat respiratory depression particularly in case of coma and fainting. Most of them are central nervous system stimulants with very censorious therapeutic indexes. They stimulate respiration and can have resuscitative value in breathing failure or apnoea. Since most of them have narrow margin of safety, hence they are meticulously preferred for the purpose of treatment. Doxapram is one of the best known analeptic medicament approved for human use in the treatment of drug induced respiratory depression and apnoea of prematurity. It has tendency to stimulate chemoreceptors in carotid body of carotid artery and respiratory centre in medulla oblongata. It blocks potassium channel also. Unlike other analeptic drugs, doxapram hasn't drug dependence or addictive property. Although, almitrine is a safe drug, but doxapram has better clinical preference in the treatment of apnoea and respiratory depression. Chronic maladies of obstructive pulmonary ailments are generally treated by almitrine, which is a well tolerated through oral route. It enhances respiration by agonising peripheral chemoreceptors of receptors of carotid body without impairing the quality of sleep.

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychiatric disorder in children and adolescents in the United States. In 2016, approximately 3.8 million U.S. children ages 2 to 17 years with ADHD were being treated with medication. There are approximately 30 different amphetamine (AMPH) and methylphenidate (MPH) formulations on the market. These include immediate-release and extended-release compounds. The extended-release formulations contain various ratios of immediate-release and extended-release components, which determine the pharmacokinetic (PK) profile. For stimulants, the PK and pharmacodynamic (PD) profiles are tightly linked, and the immediate-release and extended-release percentages influence onset and duration of drug effects. Choosing the right stimulant medication for a patient depends on an understanding of the PK/PD profile, the time of day that symptoms are most impairing, the need for morning and evening symptom control and individual patient preferences.

Background Caffeine is a widely used dietary stimulant, and cases of caffeine overdoses, sometimes leading to death, are increasing. We encountered a case of caffeine intoxication resolved with administration of the sedative agent dexmedetomidine. Case presentation We administered dexmedetomidine for sedation and to suppress sympathetic nerve stimulation in the case of an 18-year-old Japanese male who ingested a massive dose of caffeine with the intention of committing suicide. The patient was in an excited state and had hypertension, sinus tachycardia, and hypokalemia with prominent QT prolongation. After dexmedetomidine administration, the patient’s mental state, hemodynamics, and electrolyte levels were improved immediately. He was discharged without any sequelae 3 days later. Conclusion Cases of acute caffeine intoxication with agitation, sympathetic overactivity and adverse cardiac events would benefit with dexmedetomidine treatment.

One of the human basic is the need to rest. Resting for humans is useful for restoring energy, repairing cells and resting the organs of the body which all day long activity. One way humans rest their bodies is by sleeping. Nicotine is a stimulant, and nicotine side effects can cause insomnia. The purpose of this study was to identify a significant relationship between the degree of smoking based on the Brinkman Index and insomnia through analytical survey research using cross sectional studies. The subjects of this study were people who smoked in Kaima village, Kauditan sub-district, North Minahasa district with a total sampling technique, which amounted to 80 respondents according to the results of the initial survey of researchers through direct interviews. Statistical test results show a significance value (p = 0.009 < 0.05) with a weak correlation coefficient ( r = 0.288) with a positive direction. There is a significant relationship between the degree of smoking and the incidence of insomnia. The community is expected to be able to change smoking behavior by reducing the number of cigarettes consumed or even stop smoking.

BACKGROUND AND OBJECTIVES Methamphetamine use is increasing in the United States, potentially including the simultaneous injection of methamphetamine with heroin (goofball). We compared demographic, behavioral, contextual, and health factors among people who inject drugs (PWID) in the Seattle area and who reported that their main drug was goofball, heroin, or methamphetamine. METHODS We used data from 2017 and 2019 cross-sectional surveys of clients at Public Health-Seattle & King County's syringe services program (N = 792). RESULTS Among PWID participants, 55.3% reported using goofball in the last 3 months, and the proportion reporting goofball as their main drug doubled between 2017 (10.3%) and 2019 (20.1%, P

Deaths attributable to psychostimulants with abuse potential have increased in the United States (US) in recent years. Methamphetamine use, in particular, has risen sharply. We evaluated the correlation between amphetamine- and methamphetamine-related case exposures reported to the Michigan Poison Center (MiPC) coinciding with psychostimulant age-adjusted mortality rates from the Michigan Department of Health and Human Services (MDHHS).We compared amphetamine and methamphetamine exposures reported to the MiPC from 2012 to 2018, queried from ToxSentryPsychostimulant deaths reported by MDHHS increased from 17 to 165 between 2012 and 2018. The average age-adjusted rate of psychostimulant-involved overdose deaths per 100,000 state residents rose from 0.2 to 1.8. Linear regression of MiPC amphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 1.93, SE 0.5,Psychostimulant use and associated deaths in the US are increasing, representing an evolving public health threat. Michigan demonstrates consistency with national trends and data from the MiPC correlates strongly with state-reported age-adjusted psychostimulant mortality rates. Strengthening collaboration between poison centers and state health departments is critical for detection and mitigation efforts and can thereby inform resource allocation.

BackgroundTo evaluate the relative bioavailability of a single dose of amphetamine extended-release oral suspension (AMPH EROS) compared with a single dose of extended-release mixed amphetamine salts (ER MAS) in healthy, fasted adult subjects.MethodsThe study population consisted of healthy adult volunteers. The study drug used in this study was 7.5 mL of 2.5 mg/mL AMPH EROS equivalent to 18.8 mg of amphetamine base administered after an overnight fast of at least 10 hours. AMPH EROS comprises a 3.2:1 enantiomeric ratio of d-amphetamine to l-amphetamine. The reference product was one 30 mg ER MAS capsule (equivalent to 18.8 mg of amphetamine base). Relative bioavailability between the products was determined by a statistical comparison of the area under the curve and maximum concentration (Cmax) for d-amphetamine and l-amphetamine. PK (PK) blood samples were collected prior to dosing (0-hour) and at 1, 2, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48, and 60 hours after drug administration, totaling 20 samples in each period.ResultsThe mean subject age was 35.0 (standard deviation ±8) years, and the overall study population comprised 19 (63.3%) males and 11 (36.7%) females. The contrasts for geometric mean ratios for all assessed PK parameters (for both l- and d-amphetamine) between the test article AMPH EROS and reference product ER MAS fell within the prescribed 80% to 125% limits.ConclusionsThe overall PK profile of single-dose AMPH EROS 7.5 mL was found to be comparable with a single dose of oral ER MAS 30 mg.

The article is devoted to topical issues of management of patients with pulmonary arterial hypertension and strategies for switching to riociguat therapy in patients with insufficient clinical response against the background of phosphodiesterase type 5 (PDE-5) inhibitors. The role of the NO metabolic pathway in the development of pulmonary arterial hypertension (PAH) was shown. From the standpoint of pathogenesis, the importance of the effect of medication on this pathway through soluble guanylate cyclase (sGC) has been assessed. The effects of the drug riociguat, the only member of the sGC stimulant class approved for the treatment of PAH, are associated with a dual mechanism of action: riociguat sensitizes the sGC enzyme to endogenous NO by stabilizing the NO-sGC bond, and also directly stimulates the latter through another site of the bond, regardless of NO. The favorable efficacy and safety profile of riociguat has been demonstrated in the PATENT-1,2 studies. During therapy, patients showed an improvement in exercise tolerance, functional class, and a number of other indicators. Studies that indicate the feasibility of using a change in therapy in clinical practice are reviewed. In particular, the article provides a detailed analysis of the REPLACE study. It demonstrated a significantly greater likelihood of achieving clinical improvement and a significant decrease in the rate of development of clinical deterioration when switching patients with PAH from PDE-5 inhibitors to riociguat. This therapy was well tolerated and can be considered as a strategy for managing patients at intermediate risk with insufficient patient response to PDE-5 inhibitors. In conclusion, the need to plan the need for specific therapy for pulmonary arterial hypertension in the region is noted in order to rapidly escalate therapy to achieve a low risk of mortality in these patients.

Purpose HLD200 is the first evening-dosed, delayed-release and extended-release methylphenidate (DR/ER-MPH) designed to delay initial release of MPH and provide treatment effects throughout the day and into the evening for individuals with attention-deficit/hyperactivity disorder (ADHD). Because DR/ER-MPH is uniquely absorbed in the colon, it cannot be substituted for other ADHD medications on a milligram-per-milligram basis. To provide clinicians with a target dose range for DR/ER-MPH when transitioning patients from a prior ADHD medication, dose conversion ratios (DCRs) between prior medication doses and optimized doses of DR/ER-MPH were determined post hoc from a pivotal Phase III study of children (aged 6–12 years) with ADHD. Methods DR/ER-MPH doses were optimized over a 6-week open-label period. DCRs were calculated between optimized doses of DR/ER-MPH at week 6 and prior stable doses of ADHD medication. Findings Mean DCRs ranged from 1.8 to 4.3 for optimized DR/ER-MPH dose versus previous stable dose for individuals taking an extended-release stimulant monotherapy. DCRs for those taking an immediate-release stimulant monotherapy ranged from 4.7 to 6.0. Implications In a Phase III trial of children with ADHD, optimized doses of DR/ER-MPH were higher than doses of prior ADHD medications, but the adverse event profile was consistent with that of other MPHs. Higher DCRs compared with those predicted by bioavailability differences are consistent with a predicted dose-dependent duration of effect for DR/ER-MPH: with increasing doses, absorption is extended but with an attenuated increase in Cmax compared with MPH formulations absorbed in the upper bowel. These data may help guide clinicians to optimize DR/ER-MPH doses. ClinicalTrials.gov identifier: NCT02493777.

Levamisole is a drug originally prescribed as an antihelmintic. Because of the occurrence of severe cases of agranulocytosis and leukoencephalitis it was removed from the French market in 1998 for human use, while it remains available for veterinary use. Nowadays in France its only use in humans is regulated by authorization for temporary use for its immunomodulatory properties in the treatment of nephritic syndrome. A 52-year-old man was found dead at his farm. Injection points were observed on his arm and a syringe containing a dark orange-brown liquid was found near the body. At his home, the discovery of a letter highlighted suicidal intent. Analysis of the aforementioned liquid, peripheral blood and urine confirmed the unique presence of levamisole. The femoral blood concentration of levamisole was of 25 mg/L whereas the femoral blood concentrations reported in cases of fatalities after cocaine use do not exceed 0.0056 mg/L. In humans, levamisole can be detected in biological samples after cocaine use as this drug is also an adulterant and one of its metabolites (aminorex) seems to have amphetamine-like properties. In this case, the man consumed levamisole from time to time for its stimulant and strengthening effects. Cases of fatal poisoning using levamisole are very rare and poorly documented, which makes the interpretation of postmortem blood levamisole concentration difficult.