Psychostimulant Use Research Articles

Psychostimulant Use Among Myeloproloferative Neoplasm Patients

Background: Fatigue remains one of the most severe and disabling symptoms experienced by patients with myeloproliferative neoplasms (MPNs) resulting in impaired social, role, and physician functioning and reduced quality of life (Cancer 2007). Current NCCN Clinical Practice Guidelines in Oncology recommend consideration of use of psychostimulants (PSs) if other causes of fatigue have been ruled out. In this analysis, we evaluate the role of pharmacologic PSs in this population utilizing data from a previously conducted a survey regarding fatigue in MPN patients (Cancer 2016).Methods: A 70-item internet-based survey was developed by a multidisciplinary team of MPN investigators, patients, and patient advocates that included questions on medication PS use. The survey was promoted online via multiple MPN-related websites during late February to March of 2014. Survey data was immediately captured, downloaded, and stored on secure servers at the Mayo Clinic Survey Research Center. Success of PSs was patient-reported on a 5-level tiered response range from not at all successful to very successful. Categorical variables were compared using chi-square tests, continuous variables using T-tests, and Pearson's rho estimated correlations. P values < 0.05 were considered statistically significant.Results: Respondents : 1788 MPN patients participated in the online survey. Of these, 1748 consented to the survey and 1676 were included for completing 10 or more survey questions. 116 patients (8.4%) of the 1377 patients who responded to the question regarding PS use reported use of these medications. Use among MPN subtypes varied (9.9% of essential thrombocythemia patients, 9.1% of polycythemia vera patients, and 5.8% of myelofibrosis patients).Characteristics : Females used PSs more frequently than males (9.9% females vs 5.4% males, P= 0.006). Use of PSs was most often observed among individuals with severe fatigue (mean brief fatigue inventory (BFI) score 5.7 among those using PSs versus 4.4 among those not using, P < 0.001). Individuals who reported that fatigue impaired sleep were more often PS users (12% of users had impaired sleep versus 6% of users without impaired sleep, P < 0.001). Patients who used PSs were also more symptomatic for the 10 most MPN-specific symptoms assessed via the MPN Total Symptom Score (MPN-TSS; mean 36.3 vs 28.4, P < 0.001). Individual MPN Symptom Assessment Form (MPN-SAF) item scores are shown in Figure 1.Efficacy : We then evaluated the characteristics of PS users by their reported success in reducing fatigue (102/166). Success in reducing fatigue was reported more often in older respondents (mean age of 58.9 years in those reporting that PSs were somewhat to very helpful vs 53.9 years for not helpful, P = 0.03). Although not significant, patients who reported success in reducing fatigue tended to have a diagnosis of PV (somewhat or very successful in 34/45 for PV; 7/13 for MF, 21/42 for ET, P= 0.05) or female (somewhat or very successful in 54/80 vs 9/20 for male, P= 0.06).Correlates : Of PS users who completed the secondary portion on fatigue reduction success level (n=102), there was no apparent correlation between MPN-TSS (0-10) and reported success in reduction of fatigue (rho = -0.1; P= 0.5).Conclusions: Medication PSs are utilized in a notable proportion of MPN patients. MPN patients who use PSs often had significantly worse fatigue than their peers, which may reflects the population in which PSs are most likely to be of suspected benefit. Given the severity of fatigue in this population and the lack of effective fatigue-alleviating strategies, more studies regarding the efficacy of PSs are needed. [Display omitted] DisclosuresHarrison:CTI: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Celgene: Consultancy. Mesa:Celgene Corporation: Research Funding; Ariad: Consultancy; Promedico: Research Funding; Incyte Corporation: Research Funding; Galena Biopharma, Inc.: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy; CTI BioPharma Corp.: Research Funding; Gilead Sciences, Inc.: Research Funding.

Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use.

Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.

Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap?

The number of individuals affected by psychostimulant use disorder (PSUD) has increased rapidly over the last few decades resulting in economic, emotional, and physical burdens on our society. Further compounding this issue is the current lack of clinically approved medications to treat this disorder. The dopamine transporter (DAT) is a common target of psychostimulant actions related to their use and dependence, and the recent availability of atypical DAT inhibitors as a potential therapeutic option has garnered popularity in this research field. Modafinil (MOD), which is approved for clinical use for the treatment of narcolepsy and sleep disorders, blocks DAT just like commonly abused psychostimulants. However, preclinical and clinical studies have shown that it lacks the addictive properties (in both behavioral and neurochemical studies) associated with other abused DAT inhibitors. Clinical availability of MOD has facilitated its off-label use for several psychiatric disorders related to alteration of brain dopamine (DA) systems, including PSUD. In this review, we highlight clinical and preclinical research on MOD and its R-enantiomer, R-MOD, as potential medications for PSUD. Given the complexity of PSUD, we have also reported the effects of MOD on psychostimulant-induced appearance of several symptoms that could intensify the severity of the disease (i.e., sleep disorders and impairment of cognitive functions), besides the potential therapeutic effects of MOD on PSUD.

Brief history of the medical and non-medical use of amphetamine-like psychostimulants

The alkaloid ephedrine derived from Ephedra vulgaris is at the origin of psychostimulant-drugs as amphetamine. These drugs have been principally utilized for medical treatments in the past, while their utilization has been largely reduced from the 1970s when the high risk of addiction and abuse has been recognized. The first reported treatments were as anti-asthmatics and to contrast narcolepsy until their recreational stimulant and anorexic effects were reported. Benzedrine and Pervitin use were of great importance during the Second World War due to their abundant utilization among military troops. Nowadays the use of selective amphetamine-like drugs is limited to ADHD treatment.

Increased NMDA Receptor Function during Protracted Withdrawal from Chronic Intermittent Ethanol Exposure

Functional dysregulation of the glutamatergic receptor system during withdrawal from chronic drug exposure is a primary driver of drug craving and relapse. Animal models of psychostimulant use have demonstrated dynamic alterations in both AMPA and NMDA receptor function and expression that contribute to drug seeking behavior. Regulation of these receptor systems can begin as early as a few days following cessation of drug use and are persistently expressed into long term withdrawal (>60d). Short term withdrawal (24hr) from chronic exposure to ethanol also induces functional dysregulation of AMPA and NMDA receptors suggesting that similar mechanisms may be regulating drug craving and relapse behaviors across drugs of abuse. To this end, we investigated NMDA receptor mediated synaptic function during protracted withdrawal (>35d) from chronic intermittent ethanol (CIE) exposure using whole cell patch clamp electrophysiology. We focused on the basolateral amygdala (BLA), as glutamatergic signaling in this region is robustly modulated by short term (24h) withdrawal from CIE (10d, 12hr/day) and regulates anxiety like behavior expressed during withdrawal. Adolescent rats exposed to repeated cycles of CIE (12hr/day, 4d on/3d off, 3 cycles) demonstrated increased functional contributions of NMDA receptors in male but not female animals in comparison to sex matched control animals exposed to room air (CON). These functional increases occurred at resting (-80mV) and depolarized (+40mV) membrane potentials. Psychostimulant studies showing similar increases at resting potentials (-80mV) have implicated GluN3-containing NMDA receptors as the primary mechanism driving this effect. Pharmacological studies using the GluN2B antagonist ifenprodil, suggest that increased NMDAR contributions in male animals is mediated through GluN2B containing receptors. Interestingly, ifenprodil antagonized the increased responses at both resting and depolarized membrane potentials. These results mirror increased NMDA receptor function found during protracted withdrawal from cocaine self-administration suggesting possible common mechanisms underlying aberrant synaptic function during withdrawal from multiple drugs of abuse. Ongoing studies are focused on elucidating the specific contributions of NMDA receptor subunits (GluN2B/GluN3) to the overall functional increases found and exploring sex differences in NMDA receptor regulation.

Early Chronic Methamphetamine Exposure Induces Cognitive Impairments and Oxidative Damage in Adult Mice

Prescription stimulant misuse among young adults has gained popularity in the United States over the last decade, with amphetamine compounds becoming the second most common illicit drug used in college students. Misuse of these drugs can pose serious risks due to their high potential for abuse that can lead to dependency and neurotoxicity. Furthermore, there are prominent sex differences in psychostimulant use: men use more frequently and women have higher success rates in treatment but are more vulnerable to dependence and adverse effects. Psychostimulants, even at moderate doses, have been shown to promote oxidative stress, via auto-oxidation or metabolism of accumulated redox active dopamine. Oxidative stress has also been implicated in neurobehavioral impairments. Therefore, exposure to psychostimulants as a consequence of abuse would provide a second hit predicted to increase brain impairments. Moreover, the mesocorticolimbic pathway, a critical dopaminergic pathway, is particularly vulnerable to oxidative insults, and reveals sex-dependent differences in dopamine dynamics. We hypothesized that oxidative stress may act as a prominent cellular mechanism in mediating psychostimulant-induced neurotoxicity and neurobehavioral deficits. The purpose of this pilot study was to determine the short-term consequences of chronic, low toxic dosing of the prototypical psychostimulant, methamphetamine (METH), on cognition and markers of oxidative stress and dopaminergic function. Groups of young male and female (4-month-old) C57BL/6J mice received non-contingent intraperitoneal injections of either saline or methamphetamine (1.4 mg/kg) twice a day for 4 weeks. Two weeks following the last injection, animals were tested for cognitive function using 3 different tests: Morris water maze, active avoidance, and fear conditioning. After the completion of behavioral testing, brain regions were dissected and markers of oxidative stress and dopaminergic function were assayed. METH administration appeared to induce deficits in spatial learning and memory in both males and females, and in active avoidance and fear conditioning response in female mice only. Markers of dopaminergic function do not seem to be majorly affected by METH administration, while markers of lipid peroxidation were increased in the cortex and hippocampus of METH-treated females. These preliminary results suggest that chronic administration of METH induced impairments in cognitive function and changes in oxidative stress. These data indicate functional and biochemical changes that may have long-term consequences on brain function which will be the focus of future studies.

PMAT Deficiency Sex‐Selectively Contributes to Cocaine and Amphetamine Locomotor Sensitization

Background The plasma membrane monoamine transporter (PMAT) is a polyspecific cation transporter that, in the brain, predominantly takes up monoamines such as dopamine and serotonin. We hypothesize the functional contribution of PMAT emerges when impairment of higher affinity transporters, including dopamine transporter (DAT) or serotonin transporter (SERT), occurs. An example would be under conditions of pharmacological blockade, as occurs from psychostimulants like cocaine, which inhibits both DAT and SERT, or D-amphetamine, which reverses transport of dopamine by DAT. No studies have evaluated the contribution of PMAT to psychostimulant responses. Mice constitutively deficient in PMAT were utilized for the present experiments, because no selective inhibitor of PMAT currently exists. We hypothesized that relative to wildtype controls, mice with reduced or diminished PMAT function would exhibit augmented cocaine and D-amphetamine sensitization, because compensatory monoamine uptake by PMAT is impaired in these mice when DAT and SERT are pharmacologically inhibited. Methods To analyze the effects of cocaine and amphetamine in PMAT-deficient mice, males and females went through a cocaine- or D-amphetamine-induced locomotor sensitization paradigm for 5 total days. Each day, after a baseline test (30 min) of locomotor activity in an open field arena, injections of saline (vehicle) then cocaine or D-amphetamine were administered. Subsequent locomotor responses to each injection were recorded in 10-minute intervals using ANY-maze software. The total (cumulative) doses used for cocaine were 5-40 mg/kg every day for 5 days; for D-amphetamine, 0.1-4.62 mg/kg every 3 days for a total of 5 days of injections. The drug dose-response for each day was converted to an area under the curve (AUC), and sensitization was assessed by normalizing each day's AUC to the first injection day (Day 1) AUC. Data were analyzed using a two-way repeated measures ANOVA, with Tukey's post-hoc tests. Results : Preliminary data indicate a sex-specific effect of PMAT deficiency on cocaine-induced locomotor sensitization, where male heterozygous mice had reduced sensitization to cocaine relative to wildtypes. Our data also revealed decreased responses to D-amphetamine in female PMAT-deficient mice relative to same-sex wildtypes. However, male heterozygotes exhibited augmented D-amphetamine sensitization relative to male knockouts (trending vs wildtypes). Conclusion Our findings suggest PMAT deficiency attenuates cocaine-induced locomotor sensitization in males but not females, and that partial PMAT deletion sex-specifically affects D-amphetamine-induced locomotor sensitization. These results indicate that PMAT is not inhibited by cocaine, but PMAT contributes to D-amphetamine-induced dopamine efflux. Moreover, PMAT may sex-specifically influence psychostimulant sensitization processes. Future examinations will determine how PMAT function might influence other dimensions related to psychostimulant use and abuse, such as subjective drug experience and drug reinforcing effects.

Eating Disorders and the Use of Cognitive Enhancers and Psychostimulants Among University Students: A Cross-Sectional Study.

BackgroundUniversity students, who are at risk of eating disorders (ED), are more liable to use cognitive enhancers and psychostimulants to improve their cognitive functions and lose weight. ED in Palestinian male students is a neglected health issue. We aimed to investigate the prevalence and the association between ED and cognitive enhancers, and psychostimulants use among An-Najah National University students (ANNU).MethodsIn a cross-sectional study conducted in 2020 at ANNU, 1047 students completed anonymous surveys for cognitive enhancers practice, the Eating Attitude Test-26 (EAT-26), Sick, Control, One, Fat and FOOD (SCOFF) screening tests.ResultsThe prevalence of ED among ANNU students was 21.2% based on EAT-26 (17.1% in males, 23.8% in females) and 31.5% based on SCOFF (24.0% in males, 36.3% in females). The binary logistic regression revealed that students at risk to have ED were water-pipe smokers (OR: 1.471, p-value 0.047), especially males, while students who were less likely to have ED were males (OR: 0.341, p-value<0.001), coffee users (OR: 0.581, p-value 0.014) and chocolate users (OR: 0.530, p-value 0.041) than nonusers. Moreover, the risk of ED increased with increasing body mass index (p-value<0.01). Clinical medical students showed the lowest prevalence (11.1%) compared to preclinical (22.5%), health sciences (23.7%), and non-medical students (20.9%) (p-value 0.059).ConclusionOur findings highlight water-pipe smoking as a significant health problem in males with ED, which may require unique treatment and prevention strategies. Moreover, coffee and chocolate consumption were associated with decreased risk of ED, only among males. The gender-gap in ED prevalence was very narrow compared to international results. These results prompt the need to focus on both genders in future studies instead of females. They also suggest the urgent need to address ED among Palestinian university students by educating students about mental health, identifying high-risk students, and offering easily accessible psychological help.

Effects of a novel tamoxifen‐analogue (6c) on methamphetamine induced neurotoxicity

The use and abuse of psychostimulants have been associated with countless adverse effects (including addiction, neurotoxicity and death) and billions of dollars of damage to the global economy. Yet, to date, there is no effective pharmacotherapeutic. Amphetamine has been shown to activate the β-isoform of protein kinase C (PKC), which phosphorylates the dopamine transporter (DAT) at N-terminal serines and threonines to increase extracellular dopamine. Recently, a novel PKC inhibitor (6C) has been developed to attenuate or block amphetamine use and addiction. Prior studies have shown that the administration of 6C with amphetamine inhibited amphetamine monoamine release, hyperlocomotion and self-administration.1 Although the neurotoxicity accompanying the acute and chronic use of amphetamine and methamphetamine are well characterized, no treatment exists for the neurotoxicity associated with their use. To assess the potential of 6C to impact psychostimulant-induced neurotoxicity (and extend its therapeutic efficacy in psychostimulant abuse), female mice received a single injection of 0 (vehicle) or 6 mg/kg of 6C subcutaneously 2 h prior to a binge-like regimen of 5 mg/kg of methamphetamine or saline during which mice were injected with 5 mg/kg of methamphetamine or saline (IP) every 2 h for a total of four injections. Two days following injections, mice were euthanized by decapitation for brain removal. The striatum was dissected from both sides of the brain. Each side of the striatum was frozen separately using dry ice and stored at −80°C until analysis occurred. As shown in Figure 1, 6C significantly reduced methamphetamine-induced neurotoxicity when probing for DAT and tyrosine hydroxylase (TH) (western/immunoblot analysis) and DA levels (HPLC). To assess any generalization of these effects of 6C on psychostimulant intake and neurotoxicity, similar analyses will be made with a new class of beta ketone analogues of amphetamine, the synthetic cathinones, whose reinforcing effects are mediated by neurochemical mechanisms similar to and different from those of amphetamine2. 1. C. Carpenter, A. G. Zestos, R. Altshuler, R. J. Sorenson, B. Guptaroy, H. D. Showalter, R. T. Kennedy, E. Jutkiewicz and M. E. Gnegy, Neuropsychopharmacology, 2017, 42, 1940-1949. 2. A. L. Riley, K. Nelson, P. To, R. López-Arnau, P. Xu, D. Wang, Y. Wang, H-W. Shen, D. Kuhn, M. Angoa-Perez, J. Anneken, D. Muskiewicz, and F. Hall. Neuroscience & Biobehavioral Reviews, 2020, 110, 150-173.

A "Drug-Dependent" Immune System Can Compromise Protection against Infection: The Relationships between Psychostimulants and HIV.

Psychostimulant use is a major comorbidity in people living with HIV, which was initially explained by them adopting risky behaviors that facilitate HIV transmission. However, the effects of drug use on the immune system might also influence this phenomenon. Psychostimulants act on peripheral immune cells even before they reach the central nervous system (CNS) and their effects on immunity are likely to influence HIV infection. Beyond their canonical activities, classic neurotransmitters and neuromodulators are expressed by peripheral immune cells (e.g., dopamine and enkephalins), which display immunomodulatory properties and could be influenced by psychostimulants. Immune receptors, like Toll-like receptors (TLRs) on microglia, are modulated by cocaine and amphetamine exposure. Since peripheral immunocytes also express TLRs, they may be similarly affected by psychostimulants. In this review, we will summarize how psychostimulants are currently thought to influence peripheral immunity, mainly focusing on catecholamines, enkephalins and TLR4, and shed light on how these drugs might affect HIV infection. We will try to shift from the classic CNS perspective and adopt a more holistic view, addressing the potential impact of psychostimulants on the peripheral immune system and how their systemic effects could influence HIV infection.

First episode psychosis and the use of psychostimulants - a case report

IntroductionStimulants are considered the mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD), and most patients are put on a long-term regimen with these psychostimulants. However some children treated with psychostimulants have reported psychosis as an adverse effect.ObjectivesUnderstand the capacity of psychostimulant medications to induce psychotic symptoms and determine the frequency of such reactions in adolescents and young adults.MethodsNon-systematic review of the literature in English, through research in PubMed. Additionally, a clinical case is exposed, which was treated at the psychiatric inpatient unit of the Tamega e Sousa hospital center.ResultsSome patients, including some with no identifiable risk factors, can develop drugrelated signs or symptoms of psychosis or mania, such as hallucinations, at usual doses of frequently used ADHD drugs. Age of onset of psychosis can be significantly earlier in individuals with a history of stimulant use. In our clinical case, a young man of 18 years, previously diagnosed with ADHD, was medicated with atomoxetine two months prior being admitted to our psychiatric unit. There was no reported history of a similar psychiatric condition, and no risk factors were identified. At admission, he had bizarre behavior, with allucinatory activity and delusions of persecution. Atomoxetine was suspended and started oral antipsychotic, with improvement of symptoms and stabilization of the clinical condition.ConclusionsIn adolescents and young adults with ADHD undergoing stimulant therapy, any psychotic symptoms or mood changes need to be carefully assessed at regular intervals by the physicians and the caregivers, in order to observe change in the symptoms.DisclosureNo significant relationships.

Effect of Chronic Methylphenidate Treatment in a Female Experimental Model of Parkinsonism.

Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD in males and females. However, a majority of previous studies investigated the effect of MPH in only males, and little is known regarding consequences of female exposure to MPH. This is unfortunate because the few studies that have been conducted indicate that females have a greater sensitivity to MPH. Previous research in male mice has shown that chronic exposure to MPH causes dopaminergic neurons within the nigrostriatal pathway to be more sensitive to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, estrogen has been shown to protect dopaminergic neurons from MPTP neurotoxicity. Therefore, in this study, we test the hypothesis that chronic MPH exposure in female mice will render dopaminergic neurons in the nigrostriatal pathway more sensitive to MPTP, and that estrogen may play a protective role. Interestingly, proestrus females exhibited greater sensitivity to MPTP, with significantly reduced dopaminergic neurons in the SN and significant increases in DA quinone production. Chronic MPH exposure contributed to GSH depletion, but surprisingly, it did not increase dopamine quinone levels or dopaminergic cell loss. There were no significant differences in anestrus animals, with the exception of a depletion in GSH seen when animals received chronic high-dose (10mg/kg) MPH followed by MPTP. Thus, estrogen may actually sensitize neurons to MPTP in this model, and chronic MPH may contribute to GSH depletion within the striatum. This study provides insight into how chronic psychostimulant use may affect males and females differently.

Prolonged Exposure Therapy: A Case of Comorbid PTSD, ADHD, and GAD

This case study displays the successful application of Prolonged Exposure (PE) for a client with diagnoses of Posttraumatic Stress Disorder (PTSD), Attention Deficit Hyperactivity Disorder (ADHD), and Generalized Anxiety Disorder (GAD). To our knowledge ADHD has not been examined as a predictor or moderator of PE outcomes. As such, practitioners have precious little information about how to proceed in such cases, which highlights the importance of careful individual assessment and case conceptualization. There is also a dearth of information on the effects of combining PE (a research-supported psychological intervention for PTSD) with psychostimulant medication (a research-supported pharmacological intervention for ADHD). The present case study illustrates a positive synergy between psychostimulant treatment and PE. The unique adjustments made to deliver services (including in the face of COVID-19) are described as well as what this case suggests about the effects of psychostimulant use on PTSD symptoms and the new learning that occurs during PE.

Retrospective review of use of adjunctive psychostimulants in patients with schizophrenia.

Adjunctive psychostimulants have been proposed as a potential treatment option for the management of cognitive and/or negative symptoms of schizophrenia. The present study is a retrospective review of use of adjunctive psychostimulants among outpatients enrolled in our tertiary Schizophrenia Program between 2014 and 2019. We assessed response to treatment, adverse effects, and the impact of various clinical factors on treatment outcome. Of the 77 (out of 1,300) participants prescribed psychostimulants during the study period, 42.22% had chart-based evidence of significant improvement, 27.77% had minimal improvement, and 25.55% reported no change. The majority (61.9%) demonstrated improvement in attention, concentration, and/or other cognitive symptoms. Approximately one-third of cases had evidence of emergence of psychosis. Of the factors assessed, comorbid attention-deficit/hyperactivity disorder was associated with an increased likelihood of response, and higher doses of stimulants were associated with likelihood of emergence of psychosis. Adjunctive psychostimulants could be a potential treatment consideration to address cognitive deficits in selected patients with schizophrenia.

New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders.

The abuse of illicit psychostimulants such as cocaine and methamphetamine continues to pose significant health and societal challenges. Despite considerable efforts to develop medications to treat psychostimulant use disorders, none have proven effective, leaving an underserved patient population and unanswered questions about what mechanism(s) of action should be targeted for developing pharmacotherapies. As both cocaine and methamphetamine rapidly increase dopamine (DA) levels in mesolimbic brain regions, leading to euphoria that in some can lead to addiction, targets in which this increased dopaminergic tone may be mitigated have been explored. Further, understanding and targeting mechanisms underlying relapse are fundamental to the success of discovering medications that reduce the reinforcing effects of the drug of abuse, decrease the negative reinforcement or withdrawal/negative affect that occurs during abstinence, or both. Atypical inhibitors of the DA transporter and partial agonists/antagonists at DA D3 receptors are described as two promising targets for future drug development.

Prevention of impulsive suicide with antidepressants in outpatients

Self-poisoning is a common method of suicide, for which various medications are used, including antidepressants. A non-systematic review of Russian-language and English-language publications, by keywords, in the databases: ELibrary.ru, PubMed, Cochrane Database of Systematic Reviews. The purpose of the review was to analyze the literature on new risk factors and methods of their reduction in suicides with self-poisoning with antidepressants. Every fifth (20%) self-poisoning performed with antidepressants. In self-poisoning attempts, one drug used in 55% of cases, and more than one drug was used in 45% of cases. Impulsive suicides account for up to half of all suicide cases. Risk factors for impulsive suicides include the presence of impulsive character traits, female gender, young age, and the use of psychostimulants. The WHO Regional Office for Europe's mhGAP-IG guidelines recommend limiting access to a patient at risk of suicide to a weekly dose of an antidepressant. Preferably, the use of antidepressants from the group of SSRIs in small forms of release.

Granulocyte-Colony Stimulating Factor Reduces Cocaine-Seeking and Downregulates Glutamatergic Synaptic Proteins in Medial Prefrontal Cortex.

Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no Food and Drug Administration (FDA)-approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony stimulating factor (G-CSF) as a neuroactive cytokine that alters behavioral response to cocaine, increases synaptic dopamine release, and enhances cognitive flexibility. Here, we investigate the role of G-CSF in affecting extinction and reinstatement of cocaine-seeking and perform detailed characterization of its proteomic effects in multiple limbic substructures. Male Sprague Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured. Quantitative assessment of changes in the proteomic landscape in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were performed via data-independent acquisition (DIA) mass spectrometry analysis. Administration of G-CSF during extinction accelerated the rate of extinction, and administration during abstinence attenuated cue-induced cocaine-seeking. Analysis of global protein expression demonstrated that G-CSF regulated proteins primarily in mPFC that are critical to glutamate signaling and synapse maintenance. Taken together, these findings support G-CSF as a viable translational research target with the potential to reduce drug craving or seeking behaviors. Importantly, recombinant G-CSF exists as an FDA-approved medication which may facilitate rapid clinical translation. Additionally, using cutting-edge multiregion discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.SIGNIFICANCE STATEMENT Pharmacological treatments for psychostimulant use disorder are desperately needed, especially given the disease's chronic, relapsing nature. However, there are currently no Food and Drug Administration (FDA)-approved pharmacotherapies. Emerging evidence suggests that targeting the immune system may be a viable translational research strategy; preclinical studies have found that the neuroactive cytokine granulocyte-colony stimulating factor (G-CSF) alters cocaine reward and reinforcement and can enhance cognitive flexibility. Given this basis of evidence we studied the effects of G-CSF treatment on extinction and reinstatement of cocaine seeking. We find that administration of G-CSF accelerates extinction and reduces cue-induced drug seeking after cocaine self-administration. In addition, G-CSF leads to downregulation of synaptic glutamatergic proteins in medial prefrontal cortex (mPFC), suggesting that G-CSF influences drug seeking via glutamatergic mechanisms.

Stimulant storm – state health department psychostimulant age-adjusted mortality rate correlates with psychostimulant-based Michigan Poison Center case exposures over time

Background 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). Methods We compared amphetamine and methamphetamine exposures reported to the MiPC from 2012 to 2018, queried from ToxSentry® database, to MDHHS reports on resident death certificates with attributed death due to “overdose, regardless of intent” and related cause of death attributed to psychostimulants with abuse potential. Linear regression assessed goodness-of-fit. Slope with standard error and adjusted R2 were reported. Psychostimulants included methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, and methylphenidate. Results Psychostimulant 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, p value 0.035, and adjusted R2 0.55. Linear regression of MiPC methamphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 0.78, SE 0.27, p value 0.012, and adjusted R2 0.70 suggesting a strong correlation. Conclusion 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.

Maternal and Neonatal Outcomes Associated with Psychostimulant Use in Pregnancy

IntroductionRecent evidence from the USA and Nordic countries suggests a possible association between psychostimulant use during gestation and adverse pregnancy and birth outcomes.&#x0D; Objectives and ApproachWe employed a distributed cohort analysis using linked administrative data for women who gave birth in New South Wales (NSW; Australia) and Ontario (Canada), whereby a common protocol was implemented separately in each jurisdiction. The study population comprised women who were hospitalized for a singleton delivery over an 8 (NSW) and 4 (Ontario) year period, respectively, with the NSW cohort restricted to social security beneficiaries. Psychostimulant exposure was defined as at least one dispensing of methylphenidate, amphetamine, dextroamphetamine or lisdexamfetamine during pregnancy. We examined the risk of maternal and neonatal outcomes among psychostimulant exposed mothers compared with unexposed mothers.&#x0D; ResultsThere were 140,356 eligible deliveries in NSW and 449,499 in Ontario during the respective study periods. Fewer than 1% of these pregnancies were exposed to psychostimulants during gestation, although use was higher in Ontario (0.30% vs 0.11% in NSW). Preliminary unadjusted analyses indicated possible associations between psychostimulant use in pregnancy and higher risks of pre-term birth (relative risk [RR] 1.7, 95% confidence interval [CI] 1.4-2.0 (Ontario); RR 1.8, 95% CI 1.2-2.6 (NSW)) and pre-eclampsia (RR 2.0, 95% CI 1.5-2.6 (Ontario); RR 2.0, 95% CI 1.2-3.5 (NSW)). Similarly, psychostimulant use was associated with higher risks of low birthweight (RR 1.6, 95% CI 1.3-1.9 (Ontario); RR 2.0, 95% CI 1.3-3.0 (NSW)) and admission to neonatal intensive care (RR 2.1, 95% CI 1.9-2.3 (Ontario); RR 1.5, 95% CI 1.1-1.9 (NSW)).&#x0D; Conclusion / ImplicationsUnadjusted analyses indicate an increased risk of adverse maternal and birth outcomes associated with psychostimulant exposure during pregnancy, potentially representing a placental effect. We are currently refining the analyses, employing propensity score methods to adjust for confounding.

Psychostimulant Subtances Use Among Resident Doctors

Abstract The use of psychostimulants is more and more common lately, especially in the medical guild. The term “burn-out” is an occupational phenomenon, not a disease, and 25-60% of doctors in different specialties have the burn-out syndrome. The method was to complete a questionnaire-type test by 204 medical residents. The results shows us that 72.1% (147) of the respondents drinks coffee, 25.9% of them smokes cigarettes during hospital hours and 13.7% consumes energy drinks. Furthemore 5.9% drinks alcohol during shifts. Among of all, those who are consumers of at least one psychostimulant substance, the risk of them having at least one of the symptoms of burnout is 1.3 times higher than those who do not consume anything at work (RR-1.3453, p = 0.0152). Psychostimulant substances are consumed to improve the efficiency and resistance at work. It’s important to manage the time in order to avoid extreme fatigue and distress.