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Neuropsychopharmacology : Official... May 2021Effort-related decision-making and reward learning are both dopamine-dependent, but preclinical research suggests they depend on different dopamine signaling dynamics....
Effort-related decision-making and reward learning are both dopamine-dependent, but preclinical research suggests they depend on different dopamine signaling dynamics. Therefore, the same dose of a dopaminergic medication could have differential effects on effort for reward vs. reward learning. However, no study has tested how effort and reward learning respond to the same dopaminergic medication within subjects. The current study aimed to test the effect of therapeutic doses of d-amphetamine on effort for reward and reward learning in the same healthy volunteers. Participants (n = 30) completed the Effort Expenditure for Reward Task (EEfRT) measure of effort-related decision-making, and the Probabilistic Reward Task (PRT) measure of reward learning, under placebo and two doses of d-amphetamine (10 mg, and 20 mg). Secondarily, we examined whether the individual characteristics of baseline working memory and willingness to exert effort for reward moderated the effects of d-amphetamine. d-Amphetamine increased willingness to exert effort, particularly at low to intermediate expected values of reward. Computational modeling analyses suggested this was due to decreased effort discounting rather than probability discounting or decision consistency. Both baseline effort and working memory emerged as moderators of this effect, such that d-amphetamine increased effort more in individuals with lower working memory and lower baseline effort, also primarily at low to intermediate expected values of reward. In contrast, d-amphetamine had no significant effect on reward learning. These results have implications for treatment of neuropsychiatric disorders, which may be characterized by multiple underlying reward dysfunctions.
Topics: Decision Making; Dextroamphetamine; Humans; Motivation; Reinforcement, Psychology; Reward
PubMed: 32722661
DOI: 10.1038/s41386-020-0779-8 -
PloS One 2020The non-medical use of prescription stimulants such as methylphenidate, dexamphetamine and modafinil is increasing in popularity within tertiary academic settings. There...
INTRODUCTION AND AIMS
The non-medical use of prescription stimulants such as methylphenidate, dexamphetamine and modafinil is increasing in popularity within tertiary academic settings. There is a paucity of information on awareness, attitudes, and acceptability by professionals of use in this context. This study aimed to investigate professionals' knowledge of and attitudes towards the use of cognitive enhancers (CEs) in academic settings, and their willingness to use a hypothetical CE.
DESIGN AND METHODS
A mail survey was sent to doctors, pharmacists, nurses, accountants and lawyers in New Zealand. These disciplines were chosen as they require professional registration to practice. The questionnaire comprised four sections: (1) demographics, (2) knowledge of CEs, (3) attitudes towards the use of CEs, and (4) willingness to use hypothetical CEs.
RESULTS
The response rate was 34.5% (414/1200). Overall, participants strongly disagreed that it was fair to allow university students to use CEs for cognitive enhancement (Mdn = 1, IQR: 1,3), or that it is ethical for students without a prescription to use cognitive enhancers for any reason (Mdn = 1, IQR: 1,2). Professions differed in their attitudes towards whether it is ethical for students without a prescription to use CEs for any reason (p = 0.001, H 31.527).
DISCUSSION AND CONCLUSION
Divergent views and lack of clear consensus within professions and between professionals on the use of CEs have the potential to influence both professionals and students as future professionals. These divergent views may stem from differences in the core values of self-identity as well as extrinsic factors of acceptability within the profession in balancing the elements of opportunity, fairness and authenticity in cognitive enhancement. Further research is required to inform the development of policy and guidelines that are congruent with all professions.
Topics: Adult; Aged; Attitude of Health Personnel; Central Nervous System Stimulants; Cognition; Dextroamphetamine; Female; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Male; Methylphenidate; Middle Aged; Modafinil; New Zealand; Prescription Drugs; Students; Surveys and Questionnaires; Universities; Young Adult
PubMed: 33216781
DOI: 10.1371/journal.pone.0241968 -
Neuropsychopharmacology : Official... Apr 2022The poor translatability between preclinical and clinical drug trials has limited pro-cognitive therapeutic development. Future pro-cognitive drug trials should use... (Randomized Controlled Trial)
Randomized Controlled Trial
The poor translatability between preclinical and clinical drug trials has limited pro-cognitive therapeutic development. Future pro-cognitive drug trials should use translatable cross-species cognitive tasks with biomarkers (1) relevant to specific cognitive constructs, and (2) sensitive to drug treatment. Here, we used a difficulty-modulated variant of a cross-species cognitive control task with simultaneous electroencephalography (EEG) to identify neurophysiological biomarkers sensitive to the pro-cognitive effects of dextroamphetamine (d-amp) (10 or 20 mg) in healthy adults (n = 23), in a randomized, placebo-controlled, counterbalanced, double blind, within-subject study, conducted across three test days each separated by one week. D-amp boosted d-prime, sped reaction time, and increased frontal P3a amplitude to non-target correct rejections independent of task difficulty. Task difficulty did however, moderate d-amp effects on EEG during target performance. D-amp suppressed frontal theta power during easy target responses which negatively correlated with drug-induced improvement in hit rate while d-amp-induced changes in P3b amplitude during hard target trials strongly correlated with drug-induced improvement in hit rate. In summary, d-amp affected both behavioral and neurophysiological measures of cognitive control elements. Under low-demand, d-amp diminished cognitive control by suppressing theta, yet under high-demand it boosted control in concert with higher P3b amplitudes. These findings thus appear to reflect a gain-sharpening effect of d-amp: during high-demand processes were boosted while during low-demand processes were neglected. Future studies will use these neurophysiological measures of cognitive control as biomarkers to predict d-amp sensitivity in people with cognitive control deficits, including schizophrenia.
Topics: Adult; Humans; Cognition; Dextroamphetamine; Electroencephalography; Healthy Volunteers
PubMed: 35042948
DOI: 10.1038/s41386-021-01257-2 -
Journal of Microbiology and... Sep 2022Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the...
Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. SR79 (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)-induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3β signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6-OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.
Topics: Animals; Base Composition; Clostridiales; Dextroamphetamine; Disease Models, Animal; Dopaminergic Neurons; Glycogen Synthase Kinase 3 beta; Mice; NF-E2-Related Factor 2; Neurodegenerative Diseases; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Phylogeny; Proto-Oncogene Proteins c-akt; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 36168204
DOI: 10.4014/jmb.2205.05032 -
BMC Psychiatry Oct 2015Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood.... (Review)
Review
BACKGROUND
Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic.
METHODS
Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles.
RESULTS
We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol.
CONCLUSIONS
The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.
Topics: Adolescent; Adrenergic Uptake Inhibitors; Alcohol Drinking; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Drug Interactions; Humans; Illicit Drugs; Lisdexamfetamine Dimesylate; Methylphenidate; Substance-Related Disorders
PubMed: 26517983
DOI: 10.1186/s12888-015-0657-9 -
Journal of Psychiatry & Neuroscience :... Mar 2003To explore the possible involvement of second-messenger pathways in the pathophysiology of bipolar disorder and the mechanism of action of mood stabilizers, we...
OBJECTIVE
To explore the possible involvement of second-messenger pathways in the pathophysiology of bipolar disorder and the mechanism of action of mood stabilizers, we investigated the effects of dextroamphetamine (a model for mania) and the most widely used mood stabilizers, lithium chloride, sodium valproate and carbamazepine, on intraplatelet levels of calcium ion ([Ca2+).
DESIGN
In the first part of the study, dextroamphetamine was administered in vivo in a double-blind, placebo-controlled, crossover design. In the second part of the study, platelets from untreated subjects were incubated in vitro with dextroamphetamine, lithium chloride, sodium valproate or carbamazepine.
PARTICIPANTS
Fifteen healthy men between 18 and 45 years of age.
OUTCOME MEASURES
Basal, thrombin-induced and serotonin- (5-HT) induced intraplatelet [Ca2+] determined by means of fura-2 fluorescent intensity.
RESULTS
In vivo administration of dextroamphetamine had no effect on basal or agonist-induced intraplatelet [Ca2+]. However, in vitro basal platelet [Ca2+] was significantly higher in samples incubated with dextroamphetamine (86.8 nmol/L [standard error of the mean, SEM, 3.9], p < 0.001), lithium chloride (76.4 nmol/L [SEM 3.1], p < 0.002), sodium valproate (82.7 nmol/L [SEM 3.7], p < 0.001) and carbamazepine (84.8 nmol/L [SEM 3.3], p < 0.001) than in the controls (58.2 nmol/L [SEM 2.3]). Thrombin-induced and 5-HT-induced peak cytosolic [Ca2+] were significantly greater than control levels in samples incubated with carbamazepine (277.1 nmol/L [SEM 19.9] v. 195.8 nmol/L [SEM 12.2], p < 0.002; and 153.0 nmol/L [SEM 8.2] v. 115.4 nmol/L [SEM 5.7], p < 0.003, respectively).
CONCLUSIONS
This study does not support the involvement of intraplatelet [Ca2+] in the dextroamphetamine model of mania; however, the modulation of intraplatelet [Ca2+] by the mood stabilizers lithium chloride, sodium valproate and carbamazepine implicates intracellular [Ca2+] in the therapeutic mechanisms of these drugs and the pathophysiological basis of mania.
Topics: Adolescent; Adult; Antipsychotic Agents; Blood Platelets; Calcium Channels; Carbamazepine; Dextroamphetamine; Female; Humans; Lithium Chloride; Male; Middle Aged; Thrombin; Valproic Acid
PubMed: 12670128
DOI: No ID Found -
Psychopharmacology Jul 2014Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric-acidA (GABAA) receptors (e.g., alprazolam) modestly attenuate the abuse-related effects... (Comparative Study)
Comparative Study Randomized Controlled Trial
RATIONALE
Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric-acidA (GABAA) receptors (e.g., alprazolam) modestly attenuate the abuse-related effects of stimulants like amphetamine. The use of higher doses to achieve greater efficacy is precluded by side effects. Combining naltrexone and alprazolam might safely maximize efficacy while avoiding the untoward effects of the constituent compounds.
OBJECTIVES
The present pilot study tested the hypothesis that acute pretreatment with the combination of naltrexone and alprazolam would not produce clinically problematic physiological effects or negative subjective effects and would reduce the positive subjective effects of d-amphetamine to a greater extent than the constituent drugs alone.
METHODS
Eight nontreatment-seeking, stimulant-using individuals completed an outpatient experiment in which oral d-amphetamine (0, 15, and 30 mg) was administered following acute pretreatment with naltrexone (0 and 50 mg) and alprazolam (0 and 0.5 mg). Subjective effects, psychomotor task performance, and physiological measures were collected.
RESULTS
Oral d-amphetamine produced prototypical physiological and stimulant-like positive subjective effects (e.g., VAS ratings of Active/Alert/Energetic, Good Effect, and High). Pretreatment with naltrexone, alprazolam, and their combination did not produce clinically problematic acute physiological effects or negative subjective effects. Naltrexone and alprazolam each significantly attenuated some of the subjective effects of d-amphetamine. The combination attenuated a greater number of subjective effects than the constituent drugs alone.
CONCLUSIONS
The present results support the continued evaluation of an opioid receptor antagonist combined with a GABAA-positive modulator using more clinically relevant experimental conditions like examining the effect of chronic dosing with these drugs on methamphetamine self-administration.
Topics: Administration, Oral; Adult; Alprazolam; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; GABA Modulators; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Pilot Projects; Psychomotor Performance
PubMed: 24464531
DOI: 10.1007/s00213-014-3449-x -
Harm Reduction Journal May 2021For people with opioid use disorder who are not responding to oral opioid agonist treatment, evidence supports the effectiveness of injectable opioid agonist treatment...
BACKGROUND
For people with opioid use disorder who are not responding to oral opioid agonist treatment, evidence supports the effectiveness of injectable opioid agonist treatment with injectable hydromorphone (an opioid analgesic) and diacetylmorphine (pharmaceutical grade heroin). While this treatment is effective at reducing illicit opioid use, concurrent cocaine use is prevalent. Dextroamphetamine (a central nervous system stimulant) has been found to be a safe and effective treatment for cocaine dependence among people receiving injectable opioid agonist treatment in Europe. We present the first report of dextroamphetamine prescribing offered for the treatment of stimulant use disorder among a patient receiving iOAT outside of a clinical trial. This case report can be used to inform clinical practice in the treatment of cocaine use disorder, an area where interventions are currently lacking.
CASE PRESENTATION
Dextroamphetamine was prescribed to a 51-year-old male who was diagnosed with concurrent opioid and stimulant use disorder in an injectable opioid agonist treatment clinic in Vancouver, Canada. He reported smoking crack cocaine daily for more than two decades and was experiencing health consequences associated with this use. He presented to his routine physician visit with the goal of reducing his cocaine use and was prescribed dextroamphetamine for the treatment of stimulant use disorder. After 4-weeks the patient was tolerating the medication with no observed adverse events and was achieving his therapeutic goal of reducing his cocaine use.
CONCLUSIONS
Dextroamphetamine can be prescribed to support patients with stimulant use disorder to reduce or stop their use of cocaine. The case demonstrated that when dextroamphetamine was prescribed, a significant reduction in cocaine use was experienced among a patient that had been regularly using cocaine on a daily basis for many years. Daily contact with care for the opioid medication promoted adherence to the stimulant medication and allowed for monitoring of dose and tolerance. Settings where patients are in regular contact with care such as oral and injectable opioid agonist treatment clinics serve as a suitable location to integrate dextroamphetamine prescribing for patients that use illicit stimulants to reduce use and associated harms.
Topics: Analgesics, Opioid; Canada; Central Nervous System Stimulants; Delayed-Action Preparations; Dextroamphetamine; Humans; Male; Middle Aged; Opioid-Related Disorders
PubMed: 34016137
DOI: 10.1186/s12954-021-00500-9 -
European Journal of Clinical... Jan 2021The aim of this study was to analyse whether the global trend in drug prescriptions for attention-deficit hyperactivity disorders (ADHD), as observed during the last... (Observational Study)
Observational Study
PURPOSE
The aim of this study was to analyse whether the global trend in drug prescriptions for attention-deficit hyperactivity disorders (ADHD), as observed during the last years and often criticized as medicalization, have remained stable or shifted.
METHODS
This observational study was based on a secondary analysis of data from a large German database including patients with an ADHD diagnosis between 2008 and 2018. Prescription data comprised all important ADHD drugs.
RESULTS
A total of 620 practices delivered data from a total of 77,504 patients (31% of them females) with a diagnosis of AHDH. Nearly 38% (29,396/77,504) of all patients received, at least, one prescription for an ADHS medicine between 2008 and 2018. The number of patients receiving a drug steadily increased annually until 2012 and then slowly fell, but unevenly distributed across the age groups. While the number of younger patients ( ≤ 16 years) receiving a prescription fell by 24% and the defined daily doses (DDDs) remained stable, the number of patients between 17 and 24 years receiving a prescription increased by 113% and the DDDs by 150%. Respectively, the number of older adults (≥ 25 years) with a prescription increased by 355% and the DDDs by 515%. Nearly one-third of older adults received an ADHD medicine only once.
CONCLUSION
The ever-increasing prescription of ADHD medicines stopped some years ago for children. ADHS and its pharmacological management are increasingly observed among older adolescents and adults, with a different pattern of drug persistence compared with children.
Topics: Adolescent; Adult; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Dextroamphetamine; Drug Prescriptions; Female; Germany; Guanfacine; Humans; Male; Methylphenidate; Practice Patterns, Physicians'; Young Adult
PubMed: 32803292
DOI: 10.1007/s00228-020-02948-3 -
British Medical Journal Jul 1971
Topics: Adult; Dextroamphetamine; Enuresis; Humans
PubMed: 5557544
DOI: 10.1136/bmj.3.5769.302-c