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British Medical Journal Mar 1973
Topics: Brain; Child; Dextroamphetamine; Humans; Hyperkinesis; Methylphenidate; Substance-Related Disorders
PubMed: 4694422
DOI: 10.1136/bmj.1.5853.616-f -
Biological Psychiatry. Cognitive... May 2024While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain.
METHODS
We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal modeling, we mapped substance-induced changes in effective connectivity between the thalamus and different cortex types (unimodal vs. transmodal) derived from a previous study with resting-state functional magnetic resonance imaging data. Due to the distinct pharmacological modes of action of the 3 substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions.
RESULTS
Compared with placebo, all 3 substances increased the effective connectivity from the thalamus to specific unimodal cortices, whereas the influence of these cortices on the thalamus was reduced. These results indicate increased bottom-up and decreased top-down information flow between the thalamus and some unimodal cortices. However, for the amphetamines, we found the opposite effects when examining the effective connectivity with transmodal cortices, including parts of the salience network. Intriguingly, LSD increased the effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in the hierarchical organization of ongoing brain activity.
CONCLUSIONS
The results advance our knowledge about the action of psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes.
Topics: Humans; Lysergic Acid Diethylamide; N-Methyl-3,4-methylenedioxyamphetamine; Thalamus; Male; Double-Blind Method; Adult; Magnetic Resonance Imaging; Hallucinogens; Dextroamphetamine; Cross-Over Studies; Female; Cerebral Cortex; Young Adult; Neural Pathways; Connectome
PubMed: 37532129
DOI: 10.1016/j.bpsc.2023.07.010 -
Substance Abuse Treatment, Prevention,... Sep 2021A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has...
Exploring the effectiveness of dextroamphetamine for the treatment of stimulant use disorder: a qualitative study with patients receiving injectable opioid agonist treatment.
BACKGROUND
A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has been associated with higher rates of continued illicit opioid use and treatment dropout. A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine among patients receiving injectable opioid agonist treatment. Following this evidence, dextroamphetamine has been prescribed to patients with stimulant use disorder at a clinic in Vancouver. This study investigates perceptions of the effectiveness of dextroamphetamine from the perspective of these patients.
METHODS
Data were collected using small focus groups and one-on-one interviews with patients who were currently or formerly receiving dextroamphetamine (n = 20). Thematic analysis was conducted using an iterative approach, moving between data collection and analysis to search for patterns in the data across transcripts. This process led to the defining and naming of three central themes responding to the research question.
RESULTS
Participants reported a range of stimulant use types, including cocaine (n = 8), methamphetamine (n = 8), or both (n = 4). Three central themes were identified as relating to participants' perceptions of the effectiveness of the medication: 1) achieving a substitution effect (i.e. extent to which dextroamphetamine provided a substitution for the effect they received from use of illicit stimulants); 2) Reaching a preferred dose (i.e. speed of titration and effect of the dose received); and 3) Ease of medication access (i.e. preference for take home doses (i.e. carries) vs. medication integrated into care at the clinic).
CONCLUSION
In the context of continued investigation of pharmacological treatments for stimulant use disorder, the present study has highlighted how the study of clinical outcomes could be extended to account for factors that contribute to perceptions of effectiveness from the perspective of patients. In practice, elements of treatment delivery (e.g. dosing and dispensation protocols) can be adjusted to allow for various scenarios (e.g. on site vs. take home dosing) by which dextroamphetamine and other pharmacological stimulants could be implemented to provide "effective" treatment for people with a wide range of treatment goals and needs.
Topics: Analgesics, Opioid; Central Nervous System Stimulants; Dextroamphetamine; Humans; Methamphetamine; Opioid-Related Disorders
PubMed: 34530878
DOI: 10.1186/s13011-021-00399-2 -
JAMA Neurology Dec 2018Data from animal models show that the administration of dextroamphetamine combined with task-relevant training facilitates recovery after focal brain injury. Results of... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Data from animal models show that the administration of dextroamphetamine combined with task-relevant training facilitates recovery after focal brain injury. Results of clinical trials in patients with stroke have been inconsistent.
OBJECTIVES
To collect data important for future studies evaluating the effect of dextroamphetamine combined with physiotherapy for improving poststroke motor recovery and to test the efficacy of the approach.
DESIGN, SETTING, PARTICIPANTS
This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits from 5 rehabilitation hospitals or units. Participants were screened and enrolled from March 2001 through March 2003. The primary outcome was assessed 3 months after stroke. Study analysis was completed December 31, 2015. A total of 1665 potential participants were screened and 64 were randomized. Participants had to begin treatment 10 to 30 days after ischemic stroke. Data analysis was based on intention to treat.
INTERVENTIONS
Participants were allocated to a regimen of 10 mg of dextroamphetamine (n = 32) or placebo (n = 32) combined with a 1-hour physical therapy session beginning 1 hour after drug or placebo administration every 4 days for 6 sessions in addition to standard rehabilitation.
MAIN OUTCOMES AND MEASURES
The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to 3 months after stroke (intention to treat with dextroamphetamine). Secondary exploratory measures included the National Institutes of Health Stroke Scale, Canadian Neurological Scale, Action Research Arm Test, modified Rankin Scale score, Functional Independence Measure, Ambulation Speed and Distance, Mini-Mental State Examination, Beck Depression Inventory, and Stroke Impact Scale.
RESULTS
Among the 64 patients randomized to dextroamphetamine vs placebo (55% men; median age, 66 years; age range, 27-91 years), no overall treatment-associated difference in the mean (SEM) change in Fugl-Meyer motor scores from baseline to 3 months after stroke was noted (-18.65 [2.27] points with dextroamphetamine vs -20.83 [2.94] points with placebo; P = .58). No overall treatment-associated differences in any of the study's secondary measures and no differences in subgroups based on stroke location or baseline severity were found. No adverse events were attributed to study treatments.
CONCLUSIONS AND RELEVANCE
Treatment with dextroamphetamine combined with physical therapy did not improve recovery of motor function compared with placebo combined with physical therapy as assessed 3 months after hemispheric ischemic stroke. The studied treatment regimen was safe.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01905371.
Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Central Nervous System Stimulants; Combined Modality Therapy; Dextroamphetamine; Double-Blind Method; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Physical Therapy Modalities; Pilot Projects; Recovery of Function; Severity of Illness Index; Stroke; Stroke Rehabilitation
PubMed: 30167675
DOI: 10.1001/jamaneurol.2018.2338 -
The American Journal of Drug and... 2009Although preclinical studies support the contribution of the noradrenergic system activation in mediating the acute effects of amphetamines, these findings have not been... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Although preclinical studies support the contribution of the noradrenergic system activation in mediating the acute effects of amphetamines, these findings have not been followed up in clinical studies.
OBJECTIVES
To examine the effects of atomoxetine, a norepinephrine transporter inhibitor, on subjective, physiological, and plasma cortisol responses to dextroamphetamine in 10 healthy volunteers.
METHODS
Subjects were randomly assigned to a sequence of atomoxetine (40 mg/day) or placebo treatments each lasting for 4 days. On Day 4 of each treatment period, responses to a single 20 mg/70 kg dose of dextroamphetamine were assessed.
RESULTS
Atomoxetine treatment attenuated dextroamphetamine-induced increases in systolic and diastolic blood pressure and plasma cortisol as well as the self-report ratings of "stimulated," "high," and "good drug effects."
CONCLUSIONS
These findings are consistent with previous preclinical studies supporting the role of the noradrenergic system in mediating acute amphetamine responses.
SCIENTIFIC SIGNIFICANCE
Atomoxetine's capacity to attenuate some of the physiological and subjective responses to dextroamphetamine supports its potential use for stimulant addiction.
Topics: Adrenergic Uptake Inhibitors; Adult; Affect; Atomoxetine Hydrochloride; Blood Pressure; Central Nervous System Stimulants; Dextroamphetamine; Drug Interactions; Female; Heart Rate; Humans; Hydrocortisone; Male; Norepinephrine Plasma Membrane Transport Proteins; Propylamines
PubMed: 20014909
DOI: 10.3109/00952990903383961 -
BMJ Clinical Evidence Oct 2008Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence... (Review)
Review
INTRODUCTION
Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence estimates among school children in the US are 3-5%, but other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the diagnosis of ADHD, which remains a clinical diagnosis. Other conditions frequently co-exist with ADHD.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological treatments for ADHD in children and adolescents? What are the effects of psychological treatments for ADHD in children and adolescents? What are the effects of combination treatments for ADHD in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate, homeopathy, methylphenidate, modafinil, omega 3-polyunsaturated fatty acids, and psychological/behavioural treatment (either alone or in combination with a drug treatment).
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Child; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Humans; Methylphenidate
PubMed: 19445793
DOI: No ID Found -
Journal of Child and Adolescent... Nov 2013The purpose of this study was to investigate clinical gains from including both dextroamphetamine and methylphenidate in stimulant trials. (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
The purpose of this study was to investigate clinical gains from including both dextroamphetamine and methylphenidate in stimulant trials.
METHOD
Thirty-six medication-naïve children ages 9-14 years diagnosed with attention-deficit/hyperactivity disorder (ADHD) were enrolled for 6 weeks in a crossover trial, with 2 weeks of methylphenidate, dextroamphetamine, and placebo, in a randomly assigned, counterbalanced sequence. Outcome measures constituted a computer-based continuous performance test combined with a motion tracking system (Qb Test) and an ADHD questionnaire rated by parents and teachers.
RESULTS
Group analyses found significant treatment effects of similar size for the two stimulants on both outcome measures. Single-subject analyses revealed that each stimulant produced a favourable response in 26 children; however, an individual child frequently responded qualitatively or quantitatively differently to the two stimulants. By including both stimulants in the trial, the number of favorable responders increased from 26 (72%) to 33 (92%). In children with favorable responses of unequal strength to the two stimulants, a shift from inferior drug to best drug was associated with a 64% mean increase in the overall response strength score, as measured by the ADHD questionnaire.
CONCLUSIONS
The likelihood of a favorable response and optimal response strength is increased by including both stimulants in the stimulant trial. The study was first registered in clinical trials 28 September 2010. Clinical Trials.gov Identifier: NCT01220440.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Dextroamphetamine; Diagnosis, Computer-Assisted; Double-Blind Method; Female; Humans; Male; Methylphenidate; Parents; Surveys and Questionnaires; Time Factors; Treatment Outcome
PubMed: 23659360
DOI: 10.1089/cap.2012.0085 -
Journal of Psychiatry & Neuroscience :... 2023The pathophysiology of psychosis is complex, but a better understanding of stimulus binding windows (BWs) could help to improve our knowledge base. Previous studies have... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The pathophysiology of psychosis is complex, but a better understanding of stimulus binding windows (BWs) could help to improve our knowledge base. Previous studies have shown that dopamine release is associated with psychosis and widened BWs. We can probe BW mechanisms using drugs of specific interest to psychosis. Therefore, we were interested in understanding how manipulation of the dopamine or catecholamine systems affect psychosis and BWs. We aimed to investigate the effect of dexamphetamine, as a dopamine-releasing stimulant, on the BWs in a unimodal illusion: the tactile funneling illusion (TFI).
METHODS
We conducted a randomized, double-blind, counterbalanced placebo-controlled crossover study to investigate funnelling and errors of localization. We administered dexamphetamine (0.45 mg/kg) to 46 participants. We manipulated 5 spatial (5-1 cm) and 3 temporal (0, 500 and 750 ms) conditions in the TFI.
RESULTS
We found that dexamphetamine increased funnelling illusion ( = 0.009) and increased the error of localization in a delay-dependent manner ( = 0.03). We also found that dexamphetamine significantly increased the error of localization at 500 ms temporal separation and 4 cm spatial separation ( = 0.009; = 0.01).
LIMITATIONS
Although amphetamine-induced models of psychosis are a useful approach to understanding the physiology of psychosis related to dopamine hyperactivity, dexamphetamine is equally effective at releasing noradrenaline and dopamine, and, therefore, we were unable to tease apart the effects of the 2 systems on BWs in our study.
CONCLUSION
We found that dexamphetamine increases illusory perception on the unimodal TFI in healthy participants, which suggests that dopamine or other catecholamines have a role in increasing tactile spatial and temporal BWs.
Topics: Humans; Dextroamphetamine; Dopamine; Illusions; Cross-Over Studies; Healthy Volunteers; Catecholamines
PubMed: 36918195
DOI: 10.1503/jpn.220149 -
The American Journal of Psychiatry Feb 1973
Clinical Trial Comparative Study
Topics: Aggression; Amphetamine; Animals; Attention Deficit Disorder with Hyperactivity; Behavior, Animal; Child; Child Behavior Disorders; Clinical Trials as Topic; Dextroamphetamine; Dogs; Evaluation Studies as Topic; Hostility; Humans; Hyperkinesis; Isomerism; Models, Biological; Motor Activity; Placebos
PubMed: 4568123
DOI: 10.1176/ajp.130.2.165 -
Neuropharmacology Jan 2022Nicotine enhances the rewarding effects of other environmental stimuli; this reward-enhancement encourages and maintains nicotine consumption. Nicotine use precedes...
Nicotine enhances the rewarding effects of other environmental stimuli; this reward-enhancement encourages and maintains nicotine consumption. Nicotine use precedes other psychostimulant use, but receiving a stimulant prescription also predicts future smoking. Previously, no study has investigated effects of drug exposure order in reward-enhancement, nor with nicotine and d-amphetamine. Thus, we aimed to investigate how drug exposure order impacted the reward-enhancing effects of nicotine and d-amphetamine, alone and in combination. We used 20 male and 20 female Sprague-Dawley rats. Enhancement was investigated within-subjects by examining responding maintained by a visual stimulus reinforcer following a pre-session injection of either d-amphetamine (Sal, 0.1, 0.3, or 0.6 mg/kg) or nicotine (Sal, 0.03, 0.06, 0.1, 0.3 mg/kg). Twenty rats (10 M, 10 F) completed enhancement testing with nicotine before d-amphetamine. The other 20 rats (10 M, 10 F) completed testing with d-amphetamine before nicotine. Following these phases, rats were then given two pre-session injections: one of d-amphetamine (Sal, 0.1, 0.3, or 0.6 mg/kg) and another of nicotine (Sal, 0.03, 0.06, 0.1, or 0.3 mg/kg). Experiencing amphetamine before nicotine increased reward-enhancing effects of nicotine. Females exhibited greater effects of d-amphetamine on reward-enhancement, with no effect of exposure order. During the interaction phase, receiving nicotine before amphetamine enhanced the interaction between nicotine and d-amphetamine for females whereas amphetamine before nicotine heightened this interaction for males. From this, prior and current amphetamine use, in addition to sex, should be considered when treating nicotine dependency and when examining factors driving poly-substance use involving nicotine and d-amphetamine. Keywords: Adderall, ADHD, Dexedrine, operant, smoking, polysubstance use.
Topics: Animals; Conditioning, Operant; Dextroamphetamine; Drug Combinations; Female; Humans; Male; Nicotine; Rats, Sprague-Dawley; Reinforcement, Psychology; Reward; Sex Characteristics; Substance-Related Disorders; Rats
PubMed: 34678376
DOI: 10.1016/j.neuropharm.2021.108845