Adderall - Knowledge

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depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET). ... Surprisingly, this amphetamine-elicited efflux was markedly enhanced, rather than inhibited, by the addition of 10 μM Zn to the superfusion buffer (Fig. 2 A, open squares). We stress that Zn per se did not affect basal efflux (Fig. 2 A). ... In many brain regions, Zn is stored in synaptic vesicles and co-released together with glutamate; under basal conditions, the extracellular levels of Zn are low (~10 nM; see Refs. 39, 40). Upon neuronal stimulation, however, Zn is co-released with the neurotransmitters and, consequently, the free Zn concentration may transiently reach values that range from 10–20 μM (10) up to 300 μM (11). The concentrations of Zn shown in this study, required for the stimulation of dopamine release (as well as inhibition of uptake), covered this physiologically relevant range, with maximum stimulation occurring at 3–30 μM. It is therefore conceivable that the action of Zn on hDAT does not merely reflect a biochemical peculiarity but that it is physiologically relevant. ... Thus, when Zn is co-released with glutamate, it may greatly augment the efflux of dopamine.

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demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. ... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). ... In particular, in both animals and humans, lower doses maximally improve performance in tests of working memory and response inhibition, whereas maximal suppression of overt behavior and facilitation of attentional processes occurs at higher doses.

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for marketing purposes. The FDA cited the company for numerous significant CGMP violations related to Obetrol discovered during routine inspections following the acquisition (including issuing a formal warning letter for the violations), then later issued a second formal warning letter to Richwood Pharmaceuticals specifically due to violations of "the new drug and misbranding provisions of the FD&C Act". Following extended discussions with Richwood Pharmaceuticals regarding the resolution of a large number of issues related to the company's numerous violations of FDA regulations, the FDA formally approved the first Obetrol labeling/sNDA revisions in 1996, including a name change to Adderall and a restoration of its status as an approved drug product. In 1997 Richwood Pharmaceuticals was acquired by Shire Pharmaceuticals in a $ 186 million transaction.

12031:ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states. ... ΔFosB serves as one of the master control proteins governing this structural plasticity. 15171:] drug molecules through promiscuous enzymatic metabolism. ... The present study on the atomistic details of amphetamine binding and binding affinity to the tyramine oxidase along with the comparison with two natural substrates of this enzyme namely tyramine and phenylalanine provides strong evidence for the promiscuity-based metabolism of amphetamine by the tyramine oxidase enzyme of E. coli. The obtained results will be crucial in designing a surrogate molecule for amphetamine that can help either in improving the efficacy and bioavailability of the amphetamine drug via competitive inhibition or in redesigning the drug for better pharmacological effects. This study will also have useful clinical implications in reducing the gut microbiota caused variation in the drug response among different populations. 10718:

with the non-stimulants atomoxetine and extended-release guanfacine, are continuously effective for more than 2-year treatment periods with few and tolerable adverse effects. The effectiveness of long-term therapy includes not only the core symptoms of ADHD, but also improved quality of life and academic achievements. The most concerning short-term adverse effects of stimulants, such as elevated blood pressure and heart rate, waned in long-term follow-up studies. ... The current data do not support the potential impact of stimulants on the worsening or development of tics or substance abuse into adulthood. In the longest follow-up study (of more than 10 years), lifetime stimulant treatment for ADHD was effective and protective against the development of adverse psychiatric disorders.

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that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.

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amphetamine, 90% of the consumed dose is absorbed in the gastrointestinal tract, with no significant differences in the rate and extent of absorption between the two enantiomers (Carvalho et al. 2012; Childress et al. 2019). The onset of action occurs approximately 30 to 45 minutes after consumption, depending on the ingested dose and on the degree of purity or on the concomitant consumption of certain foods (European Monitoring Centre for Drugs and Drug Addiction 2021a; Steingard et al. 2019). It is described that those substances that promote acidification of the gastrointestinal tract cause a decrease in amphetamine absorption, while gastrointestinal alkalinization may be related to an increase in the compound's absorption (Markowitz and Patrick 2017).

1235:. The capsule can be swallowed like a tablet, or it can be opened and the beads sprinkled over applesauce for comparable absorption. Upon ingestion, half of the beads provide immediate administration of medication, while the other half are enveloped in a coating which must dissolve, delaying absorption of its contents. It is designed to provide a therapeutic effect and plasma concentrations identical to taking two doses of Adderall IR four hours apart. Mydayis uses a longer-lasting triple-bead formulation and is approved to treat ADHD for up to 16 hours in individuals 13 years and older. In the United States, the immediate and extended-release formulations of Adderall are both available as 8957:

originate in the ventral tegmental area (VTA); and the histaminergic pathway originates from neurons in the tuberomammillary nucleus (TMN) of the posterior hypothalamus. As discussed in Chapter 6, these neurons project widely throughout the brain from restricted collections of cell bodies. Norepinephrine, serotonin,dopamine, and histamine have complex modulatory functions and, in general, promote wakefulness. The PT in the brainstem is also an important component of the ARAS. Activity of PT cholinergic neurons (REM-on cells) promotes REM sleep, as noted earlier. During waking, REM-on cells are inhibited by a subset of ARAS norepinephrine and serotonin neurons called REM-off cells.

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symptoms and relapse in abstinent smokers (Daniel et al., 2006; Prochaska et al., 2008), and one drug recovery program has seen success in participants that train for and compete in a marathon as part of the program (Butler, 2005). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008).

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demonstrated how dopamine modulates this integrative process. For example, high frequency stimulation potentiates hippocampal inputs to the NAc while simultaneously depressing PFC synapses (Goto and Grace, 2005). The converse was also shown to be true; stimulation at PFC potentiates PFC–NAc synapses but depresses hippocampal–NAc synapses. In light of the new functional evidence of midbrain dopamine/glutamate co-transmission (references above), new experiments of NAc function will have to test whether midbrain glutamatergic inputs bias or filter either limbic or cortical inputs to guide goal-directed behavior.

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markedly increased urinary excretion of PEA, suggesting that ADHD treatments normalize PEA levels. ... Similarly, urinary biogenic trace amine PEA levels could be a biomarker for the diagnosis of ADHD, for treatment efficacy, and associated with symptoms of inattentivenesss. ... With regard to zinc supplementation, a placebo controlled trial reported that doses up to 30 mg/day of zinc were safe for at least 8 weeks, but the clinical effect was equivocal except for the finding of a 37% reduction in amphetamine optimal dose with 30 mg per day of zinc.

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underestimated and largely unexplored (Savage, 1977; Medini et al., 2008; Minot et al., 2011; Wylie et al., 2012). ... Meanwhile, a wealth of literature has long been available about the biotransformation of xenobiotics, notably by gut bacteria (reviewed in Sousa et al., 2008; Rizkallah et al., 2010; Johnson et al., 2012; Haiser and Turnbaugh, 2013). This valuable information is predominantly about drug metabolism by unknown human-associated microbes; however, only a few cases of inter-individual microbiome variations have been documented .

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substitute for the rewarding effects of drug abuse. ... The value of this form of treatment for drug addiction in laboratory animals and humans is that exercise, if it can substitute for the rewarding effects of drugs, could be self-maintained over an extended period of time. Work to date in regarding exercise as a treatment for drug addiction supports this hypothesis. ... Animal and human research on physical exercise as a treatment for stimulant addiction indicates that this is one of the most promising treatments on the horizon.

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drug addiction that may reduce drug craving and risk of relapse. Although few clinical studies have investigated the efficacy of exercise for preventing relapse, the few studies that have been conducted generally report a reduction in drug craving and better treatment outcomes ... Taken together, these data suggest that the potential benefits of exercise during relapse, particularly for relapse to psychostimulants, may be mediated via chromatin remodeling and possibly lead to greater treatment outcomes.

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reward,aspects of emotion, and learning. In fact, orexin is thought to promote feeding primarily by promoting arousal. Mutations in orexin receptors are responsible for narcolepsy in a canine model, knockout of the orexin gene produces narcolepsy in mice, and humans with narcolepsy have low or absent levels of orexin peptides in cerebrospinal fluid (Chapter 13). Lateral hypothalamus neurons have reciprocal connections with neurons that produce monoamine neurotransmitters (Chapter 6).

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regions including the striatum, VTA and NAc (Del Arco et al., 1999; Kim et al., 1981; Mora and Porras, 1993; Xue et al., 1996), but it has not been established whether this change can be explained by increased synaptic release or by reduced clearance of glutamate. ... DHK-sensitive, EAAT2 uptake was not altered by AMPH (Figure 1A). The remaining glutamate transport in these midbrain cultures is likely mediated by EAAT3 and this component was significantly decreased by AMPH

4557: 1186:. Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines. In contrast, levoamphetamine may have a greater effect on cataplexy, a symptom more sensitive to the effects of norepinephrine and serotonin. Noradrenergic and serotonergic nuclei in the ARAS are involved in the regulation of the 12768:

and putamen, but not the medial preoptic nucleus. ... these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.

2229: 2596:, a "molecular switch" and "master control protein" for addiction. Once nucleus accumbens ΔFosB is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression. While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction. Exercise therapy improves 24816: 944: 16711: 13372:

withdrawal symptoms is greater in amphetamine dependent individuals who are older and who have more extensive amphetamine use disorders (McGregor 2005). Withdrawal symptoms typically present within 24 hours of the last use of amphetamine, with a withdrawal syndrome involving two general phases that can last 3 weeks or more. The first phase of this syndrome is the initial "crash" that resolves within about a week (Gossop 1982;McGregor 2005) ...

67: 4793:(i.e., the genetic composition of an individual and all microorganisms that reside on or within the individual's body) varies considerably between individuals. Since the total number of microbial and viral cells in the human body (over 100 trillion) greatly outnumbers human cells (tens of trillions), there is considerable potential for interactions between drugs and an individual's microbiome, including: drugs altering the composition of the 24828: 14736:

man. ... The lack of effect of administration of neomycin to one patient indicates that the hydroxylation occurs in body tissues. ... a major portion of the β-hydroxylation of hydroxyamphetamine occurs in non-adrenal tissue. Unfortunately, at the present time one cannot be completely certain that the hydroxylation of hydroxyamphetamine in vivo is accomplished by the same enzyme which converts dopamine to noradrenaline.

958: 1215:, with three reviews finding clinically significant reductions in daytime sleepiness in patients with narcolepsy. Additionally, these reviews suggest that amphetamine may dose-dependently improve cataplexy symptoms. However, the quality of evidence for these findings is low and is consequently reflected in the AASM's conditional recommendation for dextroamphetamine as a treatment option for narcolepsy. 24804: 14006:

the vesicle. ... Amphetamine and its derivatives like methamphetamine are weak base compounds that are the only widely used class of drugs known to elicit transmitter release by a non-exocytic mechanism. As substrates for both DAT and VMAT, amphetamines can be taken up to the cytosol and then sequestered in vesicles, where they act to collapse the vesicular pH gradient.

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narcolepsy and other disorders of excessive sedation. ... For these reasons, observations of dependence and abuse of prescription d-amphetamine are rare in clinical practice, and this stimulant can even be prescribed to people with a history of drug abuse provided certain controls, such as daily pick-ups of prescriptions, are put in place (Jasinski and Krishnan, 2009b).

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11486:) where it recruits HDAC1 as a corepressor. ... Chronic exposure to psychostimulants increases glutamatergic from the prefrontal cortex to the NAc. Glutamatergic signaling elevates Ca2+ levels in NAc postsynaptic elements where it activates CaMK (calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5. 1571:), but amphetamine abuse does pose risks to the fetus. Amphetamine has also been shown to pass into breast milk, so the IPCS and the FDA advise mothers to avoid breastfeeding when using it. Due to the potential for reversible growth impairments, the FDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical. 2879:(RCTs) for amphetamine and methamphetamine addiction; it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration. There was low- to moderate-strength evidence of no benefit for most of the other medications used in RCTs, which included antidepressants (bupropion, 15165:

recently linked with various metabolic disorders and diseases. In addition to the impact of gut microbial diversity or dysbiosis in various human diseases, there is an increasing amount of evidence which shows that the gut microbes can affect the bioavailability and efficacy of various orally administrated [

11683:ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the 14886:

The observed lack of a significant accumulation of PHN in brain following the intraventricular administration of (+)-amphetamine and the formation of appreciable amounts of PHN from (+)-POH in brain tissue in vivo supports the view that the aromatic hydroxylation of amphetamine following its systemic

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Despite the challenges in determining synaptic vesicle pH, the proton gradient across the vesicle membrane is of fundamental importance for its function. Exposure of isolated catecholamine vesicles to protonophores collapses the pH gradient and rapidly redistributes transmitter from inside to outside

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Zinc binds at ... extracellular sites of the DAT , serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc on symptoms of ADHD . It should be stated that at this time with zinc is not integrated in any ADHD

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Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), projection areas of mesocorticolimbic DA neurons and key components of the "brain reward circuit". Amphetamine achieves this elevation in extracellular levels of

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Several other studies, including a meta-analytic review and a retrospective study, suggested that stimulant therapy in childhood is associated with a reduced risk of subsequent substance use, cigarette smoking and alcohol use disorders. ... Recent studies have demonstrated that stimulants, along

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The intravenous use of d-amphetamine and other stimulants still pose major safety risks to the individuals indulging in this practice. Some of this intravenous abuse is derived from the diversion of ampoules of d-amphetamine, which are still occasionally prescribed in the UK for the control of severe

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Specifically, in a set of experiments limited to high-quality designs, we found significant enhancement of several cognitive abilities. ... The results of this meta-analysis ... do confirm the reality of cognitive enhancing effects for normal healthy adults in general, while also indicating

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The mechanism of action of sympathomimetic alerting drugs (eg, dextro- and methamphetamine, methylphenidate) is direct or indirect stimulation of dopaminergic and noradrenergic nuclei, which in turn heightens the efficacy of the ventral periaqueductal grey area and locus coeruleus, both components of

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At the pathophysiological level, it is now clear that most narcolepsy cases with cataplexy, and a minority of cases (5–30 %) without cataplexy or with atypical cataplexy-like symptoms, are caused by a lack of hypocretin (orexin) of likely an autoimmune origin. In these cases, once the disease is

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The 35-37 kD ΔFosB isoforms accumulate with chronic drug exposure due to their extraordinarily long half-lives. ... As a result of its stability, the ΔFosB protein persists in neurons for at least several weeks after cessation of drug exposure. ... ΔFosB overexpression in nucleus accumbens

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increase cAMP levels in striatum, which activates protein kinase A (PKA) and leads to phosphorylation of its targets. This includes the cAMP response element binding protein (CREB), the phosphorylation of which induces its association with the histone acetyltransferase, CREB binding protein (CBP) to

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Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification

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Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to

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In 1980, Chandler and Blair showed significant increases in knee extension strength, acceleration, anaerobic capacity, time to exhaustion during exercise, pre-exercise and maximum heart rates, and time to exhaustion during maximal oxygen consumption (VO2 max) testing after administration of 15 mg of

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The ARAS consists of several different circuits including the four main monoaminergic pathways discussed in Chapter 6. The norepinephrine pathway originates from the LC and related brainstem nuclei; the serotonergic neurons originate from the RN within the brainstem as well; the dopaminergic neurons

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Such agents also have important therapeutic uses; cocaine, for example, is used as a local anesthetic (Chapter 2), and amphetamines and methylphenidate are used in low doses to treat attention deficit hyperactivity disorder and in higher doses to treat narcolepsy (Chapter 12). Despite their clinical

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Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in normal subjects and those with ADHD. ... stimulants act not only on working memory function, but also on general levels of arousal and, within the

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In 1994, Richwood Pharmaceuticals acquired Rexar and began promoting Obetrol as a treatment for ADHD (and later narcolepsy as well), now marketed under the new brand name of Adderall, a contraction of the phrase "A.D.D. for All" intended to convey that "it was meant to be kind of an inclusive thing"

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of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety. Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention,

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WOODCLIFF LAKE, N.J., Aug. 14 /PRNewswire-FirstCall/ – Barr Pharmaceuticals, Inc. today announced that its subsidiary Duramed Pharmaceuticals, Inc. and Shire plc have signed a Product Acquisition Agreement for ADDERALL(R) (immediate-release mixed amphetamine salts) tablets and a Product Development

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The biologic significance of the different levels of serum DβH activity was studied in two ways. First, in vivo ability to β-hydroxylate the synthetic substrate hydroxyamphetamine was compared in two subjects with low serum DβH activity and two subjects with average activity. ... In one study,

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Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine,

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It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate,

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Collectively, these findings demonstrate that exercise may serve as a substitute or competition for drug abuse by changing ΔFosB or cFos immunoreactivity in the reward system to protect against later or previous drug use. ... The postulate that exercise serves as an ideal intervention for drug

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These findings suggest that exercise may "magnitude"-dependently prevent the development of an addicted phenotype possibly by blocking/reversing behavioral and neuroadaptive changes that develop during and following extended access to the drug. ... Exercise has been proposed as a treatment for

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Aside from accounting for the reduced performance of mentally fatigued participants, this model rationalizes the reduced RPE and hence improved cycling time trial performance of athletes using a glucose mouthwash (Chambers et al., 2009) and the greater power output during a RPE matched cycling time

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The usefulness of amphetamines is limited by a potential risk of abuse, and their cardiovascular adverse effects (Table 1). That is why, even though they are cheaper than other drugs, and efficient, they remain third-line therapy in narcolepsy. Three class II studies showed an improvement of EDS in

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Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from

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and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and

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Figure 1. Glycine conjugation of benzoic acid. The glycine conjugation pathway consists of two steps. First benzoate is ligated to CoASH to form the high-energy benzoyl-CoA thioester. This reaction is catalyzed by the HXM-A and HXM-B medium-chain acid:CoA ligases and requires energy in the form of

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Although we did not find a sufficient number of studies suitable for a meta-analysis of PEA and ADHD, three studies confirmed that urinary levels of PEA were significantly lower in patients with ADHD compared with controls. ... Administration of D-amphetamine and methylphenidate resulted in a

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They did not confirm the predicted straightforward relationship between uptake and release, but rather that some compounds including AMPH were better releasers than substrates for uptake. Zinc, moreover, stimulates efflux of intracellular DA despite its concomitant inhibition of uptake (Scholze et

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DYANAVEL XR contains d-amphetamine and l-amphetamine in a ratio of 3.2 to 1 ... The most common (≥2% in the DYANAVEL XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 108 patients with ADHD (aged 6 to 12 years) were: epistaxis, allergic

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All the amphetamines enhance activity at dopamine, noradrenaline and 5HT synapses. They cause presynaptic release of preformed transmitters, and also inhibit the re-uptake of dopamine and noradrenaline. These actions are most prominent in the brainstem ascending reticular activating system and the

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More recently, the lateral hypothalamus was also found to play a central role in arousal. Neurons in this region contain cell bodies that produce the orexin (also called hypocretin) peptides (Chapter 6). These neurons project widely throughout the brain and are involved in sleep, arousal, feeding,

5901:, achievement test scores, length of education, and education level), self-esteem (e.g., self-esteem questionnaire assessments, number of suicide attempts, and suicide rates), and social function (e.g., peer nomination scores, social skills, and quality of peer, family, and romantic relationships). 4456:

of the drug being excreted unchanged at normal urinary pH. When the urinary pH is basic, amphetamine is in its free base form, so less is excreted. When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too

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in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose." This review noted that withdrawal symptoms in chronic, high-dose

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reviews on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse

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Some metagenomic studies have suggested that less than 10% of the cells that comprise our bodies are Homo sapiens cells. The remaining 90% are bacterial cells. The description of this so-called human microbiome is of great interest and importance for several reasons. For one, it helps us redefine

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AMPH also increases intracellular calcium (Gnegy et al., 2004) that is associated with calmodulin/CamKII activation (Wei et al., 2007) and modulation and trafficking of the DAT (Fog et al., 2006; Sakrikar et al., 2012). ... For example, AMPH increases extracellular glutamate in various brain

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Three important new aspects of TAs action have recently emerged: (a) inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA1 receptor-mediated activation of GIRK

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Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse (Cosgrove et al., 2002; Zlebnik et al., 2010). There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal

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Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use,

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This indicates that subjects did not feel they were producing more power and consequently more heat. The authors concluded that the "safety switch" or the mechanisms existing in the body to prevent harmful effects are overridden by the drug administration (Roelands et al., 2008b). Taken together,

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The ADHD-related outcome domains with the greatest proportion of significantly improved outcomes from long-term continuous stimulant therapy include academics (≈55% of academic outcomes improved), driving (100% of driving outcomes improved), non-medical drug use (47% of addiction-related outcomes

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to amphetamine. Tolerant individuals have been known to take as much as 5 grams of amphetamine in a day, which is roughly 100 times the maximum daily therapeutic dose. Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves

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Hydroxyamphetamine was administered orally to five human subjects ... Since conversion of hydroxyamphetamine to hydroxynorephedrine occurs in vitro by the action of dopamine-β-oxidase, a simple method is suggested for measuring the activity of this enzyme and the effect of its inhibitors in

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AMPH and METH also stimulate DA efflux, which is thought to be a crucial element in their addictive properties , although the mechanisms do not appear to be identical for each drug . These processes are PKCβ– and CaMK–dependent , and PKCβ knock-out mice display decreased AMPH-induced efflux that

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Pharmacologic treatment for psychostimulant addiction is generally unsatisfactory. As previously discussed, cessation of cocaine use and the use of other psychostimulants in dependent individuals does not produce a physical withdrawal syndrome but may produce dysphoria, anhedonia, and an intense

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Particularly in the case of the human gut, which harbors a large diversity of bacterial species, the differences in microbial composition can significantly alter the metabolic activity in the gut lumen. The differential metabolic activity due to the differences in gut microbial species has been

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Manipulations of dopaminergic signaling profoundly influence interval timing, leading to the hypothesis that dopamine influences internal pacemaker, or "clock," activity. For instance, amphetamine, which increases concentrations of dopamine at the synaptic cleft advances the start of responding

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In high-ambient temperatures, dopaminergic manipulations clearly improve performance. The distribution of the power output reveals that after dopamine reuptake inhibition, subjects are able to maintain a higher power output compared with placebo. ... Dopaminergic drugs appear to override a

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The TF identified 1 double-blind RCT, 1 single-blind RCT, and 1 retrospective observational long-term self-reported case series assessing the efficacy of dextroamphetamine in patients with narcolepsy type 1 and narcolepsy type 2. These studies demonstrated clinically significant improvements in

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Only one paper examining outcomes beyond 36 months met the review criteria. ... There is high level evidence suggesting that pharmacological treatment can have a major beneficial effect on the core symptoms of ADHD (hyperactivity, inattention, and impulsivity) in approximately 80% of cases

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VMAT2 is the CNS vesicular transporter for not only the biogenic amines DA, NE, EPI, 5-HT, and HIS, but likely also for the trace amines TYR, PEA, and thyronamine (THYR) ... neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme

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A minority of individuals who use amphetamines develop full-blown psychosis requiring care at emergency departments or psychiatric hospitals. In such cases, symptoms of amphetamine psychosis commonly include paranoid and persecutory delusions as well as auditory and visual hallucinations in the

4337:. In summary, by interacting with both VMAT2 and TAAR1, amphetamine releases neurotransmitters from synaptic vesicles (the effect from VMAT2) into the intracellular fluid where they subsequently exit the neuron through the membrane-bound, reversed monoamine transporters (the effect from TAAR1). 9811:

misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. ... Indeed, large numbers of students claim to have engaged in the nonmedical use of prescription stimulants, which is reflected in

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The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously

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Key cell populations of the ascending arousal pathway include cholinergic, noradrenergic, serotoninergic, dopaminergic, and histaminergic neurons located in the pedunculopontine and laterodorsal tegmental nucleus (PPT/LDT), locus coeruleus, dorsal and median raphe nucleus, and tuberomammillary

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Amphetamine is usually consumed via inhalation or orally, either in the form of a racemic mixture (levoamphetamine and dextroamphetamine) or dextroamphetamine alone (Childress et al. 2019). In general, all amphetamines have high bioavailability when consumed orally, and in the specific case of

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The effects of amphetamine on gene regulation are both dose- and route-dependent. Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. The few studies that have used equivalent (weight-adjusted) human

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The simplest unsubstituted phenylisopropylamine, 1-phenyl-2-aminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class

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The prevalence of this withdrawal syndrome is extremely common (Cantwell 1998; Gossop 1982) with 87.6% of 647 individuals with amphetamine dependence reporting six or more signs of amphetamine withdrawal listed in the DSM when the drug is not available (Schuckit 1999) ... The severity of

8327:

The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function

4986:

program (which indicated a lack of efficacy). The new formulation simply replaced the two methamphetamine components with dextroamphetamine and amphetamine components of the same weight (the other two original dextroamphetamine and amphetamine components were preserved), preserved the Obetrol

15054:

The composition of the microbiome varies by anatomical site (Figure 1). The primary determinant of community composition is anatomical location: interpersonal variation is substantial and is higher than the temporal variability seen at most sites in a single individual. ... How does the

13246:

There is accelerating evidence that physical exercise is a useful treatment for preventing and reducing drug addiction ... In some individuals, exercise has its own rewarding effects, and a behavioral economic interaction may occur, such that physical and social rewards of exercise can

11542:

Coincident and convergent input often induces plasticity on a postsynaptic neuron. The NAc integrates processed information about the environment from basolateral amygdala, hippocampus, and prefrontal cortex (PFC), as well as projections from midbrain dopamine neurons. Previous studies have

1041:

and academic achievement, and producing improvements in a large number of functional outcomes across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health,

13913:

The human dopamine transporter (hDAT) contains an endogenous high affinity Zn binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). ... Although Zn inhibited uptake, Zn facilitated MPP+ release induced by amphetamine, MPP+, or K+-induced

14996:

The hundred trillion microbes and viruses residing in every human body, which outnumber human cells and contribute at least 100 times more genes than those encoded on the human genome (Ley et al., 2006), offer an immense accessory pool for inter-individual genetic variation that has been

3613:. The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose. 14392:

Duration of effect varies depending on agent and urine pH. Excretion is enhanced in more acidic urine. Half-life is 7 to 34 hours and is, in part, dependent on urine pH (half-life is longer with alkaline urine). ... Amphetamines are distributed into most body tissues with high

12302:

The limited research conducted suggests that exercise may be an effective adjunctive treatment for SUDs. In contrast to the scarce intervention trials to date, a relative abundance of literature on the theoretical and practical reasons supporting the investigation of this topic has been

10427:

statements on package inserts are not intended to limit medical practice. Rather they are intended to limit claims by pharmaceutical companies. ... the FDA asserts explicitly, and the courts have upheld that clinical decisions are to be made by physicians and patients in individual

1361:, such as increased endurance and alertness; however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies. In healthy people at oral therapeutic doses, amphetamine has been shown to increase 4301:) into the synaptic cleft. When amphetamine enters a neuron and interacts with VMAT2, the transporter reverses its direction of transport, thereby releasing stored monoamines inside synaptic vesicles back into the neuron's intracellular fluid. Meanwhile, when amphetamine activates 8811:

Narcolepsy type 1 was called "narcolepsy with cataplexy" before 2014 (AASM, 2005), but was renamed NT1 in the third and last international classification of sleep disorders (AASM, 2014). ... A low level of Hcrt-1 in the CSF is very sensitive and specific for the diagnosis of

5923:

The statements supported by the USFDA come from prescribing information, which is the copyrighted intellectual property of the manufacturer and approved by the USFDA. USFDA contraindications are not necessarily intended to limit medical practice but limit claims by pharmaceutical

9204:

Recent clinical trials and practice guidelines have confirmed that stimulants such as modafinil, armodafinil, or sodium oxybate (as first line); methylphenidate and pitolisant (as second line ); and amphetamines (as third line) are appropriate medications for excessive daytime

8814:

All patients with low CSF Hcrt-1 levels are considered as NT1 patients, even if they report no cataplexy (in about 10–20% of cases), and all patients with normal CSF Hcrt-1 levels (or without cataplexy when the lumbar puncture is not performed) as NT2 patients (Baumann et al.,

6122:

There is substantial variation in microbiome composition and microbial concentrations by anatomical site. Fluid from the human colon – which contains the highest concentration of microbes of any anatomical site – contains approximately one trillion (10^12) bacterial

5812:. He also faults a "tremendous increase in prescribing" due to virtual prescribing and general overprescribing and overdiagnosing, adding that "if only the people that needed these drugs got them, there probably wouldn't be a shortage". The shortage has continued into 2024. 1397:

to increase in order to access a reserve capacity that is normally off-limits. At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as

11225:

In these studies, amphetamine was given in consecutively higher doses until psychosis was precipitated, often after 100–300 mg of amphetamine ... Secondly, psychosis has been viewed as an adverse event, although rare, in children with ADHD who have been treated with

2796:

of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced

5904:

Long-term combination therapy for ADHD (i.e., treatment with both a stimulant and behavioral therapy) produces even larger effect sizes for outcome improvements and improves a larger proportion of outcomes across each domain compared to long-term stimulant therapy

5046:

effects than racemic amphetamine due to the higher proportion of dextroamphetamine. Adderall is produced as both an immediate-release (IR) and extended-release (XR) formulation. As of December 2013, ten different companies produced generic Adderall IR, while

1340:(wakefulness), in turn promoting goal-directed behavior. Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. Based upon studies of self-reported illicit stimulant use, 9858:

Overall, the data suggest that ADHD medication misuse and diversion are common health care problems for stimulant medications, with the prevalence believed to be approximately 5% to 10% of high school students and 5% to 35% of college students, depending on the

14834:

hydroxyamphetamine (Paredrine), a synthetic substrate for DβH, was administered to subjects with either low or average levels of serum DβH activity. The percent of the drug hydroxylated to hydroxynorephedrine was comparable in all subjects (6.5-9.62) (Table 3).

14787:

ATP. ... The benzoyl-CoA is then conjugated to glycine by GLYAT to form hippuric acid, releasing CoASH. In addition to the factors listed in the boxes, the levels of ATP, CoASH, and glycine may influence the overall rate of the glycine conjugation pathway.

9243:

The first agents used to treat EDS (ie, amphetamines, methylphenidate) are now considered second- or third-line options because newer medications have been developed with improved tolerability and lower abuse potential (eg, modafinil/armodafinil, solriamfetol,

5875:

is used primarily throughout this article because the four-salt composition of the drug makes its nonproprietary name (dextroamphetamine sulfate 25%, dextroamphetamine saccharate 25%, amphetamine sulfate 25%, and amphetamine aspartate 25%) excessively lengthy.

1348:

ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control.

849:

is insignificant when Adderall is used as prescribed and at fairly low daily doses, such as those used for treating ADHD. However, the routine use of Adderall in larger and daily doses poses a significant risk of addiction or dependence due to the pronounced

6795: 4440: hours, respectively. Highly acidic urine will reduce the enantiomer half-lives to 7 hours; highly alkaline urine will increase the half-lives up to 34 hours. The immediate-release and extended release variants of salts of both isomers reach 5943:

In individuals who experience sub-normal height and weight gains, a rebound to normal levels is expected to occur if stimulant therapy is briefly interrupted. The average reduction in final adult height from 3 years of continuous stimulant therapy is

14884:-hydroxylation and β-hydroxylation reactions is important in species where aromatic hydroxylation of amphetamine is the predominant pathway of metabolism. Following systemic administration of amphetamine to rats, POH has been found in urine and in plasma. 14393:

concentrations occurring in the brain and CSF. Amphetamine appears in the urine within about 3 hours following oral administration. ... Three days after a dose of (+ or -)-amphetamine, human subjects had excreted 91% of the (14)C in the urine

1421:(NBA), and the National Collegiate Athletics Association (NCAA). In leagues such as the NFL, there is a very rigorous process required to obtain an exemption to this rule even when the athlete has been medically prescribed the drug by their physician. 14887:

administration occurs predominantly in the periphery, and that POH is then transported through the blood-brain barrier, taken up by noradrenergic neurones in brain where (+)-POH is converted in the storage vesicles by dopamine β-hydroxylase to PHN.

6168:

Due to pharmacological differences between these medications (e.g., differences in the release, absorption, conversion, concentration, differing effects of enantiomers, half-life, etc.), the listed values should not be considered equipotent

1828:) can occur in heavy users. Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. According to the FDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility. 2564:

is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses; in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing

15471:

Agreement for six proprietary products, and that its subsidiary Barr Laboratories, Inc. (Barr) has signed a Settlement and License Agreement relating to the resolution of two pending patent cases involving Shire's ADDERALL XR(R) ...

9991:

dextroamphetamine versus placebo. Most of the information to answer this question has been obtained in the past decade through studies of fatigue rather than an attempt to systematically investigate the effect of ADHD drugs on exercise.

12303:

published. ... numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects.

1606:

of Adderall are many and varied, but the amount of substance consumed is the primary factor in determining the likelihood and severity of side effects. Adderall is currently approved for long-term therapeutic use by the USFDA.

10098:

during interval timing, whereas antagonists of D2 type dopamine receptors typically slow timing;... Depletion of dopamine in healthy volunteers impairs timing, while amphetamine releases synaptic dopamine and speeds up timing.

5933:

According to one review, amphetamine can be prescribed to individuals with a history of abuse provided that appropriate medication controls are employed, such as requiring daily pick-ups of the medication from the prescribing

11281:

This study demonstrates that humans, like nonhumans, prefer a place associated with amphetamine administration. These findings support the idea that subjective responses to a drug contribute to its ability to establish place

5017:

The first generic version of Adderall IR was introduced to market in 2002. Later on, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the extended-release drug beginning in April 2009.

12829:

Beloate LN, Weems PW, Casey GR, Webb IC, Coolen LM (February 2016). "Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats".

3579:

develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect. According to a Cochrane review on

1566:

should monitor their symptoms while taking amphetamine. Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human

1021:(MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right 2690:) involved in addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression. It has been implicated in addictions to 15996:"The ADHD medication shortage is getting worse. What went wrong?—Neither drugmakers nor the DEA anticipated a sharp rise in ADHD diagnoses during the pandemic. Now an entire class of medications may be in short supply" 11055: 10973: 5071:

Adderall is one of several formulations of pharmaceutical amphetamine, including singular or mixed enantiomers and as an enantiomer prodrug. The table below compares these medications (based on U.S.-approved forms):

14751:

Badenhorst CP, van der Sluis R, Erasmus E, van Dijk AA (September 2013). "Glycine conjugation: importance in metabolism, the role of glycine N-acyltransferase, and factors that influence interindividual variation".

2835:-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions; however, as of February 2016, the only compounds which are known to function as TAAR1-selective agonists are 6803: 4257:

stimulation than levoamphetamine; however, levoamphetamine has slightly greater cardiovascular and peripheral effects. It has been reported that certain children have a better clinical response to levoamphetamine.

1202:

conditionally recommends dextroamphetamine for the treatment of both type 1 and type 2 narcolepsy. Treatment with pharmaceutical amphetamines is generally less preferred relative to other psychostimulants (e.g.,

11573:

DA by promoting efflux from synaptic terminals. ... Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain.

47: 4022:

of amphetamine, respectively. Gastrointestinal alkalinizing agents increase the absorption of amphetamine. Urinary alkalinizing agents increase concentration of non-ionized species, decreasing urinary excretion.

9043:

Alertness and associated forebrain and cortical arousal are mediated by several ascending pathways with distinct neuronal components that project from the upper brain stem near the junction of the pons and the

861:

The two amphetamine enantiomers that compose Adderall, such as Adderall tablets/capsules (levoamphetamine and dextroamphetamine), alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the

1705:, producing faster and deeper breaths. In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident. Amphetamine also induces 801:. At these doses, it induces physical effects such as a faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause 13047:

When considered together with the rapidly growing literature in the field a compelling case emerges in support of developing TAAR1-selective agonists as medications for preventing relapse to psychostimulant

8889:

The D-isomer is more specific for DA transmission and is a better stimulant compound. Some effects on cataplexy (especially for the L-isomer), secondary to adrenergic effects, occur at higher doses. ...

2744:

can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). Similarly, accumbal G9a hyperexpression results in markedly increased

7037:

nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors. ...

3009:. This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density. One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or 1042:

financial, and legal services), and social function. One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5

15129:

Kumar K, Dhoke GV, Sharma AK, Jaiswal SK, Sharma VK (January 2019). "Mechanistic elucidation of amphetamine metabolism by tyramine oxidase from human gut microbiota using molecular dynamics simulations".

1332:. Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. Amphetamine and other ADHD stimulants also improve 8887:

Amphetamines are exceptionally wake-promoting, and at high doses also reduce cataplexy in narcoleptic patients, an effect best explained by its action on adrenergic and serotoninergic synapses. ...

1190:

sleep cycle and function as "REM-off" cells, with amphetamine's effect on norepinephrine and serotonin contributing to the suppression of REM sleep and a possible reduction of cataplexy at high doses.

7289:

uses, these drugs are strongly reinforcing, and their long-term use at high doses is linked with potential addiction, especially when they are rapidly administered or when high-potency forms are given.

1611:

of Adderall generally involves far larger doses and is therefore significantly more dangerous, involving a much greater risk of serious adverse drug effects than dosages used for therapeutic purposes.

15055:

microbiome affect the pharmacology of medications? Can we "micro-type" people to improve pharmacokinetics and/or reduce toxicity? Can we manipulate the microbiome to improve pharmacokinetic stability?

11813:

gene that helps create the molecular switch—from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure

8040:"Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects" 7211:

presence of extreme agitation. More common (about 18%) is for frequent amphetamine users to report psychotic symptoms that are sub-clinical and that do not require high-intensity intervention ...

4457:

basic or acidic, respectively. Following oral administration, amphetamine appears in urine within 3 hours. Roughly 90% of ingested amphetamine is eliminated 3 days after the last oral dose.

14663:

Cashman JR, Xiong YN, Xu L, Janowsky A (March 1999). "N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication".

8817:

In patients with NT1, the absence of Hcrt leads to the inhibition of regions that suppress REM sleep, thus allowing the activation of descending pathways inhibiting motoneurons, leading to cataplexy.

2990:(i.e., a supplemental treatment) for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. In particular, 7039:

Beyond these general permissive effects, dopamine (acting via D1 receptors) and norepinephrine (acting at several receptors) can, at optimal levels, enhance working memory and aspects of attention.

2813:

therapeutic doses and oral administration show that these changes, if they occur, are relatively minor. This suggests that medical use of amphetamine does not significantly affect gene regulation.

14573:(39). ... The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: cytochrome P450 and flavin monooxygenase. ... Amphetamine can also undergo aromatic hydroxylation to 21223: 2543: months, slowly accumulates following repeated high-dose exposure to stimulants through this process. ΔFosB functions as "one of the master control proteins" that produces addiction-related 7217:

psychotic symptoms of individuals with amphetamine psychosis may be due exclusively to heavy use of the drug or heavy use of the drug may exacerbate an underlying vulnerability to schizophrenia.

12909:

Chan B, Freeman M, Kondo K, Ayers C, Montgomery J, Paynter R, et al. (December 2019). "Pharmacotherapy for methamphetamine/amphetamine use disorder-a systematic review and meta-analysis".

7084:

Amphetamines and caffeine are stimulants that increase alertness, improve focus, decrease reaction time, and delay fatigue, allowing for an increased intensity and duration of training ...

2860:. One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain. 15110:

what a biological individual is. We suggest that a human individual is now best described as a super-individual in which a large number of different species (including Homo sapiens) coexist.

13510:"Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013" 5769:

drugs. The maximum penalty for unauthorized possession is five years in prison and an unlimited fine. The maximum penalty for illegal supply is 14 years in prison and an unlimited fine.

1017:

development or nerve damage, but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth. Reviews of

6762: 4998:, introduced the current Adderall brand in 1996 as an instant-release tablet. In 2006, Shire agreed to sell rights to the Adderall name for the instant-release form of the medication to 8428:"The long-term outcomes of interventions for the management of attention-deficit hyperactivity disorder in children and adolescents: a systematic review of randomized controlled trials" 1123:. Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms. Type 1 narcolepsy results from the loss of approximately 70,000 1211:

option. Medical reviews indicate that amphetamine is safe and effective for the treatment of narcolepsy. Amphetamine appears to be most effective at improving symptoms associated with

391: 10367: 10274: 16641: 14410:

Santagati NA, Ferrara G, Marrazzo A, Ronsisvalle G (September 2002). "Simultaneous determination of amphetamine and one of its metabolites by HPLC with electrochemical detection".

11482:

in response to psychostimulant exposure. ΔFosB is also upregulated by chronic psychostimulant treatments, and is known to activate certain genes (eg, cdk5) and repress others (eg,

7338:

When oral formulations of psychostimulants are used at recommended doses and frequencies, they are unlikely to yield effects consistent with abuse potential in patients with ADHD.

5890:

improved), obesity (≈65% of obesity-related outcomes improved), self-esteem (50% of self-esteem outcomes improved), and social function (67% of social function outcomes improved).

3630:

An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The severity of overdose symptoms increases with dosage and decreases with

901:

than dextroamphetamine. The levoamphetamine component of Adderall has been reported to improve the treatment response in some individuals relative to dextroamphetamine alone. The

1530:(MAOIs) should not take amphetamine, although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented. These agencies also state that anyone with 1231:(XR) capsules. Mydayis is only available as an extended-release formulation. Adderall XR is approved to treat ADHD for up to 12 hours in individuals 6 years and older and uses a 15387: 10248: 14373: 14090: • tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of dopamine (DA) neurons of the ventral tegmental area (VTA) 11047: 10965: 13148:"Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis" 1879:– psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain 24873: 6985: 5804:

stated that "a number of generic drugs are in shortage at any given time because there's not enough profit". He points out that Adderall is a special case because it is a

2265: 5970:

relationship means that ΔFosB overexpression in the nucleus accumbens and addiction-related behavioral and neural adaptations always occur together and never occur alone.

23978: 963:

A group of 20 mg Adderall tablets, some broken in half, with a lengthwise-folded US dollar bill along the bottom (3.07 inches; 7.8 cm) for size comparison

7304:

Kollins SH (May 2008). "A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders".

1050:

conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a

746:

distinct from those of racemic amphetamine or dextroamphetamine, which are marketed as Evekeo and Dexedrine/Zenzedi, respectively. Adderall is used in the treatment of

13926:

Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (October 2012). "Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses".

9393: 6532:

Kociancic T, Reed MD, Findling RL (March 2004). "Evaluation of risks associated with short- and long-term psychostimulant therapy for treatment of ADHD in children".

24893: 21722: 15329: 10153:

trial following amphetamine ingestion (Swart, 2009). ... Dopamine stimulating drugs are known to enhance aspects of exercise performance (Roelands et al., 2008)

11757:

gene occurs in concert with the recruitment of a histone deacetylase and presumably several other repressive proteins such as a repressive histone methyltransferase

6383:

Joyce BM, Glaser PE, Gerhardt GA (April 2007). "Adderall produces increased striatal dopamine release and a prolonged time course compared to amphetamine isomers".

4161:

DAT, internalize and cease transport. Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a

13009:""TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference" 1046:

points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. Another review indicated that, based upon the longest

20977: 18338: 15828: 10008:

Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R (May 2013). "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing".

6825:

Babiskin AH, Zhang X (September 2015). "Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation".

2539:

acts as a molecular switch that enables the accumulation of ΔFosB in the neuron. A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for

24968: 10226: 4134: 2170: 20982: 18333: 414: 21268: 13103:

Existing data provided robust preclinical evidence supporting the development of TAAR1 agonists as potential treatment for psychostimulant abuse and addiction.

10966:"FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults" 4073: 8084:"Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies" 1740:

FDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (

11901: 2959:

had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). Other treatment modalities examined in the analysis included

1439:. Adderall tablets can either be swallowed, crushed and snorted, or dissolved in water and injected. Injection into the bloodstream can be dangerous because 438: 336: 15453: 12316: 8891:

Numerous studies have shown that increased dopamine release is the main property explaining wake-promotion, although norepinephrine effects also contribute.

22086: 22052: 15230:

Khan MZ, Nawaz W (October 2016). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system".

4333:; in other words, the reversed membrane transporter will push dopamine, norepinephrine, and serotonin out of the neuron's intracellular fluid and into the 2391: 1835:

in humans taking therapeutic doses, meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine.

15362: 8264:

Ongoing research has provided answers to many of the parents' concerns, and has confirmed the effectiveness and safety of the long-term use of medication.

6132:

For uniformity, molar masses were calculated using the Lenntech Molecular Weight Calculator and were within 0.01 g/mol of published pharmaceutical values.

21971: 16561: 15428: 14799:

Horwitz D, Alexander RW, Lovenberg W, Keiser HR (May 1973). "Human serum dopamine-β-hydroxylase. Relationship to hypertension and sympathetic activity".

13753: 11587:"Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat" 4125:. When amphetamine enters synaptic vesicles through VMAT2, it collapses the vesicular pH gradient, which in turn causes dopamine to be released into the 2216: 1446:

Many postsecondary students have reported using Adderall for study purposes in different parts of the developed world. Among these students, some of the

20962: 13656: 9276: 1032:

Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD.

24908: 24883: 14846:

Freeman JJ, Sulser F (December 1974). "Formation of p-hydroxynorephedrine in brain following intraventricular administration of p-hydroxyamphetamine".

7088: • Amphetamines increase dopamine/norepinephrine release and inhibit their reuptake, leading to central nervous system (CNS) stimulation 10826:"Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function" 10774:"Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function" 6428:"Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function" 2801:, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. These sexual addictions are associated with a 24923: 19744: 14899:

Matsuda LA, Hanson GR, Gibb JW (December 1989). "Neurochemical effects of amphetamine metabolites on central dopaminergic and serotonergic systems".

8349:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.).

7413:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.).

2589:

high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increases the level of

21713: 15792: 13259:

Perez-Mana C, Castells X, Torrens M, Capella D, Farre M (September 2013). "Efficacy of psychostimulant drugs for amphetamine abuse or dependence".

11417:

meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.

10307:"Mitigating risks of students use of study drugs through understanding motivations for use and applying harm reduction theory: a literature review" 9164:

Despite the potential for drug abuse or tolerance using stimulants, patients with narcolepsy rarely exhibit addiction to their medication. ...

7857: 2740:

enzyme, both oppose the function of ΔFosB and inhibit increases in its expression. Sufficiently overexpressing ΔJunD in the nucleus accumbens with

15487: 9771:"Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants" 20774: 16601: 15766: 12992:

Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved.

4965: 1430: 10683:

Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge".

10613:

Feinberg SS (November 2004). "Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication".

8196:

Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge".

7233: 4541:-dealkylation, and deamination. The known metabolic pathways, detectable metabolites, and metabolizing enzymes in humans include the following: 24767: 20691: 16017: 14216: 10542:"Adderall XR- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate capsule, extended release" 7142:"Adderall XR- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate capsule, extended release" 6754: 9607:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu". In Sydor A, Brown RY (eds.).

5792:

In February 2023, news organizations began reporting on shortages of Adderall in the United States that have lasted for over five months. The

11958:ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. 221: 11048:"FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults" 6027:

The 95% confidence interval indicates that there is a 95% probability that the true number of deaths lies between 3,425 and 4,145.

24151: 16389: 10206:

these data indicate strong ergogenic effects of an increased DA concentration in the brain, without any change in the perception of effort.

4218: 3069: 2979: 2384: 2000: 10371: 10278: 9580:

Devous MD, Trivedi MH, Rush AJ (April 2001). "Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers".

9217:

Thorpy MJ, Bogan RK (April 2020). "Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications".

8136:"Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects" 5063:, the company that held the original patent for Adderall and Adderall XR, still manufactured brand name Adderall XR, but not Adderall IR. 4432:

of amphetamine enantiomers differ and vary with urine pH. At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are

24888: 22040: 17057: 9371: 7465:"The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity" 2412: 2163: 465: 23707: 21007: 21002: 18368: 18363: 15395: 9883: 22046: 17416: 17366: 15860: 8506: 7858:"Dextroamphetamine; Dextroamphetamine Saccharate; Amphetamine; Amphetamine Aspartate Drug Usage Statistics, United States, 2013 - 2022" 5773: 5755:

In Taiwan, amphetamines including Adderall are Schedule 2 drugs with a minimum five years prison term for possession. On the contrary,

4066: 1487: 1483: 20997: 20972: 20967: 18383: 18358: 15995: 15509: 14523: 11154: 10252: 9341: 7020:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY (eds.).

21263: 21158: 17102: 17097: 17092: 17087: 17077: 17072: 17067: 17062: 17052: 17042: 17032: 17012: 17002: 16997: 16992: 16807: 16747: 9568:

Amphetamine has been shown to improve consolidation of information (0.02 ≥ P ≤ 0.05), leading to improved recall.

1934:– dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome) 1721:. The effects of amphetamine on the gastrointestinal tract are unpredictable. If intestinal activity is high, amphetamine may reduce 20992: 18378: 18373: 18353: 18348: 11687:

gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is

403: 24229: 22079: 21965: 21790: 16972: 16967: 16917: 16556: 4987:

branding, and despite it lacking FDA approval, it still made it onto the market and was marketed and sold by Rexar for many years.

1286:

found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including

998: 747: 8885:

established, the majority of the 70,000 hypocretin-producing cells have been destroyed, and the disorder is irreversible. ...

24033: 20907: 16937: 16827: 16817: 16812: 16069: 12954:"Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research" 11490: 2947:

of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that

2209: 878: 17: 10878: 10541: 10498: 9690: 7935:

Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, et al. (August 2012). "Toxicity of amphetamines: an update".

7141: 6977: 926:

of amphetamine. In 2022, Adderall was the fourteenth most commonly prescribed medication in the United States, with more than 34

24878: 24266: 24213: 22034: 21163: 20987: 17386: 14104:"Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons" 13425:"Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management" 13294: 7215:

Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis.

6901: 4934: 3241: 2156: 1890:– an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake) 897:) stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer 8906:

Malenka RC, Nestler EJ, Hyman SE, Holtzman DM (2015). "Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu".

4533:, and norephedrine. The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, 3589: weeks with a marked "crash" phase occurring during the first week. Amphetamine withdrawal symptoms can include anxiety, 2481:

that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like

24963: 24275: 17911: 16212: 15931: 15887: 15713: 13611:

Albertson TE (2011). "Amphetamines". In Olson KR, Anderson IB, Benowitz NL, Blanc PD, Kearney TE, Kim-Katz SY, Wu AH (eds.).

9530:"Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: a systematic review" 7835: 6730: 5780: 4059: 3271: 2648: 1140: 19274: 7767: 6860: 1302:, in normal healthy adults; these cognition-enhancing effects of amphetamine are known to be partially mediated through the 23852: 23144: 22492: 21706: 18861: 16044: 15313: 14378:. Hazardous Substances Data Bank. United States National Library of Medicine – Toxicology Data Network. Archived from 14238:

Smith RC, Davis JM (June 1977). "Comparative effects of d-amphetamine, l-amphetamine, and methylphenidate on mood in man".

13483:

Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists". In Brunton LL, Chabner BA, Knollmann BC (eds.).

11297:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.).

9722:"Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration" 7664:

Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists". In Brunton LL, Chabner BA, Knollmann BC (eds.).

4979: 15739: 14880:-hydroxynorephedrine (PHN) may contribute to the pharmacological profile of the parent drug. ... The location of the 13118:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 5: Excitatory and Inhibitory Amino Acids". In Sydor A, Brown RY (eds.).

6978:"Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet" 30:

This article is about a common mixture of amphetamine salts. For general information about the drug and its racemate, see

23058: 22370: 22072: 21976: 21321: 18753: 15680: 13302: 5743: 4749:

of amphetamine is excreted unchanged and roughly 50% is excreted as the inactive metabolites (bottom row). The remaining

4096: 1454:

characteristics (i.e., exhibiting delinquent or deviant behavior), inadequate accommodation of disability, basing one's

1389:

of dopamine in the central nervous system. Amphetamine and other dopaminergic drugs also increase power output at fixed

23862: 23169: 22512: 20952: 20253: 20159: 18929: 17283: 16149: 15937: 15835: 14958:"Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics" 10222: 8684:"Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders" 4983: 2202: 1713:, the muscle which controls urination, which can result in difficulty urinating. This effect can be useful in treating 1195: 15963: 12729:"Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms" 9479:"Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis" 9075:"Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline" 4253:(VMAT2), with dextroamphetamine being the more potent agonist of TAAR1. Consequently, dextroamphetamine produces more 24948: 23907: 22016: 17411: 17401: 17381: 16495: 16490: 16083: 14565: 13620: 13492: 13397: 13127: 12882: 12439: 12430:

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 4: Signal Transduction in the Brain". In Sydor A, Brown RY (eds.).

11306: 10739: 10112:"Is it time to turn our attention toward central mechanisms for post-exertional recovery strategies and performance?" 9616: 8980: 8949: 8915: 8490: 8358: 8287:"Effect of treatment modality on long-term outcomes in attention-deficit/hyperactivity disorder: a systematic review" 8257: 7761: 7673: 7422: 7359: 7281: 7029: 6656: 4917: 4872: 4827: 4697: 4468: 4250: 4246: 882: 103: 1968:– a condition in which the use of substances leads to clinically and functionally significant impairment or distress 1725:(the rate at which content moves through the digestive system); however, amphetamine may increase motility when the 1086:

family members, perform better in school, are less distractible and impulsive, and have longer attention spans. The

689: 272: 24933: 24451: 24446: 23867: 23174: 22517: 20258: 17921: 17739: 17406: 17391: 17376: 17159: 13686:"Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism" 2956: 1993: 16566: 14379: 6166:) × scaling factor. The values in this column were scaled to a 30 mg dose of dextroamphetamine sulfate. 4910:

of amphetamine (i.e., it has an identical molecular formula). In humans, phenethylamine is produced directly from

4868: 3752: 24038: 23559: 22804: 21699: 20658: 20352: 20263: 18034: 17734: 17684: 17396: 16661: 16097: 15457: 14581:-hydroxynorephedrine. Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine. 12355: 9964:

Parr JW (July 2011). "Attention-deficit hyperactivity disorder and the athlete: new advances and understanding".

8332: 5809: 4085: 2802: 1418: 755: 376: 253: 16629: 15539: 13778:

Krause J (April 2008). "SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder".

10043:

safety switch and allow athletes to use a reserve capacity that is 'off-limits' in a normal (placebo) situation.

9425: 7213:

About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983) ...

2875:

A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in

24233: 24003: 23847: 23410: 23379: 23154: 22673: 22647: 22502: 20947: 20917: 20243: 20238: 19938: 19854: 18474: 18343: 18328: 18323: 17906: 15351: 5048: 2642: 2361: 2352: 15417: 13742: 11185:"Amphetamine-induced psychosis—a separate diagnostic entity or primary psychosis triggered in the vulnerable?" 9824:

Clemow DB, Walker DJ (September 2014). "The potential for misuse and abuse of medications in ADHD: a review".

6583:

Clemow DB, Walker DJ (September 2014). "The potential for misuse and abuse of medications in ADHD: a review".

4941:, the same enzyme that metabolizes norepinephrine into epinephrine. Like amphetamine, both phenethylamine and 4487:

amphetamine or its metabolites in humans. Amphetamine has a variety of excreted metabolic products, including

1013:

Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal

555: 24503: 23892: 23842: 23837: 23554: 23149: 22497: 20937: 20922: 20322: 20233: 20228: 19769: 18318: 18313: 17901: 17896: 17661: 16740: 16571: 14560:(7th ed.). Philadelphia, US: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 646–648. 14310: 13645: 9623:

Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.

9265: 5026:

Chemically, Adderall is a mixture of four amphetamine salts; specifically, it is composed of equal parts (by

4556: 12596: 9166:

Some stimulants, such as mazindol, amphetamines, and pitolisant, may also have some anticataplectic effects.

7700:"Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class" 24781: 24209: 24018: 24008: 23988: 23947: 23922: 23872: 23782: 23389: 23384: 23179: 22657: 22652: 22522: 20751: 20741: 20595: 20495: 20268: 20050: 18275: 17278: 14925:-OHNor is well documented and dopamine-β hydroxylase present in noradrenergic neurons could easily convert 14240: 13146:

De Crescenzo F, Ciabattini M, D'Alò GL, De Giorgi R, Del Giovane C, Cassar C, et al. (December 2018).

12873:

Malenka RC, Nestler EJ, Hyman SE, Holtzman DM (2015). "Chapter 16: Reinforcement and Addictive Disorders".

11478:

acetylate histones and facilitate gene activation. This is known to occur on many genes including fosB and

9769:

Weyandt LL, Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Zavras BM, et al. (September 2014).

7272:

Malenka RC, Nestler EJ, Hyman SE, Holtzman DM (2015). "Chapter 16: Reinforcement and Addictive Disorders".

5797: 5793: 3214: 2964: 2876: 2617: 1832: 1390: 1212: 1066: 606: 426: 152: 20942: 13568:

Greene SL, Kerr F, Braitberg G (October 2008). "Review article: amphetamines and related drugs of abuse".

5897:

for outcome improvements from long-term stimulant therapy occur in the domains involving academics (e.g.,

5859:

of amphetamine in a (3:1) ratio, although none of the components of the mixture are levoamphetamine salts.

4844:

commonly found in the human gut, was identified in 2019. This enzyme was found to metabolize amphetamine,

24028: 24023: 23998: 23952: 23662: 23394: 23374: 22998: 22926: 22295: 22225: 21998: 21362: 20902: 20789: 20784: 20500: 19739: 18748: 18255: 18250: 17295: 15658: 15636: 15614: 15564: 11183:

Bramness JG, Gundersen ØH, Guterstam J, Rognli EB, Konstenius M, Løberg EM, et al. (December 2012).

6680:"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)" 6475:

Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, et al. (January 2011).

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molecules produced in the human body and brain. Among this group, the most closely related compounds are

4414: 4360: 3954: 1986: 1768:

At normal therapeutic doses, the most common psychological side effects of amphetamine include increased

1527: 1314: 1199: 1033: 854:

that are present at high doses. Recreational doses of Adderall are generally much larger than prescribed

15788: 15483: 14577:-hydroxyamphetamine. ... Subsequent oxidation at the benzylic position by DA β-hydroxylase affords 12383:"Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants" 1752:) and the medical use of amphetamine or other ADHD stimulants. However, amphetamine pharmaceuticals are 1608: 1057:

Current models of ADHD suggest that it is associated with functional impairments in some of the brain's

24794: 24456: 24313: 24259: 23579: 23529: 22010: 21017: 20435: 20357: 19731: 17886: 16764: 16756: 16480: 16467: 15762: 12206:"Sex differences in drug addiction and response to exercise intervention: From human to animal studies" 10368:"National Institute on Drug Abuse. 2009. Stimulant ADHD Medications – Methylphenidate and Amphetamines" 6208: 6066: 4445: 4376: 4318: 4019: 2066: 1952:– stimuli that the brain interprets as intrinsically positive and desirable or as something to approach 1167: 1018: 779: 19908: 13065:"Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction" 12628:"Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation" 4862: 4356: 3501: 1816:

behaviors, and restlessness; these effects depend on the user's personality and current mental state.

675: 24938: 22103: 22095: 21981: 21070: 19834: 19249: 18199: 18029: 16205: 14208: 9812:

lifetime prevalence rates of prescription stimulant misuse ranging from 5% to nearly 34% of students.

7527:"VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse" 7244: 6679: 5980: 4975: 4725: 4682: 4675: 4476: 4372: 4015: 3777: 2737: 2505: 2062:– a protein that binds to DNA and regulates gene expression by promoting or suppressing transcription 1722: 175: 24528: 22993: 22290: 19903: 17226: 15274:

Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family".

12148:"Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis" 11598: 9426:"The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex" 4464: 2228: 24958: 24928: 24853: 24538: 23777: 23500: 23053: 22773: 22350: 21847: 21839: 20505: 20342: 19394: 18989: 18854: 16733: 16500: 9073:

Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD, et al. (September 2021).

5914:

Cochrane reviews are high quality meta-analytic systematic reviews of randomized controlled trials.

5766: 5007: 3648: 3640: 3076: 2723: 2679: 2039: 1930: 1410: 1187: 1179: 1058: 1047: 511: 12866: 12782:"Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator" 11695: 4190:

Amphetamine, the active ingredient of Adderall, works primarily by increasing the activity of the

1115:

Narcolepsy is a chronic sleep-wake disorder that is associated with excessive daytime sleepiness,

24953: 24898: 24553: 24064: 23942: 23757: 23717: 23682: 23672: 22946: 22936: 22245: 22235: 21753: 20804: 20799: 20490: 19923: 19864: 19814: 19809: 19759: 19359: 18265: 18224: 17948: 17816: 17811: 17801: 17729: 17719: 17473: 17463: 17446: 17305: 16691: 14530:. United States National Library of Medicine – National Center for Biotechnology Information 14504:. United States National Library of Medicine – National Center for Biotechnology Information 14497: 14478:. United States National Library of Medicine – National Center for Biotechnology Information 14471: 14452:. United States National Library of Medicine – National Center for Biotechnology Information 14073: 13725: 12483:"Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens" 11924:

Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?".

8633:

Punja S, Shamseer L, Hartling L, Urichuk L, Vandermeer B, Nikles J, et al. (February 2016).

7090: • Amphetamines seem to enhance athletic performance in anaerobic conditions 39 40 6109:; however, other evidence from animal studies suggests that this reaction is catalyzed by DBH in 6053: 6041: 5869: 4999: 4721: 3606: 3043: 2806: 1635: 1547: 1232: 1087: 707: 306: 295: 203: 24244: 14445: 10648:

Stewart JW, Deliyannides DA, McGrath PJ (June 2014). "How treatable is refractory depression?".

8082:

Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, et al. (September 2013).

5749:

In Japan, the use, production, and import of any medicine containing amphetamines is prohibited.

2074:

the rate of gene transcription for example by helping or hindering RNA polymerase binding to DNA

24766:

or in the associated compound articles. For TAAR2 and TAAR5 agonists and inverse agonists, see

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produce significant changes in addictive behavior; other forms of magnesium were not mentioned.

4899: 4565: 4501: 4238: 4035: 3833: 3787: 3722: 2952: 2757: 2753: 2578: 2566: 2548: 2513: 2405: 2130: 2118: 1964: 1757: 1683: 1499: 1463: 1394: 1175: 1051: 915: 890: 771: 15589: 14553: 9872: 9363: 8635:"Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents" 5796:

first reported the shortage in October 2022. In May 2023, seven months into the shortage, the

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Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, et al. (November 2011).

8970: 7375:

Howell LL, Kimmel HL (January 2008). "Monoamine transporters and psychostimulant addiction".

6644: 6062: 5856: 4835: 4614: 4495: 4322: 4310: 4025: 3929: 3843: 3671: 3037: 2972: 2944: 2769: 2524:

phosphorylation. Phosphorylated CREB increases levels of ΔFosB, which in turn represses the

2461: 2398: 1817: 1813: 1745: 1436: 1414: 1043: 905:

in Adderall, amphetamine, shares many chemical and pharmacological properties with the human

898: 655: 546: 310: 21341: 16642:

Neurobiological effects of physical exercise § Attention deficit hyperactivity disorder

15920:

Preventing Amphetamine-type Stimulant Use Among Young People: A Policy and Programming Guide

15864: 15517: 12895: 11079:"ADHD medications and risk of serious cardiovascular events in young and middle-aged adults" 11077:

Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, et al. (December 2011).

2792:, such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs 2663:(i.e., an abnormally high level of gene expression which produces a pronounced gene-related 1139:

for type 1 narcolepsy. Lateral hypothalamic orexin neurons innervate every component of the

24903: 24858: 24488: 24217: 23937: 23912: 23772: 23727: 23677: 23292: 23236: 23118: 23048: 22763: 22558: 22420: 22345: 21992: 21577: 21088: 20485: 20392: 20362: 20169: 20006: 19784: 19254: 18934: 18924: 18581: 18440: 18435: 18092: 18082: 18072: 17936: 17724: 17676: 17621: 17611: 17361: 16714: 16530: 16475: 16439: 16427: 16198: 12595:

Biliński P, Wojtyła A, Kapka-Skrzypczak L, Chwedorowicz R, Cyranka M, Studziński T (2012).

12494: 12456: 12335: 12264:"Exercise-based treatments for substance use disorders: evidence, theory, and practicality" 11556: 9333: 7944: 7538: 6217: 6037: 5880:

is a relatively new trade name that is not commonly used to refer generally to the mixture.

5805: 5056: 5011: 5003: 4810: 4607: 4489: 4429: 4314: 4031: 3708: 3639:. In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an " 3590: 3096: 2999: 2781: 2683: 2629: 2318: 2311: 2304: 2297: 2290: 2058: 1886: 1773: 1741: 1726: 1718: 1643: 1476: 1451: 1325: 1307: 1183: 1136: 1128: 846: 615: 283: 90: 21336: 15124: 15122: 15120: 15118: 4350: 4184: 3439: 3433: 3427: 3422: 3416: 3157: 2784:

for ΔFosB and H3K9me2-mediated repression of various ΔFosB transcriptional targets (e.g.,

8: 24943: 24918: 24913: 24863: 24493: 24079: 23817: 23667: 23509: 23287: 23209: 23043: 22941: 22931: 22854: 22788: 22465: 22355: 22240: 22230: 22153: 21093: 20663: 20475: 20306: 20184: 20075: 20011: 19804: 19789: 19749: 19135: 19022: 18847: 18743: 18489: 18292: 18239: 17891: 17806: 17796: 17744: 17714: 17650: 17537: 17468: 17458: 17341: 16586: 16540: 9304: 6008: 5898: 4953: 4820: 4600: 4472: 4441: 4418: 4286: 4130: 3958: 3702: 3678: 3504: 3186: 2948: 2865: 2687: 2671: 2586: 1976:– the diminishing effect of a drug resulting from repeated administration at a given dose 1914: 1132: 798: 507: 498: 129: 12780:

Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013).

12727:

Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, et al. (March 2012).

12498: 11127: 10587: 8659: 8634: 7948: 7542: 4129:(light tan-colored area) through VMAT2. When amphetamine binds to TAAR1, it reduces the 1902:– the escalating effect of a drug resulting from repeated administration at a given dose 1595: 1262: 990: 24600: 24397: 24094: 23430: 23425: 22921: 22688: 22220: 21781: 20853: 20839: 20794: 20779: 19279: 19264: 18916: 18102: 18097: 17199: 16424: 15155: 15115: 15095: 15068: 15040: 15015: 14982: 14957: 14872:

In species where aromatic hydroxylation of amphetamine is the major metabolic pathway,

14824: 14777: 14721: 14712: 14696: 14265: 14181: 14156: 14128: 14103: 14046: 14019: 13991: 13966: 13851: 13826: 13803: 13710: 13685: 13593: 13542: 13509: 13454: 13392:(6th ed.). Cambridge, United Kingdom: Cambridge University Press. pp. 45–51. 13357: 13332: 13230: 13204:"Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments" 13203: 13174: 13147: 13089: 13064: 13033: 13008: 12978: 12953: 12934: 12855: 12806: 12781: 12753: 12728: 12706: 12652: 12627: 12626:

Kennedy PJ, Feng J, Robison AJ, Maze I, Badimon A, Mouzon E, et al. (April 2013).

12569: 12544: 12517: 12482: 12407: 12382: 12347: 12288: 12263: 12230: 12205: 12172: 12147: 12112: 12087: 12017: 11992: 11949: 11795: 11770: 11738: 11713: 11669: 11644: 11615: 11586: 11528: 11503: 11463: 11454: 11438: 11402: 11377: 11349: 11332: 11267: 11242: 11211: 11184: 11103: 11078: 11021: 10996: 10850: 10825: 10798: 10773: 10708: 10466: 10441: 10418: 10341: 10306: 10196: 10138: 10111: 10083: 10056: 10033: 9934: 9909: 9849: 9797: 9770: 9746: 9721: 9666: 9641: 9554: 9529: 9506: 9450: 9099: 9074: 9029: 9004: 8940:

Malenka RC, Nestler EJ, Hyman SE, Holtzman DM (2015). "Chapter 13: Sleep and Arousal".

8870: 8845: 8757: 8732: 8708: 8683: 8610: 8585: 8563: 8454: 8427: 8403: 8378: 8313: 8286: 8221: 8165: 8108: 8083: 8012: 7987: 7968: 7908: 7883: 7809: 7724: 7699: 7559: 7526: 7489: 7464: 7329: 7196: 7171: 6947: 6930: 6651:(6th ed.). Cambridge, United Kingdom: Cambridge University Press. pp. 45–51. 6616: 6600: 6565: 6549: 6509: 6496: 6476: 6452: 6427: 6408: 6357: 6332: 6015: 4234: 3986: 3935: 3813: 3771: 3712: 3064: 2861: 2570: 2478: 1706: 1702: 1667: 1631: 1382: 1378: 1366: 1333: 1295: 834: 16084:"FDA Commissioner Blames Adderall Shortage on Stimulant Overuse, Telehealth, Generics" 15352:"(Collection of internal FDA information pertaining to the topic of Obetrol/Adderall)" 14614: 14423: 13525: 11826: 10393:

Kessler S (January 1996). "Drug therapy in attention-deficit hyperactivity disorder".

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from the gut, and bioavailability is typically 90%. Amphetamine is a weak base with a

1107:

worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.

24848: 24734: 24355: 24350: 23305: 23129: 22976: 22591: 22425: 22274: 21761: 21627: 21012: 20864: 20515: 19883: 19610: 19374: 19314: 19269: 18430: 18177: 18167: 18137: 18067: 17759: 17502: 17174: 16414: 16371: 16314: 16179: 15927: 15885: 15321: 15291: 15247: 15225: 15223: 15209: 15205: 15147: 15100: 15045: 14987: 14908: 14863: 14859: 14816: 14769: 14726: 14672: 14619: 14561: 14427: 14257: 14186: 14133: 14051: 13996: 13943: 13904: 13856: 13795: 13715: 13701: 13616: 13585: 13581: 13547: 13488: 13446: 13393: 13362: 13276: 13235: 13179: 13123: 13094: 13038: 13024: 12983: 12938: 12926: 12878: 12847: 12843: 12811: 12758: 12698: 12657: 12608: 12574: 12560: 12522: 12435: 12412: 12339: 12293: 12235: 12177: 12117: 12103: 12022: 11941: 11883: 11800: 11743: 11674: 11620: 11533: 11468: 11407: 11354: 11302: 11272: 11216: 11108: 11026: 10960: 10958: 10928: 10900:

Extended-release oral suspension contains 2.5 mg amphetamine base equivalents per mL.

10855: 10803: 10735: 10700: 10696: 10665: 10630: 10471: 10410: 10406: 10346: 10328: 10188: 10158: 10143: 10088: 10025: 9981: 9939: 9853: 9841: 9802: 9751: 9698: 9671: 9612: 9589: 9559: 9498: 9455: 9234: 9195: 9152: 9104: 9034: 8976: 8945: 8911: 8875: 8802: 8762: 8713: 8664: 8615: 8555: 8486: 8459: 8408: 8354: 8318: 8253: 8213: 8209: 8157: 8152: 8135: 8113: 8061: 8017: 7960: 7913: 7757: 7729: 7669: 7603: 7599: 7564: 7550: 7494: 7480: 7418: 7392: 7355: 7321: 7277: 7201: 7075: 7025: 6952: 6842: 6726: 6652: 6620: 6608: 6557: 6514: 6457: 6400: 6362: 5836: 5153: 4858: 4346: 4330: 4230: 4222: 3872: 3860: 3696: 3598: 3346: 3090: 2840: 2836: 2675: 2582: 2517: 2194: 2190: 1894: 1687: 1591: 1581: 1563: 1374: 1362: 1321: 1275: 1258: 1248: 1224: 1166:

Amphetamine’s therapeutic mode of action in narcolepsy primarily involves increasing

1100: 1078: 1014: 986: 976: 923: 902: 727: 245: 52: 16124: 15159: 14828: 14781: 14269: 14020:"Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons" 13807: 13597: 13458: 13141: 13139: 12859: 12710: 12398: 12351: 12163: 11953: 10422: 10200: 10037: 9642:"Psychostimulants and cognition: a continuum of behavioral and cognitive activation" 9510: 9478: 9394:"Mydayis® (mixed-salts of a single-entity amphetamine product) – First-time generic" 8567: 8169: 8056: 8039: 7813: 7333: 6890: 6569: 6412: 6101:

metabolism in humans suggests that a different enzyme may mediate the conversion of

4848:, and phenethylamine with roughly the same binding affinity for all three compounds. 2682:

for many of the neural adaptations and regulates multiple behavioral effects (e.g.,

1299: 24820: 24368: 23983: 23827: 23737: 23626: 23490: 23364: 23277: 23134: 22870: 22758: 22637: 22581: 22430: 22169: 21765: 21148: 20957: 20819: 20696: 20455: 20327: 20317: 20218: 20118: 19953: 19686: 19379: 19027: 18172: 18152: 17992: 17656: 17631: 17575: 17215: 16455: 16383: 16342: 15895: 15709: 15283: 15239: 15201: 15192:

Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines".

15139: 15090: 15080: 15035: 15027: 14977: 14969: 14855: 14808: 14761: 14716: 14708: 14609: 14419: 14339: 14249: 14176: 14168: 14123: 14115: 14041: 14031: 13986: 13978: 13935: 13894: 13846: 13838: 13787: 13705: 13697: 13577: 13537: 13529: 13521: 13436: 13352: 13348: 13344: 13272: 13268: 13225: 13215: 13169: 13159: 13084: 13076: 13028: 13020: 12973: 12965: 12918: 12839: 12801: 12797: 12793: 12748: 12740: 12688: 12647: 12639: 12564: 12556: 12512: 12502: 12402: 12394: 12331: 12283: 12275: 12225: 12217: 12167: 12159: 12107: 12099: 12012: 12004: 11933: 11875: 11790: 11782: 11733: 11725: 11664: 11656: 11610: 11602: 11523: 11515: 11458: 11450: 11397: 11389: 11344: 11262: 11258: 11254: 11206: 11196: 11098: 11090: 11016: 11008: 10845: 10837: 10793: 10785: 10712: 10692: 10657: 10622: 10461: 10453: 10402: 10336: 10318: 10178: 10133: 10123: 10078: 10068: 10017: 9973: 9929: 9921: 9833: 9792: 9782: 9741: 9733: 9661: 9653: 9549: 9541: 9490: 9445: 9441: 9437: 9226: 9187: 9144: 9094: 9086: 9024: 9016: 9005:"Neurophysiology of sleep and wakefulness: basic science and clinical implications" 8865: 8857: 8794: 8752: 8744: 8703: 8699: 8695: 8654: 8650: 8646: 8605: 8601: 8597: 8545: 8449: 8439: 8398: 8390: 8308: 8298: 8225: 8205: 8147: 8103: 8095: 8051: 8007: 7999: 7972: 7952: 7903: 7895: 7801: 7719: 7711: 7595: 7586:

Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines".

7554: 7546: 7484: 7476: 7384: 7313: 7243:(Review Article). ACHA Professional Development Program. p. 20. Archived from 7191: 7187: 7183: 7067: 6942: 6834: 6718: 6592: 6541: 6504: 6488: 6447: 6439: 6392: 6352: 6344: 6110: 5828: 4839: 4794: 4790: 4522: 4294: 4191: 4142: 4138: 3964: 3837: 3015: 2991: 2983: 2798: 2659:). ΔFosB is the most significant biomolecular mechanism in addiction because ΔFosB 2574: 2547:, and upon sufficient accumulation, with the help of its downstream targets (e.g., 2509: 2370: 2345: 2335: 2325: 2251: 2142: 1923: 1535: 1531: 1523: 1507: 1303: 1228: 863: 855: 743: 715: 711: 475: 359: 349: 81: 56: 15754: 15220: 13881:

Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH (June 2002).

10955: 7827: 4183:

For a more complete and detailed description of amphetamine pharmacodynamics, see

4113:

Amphetamine enters the presynaptic neuron across the neuronal membrane or through

3623: 1208: 1170:

neurotransmitter activity in the ARAS. This includes noradrenergic neurons in the

24808: 24618: 24561: 24543: 24533: 24384: 24376: 23917: 23762: 23505: 23420: 23310: 23199: 22981: 22844: 22783: 22778: 22683: 22596: 22455: 22279: 22143: 21870: 21776: 21771: 21757: 21572: 21065: 20874: 20849: 20809: 20648: 20565: 20520: 20387: 20382: 20302: 20298: 20114: 19887: 19869: 19339: 19037: 18768: 18611: 18532: 17779: 17764: 17671: 17646: 17571: 17506: 17351: 17263: 16611: 16606: 16581: 16404: 16302: 15243: 14765: 14367: 14365: 14363: 14361: 14359: 14119: 13842: 13164: 13136: 13080: 12969: 12744: 12279: 12245:

addiction has been widely recognized and used in human and animal rehabilitation.

11937: 10913: 10723: 9191: 8303: 7751: 6868: 5954: 5844: 4912: 4802: 4798: 4484: 4368: 4226: 3996: 3982: 3827: 3581: 3540: 3408: 3279: 3032: 2987: 2968: 2857: 2828: 2777: 2765: 2703: 2621: 2613: 2601: 2544: 2536: 2486: 2258: 2024: 1906: 1864: 1777: 1753: 1710: 1603: 1515: 1491: 1386: 1329: 1324:. A systematic review from 2014 found that low doses of amphetamine also improve 1291: 1171: 1120: 1082: 1074: 1038: 1022: 731: 723: 535: 483: 21682: 21331: 21326: 21306: 21301: 21296: 21291: 15814: 14594: 12822: 12317:"Neural mechanisms of addiction: the role of reward-related learning and memory" 12221: 9230: 8175:

child to adulthood. Treatment seems to have positive effects on brain structure.

7058:

Liddle DG, Connor DJ (June 2013). "Nutritional supplements and ergogenic AIDS".

6158:

dose = (1 / amphetamine base percentage) × scaling factor = (molecular mass

6097:. Evidence from studies that measured the effect of serum DBH concentrations on 4886: 4805:

profile, and microbial drug metabolism affecting a drug's clinical efficacy and

2845: 231: 24832: 24704: 24392: 24333: 23752: 23515: 23445: 23267: 23164: 23078: 22713: 22571: 22450: 22380: 22004: 21567: 21562: 21367: 20829: 20534: 20372: 20080: 19148: 19042: 18997: 18959: 18802: 18683: 18596: 17926: 17547: 17210: 16666: 16651: 15735: 15287: 14172: 14018:

Ledonne A, Berretta N, Davoli A, Rizzo GR, Bernardi G, Mercuri NB (July 2011).

13982: 13939: 13883:"The role of zinc ions in reverse transport mediated by monoamine transporters" 10730:

Millichap JG (2010). "Chapter 9: Medications for ADHD". In Millichap JG (ed.).

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Barateau L, Lopez R, Dauvilliers Y (October 2016). "Management of Narcolepsy".

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Millichap JG (2010). "Chapter 9: Medications for ADHD". In Millichap JG (ed.).

8248:

Millichap JG (2010). "Chapter 9: Medications for ADHD". In Millichap JG (ed.).

7805: 5039: 4894: 4890: 4410: 4394: 4334: 4282: 4198: 3887: 3847: 3803: 3631: 3576: 3455: 2793: 2789: 2660: 2501: 2490: 2098: 2052: 1972: 1943:– stimuli that increase the probability of repeating behaviors paired with them 1868: 1797: 1671: 1651: 1619: 1399: 1345: 1287: 1283: 1144: 1070: 910: 866: 802: 24752: 15085: 14956:

ElRakaiby M, Dutilh BE, Rizkallah MR, Boleij A, Cole JN, Aziz RK (July 2014).

14697:"Dopamine-beta-oxidase activity in man, using hydroxyamphetamine as substrate" 14356: 13441: 13424: 12773: 11729: 11606: 10841: 10789: 10732:

Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD

10661: 10323: 10021: 9977: 9910:"Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)" 9148: 8861: 8483:

Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD

8394: 8250:

Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD

7956: 7715: 7388: 7071: 6722: 6492: 6443: 6396: 6149:. Amphetamine base percentage for Adderall = sum of component percentages / 4. 4401:. Conversely, an acidic pH means the drug is predominantly in a water-soluble 2822: 1239:. Generic formulations of Mydayis became available in the US in October 2023. 785:

At therapeutic doses, Adderall causes emotional and cognitive effects such as

24842: 24420: 24412: 23485: 23475: 23415: 23338: 23216: 23194: 23003: 22849: 22753: 22743: 22678: 22611: 22472: 22305: 22148: 22064: 21949: 21918: 21878: 21647: 21547: 21497: 21412: 20653: 20580: 20555: 20470: 20465: 20440: 20405: 20278: 19918: 19859: 19404: 19349: 19188: 19183: 19178: 19173: 19143: 19017: 18939: 18818: 18813: 18728: 18637: 18616: 18590: 18548: 18413: 18157: 18012: 17861: 17784: 17522: 17144: 17129: 16676: 16393: 15325: 14036: 13791: 13220: 12199: 12197: 12195: 11201: 10457: 10332: 10128: 10073: 9837: 7899: 7317: 6604: 6596: 6553: 6500: 6348: 5801: 5031: 4970:

The pharmaceutical company Rexar reformulated their popular weight loss drug

4826:(i.e., drugs), amphetamine is predicted to undergo promiscuous metabolism by 4586: 4572: 4518: 4510: 4306: 3734: 3019: 2995: 2849: 2715: 2283: 2276: 2044: 1956: 1947: 1938: 1880: 1506:, or severe anxiety. It is also contraindicated in individuals with advanced 1459: 1358: 1279: 1026: 851: 822: 450: 35: 21143: 21138: 16018:"Adderall shortage raises questions about widespread dependency on the drug" 15918: 14812: 14157:"Mechanisms of dopamine transporter regulation in normal and disease states" 13818: 12507: 11863: 10442:"Amphetamine, past and present – a pharmacological and clinical perspective" 9873:"National Study of Substance Use Trends Among NCAA College Student-Athletes" 9737: 9521: 8586:"Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults" 8550: 8533: 8003: 7884:"Amphetamine, past and present – a pharmacological and clinical perspective" 6712: 6545: 4201:

in the brain. It also triggers the release of several other hormones (e.g.,

2839:. Amphetamine addiction is largely mediated through increased activation of 2788:). ΔFosB also plays an important role in regulating behavioral responses to 2597: 2585:, plays a central role in amphetamine addiction. Individuals who frequently 1960:– an amplified response to a stimulus resulting from repeated exposure to it 1698:. Dangerous physical side effects are rare at typical pharmaceutical doses. 825:). The side effects vary widely among individuals but most commonly include 24581: 24498: 24473: 24188: 24115: 24059: 24054: 23802: 23702: 23692: 23657: 23460: 23440: 23343: 23088: 23083: 23068: 22988: 22961: 22829: 22824: 22728: 22708: 22616: 22390: 22385: 22365: 22285: 22260: 22128: 22123: 21602: 21552: 21472: 21452: 21447: 21427: 21422: 21377: 21133: 21128: 21118: 21103: 21042: 20613: 20608: 20585: 20545: 20377: 20283: 20199: 20129: 20110: 20105: 20090: 19963: 19893: 19844: 19522: 19487: 19452: 19319: 19158: 18979: 18964: 18808: 18723: 18601: 18556: 18504: 18445: 18403: 18142: 17789: 17567: 17562: 17512: 17493: 17169: 15970: 15295: 15251: 15213: 15151: 15104: 15049: 14991: 14773: 14730: 14676: 14431: 14190: 14137: 14102:

Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG (July 2014).

14055: 14000: 13947: 13908: 13899: 13882: 13860: 13799: 13719: 13589: 13551: 13450: 13366: 13280: 13239: 13183: 13098: 13042: 12987: 12930: 12851: 12815: 12762: 12702: 12661: 12612: 12594: 12578: 12526: 12481:

Kim Y, Teylan MA, Baron M, Sands A, Nairn AC, Greengard P (February 2009).

12416: 12343: 12297: 12239: 12181: 12121: 12026: 11945: 11887: 11804: 11786: 11747: 11678: 11624: 11537: 11472: 11411: 11358: 11276: 11220: 11112: 11094: 11030: 10997:"ADHD drugs and serious cardiovascular events in children and young adults" 10932: 10859: 10807: 10704: 10676: 10669: 10634: 10475: 10350: 10192: 10147: 10092: 10029: 9985: 9943: 9845: 9806: 9755: 9675: 9593: 9563: 9502: 9459: 9238: 9199: 9156: 9108: 9038: 8879: 8806: 8766: 8717: 8668: 8619: 8559: 8463: 8412: 8322: 8217: 8161: 8117: 8065: 8021: 7964: 7917: 7733: 7607: 7568: 7498: 7396: 7325: 7205: 7079: 6956: 6846: 6612: 6561: 6518: 6461: 6404: 6366: 6333:"Amphetamine, past and present--a pharmacological and clinical perspective" 6045: 4831: 4579: 4514: 4506: 4242: 4214: 3925: 3916: 3901: 3683: 2982:

suggests that daily aerobic exercise, especially endurance exercise (e.g.,

2888: 2741: 2244: 2134:– a protein (or a small molecule) that works with transcription factors to 2122:– a protein (or a small molecule) that works with transcription factors to 2078: 1809: 1655: 1623: 1519: 1503: 1403: 1236: 1096: 806: 354: 344: 21316: 21311: 15888:"Trends in Methamphetamine/Amphetamine Admissions to Treatment: 1993–2003" 14973: 14912: 14867: 14820: 14623: 14547: 14545: 12192: 11879: 11519: 11393: 11042: 11040: 11012: 10414: 9657: 8846:"A practical guide to the therapy of narcolepsy and hypersomnia syndromes" 8785:

Barateau L, Pizza F, Plazzi G, Dauvilliers Y (August 2022). "Narcolepsy".

6638: 6636: 6634: 6632: 6630: 5776:

prescription drug, classified as a central nervous system (CNS) stimulant.

4007:) may increase (decrease) the drug effects of amphetamine, and vice versa. 1919: 24608: 24566: 24548: 24441: 24345: 24328: 24304: 24183: 24168: 24013: 23897: 23807: 23747: 23455: 23300: 23282: 23098: 23093: 23038: 23033: 22971: 22966: 22905: 22885: 22723: 22586: 22482: 22400: 22395: 22335: 22330: 22270: 22265: 22204: 22184: 21928: 21913: 21908: 21893: 21819: 21814: 21749: 21691: 21652: 21637: 21622: 21592: 21587: 21532: 21517: 21512: 21487: 21442: 21432: 21417: 21397: 21387: 21382: 21248: 20894: 20814: 20540: 20510: 20460: 20415: 20332: 20312: 20288: 20124: 20095: 20060: 19983: 19973: 19968: 19943: 19879: 19849: 19721: 19701: 19648: 19590: 19567: 19562: 19552: 19532: 19517: 19512: 19507: 19502: 19497: 19477: 19472: 19437: 19329: 19284: 19203: 19163: 19110: 19007: 18974: 18906: 18828: 18793: 18763: 18693: 18688: 18663: 18561: 18464: 18117: 18107: 18087: 18041: 18022: 18002: 17981: 17769: 17754: 17689: 17641: 17581: 17552: 17532: 17498: 17426: 17220: 17154: 16696: 16671: 16240: 16221: 14261: 13331:

Shoptaw SJ, Kao U, Heinzerling K, Ling W (April 2009). Shoptaw SJ (ed.).

12619: 11495: 10626: 9925: 9494: 8099: 7792:

Arnold LE (2000). "Methyiphenidate vs. Amphetamine: Comparative review".

6195: 5894: 5832: 5670: 5225: 4880: 4816: 4758: 4593: 4422: 4326: 4241:) differ somewhat. Dextroamphetamine and levoamphetamine are both potent 4202: 4150: 3920: 3687: 3610: 3602: 2960: 2928: 2916: 2908: 2880: 2869: 2695: 2529: 2482: 1805: 1793: 1695: 1639: 1627: 1585: 1447: 1252: 1160: 1092: 980: 906: 874: 838: 794: 735: 719: 239: 75: 48: 31: 21286: 15916: 14343: 13145: 11753:

induces NFκB ... In contrast, the ability of ΔFosB to repress the

9787: 8998: 8996: 8444: 6477:"European guidelines on managing adverse effects of medication for ADHD" 4444:

at 3 hours and 7 hours post-dose respectively. Amphetamine is

3975:) will prolong the elimination of amphetamine and increase drug effects. 575: 24576: 24478: 24468: 24407: 24402: 24158: 24099: 23882: 23877: 23832: 23822: 23812: 23722: 23712: 23641: 23636: 23470: 23465: 23450: 23319: 23315: 23272: 23241: 23221: 23189: 23139: 23108: 23013: 23008: 22956: 22951: 22895: 22890: 22880: 22738: 22733: 22718: 22703: 22576: 22566: 22537: 22477: 22445: 22435: 22410: 22340: 22310: 22300: 22255: 22250: 22194: 22189: 22179: 21944: 21923: 21903: 21898: 21860: 21829: 21806: 21741: 21632: 21617: 21607: 21557: 21527: 21522: 21492: 21482: 21407: 21372: 21153: 21060: 21037: 20766: 20756: 20678: 20668: 20643: 20638: 20623: 20550: 20530: 20525: 20480: 20420: 20410: 20400: 20367: 20223: 20213: 20204: 20194: 20189: 20154: 20144: 20139: 20085: 20070: 20040: 20016: 20001: 19993: 19988: 19958: 19928: 19913: 19898: 19839: 19829: 19711: 19706: 19696: 19658: 19653: 19620: 19615: 19585: 19577: 19467: 19384: 19354: 19344: 19294: 19289: 19193: 19153: 19095: 19090: 19075: 19012: 19002: 18954: 18896: 18891: 18886: 18878: 18798: 18733: 18713: 18708: 18703: 18698: 18678: 18668: 18642: 18621: 18576: 18571: 18540: 18509: 18494: 18484: 18398: 18229: 18192: 18182: 18162: 18122: 18112: 17967: 17963: 17953: 17749: 17699: 17694: 17626: 17616: 17601: 17596: 17586: 17517: 17488: 17483: 17356: 17290: 17273: 17184: 17179: 17149: 16636: 16591: 15894:. United States Department of Health and Human Services. Archived from 14542: 14253: 13967:"Striatal dopamine neurotransmission: regulation of release and uptake" 13533: 11037: 6755:"Shire launches new ADHD drug Mydayis as it weighs a neuroscience exit" 6627: 6204: 5087: 4823: 4398: 4385:

of 9.9; consequently, when the pH is basic, more of the drug is in its

4298: 4004: 3992: 3766: 3585:

users are frequent, occurring in roughly 88% of cases, and persist for

3478: 3466: 2912: 2904: 2900: 2892: 2884: 2691: 2625: 2377: 1675: 1568: 1495: 1455: 1002: 767: 751: 739: 586: 321: 314: 15143: 14750: 12922: 11775:

Philosophical Transactions of the Royal Society B: Biological Sciences

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Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ (October 2006).

9545: 9090: 8798: 7417:(2nd ed.). New York, USA: McGraw-Hill Medical. pp. 154–157. 7094: • Increased muscle strength and delayed muscle fatigue 7024:(2nd ed.). New York, US: McGraw-Hill Medical. pp. 318, 321. 6838: 4753:

is excreted as the active metabolites. Benzoic acid is metabolized by

4162: 24586: 24571: 24483: 24338: 24323: 24178: 24173: 24146: 24120: 24074: 24069: 23887: 23600: 23495: 23480: 23226: 23184: 23113: 23063: 23028: 22768: 22748: 22527: 22440: 22415: 22360: 22325: 22022: 21888: 21883: 21855: 21824: 21667: 21642: 21507: 21477: 21467: 21392: 21258: 21108: 21098: 21032: 21022: 20869: 20859: 20731: 20726: 20721: 20716: 20711: 20450: 20273: 20179: 20164: 20149: 20100: 20055: 19874: 19678: 19668: 19663: 19643: 19600: 19527: 19447: 19442: 19432: 19417: 19389: 19369: 19364: 19334: 19309: 19299: 19226: 19221: 19216: 19120: 19105: 19100: 19032: 18969: 18949: 18901: 18870: 18778: 18673: 18586: 18566: 18499: 18388: 18219: 18187: 18132: 18127: 17636: 17606: 17557: 17542: 17478: 17205: 17164: 16795: 16790: 16785: 16780: 16775: 16686: 16646: 13925: 13418: 13416: 13122:(2nd ed.). New York, US: McGraw-Hill Medical. pp. 124–125. 12146:

Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA (September 2013).

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Berman S, O'Neill J, Fears S, Bartzokis G, London ED (October 2008).

5060: 4995: 4974:

following its mandatory withdrawal from the market in 1973 under the

4762: 4417:

into most tissues in the body, with high concentrations occurring in

4390: 4325:) to either stop transporting monoamines altogether (via transporter 4278: 4274: 4266: 4210: 4206: 3978: 3906: 3594: 3492: 3486: 3472: 3461: 2932: 2868:(i.e., doses given to oneself) in humans, but it is not an effective 2853: 2831:

for amphetamine addiction. Reviews from 2015 and 2016 indicated that

2664: 2561: 2498: 2454: 1875: 1859: 1785: 1769: 1730: 1543: 1440: 1381:. Amphetamine improves endurance and reaction time primarily through 1370: 1204: 1156: 1152: 1116: 842: 830: 810: 775: 763: 759: 521: 329: 225: 109: 20932: 20927: 15031: 14951: 14949: 14947: 14945: 14943: 14941: 13827:"How addictive drugs disrupt presynaptic dopamine neurotransmission" 12693: 12676: 12643: 12008: 11660: 11578: 9768: 7170:

Shoptaw SJ, Kao U, Ling W (January 2009). Shoptaw SJ, Ali R (eds.).

2612:

Chronic use of amphetamine at excessive doses causes alterations in

24827: 24318: 24193: 23973: 23797: 23792: 23742: 23732: 23631: 23359: 23333: 23328: 23262: 23231: 23103: 23073: 23018: 22900: 22875: 22839: 22834: 22632: 22606: 22601: 22532: 22405: 22375: 22315: 22199: 22174: 22138: 22133: 21986: 21678: 21542: 21502: 21462: 21457: 21253: 20884: 20844: 20736: 20686: 20633: 20628: 20575: 20570: 20560: 20445: 20347: 20293: 20134: 20035: 19978: 19716: 19691: 19635: 19605: 19492: 19462: 19457: 19412: 19324: 19304: 19211: 19168: 19125: 19052: 18944: 18783: 18629: 18469: 18450: 18280: 18270: 18214: 18209: 18147: 18017: 18007: 17997: 17774: 17666: 17591: 17139: 16576: 14409: 14348: 14342:, Djombou Feunang Y, Guo AC, Lo EJ, Marcu A, Grant JR, et al. 13120: