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This test was developed and its analytical performance characteristics have been determined by NMS. It has not been cleared or approved by FDA.

This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes. See Laboratory Report.

Room temperature. Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

The tests listed by specialty and category are a select group of tests offered. Journal of Neurochemistry.

Drug and Alcohol Dependence. 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 abuse.

Shoptaw SJ, Ali R ed. 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 presence of extreme agitation.

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

BMC Psychiatry. In these studies, amphetamine was given in consecutively higher doses until psychosis was precipitated, often after — mg of amphetamine Archived from the original PDF on 3 November Retrieved 2 November CNS Drugs.

Several other studies, [] including a meta-analytic review [98] and a retrospective study, [97] 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 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.

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 Despite their clinical 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.

Current Medical Research and Opinion. 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.

Retrieved 19 October Trends in Plant Science. Beyond 1 R ,2 S -ephedrine and 1 S ,2 S -pseudoephedrine, myriad other substituted amphetamines have important pharmaceutical applications.

Postgraduate Medical Journal. Archives of Toxicology. Annals of the New York Academy of Sciences. JAMA Psychiatry. The Journal of Clinical Psychiatry.

Acta Psychiatrica Scandinavica. 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 child to adulthood.

Treatment seems to have positive effects on brain structure. 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.

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 outcomes.

Pharmacology Biochemistry and Behavior. Psychology Research and Behavior Management. Only one paper 53 examining outcomes beyond 36 months met the review criteria.

Retrieved 12 November European Journal of Clinical Nutrition. Cochrane Database of Systematic Reviews. Biological Psychiatry.

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.

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.

Journal of Cognitive Neuroscience. 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 Amphetamine has been shown to improve consolidation of information 0.

Journal of Nuclear Medicine. Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.

Pharmacological Reviews. JS Online. Archived from the original on 15 August Retrieved 2 December NCAA Publications.

National Collegiate Athletic Association. Retrieved 8 October British Journal of Pharmacology.

Clinics in Sports Medicine. In , Chandler and Blair 47 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 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.

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

Frontiers in Integrative Neuroscience. 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 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.

Frontiers in Physiology. 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.

Dopamine stimulating drugs are known to enhance aspects of exercise performance Roelands et al. 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.

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

Southern Medical Journal. Rather they are intended to limit claims by pharmaceutical companies. International Programme on Chemical Safety.

Retrieved 24 June Journal of Affective Disorders. Tris Pharma, Inc. Retrieved 29 April Table 2. Archived from the original on 25 August Retrieved 24 December New England Journal of Medicine.

Archived from the original on 14 December Merck Manual for Health Care Professionals. Retrieved 8 May 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 conditioning.

Dialogues in Clinical Neuroscience. 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, that define a state of addiction.

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.

Mount Sinai School of Medicine. Department of Neuroscience. Retrieved 9 February 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 meet major responsibilities at work, school, or home.

Depending on the level of severity, this disorder is classified as mild, moderate, or severe. 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 of severe substance-use disorder. This is known to occur on many genes including fosB and c-fos in response to psychostimulant exposure.

Chronic exposure to psychostimulants increases glutamatergic [signaling] from the prefrontal cortex to the NAc.

The Journal of General Physiology. 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 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, KEGG Pathway.

Retrieved 31 October 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 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.

Nature Reviews Neuroscience. The net result is gene activation and increased CDK5 expression. The net result is c-fos gene repression.

Clinical Psychopharmacology and Neuroscience. Magnesium Research. Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse Cosgrove et al.

There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal symptoms and relapse in abstinent smokers Daniel et al.

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.

Exercise has been proposed as a treatment for 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.

Frontiers in Neuroendocrinology. The postulate that exercise serves as an ideal intervention for drug addiction has been widely recognized and used in human and animal rehabilitation.

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 published.

Annual Review of Neuroscience. Progress in Neurobiology. Proceedings of the National Academy of Sciences.

Bibcode : PNAS.. Annals of Agricultural and Environmental Medicine. Nature Neuroscience. Nature Reviews.

Journal of Psychoactive Drugs. It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward.

Pitchers and colleagues reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus.

The Journal of Neuroscience. 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 desire to reinitiate drug use.

Addiction Abingdon, England. Expert Review of Clinical Pharmacology. Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved.

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

PLOS Medicine. Frontiers in Psychiatry. Physical Exercise 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 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 [laboratory animals and humans] 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.

Merck Manual Home Edition. February Archived from the original on 17 February Retrieved 28 February Shoptaw SJ ed.

The prevalence of this withdrawal syndrome is extremely common Cantwell ; Gossop with The severity of withdrawal symptoms is greater in amphetamine dependent individuals who are older and who have more extensive amphetamine use disorders McGregor The first phase of this syndrome is the initial "crash" that resolves within about a week Gossop ;McGregor 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, norepinephrine, and serotonin.

The Lancet. Retrieved 3 March Amphetamine use disorders Journal of Attention Disorders. The hyperthermia and the hypertension produced by high doses amphetamines are a primary cause of transient breakdowns in the blood-brain barrier BBB resulting in concomitant regional neurodegeneration and neuroinflammation in laboratory animals.

In animal models that evaluate the neurotoxicity of AMPH and METH, it is quite clear that hyperthermia is one of the essential components necessary for the production of histological signs of dopamine terminal damage and neurodegeneration in cortex, striatum, thalamus and hippocampus.

Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.

Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons. Neurotoxicity Research.

Acta Medica Okayama. Molecular Pharmacology. Although the monoamine transport cycle has been resolved in considerable detail, kinetic knowledge on the molecular actions of synthetic allosteric modulators is still scarce.

This potentiates both the forward-transport mode i. Functional selectivity by conformational selection. Expert Review of Neurotherapeutics.

Zinc binds at In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc [supplementation] on symptoms of ADHD [,].

It should be stated that at this time [supplementation] with zinc is not integrated in any ADHD treatment algorithm.

Basal Ganglia. 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 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.

Frontiers in Systems Neuroscience. 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 channels which produce cell membrane hyperpolarization.

University of Paris. Retrieved 29 May AMPH also increases intracellular calcium Gnegy et al. Trends in Pharmacological Sciences.

AMPH and METH also stimulate DA efflux, which is thought to be a crucial element in their addictive properties [80], although the mechanisms do not appear to be identical for each drug [81].

International Union of Basic and Clinical Pharmacology. Retrieved 8 December Bibcode : PNAS Retrieved 13 November NCBI Gene. Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons.

The physiological importance of CART was further substantiated in numerous human studies demonstrating a role of CART in both feeding and psychostimulant addiction.

Colocalization studies also support a role for CART in the actions of psychostimulants. Clinical and Experimental Pharmacology and Physiology.

Several studies on CART cocaine- and amphetamine-regulated transcript -peptide-induced cell signalling have demonstrated that CART peptides activate at least three signalling mechanisms.

Technische Universität Braunschweig. Retrieved 4 May Retrieved 24 February More recently, Colasanti and colleagues reported that a pharmacologically induced elevation in endogenous opioid release reduced [ 11 C]carfentanil binding in several regions of the human brain, including the basal ganglia, frontal cortex, and thalamus Colasanti et al.

Oral administration of d-amphetamine, 0. The results were confirmed in another group of subjects Mick et al.

However, Guterstam and colleagues observed no change in [ 11 C]carfentanil binding when d-amphetamine, 0. It has been hypothesized that this discrepancy may be related to delayed increases in extracellular opioid peptide concentrations following amphetamine-evoked monoamine release Colasanti et al.

Frontiers in Behavioral Neuroscience. Similar MOR activation patterns were reported during positive mood induced by an amusing video clip Koepp et al.

Berlin, Germany; Heidelberg, Germany: Springer. Retrieved 4 December Journal of Enzyme Inhibition and Medicinal Chemistry. Here, we report the first such study, showing that amphetamine, methamphetamine, phentermine, mephentermine, and chlorphenteramine, potently activate several CA isoforms, some of which are highly abundant in the brain, where they play important functions connected to cognition and memory, among others26, We investigated psychotropic amines based on the phenethylamine scaffold, such as amphetamine 5, methamphetamine 6, phentermine 7, mephentermine 8, and the structurally diverse chlorphenteramine 9, for their activating effects on 11 CA isoforms of human origin This work may bring new lights on the intricate relationship between CA activation by this type of compounds and the multitude of pharmacologic actions that they can elicit.

Recommendations for trace amine receptor nomenclature". Retrieved 31 December Current Medicinal Chemistry.

The emerging class of CAAs has recently gained attraction as the enhancement of the kinetic properties in hCAs expressed in the CNS were proved in animal models to be beneficial for the treatment of both cognitive and memory impairments.

Thus, CAAs have enormous potentiality in medicinal chemistry to be developed for the treatment of symptoms associated to aging, trauma or deterioration of the CNS tissues.

Retrieved 15 October Pubchem Compound Database. Retrieved 12 October British Journal of Pharmacology and Chemotherapy.

Hydroxyamphetamine was administered orally to five human subjects The lack of effect of administration of neomycin to one patient indicates that the hydroxylation occurs in body tissues.

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.

Figure 1. Glycine conjugation of benzoic acid. The glycine conjugation pathway consists of two steps.

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.

Relationship to hypertension and sympathetic activity". Circulation Research. The percent of the drug hydroxylated to hydroxynorephedrine was comparable in all subjects 6.

In species where aromatic hydroxylation of amphetamine is the major metabolic pathway, p -hydroxyamphetamine POH and p -hydroxynorephedrine PHN may contribute to the pharmacological profile of the parent drug.

Following systemic administration of amphetamine to rats, POH has been found in urine and in plasma. The hundred trillion microbes and viruses residing in every human body, which outnumber human cells and contribute at least times more genes than those encoded on the human genome Ley et al.

Meanwhile, a wealth of literature has long been available about the biotransformation of xenobiotics, notably by gut bacteria reviewed in Sousa et al.

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 [e.

Nature Reviews Genetics. The composition of the microbiome varies by anatomical site Figure 1. The primary determinant of community composition is anatomical location: interpersonal variation is substantial 23,24 and is higher than the temporal variability seen at most sites in a single individual How does the microbiome affect the pharmacology of medications?

Can we manipulate the microbiome to improve pharmacokinetic stability? The description of this so-called human microbiome is of great interest and importance for several reasons.

For one, it helps us redefine 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.

Journal of Cellular Biochemistry. 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 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.

Federal Register. Retrieved 3 January Retrieved 8 November Patent Application No. United States Patent Office. Tetrahedron Letters.

Clinical Toxicology. Forensic Science International. Vermont Department of Health. Government of Vermont.

Archived from the original on 5 October Retrieved 29 January Crime Scene. Northwest Association of Forensic Scientists. Retrieved 6 December United Nations Office on Drugs and Crime.

Retrieved 14 October The Journal of Organic Chemistry. The Art of Drug Synthesis. Journal of the American Chemical Society. Organic Reactions.

Rapid Communications in Mass Spectrometry. Journal of Chromatography B. Analytical and Bioanalytical Chemistry. Journal of Chromatography A.

University of Colorado Denver. Technical Assistance Publication Series Archived PDF from the original on 14 May

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