понедельник, 3 октября 2016 г.

Adderall (часть 2)

See also[edit]

Notes[edit]

  1. Jump up^ The US nonproprietary name of Adderall is dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate.[1]
  2. Jump up^ Enantiomers are molecules that are 'mirror images' of one another; they are structurally identical but of the opposite orientation, like left and right hands. The amphetamine compound properly refers to a racemate, which is an equal parts mixture of the two enantiomers (i.e., a mixture of 50% levoamphetamine and 50% dextroamphetamine).
  3. Jump up^ Cochrane Collaboration reviews are high quality meta-analytic systematic reviews of randomized controlled trials.[36]
  4. Jump up^ 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 companies.[63]
  5. Jump up^ 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 physician.[2]
  6. Jump up^ 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.[29][31][69] The average reduction in final adult height from continuous stimulant therapy over a 3 year period is 2 cm.[69]
  7. Jump up^ The 95% confidence interval indicates that there is a 95% probability that the true number of deaths lies between 3,425 and 4,145.
  8. Jump up^ Transcription factors are proteins that increase or decrease the expression of specific genes.[100]
  9. Jump up^ In simpler terms, this necessary and sufficient relationship means that ΔFosB overexpression in the nucleus accumbens and addiction-related behavioral and neural adaptations always occur together and never occur alone.
  10. Jump up^ NMDA receptors are voltage-dependent ligand-gated ion channels that requires simultaneous binding of glutamate and a co-agonist (d-serine or glycine) to open the ion channel.[112]
  11. Jump up^ The review indicated that magnesium L-aspartate and magnesium chloride produce significant changes in addictive behavior;[82] other forms of magnesium were not mentioned.
  12. Jump up^ The human dopamine transporter contains a high affinity extracellular zinc binding site which, upon zinc binding, inhibits dopamine reuptake and amplifies amphetamine-induced dopamine efflux in vitro.[124][125][126] The human serotonin transporter and norepinephrine transporter do not contain zinc binding sites.[126]
  13. Jump up^ For uniformity, molecular masses were calculated using the Lenntech Molecular Weight Calculator[150] and were within 0.01g/mol of published pharmaceutical values.
  14. Jump up^ Amphetamine base percentage = molecular massbase / molecular masstotal. Amphetamine base percentage for Adderall = sum of component percentages / 4.
  15. Jump up^ dose = (1 / amphetamine base percentage) × scaling factor = (molecular masstotal / molecular massbase) × scaling factor. The values in this column were scaled to a 30 mg dose of dextroamphetamine. 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 doses.
  16. Jump up^ This product (Dyanavel XR) is an oral suspension (i.e., a drug that is suspended in a liquid and taken by mouth) that contains 2.5 mg/mL of amphetamine base.[70] The amphetamine base contains dextro- to levo-amphetamine in a ratio of 3.2:1,[70] which is approximately the ratio in Adderall. The product uses an ion exchange resin to achieve extended release of the amphetamine base.[70]

Reference notes[edit]

References[edit]

  1. Jump up to:a b c d e f "National Drug Code Amphetamine Search Results"National Drug Code Directory. United States Food and Drug Administration. Archived from the original on 16 December 2013. Retrieved16 December 2013.
  2. Jump up to:a b c Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective"J. Psychopharmacol27(6): 479–496. doi:10.1177/0269881113482532PMC 3666194free to readPMID 23539642Mixed enantiomers/mixed salts amphetamine (3:1 d:l isomers)
  3. Jump up to:a b c Montgomery KA (June 2008). "Sexual desire disorders"Psychiatry (Edgmont)5 (6): 50–55. PMC 2695750free to readPMID 19727285.
  4. Jump up^ Wilens TE, Adler LA, Adams J, Sgambati S, Rotrosen J, Sawtelle R, Utzinger L, Fusillo S (January 2008). "Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature". J. Am. Acad. Child Adolesc. Psychiatry47(1): 21–31. doi:10.1097/chi.0b013e31815a56f1PMID 18174822Stimulant misuse appears to occur both for performance enhancement and their euphorogenic effects, the latter being related to the intrinsic properties of the stimulants (e.g., IR versus ER profile) ...
    Although useful in the treatment of ADHD, stimulants are controlled II substances with a history of preclinical and human studies showing potential abuse liability.
  5. Jump up to:a b c d e f g h i j k l m n o "Adderall XR Prescribing Information" (PDF)United States Food and Drug Administration. Shire US Inc. December 2013. pp. 12–13. Retrieved 30 December 2013.
  6. Jump up to:a b c d e "Adderall IR Prescribing Information" (PDF)United States Food and Drug Administration. Teva Pharmaceuticals USA, Inc. October 2015. pp. 1–6. Retrieved 18 May 2016.
  7. Jump up to:a b c d e f g Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. pp. 318, 321. ISBN 9780071481274Therapeutic (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 nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors. ...
    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. Drugs used for this purpose include, as stated above, methylphenidate, amphetamines, atomoxetine, and desipramine.
  8. Jump up to:a b c d Liddle DG, Connor DJ (June 2013). "Nutritional supplements and ergogenic AIDS". Prim. Care40 (2): 487–505. doi:10.1016/j.pop.2013.02.009PMID 23668655Amphetamines and caffeine are stimulants that increase alertness, improve focus, decrease reaction time, and delay fatigue, allowing for an increased intensity and duration of training ...
    Physiologic and performance effects
     • Amphetamines increase dopamine/norepinephrine release and inhibit their reuptake, leading to central nervous system (CNS) stimulation
     • Amphetamines seem to enhance athletic performance in anaerobic conditions 39 40
     • Improved reaction time
     • Increased muscle strength and delayed muscle fatigue
     • Increased acceleration
     • Increased alertness and attention to task
  9. Jump up to:a b c d e f g h "Adderall XR Prescribing Information" (PDF)United States Food and Drug Administration. Shire US Inc. December 2013. p. 11. Retrieved 30 December 2013.
  10. Jump up to:a b c d e f g h i j k l m n "Adderall XR Prescribing Information" (PDF)United States Food and Drug Administration. Shire US Inc. December 2013. pp. 4–8. Retrieved 30 December 2013.
  11. Jump up to:a b c d e Shoptaw SJ, Kao U, Ling W (January 2009). Shoptaw SJ, Ali R, ed. "Treatment for amphetamine psychosis". Cochrane Database Syst. Rev. (1): CD003026. doi:10.1002/14651858.CD003026.pub3PMID 19160215A 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. 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 ...
    About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983) ...
    Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis.
  12. Jump up to:a b c Greydanus D. "Stimulant Misuse: Strategies to Manage a Growing Problem" (PDF)American College Health Association (Review Article). ACHA Professional Development Program. p. 20. Archived from the original (PDF) on 3 November 2013. Retrieved 2 November 2013.
  13. Jump up to:a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 368. ISBN 9780071481274INITIAL ACTIONS OF DRUGS OF ABUSE AND NATURAL REINFORCERS
    Psychostimulants
    Cocaine, amphetamines, and methamphetamine are the major psychostimulants of abuse. The related drug methylphenidate is also abused, although it is far less potent. These drugs elicit similar initial subjective effects; differences generally reflect the route of administration and other pharmacokinetic factors. 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 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.
  14. Jump up to:a b 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". Curr. Med. Res. Opin24 (5): 1345–1357. doi:10.1185/030079908X280707PMID 18384709When 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.
  15. Jump up to:a b Stolerman IP (2010). Stolerman IP, ed. Encyclopedia of Psychopharmacology. Berlin, Germany; London, England: Springer. p. 78. ISBN 9783540686989.
  16. Jump up to:a b c d e Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. pp. 154–157. ISBN 9780071481274.
  17. Jump up to:a b c d e f g h Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity"J. Neurochem116 (2): 164–76. doi:10.1111/j.1471-4159.2010.07109.xPMC 3005101free to readPMID 21073468.
  18. Jump up to:a b c d e Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse"Ann. N. Y. Acad. Sci1216: 86–98. doi:10.1111/j.1749-6632.2010.05906.xPMC 4183197free to readPMID 21272013VMAT2 is the CNS vesicular transporter for not only the biogenic amines DANEEPI5-HT, and HIS, but likely also for the trace amines TYRPEA, and thyronamine (THYR) ... [Trace aminergic] neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC).
  19. Jump up to:a b c d e f Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005PMID 19948186.
  20. Jump up to:a b c d e f g h i j k l m n o p q r s t u v w x y z Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists". In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York, USA: McGraw-Hill. ISBN 9780071624428.
  21. Jump up to:a b c d e Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class"Bioorg. Med. Chem19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007PMC 3236098free to readPMID 22037049.
  22. Jump up to:a b Anthony, E. (11 November 2013). Explorations in Child Psychiatry. Springer Science & Business Media. pp. 93–94. ISBN 9781468421279.
  23. Jump up to:a b Arnold LE (2000). "Methyiphenidate vs. Amphetamine: Comparative review". Journal of Attention Disorders3 (4): 200–211. doi:10.1177/108705470000300403.
  24. Jump up to:a b Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5PMID 22392347.
  25. Jump up^ Berman S, O'Neill J, Fears S, Bartzokis G, London ED (October 2008). "Abuse of amphetamines and structural abnormalities in the brain"Ann. N. Y. Acad. Sci1141: 195–220. doi:10.1196/annals.1441.031PMC 2769923free to readPMID 18991959.
  26. Jump up to:a b Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "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". JAMA Psychiatry70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277PMID 23247506.
  27. Jump up to:a b Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies"J. Clin. Psychiatry74 (9): 902–917. doi:10.4088/JCP.12r08287PMC 3801446free to readPMID 24107764.
  28. Jump up to:a b Frodl T, Skokauskas N (February 2012). "Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.xPMID 22118249.
  29. Jump up to:a b c d Millichap JG (2010). "Chapter 9: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD(2nd ed.). New York, USA: Springer. pp. 121–123, 125–127. ISBN 9781441913968Ongoing research has provided answers to many of the parents’ concerns, and has confirmed the effectiveness and safety of the long-term use of medication.
  30. Jump up^ Arnold LE, Hodgkins P, Caci H, Kahle J, Young S (February 2015). "Effect of treatment modality on long-term outcomes in attention-deficit/hyperactivity disorder: a systematic review"PLoS ONE10 (2): e0116407. doi:10.1371/journal.pone.0116407PMC 4340791free to readPMID 25714373The 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 outcomes.
  31. Jump up to:a b c Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs25(7): 539–554. doi:10.2165/11589380-000000000-00000PMID 21699268Recent 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.
  32. Jump up to:a b Bidwell LC, McClernon FJ, Kollins SH (August 2011). "Cognitive enhancers for the treatment of ADHD"Pharmacol. Biochem. Behav99 (2): 262–274. doi:10.1016/j.pbb.2011.05.002PMC 3353150free to readPMID 21596055.
  33. Jump up^ Parker J, Wales G, Chalhoub N, Harpin V (September 2013). "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"Psychol. Res. Behav. Manag6: 87–99. doi:10.2147/PRBM.S49114PMC 3785407free to readPMID 24082796Only one paper53 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 compared with placebo controls, in the short term.
  34. Jump up^ Millichap JG (2010). "Chapter 9: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD(2nd ed.). New York, USA: Springer. pp. 111–113. ISBN 9781441913968.
  35. Jump up^ "Stimulants for Attention Deficit Hyperactivity Disorder"WebMD. Healthwise. 12 April 2010. Retrieved 12 November 2013.
  36. Jump up^ Scholten RJ, Clarke M, Hetherington J (August 2005). "The Cochrane Collaboration". Eur. J. Clin. Nutr. 59 Suppl 1: S147–S149; discussion S195–S196. doi:10.1038/sj.ejcn.1602188PMID 16052183.
  37. Jump up to:a b Castells X, Ramos-Quiroga JA, Bosch R, Nogueira M, Casas M (June 2011). Castells X, ed. "Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults". Cochrane Database Syst. Rev. (6): CD007813. doi:10.1002/14651858.CD007813.pub2PMID 21678370.
  38. Jump up^ Punja S, Shamseer L, Hartling L, Urichuk L, Vandermeer B, Nikles J, Vohra S (February 2016). "Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents". Cochrane Database Syst. Rev2: CD009996. doi:10.1002/14651858.CD009996.pub2PMID 26844979.
  39. Jump up^ Pringsheim T, Steeves T (April 2011). Pringsheim T, ed. "Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders". Cochrane Database Syst. Rev. (4): CD007990. doi:10.1002/14651858.CD007990.pub2PMID 21491404.
  40. Jump up to:a b c d "Adderall XR Prescribing Information" (PDF)United States Food and Drug Administration. Shire US Inc. December 2013. Retrieved 30 December 2013.
  41. Jump up^ Truven Health Analytics. "Amphetamine/Dextroamphetamine (By mouth)"PubMed Health. Micromedex Consumer Medication Information. Retrieved 4 September 2015.
  42. Jump up to:a b Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex". Biol. Psychiatry77 (11): 940–950. doi:10.1016/j.biopsych.2014.09.013PMID 25499957The 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 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). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation. ... 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.
  43. Jump up^ Ilieva IP, Hook CJ, Farah MJ (January 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". J. Cogn. Neurosci.: 1–21. doi:10.1162/jocn_a_00776PMID 25591060Specifically, 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 that these effects are modest in size.
  44. Jump up^ Bagot KS, Kaminer Y (April 2014). "Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: a systematic review"Addiction109 (4): 547–557. doi:10.1111/add.12460PMC 4471173free to readPMID 24749160Amphetamine has been shown to improve consolidation of information (0.02 ≥ P ≤ 0.05), leading to improved recall.
  45. Jump up^ Devous MD, Trivedi MH, Rush AJ (April 2001). "Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers". J. Nucl. Med42(4): 535–542. PMID 11337538.
  46. Jump up^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. p. 266. ISBN 9780071481274Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.
  47. Jump up to:a b c Wood S, Sage JR, Shuman T, Anagnostaras SG (January 2014). "Psychostimulants and cognition: a continuum of behavioral and cognitive activation". Pharmacol. Rev66 (1): 193–221. doi:10.1124/pr.112.007054PMID 24344115.
  48. Jump up^ Twohey M (26 March 2006). "Pills become an addictive study aid"JS Online. Archived from the original on 15 August 2007. Retrieved 2 December 2007.
  49. Jump up^ Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ (October 2006). "Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration"Pharmacotherapy26 (10): 1501–1510. doi:10.1592/phco.26.10.1501PMC 1794223free to readPMID 16999660.
  50. Jump up^ Weyandt LL, Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Zavras BM, Kuhar B (September 2014). "Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants"Psychol. Res. Behav. Manag7: 223–249. doi:10.2147/PRBM.S47013PMC 4164338free to readPMID 25228824misuse 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 lifetime prevalence rates of prescription stimulant misuse ranging from 5% to nearly 34% of students.
  51. Jump up^ Clemow DB, Walker DJ (September 2014). "The potential for misuse and abuse of medications in ADHD: a review". Postgrad. Med126 (5): 64–81. doi:10.3810/pgm.2014.09.2801PMID 25295651Overall, 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 study.
  52. Jump up^ Bracken NM (January 2012). "National Study of Substance Use Trends Among NCAA College Student-Athletes" (PDF)NCAA Publications. National Collegiate Athletic Association. Retrieved 8 October 2013.
  53. Jump up^ Docherty JR (June 2008). "Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)"Br. J. Pharmacol154 (3): 606–622. doi:10.1038/bjp.2008.124PMC 2439527free to readPMID 18500382.
  54. Jump up to:a b c d Parr JW (July 2011). "Attention-deficit hyperactivity disorder and the athlete: new advances and understanding". Clin. Sports Med30 (3): 591–610. doi:10.1016/j.csm.2011.03.007PMID 21658550In 1980, Chandler and Blair47 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. ... In 2008, Roelands and colleagues53 studied the effect of reboxetine, a pure NE reuptake inhibitor, similar to atomoxetine, in 9 healthy, well-trained cyclists. They too exercised in both temperate and warm environments. They showed decreased power output and exercise performance at both 18 and 30 degrees centigrade. Their conclusion was that DA reuptake inhibition was the cause of the increased exercise performance seen with drugs that affect both DA and NE (MPH, amphetamine, and bupropion).
  55. Jump up to:a b c Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R (May 2013). "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing". Sports Med43 (5): 301–311. doi:10.1007/s40279-013-0030-4PMID 23456493In 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.
  56. Jump up^ Parker KL, Lamichhane D, Caetano MS, Narayanan NS (October 2013). "Executive dysfunction in Parkinson's disease and timing deficits"Front. Integr. Neurosci7: 75. doi:10.3389/fnint.2013.00075PMC 3813949free to readPMID 24198770Manipulations 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.
  57. Jump up^ Rattray B, Argus C, Martin K, Northey J, Driller M (March 2015). "Is it time to turn our attention toward central mechanisms for post-exertional recovery strategies and performance?"Front. Physiol6: 79. doi:10.3389/fphys.2015.00079PMC 4362407free to readPMID 25852568Aside 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 trial following amphetamine ingestion (Swart, 2009). ... Dopamine stimulating drugs are known to enhance aspects of exercise performance (Roelands et al., 2008)
  58. Jump up^ Roelands B, De Pauw K, Meeusen R (June 2015). "Neurophysiological effects of exercise in the heat"Scand. J. Med. Sci. Sports. 25 Suppl 1: 65–78. doi:10.1111/sms.12350PMID 25943657. Retrieved 10 March 2016Physical fatigue has classically been attributed to peripheral factors within the muscle (Fitts, 1996), the depletion of muscle glycogen (Bergstrom & Hultman, 1967) or increased cardiovascular, metabolic, and thermoregulatory strain (Abbiss & Laursen, 2005; Meeusen et al., 2006b). In recent decennia however, it became clear that the central nervous system plays an important role in the onset of fatigue during prolonged exercise (Klass et al., 2008), certainly when ambient temperature is increased ... 5-HT, DA, and NA have all been implicated in the control of thermoregulation and are thought to mediate thermoregulatory responses, certainly since their neurons innervate the hypothalamus (Roelands & Meeusen, 2010). ... 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, these data indicate strong ergogenic effects of an increased DA concentration in the brain, without any change in the perception of effort. ... The combined effects of DA and NA on performance in the heat were studied by our research group on a number of occasions. ... the administration of bupropion (DA/NA reuptake inhibitor) significantly improved performance. Coinciding with this ergogenic effect, the authors observed core temperatures that were much higher compared with the placebo situation. Interestingly, this occurred without any change in the subjective feelings of thermal sensation or perceived exertion. Similar to the methylphenidate study (Roelands et al., 2008b), bupropion may dampen or override inhibitory signals arising from the central nervous system to cease exercise because of hyperthermia, and enable an individual to continue maintaining a high power output
  59. Jump up to:a b Leon Moore, David. "Do pro sports leagues have an Adderall problem?". USA TODAY. Retrieved4 May 2014.
  60. Jump up^ "Commonly Abused Prescription Drugs Chart". National Institute on Drug Abuse. Retrieved 7 May 2012.
  61. Jump up^ "Stimulant ADHD Medications – Methylphenidate and Amphetamines". National Institute on Drug Abuse. Retrieved 7 May 2012.
  62. Jump up to:a b "National Institute on Drug Abuse. 2009. Stimulant ADHD Medications – Methylphenidate and Amphetamines". National Institute on Drug Abuse. Retrieved 27 February 2013.
  63. Jump up^ Kessler S (January 1996). "Drug therapy in attention-deficit hyperactivity disorder". South. Med. J89 (1): 33–38. doi:10.1097/00007611-199601000-00005PMID 8545689statements 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 situations.
  64. Jump up to:a b c d e f g "Adderall XR Prescribing Information" (PDF)United States Food and Drug Administration. Shire US Inc. December 2013. pp. 4–6. Retrieved 30 December 2013.
  65. Jump up to:a b c d e f g h i j Heedes G, Ailakis J. "Amphetamine (PIM 934)"INCHEM. International Programme on Chemical Safety. Retrieved 24 June 2014.
  66. Jump up to:a b "Dexedrine Prescribing Information" (PDF)United States Food and Drug Administration. Amedra Pharmaceuticals LLC. October 2013. Retrieved 4 November 2013.
  67. Jump up^ Feinberg SS (November 2004). "Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication". J. Clin. Psychiatry65 (11): 1520–1524. doi:10.4088/jcp.v65n1113PMID 15554766.
  68. Jump up^ Stewart JW, Deliyannides DA, McGrath PJ (June 2014). "How treatable is refractory depression?". J. Affect. Disord167: 148–152. doi:10.1016/j.jad.2014.05.047PMID 24972362.
  69. Jump up to:a b c d Vitiello B (April 2008). "Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function"Child Adolesc. Psychiatr. Clin. N. Am17 (2): 459–474. doi:10.1016/j.chc.2007.11.010PMC 2408826free to readPMID 18295156.
  70. Jump up to:a b c d e f "Dyanavel XR Prescribing Information" (PDF). Tris Pharmaceuticals. October 2015. pp. 1–16. Retrieved 23 November 2015DYANAVEL 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 6–12 years) were: epistaxis, allergic rhinitis and upper abdominal pain. ...
    DOSAGE FORMS AND STRENGTHS
    Extended-release oral suspension contains 2.5 mg amphetamine base per mL.
  71. Jump up^ Ramey JT, Bailen E, Lockey RF (2006). "Rhinitis medicamentosa" (PDF)J. Investig. Allergol. Clin. Immunol16 (3): 148–155. PMID 16784007. Retrieved 29 April 2015Table 2. Decongestants Causing Rhinitis Medicamentosa
    – Nasal decongestants:
      – Sympathomimetic:
       • Amphetamine
  72. Jump up^ "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults"United States Food and Drug Administration. 20 December 2011. Retrieved 4 November 2013.
  73. Jump up^ Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". N. Engl. J. Med365 (20): 1896–1904. doi:10.1056/NEJMoa1110212PMID 22043968.
  74. Jump up^ "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults"United States Food and Drug Administration. 15 December 2011. Retrieved 4 November 2013.
  75. Jump up^ Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV (December 2011). "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults"JAMA306 (24): 2673–2683. doi:10.1001/jama.2011.1830PMC 3350308free to readPMID 22161946.
  76. Jump up^ O'Connor PG (February 2012). "Amphetamines"Merck Manual for Health Care Professionals. Merck. Retrieved 8 May 2012.
  77. Jump up to:a b Childs E, de Wit H (May 2009). "Amphetamine-induced place preference in humans"Biol. Psychiatry65 (10): 900–904. doi:10.1016/j.biopsych.2008.11.016PMC 2693956free to readPMID 19111278This 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.
  78. Jump up to:a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. ISBN 9780071481274.
  79. Jump up to:a b Spiller HA, Hays HL, Aleguas A (June 2013). "Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management". CNS Drugs27 (7): 531–543. doi:10.1007/s40263-013-0084-8PMID 23757186Amphetamine, 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.
  80. Jump up^ Collaborators (2015). "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" (PDF)Lancet385(9963): 117–171. doi:10.1016/S0140-6736(14)61682-2PMC 4340604free to readPMID 25530442. Retrieved 3 March 2015Amphetamine use disorders ... 3,788 (3,425–4,145)
  81. Jump up^ Kanehisa Laboratories (10 October 2014). "Amphetamine – Homo sapiens (human)"KEGG Pathway. Retrieved 31 October 2014.
  82. Jump up to:a b c d e f Nechifor M (March 2008). "Magnesium in drug dependences". Magnes. Res21 (1): 5–15. PMID 18557129.
  83. Jump up to:a b c d e Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". Am. J. Drug Alcohol Abuse40 (6): 428–437. doi:10.3109/00952990.2014.933840PMID 25083822ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure.
  84. Jump up to:a b c d e Nestler EJ (December 2013). "Cellular basis of memory for addiction"Dialogues Clin. Neurosci15 (4): 431–443. PMC 3898681free to readPMID 24459410.
  85. Jump up^ Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction"Nat. Rev. Neurosci12 (11): 623–637. doi:10.1038/nrn3111PMC 3272277free to readPMID 21989194ΔFosB serves as one of the master control proteins governing this structural plasticity.
  86. Jump up to:a b c d e f g h i j k l m n o p q r s t u v Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions"Neuropharmacology61 (7): 1109–1122. doi:10.1016/j.neuropharm.2011.03.010PMC 3139704free to readPMID 21459101Similar 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 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).
  87. Jump up to:a b c d e Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA (September 2013). "Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis"Neurosci. Biobehav. Rev37 (8): 1622–1644. doi:10.1016/j.neubiorev.2013.06.011PMC 3788047free to readPMID 23806439These 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 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.
  88. Jump up to:a b c Zhou Y, Zhao M, Zhou C, Li R (July 2015). "Sex differences in drug addiction and response to exercise intervention: From human to animal studies". Front. Neuroendocrinoldoi:10.1016/j.yfrne.2015.07.001PMID 26182835Collectively, 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. ... As briefly reviewed above, a large number of human and rodent studies clearly show that there are sex differences in drug addiction and exercise. The sex differences are also found in the effectiveness of exercise on drug addiction prevention and treatment, as well as underlying neurobiological mechanisms. The postulate that exercise serves as an ideal intervention for drug addiction has been widely recognized and used in human and animal rehabilitation. ... In particular, more studies on the neurobiological mechanism of exercise and its roles in preventing and treating drug addiction are needed.
  89. Jump up to:a b c d Linke SE, Ussher M (January 2015). "Exercise-based treatments for substance use disorders: evidence, theory, and practicality". Am. J. Drug Alcohol Abuse41 (1): 7–15. doi:10.3109/00952990.2014.976708PMID 25397661The 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. ... numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects.
  90. Jump up to:a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. p. 386. ISBN 9780071481274Currently, cognitive–behavioral therapies are the most successful treatment available for preventing the relapse of psychostimulant use.
  91. Jump up^ Greene SL, Kerr F, Braitberg G (October 2008). "Review article: amphetamines and related drugs of abuse". Emerg. Med. Australas20 (5): 391–402. doi:10.1111/j.1742-6723.2008.01114.xPMID 18973636.
  92. Jump up^ Albertson TE (2011). "Amphetamines". In Olson KR, Anderson IB, Benowitz NL, Blanc PD, Kearney TE, Kim-Katz SY, Wu AH. Poisoning & Drug Overdose (6th ed.). New York: McGraw-Hill Medical. pp. 77–79. ISBN 9780071668330.
  93. Jump up^ "Glossary of Terms"Mount Sinai School of Medicine. Department of Neuroscience. Retrieved9 February 2015.
  94. Jump up^ Volkow ND, Koob GF, McLellan AT (January 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction". N. Engl. J. Med374 (4): 363–371. doi:10.1056/NEJMra1511480PMID 26816013.
  95. Jump up^ "Amphetamines: Drug Use and Abuse"Merck Manual Home Edition. Merck. February 2003. Archived from the original on 17 February 2007. Retrieved 28 February 2007.
  96. Jump up^ Perez-Mana C, Castells X, Torrens M, Capella D, Farre M (September 2013). Pérez-Mañá C, ed. "Efficacy of psychostimulant drugs for amphetamine abuse or dependence". Cochrane Database Syst. Rev9: CD009695. doi:10.1002/14651858.CD009695.pub2PMID 23996457.
  97. Jump up^ Hyman SE, Malenka RC, Nestler EJ (July 2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci29: 565–598. doi:10.1146/annurev.neuro.29.051605.113009PMID 16776597.
  98. Jump up to:a b c d e f g h Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction"Nat. Rev. Neurosci12 (11): 623–637. doi:10.1038/nrn3111PMC 3272277free to readPMID 21989194.
  99. Jump up to:a b c d e Steiner H, Van Waes V (January 2013). "Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants"Prog. Neurobiol100: 60–80. doi:10.1016/j.pneurobio.2012.10.001PMC 3525776free to readPMID 23085425.
  100. Jump up^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 4: Signal Transduction in the Brain". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. p. 94. ISBN 9780071481274.
  101. Jump up^ Kanehisa Laboratories (29 October 2014). "Alcoholism – Homo sapiens (human)"KEGG Pathway. Retrieved 31 October 2014.
  102. Jump up^ Kim Y, Teylan MA, Baron M, Sands A, Nairn AC, Greengard P (February 2009). "Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens"Proc. Natl. Acad. Sci. U.S.A106 (8): 2915–2920. doi:10.1073/pnas.0813179106PMC 2650365free to readPMID 19202072.
  103. Jump up^ Nestler EJ (January 2014). "Epigenetic mechanisms of drug addiction"Neuropharmacology. 76 Pt B: 259–268. doi:10.1016/j.neuropharm.2013.04.004PMC 3766384free to readPMID 23643695.
  104. Jump up to:a b Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (March 2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms"J. Psychoactive Drugs44 (1): 38–55. doi:10.1080/02791072.2012.662112PMC 4040958free to readPMID 22641964.
  105. Jump up^ Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013). "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator"J. Neurosci33 (8): 3434–3442. doi:10.1523/JNEUROSCI.4881-12.2013PMC 3865508free to readPMID 23426671.
  106. Jump up^ 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". Neuropharmacology101: 154–164. doi:10.1016/j.neuropharm.2015.09.023PMID 26391065.
  107. Jump up^ Stoops WW, Rush CR (May 2014). "Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research". Expert Rev Clin Pharmacol7 (3): 363–374. doi:10.1586/17512433.2014.909283PMID 24716825Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved.
  108. Jump up^ Perez-Mana C, Castells X, Torrens M, Capella D, Farre M (September 2013). "Efficacy of psychostimulant drugs for amphetamine abuse or dependence". Cochrane Database Syst. Rev9: CD009695. doi:10.1002/14651858.CD009695.pub2PMID 23996457To date, no pharmacological treatment has been approved for [addiction], and psychotherapy remains the mainstay of treatment. ... Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy
  109. Jump up^ Forray A, Sofuoglu M (February 2014). "Future pharmacological treatments for substance use disorders"Br. J. Clin. Pharmacol77 (2): 382–400. doi:10.1111/j.1365-2125.2012.04474.xPMC 4014020free to readPMID 23039267.
  110. Jump up to:a b Grandy DK, Miller GM, Li JX (February 2016). ""TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference". Drug Alcohol Depend159: 9–16. doi:10.1016/j.drugalcdep.2015.11.014PMID 26644139When 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.
  111. Jump up to:a b Jing L, Li JX (August 2015). "Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction". Eur. J. Pharmacol761: 345–352. doi:10.1016/j.ejphar.2015.06.019PMID 26092759Taken together,the data reviewed here strongly support that TAAR1 is implicated in the functional regulation of monoaminergic systems, especially dopaminergic system, and that TAAR1 serves as a homeostatic “brake” system that is involved in the modulation of dopaminergic activity. Existing data provided robust preclinical evidence supporting the development of TAAR1 agonists as potential treatment for psychostimulant abuse and addiction. ... Given that TAAR1 is primarily located in the intracellular compartments and existing TAAR1 agonists are proposed to get access to the receptors by translocation to the cell interior (Miller, 2011), future drug design and development efforts may need to take strategies of drug delivery into consideration (Rajendran et al., 2010).
  112. Jump up to:a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 5: Excitatory and Inhibitory Amino Acids". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. pp. 124–125. ISBN 9780071481274.
  113. Jump up to:a b c d Shoptaw SJ, Kao U, Heinzerling K, Ling W (April 2009). Shoptaw SJ, ed. "Treatment for amphetamine withdrawal". Cochrane Database Syst. Rev. (2): CD003021. doi:10.1002/14651858.CD003021.pub2PMID 19370579.
  114. Jump up^ "Adderall IR Prescribing Information" (PDF)United States Food and Drug Administration. Teva Pharmaceuticals USA, Inc. October 2015. Retrieved 18 May2016.
  115. Jump up^ "Adderall XR Prescribing Information" (PDF)United States Food and Drug Administration. Shire US Inc. December 2013. Retrieved 30 December 2013.
  116. Jump up^ Advokat C (July 2007). "Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD". J. Atten. Disord11 (1): 8–16. doi:10.1177/1087054706295605PMID 17606768.
  117. Jump up^ "Amphetamine"Hazardous Substances Data Bank. United States National Library of Medicine – Toxicology Data Network. Retrieved 26 February 2014Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.
  118. Jump up^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. p. 370. ISBN 9780071481274Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.
  119. Jump up^ Sulzer D, Zecca L (February 2000). "Intraneuronal dopamine-quinone synthesis: a review". Neurotox. Res1 (3): 181–195. doi:10.1007/BF03033289PMID 12835101.
  120. Jump up^ Miyazaki I, Asanuma M (June 2008). "Dopaminergic neuron-specific oxidative stress caused by dopamine itself". Acta Med. Okayama62 (3): 141–150. PMID 18596830.
  121. Jump up^ Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York, USA: Oxford University Press. p. 329. ISBN 9780195030570.
  122. Jump up to:a b c d e f g "Adderall XR Prescribing Information" (PDF)United States Food and Drug Administration. December 2013. pp. 8–10. Retrieved 30 December 2013.
  123. Jump up to:a b Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism"Pharmacol. Ther106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001PMC 1828602free to readPMID 15922018.
    Table 5: N-containing drugs and xenobiotics oxygenated by FMO
  124. Jump up^ Krause J (April 2008). "SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder". Expert Rev. Neurother8 (4): 611–625. doi:10.1586/14737175.8.4.611PMID 18416663Zinc binds at ... extracellular sites of the DAT [103], serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc [supplementation] on symptoms of ADHD [105,106]. It should be stated that at this time [supplementation] with zinc is not integrated in any ADHD treatment algorithm.
  125. Jump up^ Sulzer D (February 2011). "How addictive drugs disrupt presynaptic dopamine neurotransmission"Neuron69 (4): 628–649. doi:10.1016/j.neuron.2011.02.010PMC 3065181free to readPMID 21338876They 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 [3H]DA despite its concomitant inhibition of uptake (Scholze et al., 2002).
  126. Jump up to:a b Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH (June 2002). "The role of zinc ions in reverse transport mediated by monoamine transporters". J. Biol. Chem277 (24): 21505–21513. doi:10.1074/jbc.M112265200PMID 11940571The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2+ binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). ... Although Zn2+ inhibited uptake, Zn2+ facilitated [3H]MPP+ release induced by amphetamine, MPP+, or K+-induced 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 Zn2+ to the superfusion buffer (Fig. 2 A, open squares). We stress that Zn2+ per se did not affect basal efflux (Fig. 2 A). ... In many brain regions, Zn2+ is stored in synaptic vesicles and co-released together with glutamate; under basal conditions, the extracellular levels of Zn2+ are low (∼10 nM; see Refs. 39, 40). Upon neuronal stimulation, however, Zn2+ is co-released with the neurotransmitters and, consequently, the free Zn2+ concentration may transiently reach values that range from 10–20 μM (10) up to 300 μM (11). The concentrations of Zn2+ 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 Zn2+ on hDAT does not merely reflect a biochemical peculiarity but that it is physiologically relevant. ... Thus, when Zn2+ is co-released with glutamate, it may greatly augment the efflux of dopamine.
  127. Jump up^ Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (October 2012). "Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses". J. Am. Acad. Child Adolesc. Psychiatry51 (10): 1003–1019.e20. doi:10.1016/j.jaac.2012.08.015PMID 23021477Although we did not find a sufficient number of studies suitable for a meta-analysis of PEA and ADHD, three studies20,57,58 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 markedly increased urinary excretion of PEA,20,60 suggesting that ADHD treatments normalize PEA levels. ... Similarly, urinary biogenic trace amine PEA levels could be a biomarker for the diagnosis of ADHD,20,57,58 for treatment efficacy,20,60 and associated with symptoms of inattentivenesss.59 ... 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.110
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  131. Jump up^ "Pharmacology"DextroamphetamineDrugBank. University of Alberta. 8 February 2013. Retrieved5 November 2013.
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  134. Jump up to:a b "Metabolism/Pharmacokinetics"AMPHETAMINEUnited States National Library of Medicine – Toxicology Data Network. Hazardous Substances Data Bank. Retrieved 5 January 2014Plasma protein binding, rate of absorption, & volumes of distribution of amphetamine isomers are similar. ... The biological half-life of amphetamine is greater in drug dependent individuals than in control subjects, & distribution volumes are increased, indicating that greater affinity of tissues for the drug may contribute to development of amphetamine tolerance. ... Concentrations of (14)C-amphetamine declined less rapidly in the plasma of human subjects maintained on an alkaline diet (urinary pH > 7.5) than those on an acid diet (urinary pH < 6). Plasma half-lives of amphetamine ranged between 16-31 hr & 8-11 hr, respectively, & the excretion of (14)C in 24 hr urine was 45 & 70%.
  135. Jump up^ Glennon RA (2013). "Phenylisopropylamine stimulants: amphetamine-related agents". In Lemke TL, Williams DA, Roche VF, Zito W. Foye's principles of medicinal chemistry (7th ed.). Philadelphia, USA: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 646–648. ISBN 9781609133450. Retrieved11 September2015The 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 (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 p-hydroxyamphetamine. ... Subsequent oxidation at the benzylic position by DA β-hydroxylase affords p-hydroxynorephedrine. Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.
  136. Jump up^ Taylor KB (January 1974). "Dopamine-beta-hydroxylase. Stereochemical course of the reaction" (PDF)J. Biol. Chem249 (2): 454–458. PMID 4809526. Retrieved 6 November 2014Dopamine-β-hydroxylase catalyzed the removal of the pro-R hydrogen atom and the production of 1-norephedrine, (2S,1R)-2-amino-1-hydroxyl-1-phenylpropane, from d-amphetamine.
  137. Jump up^ Horwitz D, Alexander RW, Lovenberg W, Keiser HR (May 1973). "Human serum dopamine-β-hydroxylase. Relationship to hypertension and sympathetic activity". Circ. Res32 (5): 594–599. doi:10.1161/01.RES.32.5.594PMID 4713201Subjects with exceptionally low levels of serum dopamine-β-hydroxylase activity showed normal cardiovascular function and normal β-hydroxylation of an administered synthetic substrate, hydroxyamphetamine.
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  144. Jump up^ "Compound Summary"PhenylpropanolaminePubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information. Retrieved 15 October 2013.
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  164. Jump up^ United Nations Office on Drugs and Crime (2007). Preventing Amphetamine-type Stimulant Use Among Young People: A Policy and Programming Guide (PDF). New York: United Nations. ISBN 92-1-148223-2.
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