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<!--exercise therapy improves [[wikt:clinical|clinical]] treatment outcomes and may be used as a {{tsl|en|combination therapy}} with [[cognitive behavioral therapy]], which is currently the best clinical treatment available.--><ref name="Running vs addiction" /><ref name="Exercise Rev 3" /><ref name="Nestler CBT"/>
<!--exercise therapy improves [[wikt:clinical|clinical]] treatment outcomes and may be used as a {{tsl|en|combination therapy}} with [[cognitive behavioral therapy]], which is currently the best clinical treatment available.--><ref name="Running vs addiction" /><ref name="Exercise Rev 3" /><ref name="Nestler CBT"/>
{{Amphetamine overdose}}
{{Amphetamine overdose}}
===Addiction===
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<includeonly>{{Addiction glossary}}</includeonly>
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{{Addiction glossary|class="toccolours mw-collapsible mw-collapsed"|width=610}}
{{Psychostimulant addiction|align=right|header=[[Signaling cascade]] in the [[nucleus accumbens]] that results in amphetamine addiction}}
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-->[[Addiction]] is a serious risk with heavy recreational amphetamine use but is unlikely to arise from typical long-term medical use at therapeutic doses.<ref name="NHM-Addiction doses">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE | editor = Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | page = 368 | edition = 2nd | chapter = Chapter 15: Reinforcement and Addictive Disorders | quote= 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.}}</ref><ref name="Addiction risk">{{cite journal | vauthors = Kollins SH | title = A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders | journal = Curr. Med. Res. Opin. | volume = 24 | issue = 5 | pages = 1345–1357 | date = May 2008 | pmid = 18384709 | doi = 10.1185/030079908X280707 | quote = 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.}}</ref><ref name="EncycOfPsychopharm">{{Cite book | author = Stolerman IP | editor = Stolerman IP | title = Encyclopedia of Psychopharmacology | year = 2010 | publisher = Springer | location = Berlin, Germany; London, England | isbn = 9783540686989 | page = 78}}</ref> {{if pagename | Lisdexamfetamine= Compared to other amphetamine pharmaceuticals, lisdexamfetamine may have a lower liability for abuse as a recreational drug.<ref name="LDX abuse">{{cite journal | vauthors = Coghill DR, Caballero B, Sorooshian S, Civil R | title = A systematic review of the safety of lisdexamfetamine dimesylate | journal = CNS Drugs | volume = 28 | issue = 6 | pages = 497–511 | date = June 2014 | pmid = 24788672 | pmc = 4057639 | doi = 10.1007/s40263-014-0166-2 | quote = The prodrug formulation of LDX may also lead to reduced abuse potential of LDX compared with immediate-release d-AMP. }}</ref>| other=}} [[Drug tolerance]] develops rapidly in amphetamine abuse (i.e., a recreational amphetamine overdose), so periods of extended use require increasingly larger doses of the drug in order to achieve the same effect.<ref>{{cite web| title = Amphetamines: Drug Use and Abuse | work = Merck Manual Home Edition | publisher = Merck | url = http://www.merckmanuals.com/home/special_subjects/drug_use_and_abuse/amphetamines.html | accessdate = 28 February 2007 | archiveurl = https://web.archive.org/web/20070217053619/http://www.merck.com/mmhe/sec07/ch108/ch108g.html |date=February 2003 | archivedate = 17 February 2007}}</ref><ref>{{cite journal |vauthors=Perez-Mana C, Castells X, Torrens M, Capella D, Farre M |title=Efficacy of psychostimulant drugs for amphetamine abuse or dependence |journal=Cochrane Database Syst. Rev. |volume=9 |pages=CD009695 |date=September 2013 |pmid=23996457 |doi=10.1002/14651858.CD009695.pub2 |editor=Pérez-Mañá C}}</ref>

====Biomolecular mechanisms====
Current models of addiction from chronic drug use involve alterations in [[gene expression]] in certain parts of the brain, particularly the [[nucleus accumbens]].<ref name="Nestler, Hyman, and Malenka 2">{{cite journal |vauthors=Hyman SE, Malenka RC, Nestler EJ |title=Neural mechanisms of addiction: the role of reward-related learning and memory |journal=Annu. Rev. Neurosci. |volume=29 |pages=565–598 |date=July 2006 |pmid=16776597 |doi=10.1146/annurev.neuro.29.051605.113009}}</ref><ref name="Nestler" /><ref name="Addiction genetics" /> The most important [[transcription factor]]s{{#tag:ref|Transcription factors are proteins that increase or decrease the [[gene expression|expression]] of specific genes.<ref name="NHM-Transcription factor">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York, USA | isbn = 9780071481274 | page = 94 | edition = 2nd | chapter = Chapter 4: Signal Transduction in the Brain | quote= <!-- All living cells depend on the regulation of gene expression by extracellular signals for their development, homeostasis, and adaptation to the environment. Indeed, many signal transduction pathways function primarily to modify transcription factors that alter the expression of specific genes. Thus, neurotransmitters, growth factors, and drugs change patterns of gene expression in cells and in turn affect many aspects of nervous system functioning, including the formation of long-term memories. Many drugs that require prolonged administration, such as antidepressants and antipsychotics, trigger changes in gene expression that are thought to be therapeutic adaptations to the initial action of the drug. -->}}</ref>|group="note"}} that produce these alterations are [[ΔFosB]], [[Cyclic adenosine monophosphate|cAMP]] response element binding protein ([[cAMP response element binding protein|CREB]]), and nuclear factor kappa B ([[NF-κB]]).<ref name="Nestler" /> ΔFosB plays a crucial role in the development of drug addictions, since its overexpression in [[D1-type]] [[medium spiny neuron]]s in the nucleus accumbens is [[necessary and sufficient#Definitions|necessary and sufficient]]{{#tag:ref|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.|group="note"}} for most of the behavioral and neural adaptations that arise from addiction.<ref name="What the ΔFosB?" /><ref name="Cellular basis" /><ref name="Nestler" /> Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression.<ref name="What the ΔFosB?" /><ref name="Cellular basis" /> It has been implicated in addictions to [[alcoholism|alcohol]], [[cannabinoid]]s, [[cocaine]], [[methylphenidate]], [[nicotine]], [[opioid]]s, [[phencyclidine]], [[propofol]], and [[substituted amphetamines]], among others.{{#tag:ref|<ref name="What the ΔFosB?" /><!--Preceding review covers ΔFosB in propofol addiction--><ref name="Natural and drug addictions" /><ref name="Nestler" /><ref name="Alcoholism ΔFosB">{{cite web | title=Alcoholism – Homo sapiens (human) | url=http://www.genome.jp/kegg-bin/show_pathway?hsa05034+2354 | work=KEGG Pathway | accessdate=31 October 2014 | author=Kanehisa Laboratories | date=29 October 2014}}</ref><ref name="MPH ΔFosB">{{cite journal | vauthors = Kim Y, Teylan MA, Baron M, Sands A, Nairn AC, Greengard P | title = Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 8 | pages = 2915–2920 | date = February 2009 | pmid = 19202072 | pmc = 2650365 | doi = 10.1073/pnas.0813179106 | quote = <!--Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use (36, 37). Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood (38). However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction (3, 6–10). Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i.v. administration may lead to addiction (39, 40).-->}}</ref>|group="sources"}}

[[ΔJunD]], a transcription factor, and [[EHMT2|G9a]], a [[histone methyltransferase]] enzyme, both directly oppose the induction of ΔFosB in the nucleus accumbens (i.e., they oppose increases in its expression).<ref name="Cellular basis" /><ref name="Nestler" /><ref name="Nestler 2014 epigenetics">{{cite journal | vauthors = Nestler EJ | title = Epigenetic mechanisms of drug addiction | journal = Neuropharmacology | volume = 76 Pt B | pages = 259–268 | date = January 2014 | pmid = 23643695 | pmc = 3766384 | doi = 10.1016/j.neuropharm.2013.04.004 | quote = <!-- Short-term increases in histone acetylation generally promote behavioral responses to the drugs, while sustained increases oppose cocaine’s effects, based on the actions of systemic or intra-NAc administration of HDAC inhibitors.&nbsp;... Genetic or pharmacological blockade of G9a in the NAc potentiates behavioral responses to cocaine and opiates, whereas increasing G9a function exerts the opposite effect (Maze et al., 2010; Sun et al., 2012a). Such drug-induced downregulation of G9a and H3K9me2 also sensitizes animals to the deleterious effects of subsequent chronic stress (Covington et al., 2011). Downregulation of G9a increases the dendritic arborization of NAc neurons, and is associated with increased expression of numerous proteins implicated in synaptic function, which directly connects altered G9a/H3K9me2 in the synaptic plasticity associated with addiction (Maze et al., 2010).<br />G9a appears to be a critical control point for epigenetic regulation in NAc, as we know it functions in two negative feedback loops. It opposes the induction of ΔFosB, a long-lasting transcription factor important for drug addiction (Robison and Nestler, 2011), while ΔFosB in turn suppresses G9a expression (Maze et al., 2010; Sun et al., 2012a).&nbsp;... Also, G9a is induced in NAc upon prolonged HDAC inhibition, which explains the paradoxical attenuation of cocaine’s behavioral effects seen under these conditions, as noted above (Kennedy et al., 2013). GABAA receptor subunit genes are among those that are controlled by this feedback loop. Thus, chronic cocaine, or prolonged HDAC inhibition, induces several GABAA receptor subunits in NAc, which is associated with increased frequency of inhibitory postsynaptic currents (IPSCs). In striking contrast, combined exposure to cocaine and HDAC inhibition, which triggers the induction of G9a and increased global levels of H3K9me2, leads to blockade of GABAA receptor and IPSC regulation. -->}}</ref> Sufficiently overexpressing ΔJunD in the nucleus accumbens with [[viral vector]]s can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).<ref name="Nestler" /> ΔFosB also plays an important role in regulating behavioral responses to [[natural reward]]s, such as palatable food, sex, and exercise.<ref name="Natural and drug addictions" /><ref name="Nestler" /><ref name="ΔFosB reward">{{cite journal |vauthors=Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M | title = Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms | journal = J. Psychoactive Drugs | volume = 44 | issue = 1 | pages = 38–55 | date = March 2012 | pmid = 22641964 | pmc = 4040958 | doi = 10.1080/02791072.2012.662112| quote = <!-- 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, and putamen, but not the medial preoptic nucleus.&nbsp;... 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.&nbsp;... 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. -->}}</ref> Since both natural rewards and addictive drugs [[inducible gene|induce expression]] 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.<ref name="Natural and drug addictions" /><ref name="Nestler">{{cite journal |vauthors=Robison AJ, Nestler EJ | title = Transcriptional and epigenetic mechanisms of addiction | journal = Nat. Rev. Neurosci. | volume = 12 | issue = 11 | pages = 623–637 |date=November 2011 | pmid = 21989194 | pmc = 3272277 | doi = 10.1038/nrn3111 | quote = <!-- ΔFosB has been linked directly to several addiction-related behaviors&nbsp;... 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<sup>14,22–24</sup>. 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<sup>14,26–30</sup>. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states. --> }}</ref> Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced [[sex addiction]]s, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use.<ref name="Natural and drug addictions" /><ref name="Amph-Sex X-sensitization through D1 signaling"><!--Supplemental primary source-->{{cite journal |vauthors=Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM | title = Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator | journal = J. Neurosci. | volume = 33 | issue = 8 | pages = 3434–3442 |date=February 2013 | pmid = 23426671 | pmc = 3865508 | doi = 10.1523/JNEUROSCI.4881-12.2013}}</ref><ref name="Amph-Sex X-sensitization through NMDA signaling"><!--Supplemental primary source-->{{cite journal | vauthors = Beloate LN, Weems PW, Casey GR, Webb IC, Coolen LM | title = Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats | journal = Neuropharmacology | volume = 101 | pages = 154–164 | date = February 2016 | pmid = 26391065 | doi = 10.1016/j.neuropharm.2015.09.023}}</ref> These sex addictions are associated with a [[dopamine dysregulation syndrome]] which occurs in some patients taking [[dopaminergic#Supplements and drugs|dopaminergic drugs]].<ref name="Natural and drug addictions" /><ref name="ΔFosB reward" />

The effects of amphetamine on gene regulation are both dose- and route-dependent.<ref name="Addiction genetics">{{cite journal |vauthors=Steiner H, Van Waes V | title=Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants | journal=Prog. Neurobiol. | volume=100 | pages=60–80 | date=January 2013 | pmid=23085425 | pmc=3525776 | doi=10.1016/j.pneurobio.2012.10.001 }}</ref> Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses.<ref name="Addiction genetics" /> The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor.<ref name="Addiction genetics" /> This suggests that medical use of amphetamine does not significantly affect gene regulation.<ref name="Addiction genetics" />

====Pharmacological treatments====
{{Further information|Addiction#Research}}
{{As of|May 2014|post=,}} there is no effective [[pharmacotherapy]] for amphetamine addiction.<ref name="pmid24716825">{{cite journal | vauthors = Stoops WW, Rush CR | title = Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research | journal = Expert Rev Clin Pharmacol | volume = 7 | issue = 3 | pages = 363–374 | date = May 2014 | pmid = 24716825 | doi = 10.1586/17512433.2014.909283 | quote = Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. | pmc = 4017926 }}</ref><ref name="Cochrane 2013 treatments">{{cite journal | vauthors = Perez-Mana C, Castells X, Torrens M, Capella D, Farre M | title = Efficacy of psychostimulant drugs for amphetamine abuse or dependence | journal = Cochrane Database Syst. Rev. | volume = 9 | pages = CD009695 | date = September 2013 | pmid = 23996457 | doi = 10.1002/14651858.CD009695.pub2 | quote = To date, no pharmacological treatment has been approved for [addiction], and psychotherapy remains the mainstay of treatment.&nbsp;... Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy}}</ref><ref name="pmid23039267">{{cite journal | vauthors = Forray A, Sofuoglu M | title = Future pharmacological treatments for substance use disorders | journal = Br. J. Clin. Pharmacol. | volume = 77 | issue = 2 | pages = 382–400 | date = February 2014 | pmid = 23039267 | pmc = 4014020 | doi = 10.1111/j.1365-2125.2012.04474.x }}</ref> Reviews from 2015 and 2016 indicated that [[TAAR1]]-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions;<ref name="Miller+Grandy 2016" /><ref name="TAAR1 addiction 2015" /> however, {{As of|February 2016|lc=y|post=,}} the only compounds which are known to function as TAAR1-selective agonists are [[experimental drug]]s.<ref name="Miller+Grandy 2016">{{cite journal | vauthors = Grandy DK, Miller GM, Li JX | title = "TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference | journal = Drug Alcohol Depend. | volume = 159 | pages = 9–16 | date = February 2016 | pmid = 26644139 | doi = 10.1016/j.drugalcdep.2015.11.014 | quote = 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.}}</ref><ref name="TAAR1 addiction 2015">{{cite journal | vauthors = Jing L, Li JX | title = Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction | journal = Eur. J. Pharmacol. | volume = 761 | pages = 345–352 | date = August 2015 | pmid = 26092759 | doi = 10.1016/j.ejphar.2015.06.019 | quote = Existing data provided robust preclinical evidence supporting the development of TAAR1 agonists as potential treatment for psychostimulant abuse and addiction. | pmc=4532615}}</ref> Amphetamine addiction is largely mediated through increased activation of [[dopamine receptor]]s and {{nowrap|[[wikt:colocalize|co-localized]]}} [[NMDA receptor]]s{{#tag:ref|NMDA receptors are voltage-dependent [[ligand-gated ion channels]] that requires simultaneous binding of glutamate and a co-agonist ([[D-serine|{{smallcaps all|D}}-serine]] or [[glycine]]) to open the ion channel.<ref name="NHM-NMDA">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York, USA | isbn = 9780071481274 | pages = 124–125 | edition = 2nd | chapter = Chapter 5: Excitatory and Inhibitory Amino Acids | quote = <!-- At membrane potentials more negative than approximately −50 mV, the Mg2+ in the extracellular fluid of the brain virtually abolishes ion flux through NMDA receptor channels, even in the presence of glutamate.&nbsp;... The NMDA receptor is unique among all neurotransmitter receptors in that its activation requires the simultaneous binding of two different agonists. In addition to the binding of glutamate at the conventional agonist-binding site, the binding of glycine appears to be required for receptor activation. Because neither of these agonists alone can open this ion channel, glutamate and glycine are referred to as coagonists of the NMDA receptor. The physiologic significance of the glycine binding site is unclear because the normal extracellular concentration of glycine is believed to be saturating. However, recent evidence suggests that D-serine may be the endogenous agonist for this site. -->}}</ref>|group="note"}} in the nucleus accumbens;<ref name="Magnesium" /> [[magnesium|magnesium ions]] inhibit NMDA receptors by blocking the receptor [[calcium channel]].<ref name="Magnesium" /><ref name="NHM-NMDA" /> One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain.<ref name="Magnesium" /> [[Dietary supplement|Supplemental magnesium]]{{#tag:ref|The review indicated that [[magnesium aspartate|magnesium L-aspartate]] and [[magnesium chloride]] produce significant changes in addictive behavior;<ref name="Magnesium" /> other forms of magnesium were not mentioned.|group="note"}} treatment has been shown to reduce amphetamine [[self-administration]] (i.e., doses given to oneself) in humans, but it is not an effective [[monotherapy]] for amphetamine addiction.<ref name="Magnesium">{{cite journal |author =Nechifor M |title=Magnesium in drug dependences |journal=Magnes. Res. |volume=21 |issue=1 |pages=5–15 |date=March 2008 |pmid=18557129}}</ref>

====Behavioral treatments====
[[Cognitive behavioral therapy]] is currently the most effective clinical treatment for psychostimulant addictions.<ref name="Nestler CBT">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York, USA | isbn = 9780071481274 | page = 386 | edition = 2nd | chapter = Chapter 15: Reinforcement and Addictive Disorders | quote= Currently, cognitive–behavioral therapies are the most successful treatment available for preventing the relapse of psychostimulant use.}}</ref> Additionally, research on the [[neurobiological effects of physical exercise]] suggests that daily aerobic exercise, especially endurance exercise (e.g., [[marathon running]]), prevents the development of drug addiction and is an effective [[adjunct therapy]] (i.e., a supplemental treatment) for amphetamine addiction.{{#tag:ref|<ref name="Natural and drug addictions" /><ref name="Running vs addiction" /><ref name="Exercise, addiction prevention, and ΔFosB" /><ref name="Exercise Rev 3" /><ref name="Addiction review 2016" />|group="sources"|name="Exercise therapy"}} Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions.<ref name="Running vs addiction">{{cite journal |vauthors=Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA | title = Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis | journal = Neurosci. Biobehav. Rev. | volume = 37 | issue = 8 | pages = 1622–1644 |date=September 2013 | pmid = 23806439 | pmc = 3788047 | doi = 10.1016/j.neubiorev.2013.06.011 | quote = 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.&nbsp;... 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&nbsp;... 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.}}</ref><ref name="Exercise Rev 3">{{cite journal | vauthors = Linke SE, Ussher M | title = Exercise-based treatments for substance use disorders: evidence, theory, and practicality | journal = Am. J. Drug Alcohol Abuse | volume = 41 | issue = 1 | pages = 7–15 | date = January 2015 | pmid = 25397661 | doi = 10.3109/00952990.2014.976708 | quote = 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.&nbsp;... numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects. | pmc=4831948}}</ref><ref name="Addiction review 2016">{{cite journal | vauthors = Carroll ME, Smethells JR | title = Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments | journal = Front. Psychiatry | volume = 6 | pages = 175 | date = February 2016 | pmid = 26903885 | pmc = 4745113 | doi = 10.3389/fpsyt.2015.00175 | quote = Physical Exercise<br />There is accelerating evidence that physical exercise is a useful treatment for preventing and reducing drug addiction&nbsp;... 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.&nbsp;... 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.&nbsp;... 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.}}</ref> In particular, [[aerobic exercise]] decreases psychostimulant self-administration, reduces the [[reinstatement]] (i.e., relapse) of drug-seeking, and induces increased [[dopamine receptor D2|dopamine receptor D<sub>2</sub>]] (DRD2) density in the [[striatum]].<ref name="Natural and drug addictions" /><ref name="Addiction review 2016" /> This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density.<ref name="Natural and drug addictions">{{cite journal | author = Olsen CM | title = Natural rewards, neuroplasticity, and non-drug addictions | journal = Neuropharmacology | volume = 61 | issue = 7 | pages = 1109–1122 | date = December 2011 | pmid = 21459101 | pmc = 3139704 | doi = 10.1016/j.neuropharm.2011.03.010 | quote = 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 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).&nbsp;... 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). }}</ref> One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or [[c-Fos]] [[immunoreactivity]] in the striatum or other parts of the [[reward system]].<ref name="Exercise, addiction prevention, and ΔFosB" />
{{FOSB addiction table|Table title=Summary of addiction-related plasticity}}

===Dependence and withdrawal===
According to another Cochrane Collaboration review on [[drug withdrawal|withdrawal]] 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&nbsp;hours of their last dose."<ref name="Cochrane Withdrawal">{{cite journal |vauthors=Shoptaw SJ, Kao U, Heinzerling K, Ling W | title = Treatment for amphetamine withdrawal | journal = Cochrane Database Syst. Rev. | issue = 2 | pages = CD003021 | date = April 2009 | pmid = 19370579 | doi = 10.1002/14651858.CD003021.pub2 | editor = Shoptaw SJ | quote = <!-- 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)&nbsp;... The severity of 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)&nbsp;... -->}}</ref> This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.<ref name="Cochrane Withdrawal" /> Amphetamine withdrawal symptoms can include anxiety, [[Craving (withdrawal)|drug craving]], [[Dysphoria|depressed mood]], [[Fatigue (medical)|fatigue]], [[hyperphagia|increased appetite]], increased movement or [[psychomotor retardation|decreased movement]], lack of motivation, sleeplessness or sleepiness, and [[lucid dream]]s.<ref name="Cochrane Withdrawal" /> The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence.<ref name="Cochrane Withdrawal" /> Manufacturer prescribing information does not indicate the presence of withdrawal symptoms following discontinuation of amphetamine use after an extended period at therapeutic doses.<ref name="Dexedrine FDA">{{cite web | title = Dexedrine Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017078s047lbl.pdf | publisher = Amedra Pharmaceuticals LLC | work = United States Food and Drug Administration | date = October 2013 | accessdate = 4 November 2013 }}</ref><ref>{{cite web | title=Adderall IR Prescribing Information | url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/011522s042lbl.pdf | publisher = Teva Pharmaceuticals USA, Inc. | work = United States Food and Drug Administration | date=October 2015 | accessdate=18 May 2016 }}</ref><ref>{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | publisher = Shire US Inc | work = United States Food and Drug Administration | date=December 2013 | accessdate = 30 December 2013 }}</ref>

===Toxicity and psychosis===
{{see also|Stimulant psychosis}}

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic [[neurotoxicity]], or damage to dopamine neurons, which is characterized by dopamine [[axon terminal|terminal]] [[Neurodegeneration|degeneration]] and reduced transporter and receptor function.<ref name="Humans&Animals">{{cite journal| author=Advokat C| title=Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD | journal=J. Atten. Disord. | date = July 2007 | volume= 11 | issue= 1 | pages= 8–16 | pmid=17606768 | doi=10.1177/1087054706295605}}</ref><ref name="Amph-induced hyperthermia and neurotoxicity review" /> There is no evidence that amphetamine is directly neurotoxic in humans.<ref>{{cite web | title=Amphetamine | url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+300-62-9 | work=Hazardous Substances Data Bank | publisher=United States National Library of Medicine&nbsp;– Toxicology Data Network | accessdate=26 February 2014 | quote = Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.}}</ref><ref name = "Malenka_2009_02">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York, USA | isbn = 9780071481274 | page = 370 | edition = 2nd | chapter = Chapter 15: Reinforcement and addictive disorders | quote = Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.}}</ref> However, large doses of amphetamine may indirectly cause dopaminergic neurotoxicity as a result of [[hyperpyrexia]], the excessive formation of [[reactive oxygen species]], and increased [[autoxidation]] of dopamine.{{#tag:ref|<ref name="pmid22392347">{{cite journal |vauthors=Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L |title=Toxicity of amphetamines: an update |journal=Arch. Toxicol. |volume=86 |issue=8 |pages=1167–1231 |date=August 2012 |pmid=22392347 |doi=10.1007/s00204-012-0815-5}}</ref><ref name="Amph-induced hyperthermia and neurotoxicity review" /><ref name="Autoxidation1">{{cite journal |vauthors=Sulzer D, Zecca L | title = Intraneuronal dopamine-quinone synthesis: a review | journal = Neurotox. Res. | volume = 1 | issue = 3 | pages = 181–195 |date=February 2000 | pmid = 12835101 | doi = 10.1007/BF03033289 }}</ref><ref name="Autoxidation2">{{cite journal |vauthors=Miyazaki I, Asanuma M | title = Dopaminergic neuron-specific oxidative stress caused by dopamine itself | journal = Acta Med. Okayama | volume = 62 | issue = 3 | pages = 141–150 |date=June 2008 | pmid = 18596830| url = http://ousar.lib.okayama-u.ac.jp/files/public/3/30980/20160528022138672578/fulltext.pdf }}</ref>|group="sources"}} [[Animal model]]s of neurotoxicity from high-dose amphetamine exposure indicate that the occurrence of hyperpyrexia (i.e., [[core body temperature]]&nbsp;≥&nbsp;40&nbsp;°C) is necessary for the development of amphetamine-induced neurotoxicity.<ref name="Amph-induced hyperthermia and neurotoxicity review">{{cite journal | vauthors = Bowyer JF, Hanig JP | title = Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity | journal = Temperature (Austin) | volume = 1 | issue = 3 | pages = 172–182 | date = November 2014 | pmid = 27626044 | pmc = 5008711 | doi = 10.4161/23328940.2014.982049 | quote = Hyperthermia alone does not produce amphetamine-like neurotoxicity but AMPH and METH exposures that do not produce hyperthermia (≥40°C) are minimally neurotoxic. Hyperthermia likely enhances AMPH and METH neurotoxicity directly through disruption of protein function, ion channels and enhanced ROS production.&nbsp;... 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.&nbsp;... 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.}}</ref> Prolonged elevations of brain temperature above 40&nbsp;°C likely promote the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting cellular protein function, and transiently increasing [[blood–brain barrier]] permeability.<ref name="Amph-induced hyperthermia and neurotoxicity review" />

A severe amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia.<ref name="Cochrane" /> A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about&nbsp;5–15% of users fail to recover completely.<ref name="Cochrane">{{cite journal | editor =<!--Shoptaw SJ--> Shoptaw SJ, Ali R |vauthors=Shoptaw SJ, Kao U, Ling W | title = Treatment for amphetamine psychosis | journal = Cochrane Database Syst. Rev. | issue = 1 | pages = CD003026 | date = January 2009 | pmid = 19160215 | doi = 10.1002/14651858.CD003026.pub3 | quote=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. 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&nbsp;...<br />About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983)&nbsp;...<br />Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis.}}</ref><ref name="Hofmann">{{cite book | author = Hofmann FG | title = A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects | publisher = Oxford University Press | isbn = 9780195030570 | location = New York, USA | year = 1983 | page = 329 | edition = 2nd }}</ref> According to the same review, there is at least one trial that shows [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="Cochrane"/> Psychosis very rarely arises from therapeutic use.<ref name="Stimulant Misuse" /><ref name="FDA Contra Warnings">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | pages = 4–6 | publisher = Shire US Inc | work = United States Food and Drug Administration | date = December 2013 | accessdate = 30 December 2013 }}</ref>
}}</onlyinclude>
===成癮===
===成癮===


2017年4月30日 (日) 10:10的版本

  「安非他命」重定向至此。关于其他用法，请见「安非他命 (消歧义)」。
  關於中樞神經興奮劑，本條目完成擴充前，請見中樞神經興奮劑、methylphenidate以及注意力不足過動症#醫藥治療。
安非他命（Amfetamine） (INN)
An image of the amphetamine compound
A 3d image of the D-amphetamine compound
臨床資料
读音聆聽i/æmˈfɛtəmiːn/
其他名稱α-methylphenethylamine
AHFS/Drugs.comamphetamine
核准狀況
依賴性生理依賴（英语：Physical dependence）: 無
心理依賴（英语：Psychological dependence）: 中等
成癮性中等
给药途径醫用: 口服给药, 鼻腔給藥, 靜脈注射[1]
非醫療用（Recreational）： 口服给药, 鼻腔給藥, Insufflation (medicine)（英语：Insufflation (medicine)）, 栓剂, 靜脈注射
ATC碼
法律規範狀態
法律規範
藥物動力學數據
生物利用度口服 75–100%[2]
血漿蛋白結合率15–40%[3]
药物代谢Amphetamine only:
CYP2D6,[4] Dopamine β-hydroxylase,[13][14][15] Flavin-containing monooxygenase（英语：Flavin-containing monooxygenase）[13][16][17]
代謝產物4-hydroxyamphetamine（英语：4-hydroxyamphetamine）, 4-hydroxynorephedrine（英语：4-hydroxynorephedrine）, 4-hydroxyphenylacetone（英语：4-hydroxyphenylacetone）, 苯甲酸, 馬尿酸, 苯丙醇胺, 苯基丙酮[4][5][6]
藥效起始時間（英语：Onset of action）IR dosing: 30–60 minutes[7]
XR dosing: 1.5–2 hours[8] [9]
生物半衰期D-amph:9–11 hours[4][10]
L-amph:11–14 hours[4][10]
PH值-dependent: 8–31 hours[11]
作用時間IR dosing: 3–7 hours[8][12]
XR dosing: 12 hours[8]

[9]

[12]
排泄途徑Primarily 腎;
PH值-dependent range: 1–75%[4]
识别信息
  • (RS)-1-phenylpropan-2-amine
CAS号300-62-9  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
PDB配體ID
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)
ECHA InfoCard100.005.543 編輯維基數據鏈接
化学信息
化学式C9H13N
摩尔质量135.20622 g/mol[18]
3D模型（JSmol（英语：JSmol））
密度0.9±0.1 g/cm3
熔点11.3 °C（52.3 °F） (predicted)[20]
沸点203 °C（397 °F） at 760 毫米汞柱[19]
  • NC(CC1=CC=CC=C1)C
  • InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3 checkY
  • Key:KWTSXDURSIMDCE-UHFFFAOYSA-N checkY

安非他命（英文名稱：Amphetamine[note 1]为一种中樞神經興奮劑，用來治療注意力不足過動症、嗜睡症、和肥胖症。“Amphetamine”一名擷取自 alpha‑methylphenethylamine。

安非他命於西元1887年被發現，以兩種對映異構體的形式存在[note 2] ，分別是左旋安非他命和右旋安非他命。

正確來說，安非他命指的是特定的化學物質-外消旋純胺類型態（英语：free base）[24][25]，這個物質等同於安非他命的的兩個對映異構體：左旋安非他命和右旋安非他命的等比化合物之純胺類型態。 然而，實際上安非他命一詞已被廣泛的用來表示任何由安非他命對映異構體構成的物質或安非他命對映異構體本身。[21][26][25]

安非他命（amphetamine）歸類為中樞神經興奮劑，適度適量地使用能提升整體衝動控制能力（inhibitory control）[27][28]。在醫療用的劑量範圍內，安非他命能帶來情緒以及執行功能的變化，例如：欣快感、性欲的改變、清醒度（英语：wakefulness）的提升、大腦執行功能的進化。安非他命所改變的生理反應包含：減少反應時間、降低疲勞、以及肌耐力的增強。然而，若攝取劑量超越醫療用的劑量範圍過多，將會導致大腦執行功能的受損以及橫紋肌溶解症。 攝取過份超越醫療用劑量範圍的安非他命將產生嚴重的藥物成癮風險。然而長期攝取醫療劑量範圍的安非他命並不會產生上癮的風險。

服用嚴重超出醫療用劑量範圍的安非他命會引起精神疾病（例如：妄想[參 1]、偏執[參 2]）。然而長期攝取醫療劑量範圍的安非他命並不會引起上述疾病。

娛樂用劑量遠超過醫療用劑量範圍且伴隨著非常嚴重甚至致命的副作用。 [sources 1]

安非他命可以也曾經被用來治療鼻塞（nasal congestion）和抑鬱。

安非他命也被用來提升表現（英语：performance-enhancing substance）、和促進大腦的認知功能及在助興時（非醫療用途情況下）被作為增強性慾[a]、和欣快感促進劑。

安非他命在許多國家為合法的處方藥[參 3]。然而，私自散布和囤積安非他命被視為非法行為，因為安非他命被用於非醫療用途的助興可能性極高。[sources 2]

首個藥用安非他命的藥品名稱為Benzedrine。當今藥用安非他命（英语：#Pharmaceutical products）[參 4]以下列幾種形式存在：外消旋安非他命[參 5]、Adderall [note 3]。 、dextroamphetamine、或對人體無藥效的前驅藥物體[參 6]：lisdexamfetamine。

安非他命藉著自身作用於兒茶酚胺神經傳導元素：正腎上腺素及多巴胺的特點來活化trace amine receptor（英语：TAAR1） ，進而增加单胺类神经递质和神经递质（excitatory neurotransmitter）在腦內的活動。[sources 3]

安非他命屬於替代性苯乙胺（英语：substituted phenethylamine）類的物質。由安非他命衍伸出的物質被歸納在替代性苯乙胺（英语：substituted phenethylamine）[參 7]的分類中[note 4]，比如說：安非他酮[參 8]、 cathinone（英语：cathinone）、 MDMA、 和 甲基苯丙胺[參 9]。安非他命也與人體內可自然生成的兩個屬於痕量胺的神經傳導物質--特別是 phenethylamine 和 N-Methylphenethylamine（英语：N-Methylphenethylamine）--有關。 Phenethylamine 是安非他命的原始化合物，而N-methylphenethylamine則是安非他命的位置異構體（只有在甲基族中才會區分出此位置異構體）。[sources 4]

用途

醫療

参见：注意力不足過動症 § 藥物治療

安非他命是用來治療注意力不足過動症（ADHD）、嗜睡症（一種睡眠疾病）、和肥胖症。有時候安非他命會以仿單標示外使用的方式處方來治療頑固性憂鬱症（英语：treatment-resistant depression）及頑固性強迫症[1][10] [43] [50]。 在動物試驗中，已知非常高劑量的安非他命會造成某些動物的多巴胺系統（英语：dopamine receptor）和神經系統的受損。[51][52] 但是，在人體試驗中，注意力不足過動症患者在接受安非他命的治療後，則發現安非他命可促進大腦的發育及神經的成長。[53][54][55]

回顧許多核磁共振照影（MRI）的研究後發現，長期以安非他命治療注意力不足過動症患者能顯著降低患者大腦結構及大腦執行功能上的異常。並且優化大腦中數個部位，例如：基底神經節的右尾狀核。 [53][54][55]


眾多臨床研究的系統性及統合性回顧已確立長期使用安非他命治療注意力不足過動症的療效及安全。[56][57][58]

持續長達兩年的隨機對照試驗[參 10][b]結果顯示：長期使用安非他命治療注意力不足過動症，是有效且安全的。[56][58]

兩個系統性/統合性回顧的結果顯示長期且持續地使用中樞神經興奮劑治療注意力不足過動症能有效地減少注意力不足過動症的核心症狀（核心症狀即為：過動、衝動和分心/無法專心）、增進生活品質、提升學業成就、廣泛地強化大腦的執行功能。[note 5] 這些執行功能分別與下列項目有關：學業、反社會行為、駕駛習慣、藥物濫用、肥胖、職業、日常活動、自尊心、服務使用（例如：學習、職業、健康、財金、和法律等）、社交功能。[57][58]

一篇系統性／統合性回顧標誌了一個重要發現：一個為期九個月的隨機雙盲試驗中，持續以安非他命治療的ADHD患者，其智力商數平均增加4.5單位[註 1]，且在專注力、衝動、過動的改善皆呈現持續進步的態勢。[56] 另一篇系統性／統合性回顧則指出：根據迄今為止為時最長的數個臨床追蹤研究[參 11]，可以得到一個結論：即便從兒童時期開始以中樞神經興奮劑治療直到老年，中樞神經興奮劑都能持續有效地控制ADHD的症狀並且減少物質濫用的風險。[58] 研究表明，ADHD與大腦的執行功能受損有關。而這些受損的執行功能分別與大腦中部分的神經傳導系統（英语：neurostransmitter systems）有關[參 12]。[59] ；又此部分受損的神經傳導系統和中腦皮質激素（英语：mesocorticolimbic projection）-多巴胺[參 13]的傳導及藍斑核[參 14]和前額葉[參 15]中的正腎上腺素[參 16]的傳導相關。[59]

中樞神經興奮劑，例如：methylphenidate和安非他命對於治療ADHD都是有效的，因為中樞神經興奮劑刺激了上述神經系統中的神經傳導物質活動。[29][59] [60]

至少超過80%的ADHD患者在使用中樞神經興奮劑治療後，其ADHD的症狀可以獲得改善。[61]

使用中樞神經興奮劑治療的ADHD患者相較之下，普遍與同儕及家庭成員的關係較佳並且在學校擁有較好的表現。興奮劑能使ADHD患者較不易分心、衝動、且擁有較長的專注力時間和範圍。[62] [63]

根據考科藍協作組織[參 17]所提供的文獻回顧結果[note 6]指出：使用中樞神經興奮劑治療的ADHD患者即便其症狀改善，相較於使用非中樞神經興奮劑，仍因副作用而有較高的停藥率。[65] [66]

回顧結果也發現，中樞神經興奮劑並不會惡化抽動綜合症的症狀，例如：妥瑞氏症，除非服用dextroamphetamine[c]的劑量過高才有可能在部分妥瑞氏症合併注意力不足過動症患者身上觀察到抽動綜合症的症狀惡化。[67]

中樞神經興奮劑只要依照醫師指示用藥，都是相當安全的。[68][69][69][70] 中樞神經興奮劑，例如：利他能與專思達，可能導致：心悸、頭痛、胃痛、喪失食慾、失眠、因相對專注而變得冷淡（面無表情）等副作用，因此6歲以下的兒童不適宜服用。（副作用產生與否因人而異） [71]

隨著時間推進與各方的努力，中樞神經興奮劑的相關副作用已可藉由包括但不限於劑量調整、服藥時間、飯前飯後服用、服藥頻率等服藥模式之改變以及改變藥物組合等方式獲得相當程度的減少。[72] [73] [74] [69] [75]

提昇表現

認知方面（Cognitive）

西元2015年中，一篇系統性回顧[參 18]和一篇元分析/整合分析[參 19]回顧了數篇優秀的臨床試驗[參 20]報告後發現， 低劑量（醫療用劑量）的安非他命能適度但不強烈地促進一個人的認知功能，包含工作記憶（working memory）、長期的情節記憶（episodic memory）、衝動控制以及在一些方面的注意力（attention）。 [27] [28] 安非他命強化認知功能的效果已知是部分透過間接活化（英语：indirect agonist）在大腦前額葉（prefrontal cortex）的dopamine receptor D1（英语：dopamine receptor D1） 和adrenoceptor α2（英语：Alpha-2 adrenergic receptor）。 [29] [27] 一篇2014年的系統性回顧發現低劑量（醫療用劑量）的安非他命能促進memory consolidation（英语：memory consolidation），進而提升一個人的recall of information（英语：Recall (memory)）。 [76] 低劑量（醫療用劑量）的安非他命也可增加大腦皮層（質）區的效率，這能讓一個人的工作記憶（working memory）獲得進步。 [29] [77] 安非他命和其他用於治療ADHD的中樞神經刺激劑能透過提升task saliency（英语：Incentive salience）來增加一個人去做事情的動機、並強化一個人的警覺心（清醒度），因而能刺激一個人開始做「以目標為導向」的行為。 [29] [78] [79] 中樞神經興奮劑（例如：安非他命）能提升一個人在困難且枯燥的任務中的表現。 [29] [79] [80] 超過醫療用劑量範圍（包含其誤差範圍及容許最大上限）的安非他命劑量將不利於工作記憶（working memory）和其他的認知功能。 [29][79]

生理（physical）

雖然安非他命可以提升速度、耐力（延遲疲勞的發生）、肌耐力、身體素質和警覺心並減少心理反應時間。[30][34] [30] [81] [82] 然而，「非因醫療需求使用安非他命」在各種運動場合都是被嚴格禁止的。[83] [84]

安非他命藉由抑制多巴胺在中樞神經系統中的回收及外流來促進耐力和反應時間的提升。 [81][82] [85] 安非他命和其他作用於多巴胺系統的藥物一樣，都能增加在固定施力（levels of perceived exertion（英语：rating of perceived exertion））下的動力(能）輸出。這是因為安非他命能奪取（override）體溫的「安全開關」的控制權並將身體核心溫度（core temperature limit）的上限提高以取得在體溫安全上限提高前被身體保留的能量。 [82] [86] [87] 於醫療用劑量範圍（包含其誤差範圍），安非他命的副作用不至於影響運動員的運動表現； [30][81] 然而，當攝取的劑量過多時，安非他命可能會引起嚴重的後果，例如：橫紋肌溶解症和體溫過高。 [31][33] [81]

醫療上的禁忌

参见：苯丙胺 § 交互作用

根據International Programme on Chemical Safety (IPCS)和美國食品藥物管理局 (USFDA)， [note 7]

安非他命不建議處方給有藥物濫用、心血管疾病、對於各種刺激嚴重反應過度、和嚴重焦慮歷史的人。 [note 8][89][90]

安非他命也不被建議處方給正經歷動脈血管硬化（英语：arteriosclerosis）（血管硬化）、中度到重度高血壓、青光眼（眼壓過高）、或甲狀腺機能亢進（身體在體內製造出過量的甲狀腺 賀爾蒙/激素）的人。 [89][90][91]

曾對中樞神經刺激劑有藥物過敏的人以及正在服用單胺氧化酶抑制劑 (MAOI)或單胺氧化酶抑制劑類藥物 (MAOIs)，可能不適合使用安非他命。即便曾有合併使用安非他命和單胺氧化酶抑制劑後仍一切平安的案例。 [89][90] [92][93] IPCS和美國食品藥物管理局也同意患有神經性厭食症（anorexia nervosa）、雙極性情感疾患（bipolar disorder）、憂鬱、高血壓、mania、思覺失調症、Raynaud's phenomenon（英语：Raynaud's phenomenon）、心臟病發（seizures）、抽動綜合症（tics）、妥瑞氏症（Tourette's disease）、和有甲狀腺問題、肝腎問題的人在使用安非他命時應密切追蹤上述疾病的變化。 [89][90]

人體試驗證明，醫療用劑量下的安非他命並不會導致胎兒或新生兒畸形(i.e., it is not a human teratogen)。然而超越醫療用劑量甚多的安非他命確實會增加胎兒或新生兒畸形的機會。 [90]

研究觀察發現，安非他命會進入母親的母乳中，因此建議母親不要在使用安非他命藥物的期間內授乳。 [89][90]

由於安非他命可能影響食慾繼而導致可反轉的身高及體重的成長遲緩， [note 9] ，因此建議兒童或青少年在用藥期間定期測量自己的身高及體重。 [89]

副作用

生理

心理

嚴重過量

安非他命過量使用會引起許多症狀，然而在適當的醫療照護下，不至於死亡。 [90][95]

藥物過量症狀的嚴重度與劑量成正比；與身體對安非他命的藥物耐受性成反比。 [34][90] 已知每天攝取達到5公克的安非他命（每天最大攝取量的五十倍）會導致身體對安非他命產生藥物耐受性。 [90] 嚴重過量的安非他命攝取所致的症狀列於下方；安非他命中毒一旦到達出現全身抽蓄（convulsion）和昏厥（coma）則必須立刻急救以避免死亡。 [31][34] 在2013年，安非他命、甲基安非他命和其他列於ICD-10 第五章：精神和行為障礙§使用化學藥物、物質或酒精引起的精神和行為障礙中的安非他命相關物質的過量使用在世界上共導致3788人死亡。(3,425–4,145 人死亡、  95% 信賴區間)。 [note 10][96]

被過度活化達到病態程度的mesolimbic pathway（英语：mesolimbic pathway）（一個連接ventral tegmental area和伏隔核（nucleus accumbens）的多巴胺通道（英语：dopamine pathway）），在安非他命的成癮中扮演著主要的腳色。 [97] [98]

當一個人經常服用嚴重過量的安非他命，將伴隨安非他命成癮的高度風險， 因為持續過量的安非他命會逐漸增加accumbal ΔFosB（「成癮」與否的分子開關和主控蛋白 原文：a "molecular switch" and "master control protein" for addiction.）的檔次。 [99][100][101] 一旦伏隔核的ΔFosB破表（over-expressed），這個人的「成癮性行為」[註 2]（例如：出現試圖取得安非他命的衝動行為）將開始隨之增加。 [99][102] 雖然目前沒有治療安非他命成癮的有效藥物，但規律的且每次都有持續一定時間的有氧運動能降低安非他命的成癮風險也是治療安非他命成癮的天然療法。 [103][104] [sources 5] 運動能提升臨床治療（英语：clinical therapy）的預後，且可能與認知行為治療（目前已知最有效的安非他命成癮的臨床治療法）相搭配為combination therapy（英语：combination therapy）。 [103][105][106]

嚴重過量的安非他命劑量所致的症狀（依照體內生物系統分類）
生物系統 輕度、中度過量[31][34][90] 過量[sources 6]
心臟血管系統
中樞神經系統
肌肉骨骼系统
呼吸系統
  • 呼吸過速
生殖泌尿系統
其他

Addiction

「成癮及生理、心理依賴」的相關術語詞彙表[108][100][109][110]
  • 成瘾：腦部失調的情形，特徵是會強迫性的接觸犒赏刺激，不去考慮其帶來的負面結果。
  • 成瘾行为：具有犒赏性及正向增強效應的行為
  • 成瘾药物：具有犒赏性及正向增強效應的藥物
  • 依赖性：之前曾頻繁接觸刺激源（例如藥物攝取），中斷接觸後出現戒斷症狀的情形
  • 药物敏化或逆耐药性：在固定藥物劑量的情形下重複給藥，而相同劑量的藥物效果增強的情形
  • 藥物戒斷：在重複藥物使用後停藥，出現的症狀
  • 生理依赖：出現持續生理戒斷症狀（例如疲勞及震顫性譫妄）的依赖性
  • 心理依赖：出現情緒或是精神戒斷症狀（例如煩躁及失乐）的依赖性
  • 增强刺激：特定類型的刺激，接觸後會增加再接觸此刺激的可能性
  • 犒赏刺激：特定類型的刺激，大腦會認為此刺激是正向的，會想再進行的
  • 敏化作用：重複接受某一刺激後產生的刺激增強性反應
  • 物質使用疾患 ：使用特定物質，而且造成臨床上或是功能上的損傷或是困境的情形
  • 藥物耐受性：重複接受某一藥物後產生的藥物降低性反應
Signaling cascade in the nucleus accumbens that results in amphetamine addiction
查 · 编
图像顶端包含可点击的链接
本圖表描繪在中腦周邊/邊緣迴路（英语：Mesolimbic pathway）中由於「長期攝取超高劑量的中樞神經刺激劑（例如：安非他命、甲基苯丙胺、和苯乙胺.）使得多巴胺的神經突觸的濃度增加」的微觀示意圖。

Addiction is a serious risk with heavy recreational amphetamine use but is unlikely to arise from typical long-term medical use at therapeutic doses.[37][38][39] Drug tolerance develops rapidly in amphetamine abuse (i.e., a recreational amphetamine overdose), so periods of extended use require increasingly larger doses of the drug in order to achieve the same effect.[111][112]

Biomolecular mechanisms

Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain, particularly the nucleus accumbens.[113][114][115] The most important transcription factors[note 11] that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NF-κB).[114] ΔFosB plays a crucial role in the development of drug addictions, since its overexpression in D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient[note 12] for most of the behavioral and neural adaptations that arise from addiction.[99][100][114] Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression.[99][100] It has been implicated in addictions to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.[sources 7]

ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both directly oppose the induction of ΔFosB in the nucleus accumbens (i.e., they oppose increases in its expression).[100][114][119] Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).[114] ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[102][114][120] Since both natural rewards and addictive drugs induce expression 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.[102][114] Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sex addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use.[102][121][122] These sex addictions are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs.[102][120]

The effects of amphetamine on gene regulation are both dose- and route-dependent.[115] Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses.[115] The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor.[115] This suggests that medical use of amphetamine does not significantly affect gene regulation.[115]

Pharmacological treatments

更多信息：Addiction § Research

截至May 2014年 (May 2014-Missing required parameter 1=month!) there is no effective pharmacotherapy for amphetamine addiction.[123][124][125] Reviews from 2015 and 2016 indicated that TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions;[46][126] however, 截至February 2016年 (February 2016-Missing required parameter 1=month!) the only compounds which are known to function as TAAR1-selective agonists are experimental drugs.[46][126] Amphetamine addiction is largely mediated through increased activation of dopamine receptors and co-localized NMDA receptors[note 13] in the nucleus accumbens;[98] magnesium ions inhibit NMDA receptors by blocking the receptor calcium channel.[98][127] One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain.[98] Supplemental magnesium[note 14] treatment has been shown to reduce amphetamine self-administration (i.e., doses given to oneself) in humans, but it is not an effective monotherapy for amphetamine addiction.[98]

Behavioral treatments

Cognitive behavioral therapy is currently the most effective clinical treatment for psychostimulant addictions.[106] Additionally, research on the neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., marathon running), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction.[sources 5] Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions.[103][105][128] In particular, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D2 (DRD2) density in the striatum.[102][128] This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density.[102] One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of the reward system.[104]

Summary of addiction-related plasticity
神經可塑性和行為可塑性（英语：行為可塑性）的形式 增強物的種類 來源
鴉片類 中樞神經刺激劑 高脂肪或高糖食物 性交 運動與神經元關係 環境豐富化
伏隔核中D1-type中的ΔFosB表現 ↑ ↑ ↑ ↑ ↑ ↑ [102]
行為可塑性
攝取量的增加 有 有 有 [102]
中樞神經刺激劑跨越-敏化作用 有 不適用 有 有 削減 削減 [102]
未經過處方而自行私下攝取中樞神經刺激劑 ↑ ↑ ↓ ↓ ↓ [102]
強化「在特定地點攝取興奮劑的習慣」 ↑ ↑ ↓ ↑ ↓ ↑ [102]
強化「試圖取得該致癮藥物的行為」 ↑ ↑ ↓ ↓ [102]
神經化學物質的可塑性
伏隔核中CREB磷酸化 ↓ ↓ ↓ ↓ ↓ [102]
伏隔核中對於多巴胺的過敏反應 沒有 有 沒有 有 [102]
經過變動的紋狀體多巴胺接收器的訊號發送 ↓DRD2 , ↑DRD3（英语：DRD3） ↑DRD1（英语：DRD1）, ↓DRD2 , ↑DRD3（英语：DRD3） ↑DRD1（英语：DRD1）, ↓DRD2, ↑DRD3（英语：DRD3） ↑DRD2 ↑DRD2 [102]
經過變動的紋狀體鴉片样肽受体的訊號發送 未改變，或
↑μ-鴉片接收器（英语：μ-opioid receptor）		 ↑μ-鴉片接收器
↑κ-鴉片接收器（英语：κ-opioid receptor）		 ↑μ-鴉片接收器 ↑μ-鴉片接收器 未改變 未改變 [102]
發生於紋狀體鴉片肽的改變 ↑強啡肽（英语：dynorphin）
腦啡肽（英语：enkephalin）未改變		 ↑強啡肽 ↓腦啡肽 ↑強啡肽 ↑強啡肽 [102]
多巴胺通道的神經突觸的可塑性
伏隔核中树突的數量 ↓ ↑ ↑ [102]
伏隔核中樹突棘的密度 ↓ ↑ ↑ [102]

註解：DRD2 = 多巴胺受體D2；↑ = 上升；↓ = 下降



Dependence and withdrawal

According to another Cochrane Collaboration review on withdrawal 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."[129] This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.[129] Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams.[129] The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence.[129] Manufacturer prescribing information does not indicate the presence of withdrawal symptoms following discontinuation of amphetamine use after an extended period at therapeutic doses.[91][130][131]

Toxicity and psychosis

参见：Stimulant psychosis

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by dopamine terminal degeneration and reduced transporter and receptor function.[132][133] There is no evidence that amphetamine is directly neurotoxic in humans.[134][135] However, large doses of amphetamine may indirectly cause dopaminergic neurotoxicity as a result of hyperpyrexia, the excessive formation of reactive oxygen species, and increased autoxidation of dopamine.[sources 8] Animal models of neurotoxicity from high-dose amphetamine exposure indicate that the occurrence of hyperpyrexia (i.e., core body temperature ≥ 40 °C) is necessary for the development of amphetamine-induced neurotoxicity.[133] Prolonged elevations of brain temperature above 40 °C likely promote the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting cellular protein function, and transiently increasing blood–brain barrier permeability.[133]

A severe amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia.[35] A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely.[35][138] According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[35] Psychosis very rarely arises from therapeutic use.[36][89] }}

成癮

依賴和戒斷症狀

交互作用

藥學（Pharmacology）

藥效動力學（Pharmacodynamics）

藥物代謝動力學

安非他命的口服生物體可利用率[參 21]與腸胃的pH值連動； [139] 安非他命非常容易在腸道被吸收，dextroampetamine的生體可利用率在多數的情況下高於75%。 [2] 安非他命呈弱鹼性，其pKa值介於9–10之間;[4] 因此，當pH值呈鹼性時，多數的安非他命會以其易溶於脂類的純胺類型態（英语：free base）形式存在。在此情況下，身體會通過腸道上皮組織富含脂類的細胞膜[參 22]來吸收安非他命。 [4] [139] 相反地，酸性的pH值表示安非他命主要以易溶於水的離子[參 23]（鹽）形式存在，因此較少能被吸收。 [4] 大約15–40%循環於血管中的安非他命與血漿蛋白[參 24]相連接。 [3] 安非他命的對映異構物的半衰期會隨著尿液的pH值而有所不同。 [4] 當尿液的酸鹼值落在正常範圍中，dextroamphetamine和levoamphetamine的半衰期分別為9–11 小時及 11–14 小時。 [4] 酸性飲食會導致安非他命的對映異構物的半衰期降低至8–11 小時；鹼性飲食則會使安非他命的對映異構物的半衰期增加到16–31 小時。 [5][11]

成分為安非他命或其衍生物的短效藥品大約在口服後三小時在體內達到最高血漿濃度（英语：plasma concentration）；而成分為安非他命或其衍生物的長效藥品則在口服後大約七小時在體內達到最高血漿濃度。 [4]

安非他命主要透過腎臟來代謝，大約30–40%的藥物以藥物本身原始的型態從酸鹼度正常的尿液中排出。 [4] 當尿液是鹼性時，安非他命傾向以其純胺類型態存在，因此較少被排泄。 [4]

當尿液的pH值失常時，各種安非他命的分解物在尿液中重新結合的程度將從最低1%到最高75%。該程度的高低大多取決於於尿液的酸鹼值，尿液越酸，結合率越高；尿液愈鹼，結合率越低。 [4] 安非他命通常於口服後兩天內自體內完全代謝完畢。 [5] 安非他命確切的半衰期及藥效作用期隨著（小於兩天的）重複服用導致的血漿內安非他命濃度（plasma concentration of amphetamine）的增加而延長。[140]

對人體無藥效的前驅藥物體（prodrug）：lisdexamfetamine並不若安非他命一樣容易受腸胃道環境的pH值影響； [141] lisdexamfetamine在腸道被吸收進入血管的血液後很快就會透過水解（hydrolysis）的方式轉化為dextroamphetamine。而參與這水解反應的酶（enzymes）與紅血球有關。 [141]

Lisdexamfetamine的半衰期通常小於一個小時。 [141]

細胞色素 P450 2D6（Cytochrome P450 2D6、或CYP2D6）、多巴胺β羥化酶（Dopamine β-hydroxylase、或DBH）、flavin-containing monooxygenase 3（英语：flavin-containing monooxygenase 3）、butyrate-CoA ligase（英语：butyrate-CoA ligase）、和 glycine N-acyltransferase（英语：glycine N-acyltransferase）為已知在人體中參與[註 3]「安非他命」及「安非他命代謝後之產物」的代謝反應的酶（enzyme）。 [sources 9]

「安非他命代謝後之產物」包含：4-hydroxyamphetamine（英语：4-hydroxyamphetamine）、4-hydroxynorephedrine（英语：4-hydroxynorephedrine）、4-hydroxyphenylacetone（英语：4-hydroxyphenylacetone）、苯甲酸（benzoic acid）、馬尿酸（hippuric acid）、苯丙醇胺（norephedrine）、苯基丙酮（phenylacetone）[註 4] [4] [5] [6]。

在這些「安非他命代謝後之產物」之中，有實際藥效的產物（sympathomimetics）為：4‑hydroxyamphetamine[144]、4‑hydroxynorephedrine[145]、和norephedrine[146]。

安非他命的主要代謝途徑包含：aromatic para-hydroxylation、aliphatic alpha- 、beta-hydroxylation、N-oxidation、N-dealkylation、和 deamination。 [4][5]

下圖為已知的「安非他命」代謝途徑和「安非他命代謝後之產物」： [4][16][6]

苯丙胺的代謝途徑
Graphic of several routes of amphetamine metabolism
苯丙胺
Para-
Hydroxylation
Para-
Hydroxylation
Para-
Hydroxylation
Beta-
Hydroxylation
Beta-
Hydroxylation
Oxidative
Deamination
Oxidation
Glycine
Conjugation
图像顶端包含可点击的链接
在這些「安非他命代謝後之產物」之中，主要的且有實際藥效的產物為：4-hydroxyamphetamine 和去甲麻黃鹼（norephedrine）。[6]

從酸鹼度正常的尿液中可發現，大約30–40%的「安非他命」以本身原始的型態排出；大約50%的安非他命以不具藥效的「安非他命代謝後之產物」（即為圖片中最下列的產物）的型態排出。 [4]

剩下的10–20%則為「安非他命代謝後之產物」之中，有實際藥效的產物。 [4]

苯甲酸（Benzoic acid）被butyrate-CoA連接酶（butyrate-CoA ligase）代謝後成為一個中介物質/中間產物（intermediate product）：benzoyl-CoA（英语：benzoyl-CoA） [142]

隨後透過glycine N-acyltransferase代謝並轉化為馬尿酸（hippuric acid）。[143]

相關的內部生成化合物/混和物（endogenous compound）

歷史、社會與文化

合法狀態與條件

藥品

備註A

  1. ^ 别名有：1-phenylpropan-2-amine (IUPAC name), α-methylbenzeneethanamine, α-methylphenethylamine, amfetamine (International Nonproprietary Name [INN]), β-phenylisopropylamine, desoxynorephedrine, and speed.[18][21][22]
  2. ^ 對映異構體指的是兩個形狀相同但方向相反的兩個分子，他們又稱為彼此的鏡中影像。[23] Levoamphetamine 和 dextroamphetamine 分別被簡稱為 L-amph 或 levamfetamine (INN) 和 D-amph 或 dexamfetamine (INN) [18]
  3. ^ "Adderall"是一個品牌名稱。因為以下幾個安非他命的異構物的英文名稱太長了：("dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate, and amphetamine aspartate")，因此本文單獨以此名稱來表示此安非他命的此種混合物。
    原文對照："Adderall" is a brand name as opposed to a nonproprietary name; because the latter ("dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate, and amphetamine aspartate" [44]) is excessively long, this article exclusively refers to this amphetamine mixture by the brand name.
  4. ^ 「安非他命」一詞也意指一個化學分類，但與「替代性安非他命」這個化學分類不同的是，「安非他命」類在學術上並無標準的定義。 [13][25] 有一個「安非他命」類的定義嚴格限定分類中僅有：安非他命的racemate and enantiomers 和 甲基安非他命methamphetamine的racemate and enantiomers。 [25] 大多數「安非他命」類的定義為那些在藥理學上以及結構上與安非他命相關的化合物。 [25]
    為避免讓amphetamine 和 amphetamines 把讀者給弄糊塗了，本條目中僅會使用amphetamine、amphetamines來表示racemic amphetamine, levoamphetamine, and dextroamphetamine；‘替代性安非他命（substituted amphetamines）’來表示安非他命的結構分類。
    原文對照： Due to confusion that may arise from use of the plural form, this article will only use the terms "amphetamine" and "amphetamines" to refer to racemic amphetamine, levoamphetamine, and dextroamphetamine and reserve the term "substituted amphetamines" for its structural class.
  5. ^ 研究證實，長期以中樞神經興奮劑治療ADHD能在下列這些方面產生大幅的進步：學業、駕駛、降低藥物濫用、降低肥胖、自尊、和社交功能等。 [57]

    在上述領域中，最為突出的領域為： 學業（例如：GPA分數 grade point average、成果測驗分數 achievement test scores、受教育的時間長度 length of education、和教育程度 education level） 、自尊（例如：自尊心測驗分數 self-esteem questionnaire assessments、嘗試自殺的次數、自殺率等） 和社交功能（例如：peer nomination scores、社交技巧、家庭關係 quality of family、同儕關係 quality of peer、和浪漫關係/情侶關係 romantic relationships） [57]

    長期以「藥物治療合併行為治療」的模式來治療ADHD，能夠比單獨以藥物治療，產生更全面且更長足的進步。 [57]
  6. ^ 考科藍協作組織對於歷年眾多的「隨機對照試驗」的系統性回顧、數據統整分析後所得出的總結，基本上都是非常有水準且深具參考價值的。 [64]
  7. ^ 美國食品藥物管理局核准的藥品使用指引及醫療上的禁忌（放在藥盒中的仿單/說明書）並非為了限制醫師的決策而是為了避免藥商恣意宣稱藥物的作用。醫師可以此為參考，並依照每位病人的實際情況做出獨立的判斷。 [88]
  8. ^ 然而根據一篇回顧性論文，安非他命可以處方給曾有藥物濫用歷史的人，不過需要有對患者適度的藥品控管，例如：每天由醫護人員配給處方劑量。[1]
  9. ^ 曾受此副作用的用藥者，身高及體重在在短暫停藥後恢復至應有水準是可以被預期的。[56][58][94] 根據追蹤，持續三年過程不停歇的安非他命治療（沒有合併任何積極減少安非他命副作用的療法的情況下）平均會減少 2公分的最終身高。 [94]
  10. ^ 「95% 信賴區間」指的是：有95%的機率，真實的死亡人數介於3,425 和 4,145 之間。
  11. ^ Transcription factors are proteins that increase or decrease the expression of specific genes.[116]
  12. ^ 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.
  13. ^ 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.[127]
  14. ^ The review indicated that magnesium L-aspartate and magnesium chloride produce significant changes in addictive behavior;[98] other forms of magnesium were not mentioned.

備註B

  1. ^ 智力測驗結果與專注力有關，詳見注意力不足過動症#智力
  2. ^ 因成癮所致的行為
  3. ^ 酶做為反應的催化劑catalyst，並不實際參與反應。
  4. ^ 不是苯丙酮

注释

  1. ^ 安非他命乃春藥的其中一種
  2. ^ 又稱為「隨機分配且包含控制組的臨床試驗」，是臨床試驗的一種
  3. ^ 中樞神經興奮劑的一種

英文名稱對照

  1. ^ 英文名稱為：delusions
  2. ^ 英文名稱為：paranoia
  3. ^ 英文名稱為：Prescription drug
  4. ^ 英文名稱為：Pharmaceutical amphetamine
  5. ^ 英文名稱為：racemic amphetamine
  6. ^ 英文名稱為：Prodrug
  7. ^ 英文名稱為：substituted amphetamine
  8. ^ 英文名稱為：Bupropion
  9. ^ 英文名稱為：meth-amphetamine
  10. ^ 英文名稱為：Randomized controlled trials
  11. ^ 英文名稱為：follow-up studies
  12. ^ 英文名稱為：neurotransmitter systems
  13. ^ 英文名稱為：dopamine
  14. ^ 英文名稱為：locus coeruleus
  15. ^ 英文名稱為：prefrontal cortex
  16. ^ 英文名稱為：nor-epinephrine或nor-adrenaline
  17. ^ 英文名稱為：Cochrane Collaboration
  18. ^ 英文名稱為：systematic review
  19. ^ 英文名稱為：meta-analysis
  20. ^ 英文名稱為：臨床試驗
  21. ^ 英文名稱為：bioavailability
  22. ^ 英文名稱為：cell membrane
  23. ^ 英文名稱為：cation
  24. ^ 英文名稱為：plasma protein

引用

  1. ^ [10][29][30][31][32][33][34][35][36][37][38][39]
  2. ^ [1][25] [29] [30] [31] [40] [41] [42] [32] [26] [24][43]
  3. ^ [1] [10] [29] [40] [43] [45] [46]
  4. ^ [47] [48] [49]
  5. ^ 5.0 5.1 [102][103][104][105][128]
  6. ^ [22][31][34][95][107]
  7. ^ [99][102][114][117][118]
  8. ^ [51][133][136][137]
  9. ^ [4][13] [14] [15] [16] [17] [142] [143]

來源

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    Dexedrine [Peak:2–3 h] [Duration:5–6 h] ...
    Adderall [Peak:2–3 h] [Duration:5–7 h]
    Dexedrine spansules [Peak:7–8 h] [Duration:12 h] ...
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    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.     
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    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     
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參見

外部連結

维基共享资源中相关的多媒体资源：苯丙胺
维基共享资源上的相关多媒体资源：Category:Amphetamine


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