Editing Amphetamine (section)

====Indications====

=====ADHD=====
Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal [[Dopamine receptor|dopamine system]] development or nerve damage,<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=Archives of Toxicology|volume=86 |issue=8 |pages=1167–1231 |date=August 2012 |pmid=22392347 |doi=10.1007/s00204-012-0815-5|bibcode=2012ArTox..86.1167C |s2cid=2873101 }}</ref><ref name="AbuseAndAbnormalities">{{cite journal|vauthors=Berman S, O'Neill J, Fears S, Bartzokis G, London ED | title=Abuse of amphetamines and structural abnormalities in the brain | journal=Annals of the New York Academy of Sciences| date = October 2008 | volume= 1141 | issue=1 | pages= 195–220 | pmid=18991959 | doi=10.1196/annals.1441.031 | pmc=2769923 | bibcode=<!-- No --> }}</ref> but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth.<ref name="Neuroplasticity 1">{{cite journal |vauthors=Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K |title=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 |journal=JAMA Psychiatry|volume=70 |issue=2 |pages=185–198 |date=February 2013 |pmid=23247506 |doi=10.1001/jamapsychiatry.2013.277|doi-access=free | title-link = doi }}</ref><ref name="Neuroplasticity 2">{{cite journal |vauthors=Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J |title=Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies |journal=The Journal of Clinical Psychiatry|volume=74 |issue=9 |pages=902–917 |date=September 2013 |pmid=24107764 |doi=10.4088/JCP.12r08287 |pmc=3801446}}</ref><ref name="Neuroplasticity 3">{{cite journal | title=Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects | journal=Acta Psychiatrica Scandinavica| date=February 2012 | volume=125 | issue=2 | pages=114–126 | pmid=22118249 |vauthors=Frodl T, Skokauskas N | quote = Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure. | doi=10.1111/j.1600-0447.2011.01786.x| s2cid=25954331| doi-access=free | title-link = doi }}</ref> Reviews of [[magnetic resonance imaging]] (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right [[caudate nucleus]] of the [[basal ganglia]].<ref name="Neuroplasticity 1" /><ref name="Neuroplasticity 2" /><ref name="Neuroplasticity 3" />

Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD.<ref name="Long-Term Outcomes Medications">{{cite journal |vauthors=Huang YS, Tsai MH | title = Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge | journal =CNS Drugs| volume = 25 | issue = 7 | pages = 539–554 |date=July 2011 | pmid = 21699268 | doi = 10.2165/11589380-000000000-00000 | s2cid = 3449435 | quote = Several other studies,<sup>[97-101]</sup> including a meta-analytic review<sup>[98]</sup> and a retrospective study,<sup>[97]</sup> suggested that stimulant therapy in childhood is associated with a reduced risk of subsequent substance use, cigarette smoking and alcohol use disorders.&nbsp;... Recent studies have demonstrated that stimulants, along with the non-stimulants atomoxetine and extended-release guanfacine, are continuously effective for more than 2-year treatment periods with few and tolerable adverse effects. The effectiveness of long-term therapy includes not only the core symptoms of ADHD, but also improved [[quality of life]] and academic achievements. The most concerning short-term adverse effects of stimulants, such as elevated blood pressure and heart rate, waned in long-term follow-up studies.&nbsp;... The current data do not support the potential impact of stimulants on the worsening or development of tics or substance abuse into adulthood. In the longest follow-up study (of more than 10&nbsp;years), lifetime stimulant treatment for ADHD was effective and protective against the development of adverse psychiatric disorders.}}</ref><ref name="Millichap" /><ref name="Long-term 2015">{{cite journal | vauthors = Arnold LE, Hodgkins P, Caci H, Kahle J, Young S | title = Effect of treatment modality on long-term outcomes in attention-deficit/hyperactivity disorder: a systematic review | journal =PLOS ONE| volume = 10 | issue = 2 | pages = e0116407 | date = February 2015 | pmid = 25714373 | pmc = 4340791 | doi = 10.1371/journal.pone.0116407 | quote = The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes.| bibcode = <!-- No --> | doi-access = free | title-link = doi }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340791/figure/pone.0116407.g003/ Figure 3: Treatment benefit by treatment type and outcome group]</ref> [[Randomized controlled trial]]s of continuous stimulant therapy for the treatment of ADHD spanning 2&nbsp;years have demonstrated treatment effectiveness and safety.<ref name="Long-Term Outcomes Medications" /><ref name="Millichap" /> Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing [[quality of life]] and academic achievement, and producing improvements in a large number of functional outcomes{{#tag:ref|The ADHD-related outcome domains with the greatest proportion of significantly improved outcomes from long-term continuous stimulant therapy include academics (≈55% of academic outcomes improved), driving (100% of driving outcomes improved), non-medical drug use (47% of addiction-related outcomes improved), obesity (≈65% of obesity-related outcomes improved), self-esteem (50% of self-esteem outcomes improved), and social function (67% of social function outcomes improved).<ref name="Long-term 2015" /><br /><br />The largest [[effect size]]s for outcome improvements from long-term stimulant therapy occur in the domains involving academics (e.g., [[grade point average]], achievement test scores, length of education, and education level), self-esteem (e.g., self-esteem questionnaire assessments, number of suicide attempts, and suicide rates), and social function (e.g., peer nomination scores, social skills, and quality of peer, family, and romantic relationships).<ref name="Long-term 2015" /><br /><br />Long-term combination therapy for ADHD (i.e., treatment with both a stimulant and behavioral therapy) produces even larger effect sizes for outcome improvements and improves a larger proportion of outcomes across each domain compared to long-term stimulant therapy alone.<ref name="Long-term 2015" /> These findings were further supported by a 2025 review of interventions for adolescents, which concluded that medications and cognitive-behavioral treatments (CBT) provide complementary benefits. Medications demonstrated strong short-term efficacy on core symptoms, while CBT contributed modest to strong, and sometimes long-lasting, improvements in functional impairments and executive skills when used as part of combination therapy.<ref>{{cite journal | vauthors = Sibley MH, Flores S, Murphy M, Basu H, Stein MA, Evans SW, Zhao X, Manzano M, van Dreel S | title = Research Review: Pharmacological and non-pharmacological treatments for adolescents with attention deficit/hyperactivity disorder - a systematic review of the literature | journal = Journal of Child Psychology and Psychiatry, and Allied Disciplines | volume = 66 | issue = 1 | pages = 132–149 | date = January 2025 | pmid = 39370392 | doi = 10.1111/jcpp.14056 | quote = The main efficacy-related conclusions of this review are: (a) medications demonstrated the strongest and most consistent effects on core ADHD symptoms (especially inattention), (b) heterogeneous C/BTs demonstrated inconsistent effects on ADHD symptoms, strong consistent effects on impairment and executive function skills, and modest consistent effects on internalizing symptoms and analogue note-taking performance, (c) C/BTs demonstrated consistent maintenance effects for executive function skills and impairment up to 6 months and possibly 3 years post-treatment, (d) though comparing the efficacy of two C/BTs rarely led to significant differences, which C/BT worked best for whom could be reliably predicted from patient- and provider-level moderators&nbsp;...<br />Thus, maximal therapeutic benefit (in terms of breadth of response and maintenance of effects) might be achieved by combining medication and C/BTs, a recommendation generally reflected in current practice parameters (AACAP, 2007; AADPA, 2022; NICE, 2018; Wolraich et al., 2019). }}</ref>|group="note"}} across 9&nbsp;categories of outcomes related to academics, [[Anti-social behaviour|antisocial behavior]], driving, non-medicinal drug use, obesity, occupation, [[self-esteem]], service use (i.e., academic, occupational, health, financial, and legal services), and social function.<ref name="Long-Term Outcomes Medications" /><ref name="Long-term 2015" /> Additionally, a 2024 [[Meta-analysis|meta-analytic]] [[systematic review]] reported moderate improvements in quality of life when amphetamine treatment is used for ADHD.<ref name="2024 QOL meta-analysis">{{Cite journal |vauthors=Bellato A, Perrott NJ, Marzulli L, Parlatini V, Coghill D, Cortese S |date=30 May 2024 |title=Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life |journal=Journal of the American Academy of Child and Adolescent Psychiatry |pages=S0890–8567(24)00304–6 |doi=10.1016/j.jaac.2024.05.023 |pmid=38823477 |quote=We conducted the first systematic review and meta-analysis investigating the effects of medication for ADHD on quality of life (QoL) in parallel or crossover RCTs. Overall, we found that methylphenidate, amphetamines, and atomoxetine were significantly more efficacious than placebo in improving QoL in people with ADHD.&nbsp;...<br /> Four studies on amphetamines (950 participants with ADHD in total; 45% adults) reported relevant data for effect sizes to be computed. The meta-analysis on 14 effect sizes showed that amphetamines led to better QoL than placebo in individuals with ADHD. |doi-access=free | title-link = doi |volume=64 |issue=3 |hdl=11586/524122 |hdl-access=free }}</ref> One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5&nbsp;[[intelligence quotient|IQ]] points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.<ref name="Millichap">{{cite book | vauthors = Millichap JG | veditors = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York, US | isbn = 9781441913968 | pages = 121–123, 125–127 | edition = 2nd | chapter = Chapter 9: Medications for ADHD | quote = Ongoing research has provided answers to many of the parents' concerns, and has confirmed the effectiveness and safety of the long-term use of medication.}}</ref> Another review indicated that, based upon the longest [[Prospective cohort study|follow-up studies]] conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a [[substance use disorder]] as an adult.<ref name="Long-Term Outcomes Medications" /> 

Models of ADHD suggest that it is associated with functional impairments in some of the brain's [[neurotransmitter systems]];<ref name="Malenka_2009_03" /> these functional impairments involve impaired [[dopamine]] neurotransmission in the [[mesocorticolimbic projection]] and [[norepinephrine]] neurotransmission in the noradrenergic projections from the [[locus coeruleus]] to the [[prefrontal cortex]].<ref name="Malenka_2009_03" /> Stimulants like [[methylphenidate]] and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems.<ref name="Malenka_2009" /><ref name="Malenka_2009_03">{{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, US | isbn = 9780071481274 | pages = 154–157 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin }}</ref><ref name="cognition enhancers">{{cite journal |vauthors=Bidwell LC, McClernon FJ, Kollins SH | title = Cognitive enhancers for the treatment of ADHD | journal =Pharmacology Biochemistry and Behavior| volume = 99 | issue = 2 | pages = 262–274 |date=August 2011 | pmid = 21596055 | pmc = 3353150 | doi = 10.1016/j.pbb.2011.05.002 }}</ref> Approximately 80% of those who use these stimulants see improvements in ADHD symptoms.<ref name="Long-term 36">{{cite journal | vauthors = Parker J, Wales G, Chalhoub N, Harpin V | title = 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 | journal =Psychology Research and Behavior Management| volume = 6 | pages = 87–99 | date = September 2013 | pmid = 24082796 | pmc = 3785407 | doi = 10.2147/PRBM.S49114 | quote = Only one paper<sup>53</sup> examining outcomes beyond 36 months met the review criteria.&nbsp;... 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. | doi-access = free | title-link = doi }}</ref> Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans.<ref name="Millichap_3">{{cite book | vauthors = Millichap JG | veditors = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York, US | isbn = 9781441913968 | pages = 111–113 | edition = 2nd | chapter = Chapter 9: Medications for ADHD}}</ref><ref name="ADHD">{{cite web | title=Stimulants for Attention Deficit Hyperactivity Disorder | url=http://www.webmd.com/add-adhd/childhood-adhd/stimulants-for-attention-deficit-hyperactivity-disorder | website = WebMD | publisher = Healthwise | date = 12 April 2010 | access-date=12 November 2013 }}</ref> The [[Cochrane (organisation)|Cochrane]] reviews{{#tag:ref|Cochrane reviews are high quality meta-analytic systematic reviews of randomized controlled trials.<ref name="pmid16052183">{{cite journal |vauthors=Scholten RJ, Clarke M, Hetherington J |title=The Cochrane Collaboration |journal=European Journal of Clinical Nutrition|volume=59 |issue=Suppl 1 |pages=S147–S149; discussion S195–S196 |date=August 2005 |pmid=16052183 |doi=10.1038/sj.ejcn.1602188|s2cid=29410060 |doi-access=free | title-link = doi }}</ref>| group = "note" }} on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse [[side effect]]s.<ref name="Cochrane Amphetamines ADHD">{{cite journal | vauthors = Castells X, Blanco-Silvente L, Cunill R | title = Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults | journal =Cochrane Database of Systematic Reviews| volume = 2018 | pages = CD007813 | date = August 2018 | issue = 8 | pmid = 30091808 | doi = 10.1002/14651858.CD007813.pub3 | pmc = 6513464 }}</ref><ref name="pmid26844979">{{cite journal | vauthors = Punja S, Shamseer L, Hartling L, Urichuk L, Vandermeer B, Nikles J, Vohra S | title = Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents | journal =Cochrane Database of Systematic Reviews| volume = 2016 | pages = CD009996 | date = February 2016 | issue = 2 | pmid = 26844979 | doi = 10.1002/14651858.CD009996.pub2| pmc = 10329868 }}</ref> However, a 2025 meta-analytic systematic review of 113 randomized controlled trials found that stimulant medications were the only intervention with robust short-term efficacy, and were associated with lower all-cause treatment [[discontinuation]] rates than non-stimulant medications (e.g., [[atomoxetine]]).{{#tag:ref|In contrast to the Cochrane reviews that observed higher treatment discontinuation from adverse effects alone, this figure represents '''any cause''' of discontinuation (e.g., insufficient perceived treatment benefit).<ref name="2025_113_RCTs" /> |name="all-cause discontinuation"|group="note"}}<ref name="2025_113_RCTs">{{Cite journal |vauthors=Ostinelli EG, Schulze M, Zangani C, Farhat LC, Tomlinson A, Del Giovane C, Chamberlain SR, Philipsen A, Young S, Cowen PJ, Bilbow A, Cipriani A, Cortese S |year=2025 |title=Comparative efficacy and acceptability of pharmacological, psychological, and neurostimulatory interventions for ADHD in adults: a systematic review and component network meta-analysis |journal=The Lancet. Psychiatry |volume=12 |issue=1 |pages=32–43 |doi=10.1016/S2215-0366(24)00360-2 |pmid=39701638 |quote=Our findings were based on 113 RCTs, including 14 887 participants, and indicated that stimulants were the only intervention that was supported by evidence of efficacy in the short term (ie, at timepoints closest to 12 weeks) for core symptoms of ADHD in adults (both self-reported and clinician-reported) and was associated with good acceptability (all-cause discontinuation). |doi-access=free |title-link=doi}}</ref> A Cochrane review on the treatment of ADHD in children with [[tic disorder]]s such as [[Tourette syndrome]] indicated that stimulants in general do not make [[tic]]s worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.<ref name="pmid29944175">{{cite journal | vauthors = Osland ST, Steeves TD, Pringsheim T | title = Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders | journal =Cochrane Database of Systematic Reviews| volume = 2018 | pages = CD007990 | date = June 2018 | issue = 6 | pmid = 29944175 | pmc = 6513283 | doi = 10.1002/14651858.CD007990.pub3 }}</ref>
<!-- section end:ADHD -->
<!-- Section begin:BED -->

=====Binge eating disorder=====
<!-- BED content is not transcluded to Adderall and dextroamphetamine articles because unlike LDX, those formulations are not recognised their use in treating BED -->
[[Binge eating disorder]] (BED) is characterized by recurrent and persistent episodes of compulsive binge eating.<ref name="BED definition">{{cite journal | vauthors = Giel KE, Bulik CM, Fernandez-Aranda F, Hay P, Keski-Rahkonen A, Schag K, Schmidt U, Zipfel S | title = Binge eating disorder | journal = Nature Reviews. Disease Primers | volume = 8 | issue = 1 | pages = 16 | date = March 2022 | pmid = 35301358 | pmc = 9793802 | doi = 10.1038/s41572-022-00344-y }}</ref> These episodes are often accompanied by marked distress and a feeling of loss of control over eating.<ref name="BED definition" /> The [[pathophysiology]] of BED is not fully understood, but it is believed to involve dysfunctional dopaminergic reward circuitry along the [[Cortico-basal ganglia-thalamo-cortical loop|cortico-striatal-thalamic-cortical loop]].<ref name="BED ADHD overlap">{{cite journal | vauthors = Heal DJ, Smith SL | title = Prospects for new drugs to treat binge-eating disorder: Insights from psychopathology and neuropharmacology | journal = Journal of Psychopharmacology | volume = 36 | issue = 6 | pages = 680–703 | date = June 2022 | pmid = 34318734 | pmc = 9150143 | doi = 10.1177/02698811211032475 | quote = BED subjects have substantial decrements in their ventral striatal reward pathways and diminished ability to recruit fronto-cortical impulse-control circuits to implement dietary restraint.&nbsp;...<br /> There is not only substantial overlap between the psychopathology of BED and ADHD but also a clear association between these two disorders. Lisdexamfetamine's ability to reduce impulsivity and increase cognitive control in ADHD supports the hypothesis that efficacy in BED is dependent on treating its core obsessive, compulsive and impulsive behaviours. }}</ref><ref name="BED secondary outcomes">{{cite journal | vauthors = McElroy SL | title = Pharmacologic Treatments for Binge-Eating Disorder | journal = The Journal of Clinical Psychiatry | volume = 78 | issue = Suppl 1 | pages = 14–19 | date = 2017 | pmid = 28125174 | doi = 10.4088/JCP.sh16003su1c.03 | quote = Genetic polymorphisms associated with abnormal dopaminergic signaling have been found in individuals who exhibit binge-eating behavior, and the binge-eating episodes, which often involve the consumption of highly palatable food, further stimulate the dopaminergic system. This ongoing stimulation may contribute to progressive impairments in dopamine signaling. Lisdexamfetamine is hypothesized to reduce binge-eating behavior by normalizing dopaminergic activity.&nbsp;...<br /> After 12 weeks, both studies found significant reductions in the number of binge-eating days per week in the active treatment group compared with placebo (P < .001 for both studies; Figure 1). Lisdexamfetamine was also found to be superior to placebo on a number of secondary outcome measures including global improvement, binge-eating cessation for 4 weeks, and reduction of obsessive-compulsive binge-eating symptoms, body weight, and triglycerides. }}</ref> As of July 2024, lisdexamfetamine is the only [[Food and Drug Administration|USFDA]]- and [[Therapeutic Goods Administration|TGA]]-approved [[pharmacotherapy]] for BED.<ref name="BED rapid review">{{cite journal | vauthors = Rodan SC, Bryant E, Le A, Maloney D, Touyz S, McGregor IS, Maguire S | title = Pharmacotherapy, alternative and adjunctive therapies for eating disorders: findings from a rapid review | journal = Journal of Eating Disorders | volume = 11 | issue = 1 | pages = 112 | date = July 2023 | pmid = 37415200 | pmc = 10327007 | doi = 10.1186/s40337-023-00833-9 | quote = LDX is commonly used in the treatment of ADHD, and is the only treatment for BED that is approved by the Food and Drug Administration (FDA) and the Therapeutic Goods Administration (TGA). LDX, like all amphetamine stimulants, has direct appetite suppressant effects that may be therapeutically useful in BED, although long-term neuroadaptations in dopaminergic and noradrenergic systems caused by LDX may also be relevant, leading to improved regulation of eating behaviours, attentional processes and goal-directed behaviours.&nbsp;...<br /> Evidently, there is a substantial volume of trials with high-quality evidence supporting the efficacy of LDX in reducing binge eating frequency in treatment of adults with moderate to severe BED at 50–70 mg/day. | doi-access = free | title-link = doi }}</ref><ref name="BED neuroplasticity">{{cite journal | vauthors = Boswell RG, Potenza MN, Grilo CM | title = The Neurobiology of Binge-eating Disorder Compared with Obesity: Implications for Differential Therapeutics | journal = Clinical Therapeutics | volume = 43 | issue = 1 | pages = 50–69 | date = January 2021 | pmid = 33257092 | pmc = 7902428 | doi = 10.1016/j.clinthera.2020.10.014 | quote = Stimulant medications may be especially effective for individuals with BED because of dual effects on reward and executive function systems. Indeed, the only FDA-approved pharmacotherapy for BED is LDX, a d-amphetamine prodrug.&nbsp;...<br /> In humans, RCTs found that LDX reduced binge eating and impulsivity/compulsivity symptoms. Notably, there is a strong correlation between compulsivity symptoms and severity/frequency of binge eating episodes observed in LDX trials. Further, in individuals with BED, changes in prefrontal brain systems associated with LDX treatment were related to treatment outcome. }}</ref> Evidence suggests that lisdexamfetamine's treatment efficacy in BED is underpinned at least in part by a [[Psychopathology|psychopathological]] overlap between BED and ADHD, with the latter conceptualized as a [[Executive functions|cognitive control]] disorder that also benefits from treatment with lisdexamfetamine.<ref name="BED ADHD overlap" /><ref name="BED secondary outcomes" />

[[File:TAAR1 organ-specific expression and function.jpg|class=skin-invert-image|thumb|right|370px|alt=Diagram of TAAR1 organ-specific expression and function|This diagram illustrates how [[TAAR1]] activation induces [[incretin]]-like effects through the release of gastrointestinal hormones and influences food intake, [[blood glucose]] levels, and [[insulin]] release.<ref name="Berry hTAAR pharmacology December 2017 review" /> TAAR1 expression in the periphery is indicated with "x".<ref name="Berry hTAAR pharmacology December 2017 review" />]]

Lisdexamfetamine's therapeutic effects for BED primarily involve direct action in the [[central nervous system]] after conversion to its pharmacologically active metabolite, dextroamphetamine.<ref name="BED neuroplasticity" /> Centrally, dextroamphetamine increases neurotransmitter activity of dopamine and norepinephrine in prefrontal cortical regions that regulate cognitive control of behavior.<ref name="BED ADHD overlap" /><ref name="BED neuroplasticity" /> Similar to its therapeutic effect in ADHD, dextroamphetamine enhances cognitive control and may reduce impulsivity in patients with BED by enhancing the cognitive processes responsible for overriding [[prepotent responses|prepotent feeding responses]] that precede binge eating episodes.<ref name="BED ADHD overlap" /><ref>{{Cite book |title=Molecular neuropharmacology: a foundation for clinical neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE, Holtzman DM |publisher=McGraw-Hill Medical |year=2015 |isbn=9780071827706 |edition=3rd |location=New York |chapter=Chapter 14: Higher Cognitive Function and Behavioral Control |quote=Because behavioral responses in humans are not rigidly dictated by sensory inputs and drives, behavioral responses can instead be guided in accordance with short- or long-term goals, prior experience, and the environmental context. The response to a delicious-looking dessert is different depending on whether a person is alone staring into his or her refrigerator, is at a formal dinner party attended by his or her punctilious boss, or has just formulated the goal of losing 10 lb.&nbsp;...<br /> Adaptive responses depend on the ability to inhibit automatic or prepotent responses (eg, to ravenously eat the dessert or run from the snake) given certain social or environmental contexts or chosen goals and, in those circumstances, to select more appropriate responses. In conditions in which prepotent responses tend to dominate behavior, such as in drug addiction, where drug cues can elicit drug seeking (Chapter 16), or inattention deficit hyperactivity disorder (ADHD; described below), significant negative consequences can result.}}</ref><ref name="BED systematic review">{{cite journal | vauthors = Schneider E, Higgs S, Dourish CT | title = Lisdexamfetamine and binge-eating disorder: A systematic review and meta-analysis of the preclinical and clinical data with a focus on mechanism of drug action in treating the disorder | journal = European Neuropsychopharmacology | volume = 53 | pages = 49–78 | date = December 2021 | pmid = 34461386 | doi = 10.1016/j.euroneuro.2021.08.001 | url = http://pure-oai.bham.ac.uk/ws/files/147133958/LDX_final_pure.pdf | quote = Our meta-analysis of the four RCT data sets (Guerdjikova et al., 2016; McElroy et al., 2015b; McElroy et al., 2016a) showed an overall significant effect of LDX on binge-eating symptom change.&nbsp;...<br /> BED has been described as an impulse control disorder since one of the key symptoms of the disorder is a lack of control over eating (American Psychiatric Association, 2013) and it is possible that LDX may be effective in treating BED at least in part by reducing impulsivity, compulsivity, and the repetitive nature of binge eating. There is extensive evidence that loss of impulse control in BED is a causal factor in provoking bingeing symptoms (Colles et al., 2008; Galanti et al., 2007; Giel et al., 2017; McElroy et al., 2016a; Nasser et al., 2004; Schag et al., 2013). More specifically, BED is associated with motor impulsivity and non-planning impulsivity which could initiate and maintain binge eating (Nasser et al., 2004). Neuroimaging studies using the Stroop task to measure impulse control have shown that BED patients have decreased BOLD fMRI activity in brain areas involved in self-regulation and impulse control including VMPFC, inferior frontal gyrus (IFG), and insula during performance of the task compared to lean and obese controls (Balodis et al., 2013b).&nbsp;...<br /> It is conceivable that in BED patients a low 30 mg dose of LDX could reduce food intake by suppressing appetite or enhancing satiety and higher (50 and 70 mg) doses of the drug may have a dual suppressant effect on food intake and binge-eating frequency. }}</ref> In addition, dextroamphetamine's actions outside of the central nervous system may also contribute to its treatment effects in BED. Peripherally, dextroamphetamine triggers [[lipolysis]] through noradrenergic signaling in [[Adipose tissue|adipose fat]] cells, leading to the release of [[triglyceride]]s into blood plasma to be utilized as a fuel substrate.<ref name="BED secondary outcomes" /><ref>{{cite journal | vauthors = Branis NM, Wittlin SD | title = Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis | journal = Case Reports in Endocrinology | volume = 2015 | pages = 917869 | date = 2015 | pmid = 25960894 | pmc = 4417573 | doi = 10.1155/2015/917869 | quote = Peripheral norepinephrine concentration rises as well. As demonstrated after Dextroamphetamine administration, plasma norepinephrine can rise up to 400 pg/mL, a level comparable to that achieved during mild physical activity. Cumulative effect on norepinephrine concentration is likely when amphetamine-type medications are given in the setting of acute illness or combined with activities leading to catecholamine release, such as exercise.&nbsp;... The primary effect of norepinephrine on ketogenesis is mediated through increased substrate availability. As shown by Krentz et al., at high physiological concentrations, norepinephrine induces accelerated lipolysis and increases NEFA formation significantly. Secondly, norepinephrine stimulates ketogenesis directly at the hepatocyte level. As reported by Keller et al., norepinephrine infusion increased ketone bodies concentration to a greater degree when compared to NEFA concentration (155 ± 30 versus 57 ± 16%), suggesting direct hepatic ketogenic effect. | doi-access = free | title-link = doi }}</ref> Dextroamphetamine also activates [[TAAR1]] in peripheral organs along the [[gastrointestinal tract]] that are involved in the regulation of food intake and body weight.<ref name="Berry hTAAR pharmacology December 2017 review">{{cite journal | vauthors = Berry MD, Gainetdinov RR, Hoener MC, Shahid M | title = Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges | journal = Pharmacology & Therapeutics | volume = 180 | pages = 161–180 | date = December 2017 | pmid = 28723415 | doi = 10.1016/j.pharmthera.2017.07.002 | doi-access = free | title-link = doi }}</ref> Together, these actions confer an [[anorexigenic]] effect that promotes [[satiety]] in response to feeding and may decrease binge eating as a secondary effect.<ref name="BED systematic review" /><ref name="Berry hTAAR pharmacology December 2017 review" /> While lisdexamfetamine's anorexigenic effects contribute to its efficacy in BED, evidence indicates that the enhancement of cognitive control is [[necessary and sufficient]] for addressing the disorder's underlying psychopathology.<ref name="BED ADHD overlap"/><ref name="Heal 2024 BED">{{Cite book |vauthors=Heal DJ, Gosden J, Smith SL |title=Pharmacological Advances in Central Nervous System Stimulants |date=2024 |chapter=Stimulant prodrugs: A pharmacological and clinical assessment of their role in treating ADHD and binge-eating disorder |chapter-url=https://pubmed.ncbi.nlm.nih.gov/38467483/ |series=Advances in Pharmacology (San Diego, Calif.) |volume=99 |pages=251–286 |doi=10.1016/bs.apha.2023.10.002 |pmid=38467483 |isbn=978-0-443-21933-7 |quote=Together, the findings indicate that LDX has independent actions to tackle the underlying psychopathology of BED to inhibit binge-eating and produce weight-loss by reducing food intake through appetite suppression or enhanced satiety.&nbsp;... Although BED is a predisposing factor for the development of obesity, it is unresponsive to appetite suppressants or anti-obesity drugs, emphasizing their different pathophysiological causes.}}</ref> This view is supported by the failure of [[anti-obesity medication]]s and other appetite suppressants to significantly reduce BED symptom severity, despite their capacity to induce weight loss.<ref name="Heal 2024 BED"/>

Medical reviews of randomized controlled trials have demonstrated that lisdexamfetamine, at doses between 50–70&nbsp;mg, is safe and effective for the treatment of moderate-to-severe BED in adults.{{#tag:ref|<ref name="BED secondary outcomes" /><ref name="BED rapid review" /><ref name="BED systematic review" /><ref name="BED neuroplasticity" /><ref name="BED review">{{cite journal | vauthors = Muratore AF, Attia E | title = Psychopharmacologic Management of Eating Disorders | journal = Current Psychiatry Reports | volume = 24 | issue = 7 | pages = 345–351 | date = July 2022 | pmid = 35576089 | pmc = 9233107 | doi = 10.1007/s11920-022-01340-5 | quote = An 11-week, double-blind RCT examined the effects of three doses of lisdexamfetamine (30 mg/day, 50 mg/day, 70 mg/day) and placebo on binge eating frequency. Results indicated that 50 mg and 70 mg doses were superior to placebo in reducing binge eating. Two follow-up 12-week RCTs confirmed the superiority of 50 and 70 mg doses to placebo in improving binge eating and secondary outcome measures, including obsessive–compulsive symptoms, body weight, and global improvement. ... Subsequent studies of lisdexamfetamine provided further support for the medication’s safety and efficacy and provided additional evidence that continued use may be better than placebo in preventing relapse. While it is considered safe and effective, lisdexamfetamine’s side effect profile and risk for misuse may make it inappropriate for certain patients. }}</ref>|group="sources"|name="BED efficacy"}} These reviews suggest that lisdexamfetamine is persistently effective at treating BED and is associated with significant reductions in the number of binge eating days and binge eating episodes per week.<ref name="BED efficacy" group="sources" /> Furthermore, a meta-analytic systematic review highlighted an open-label, 12-month extension safety and tolerability study that reported lisdexamfetamine remained effective at reducing the number of binge eating days for the duration of the study.<ref name="BED systematic review" /> In addition, both a review and a meta-analytic systematic review found lisdexamfetamine to be superior to placebo in several secondary outcome measures, including persistent binge eating cessation, reduction of obsessive-compulsive related binge eating symptoms, reduction of body-weight, and reduction of triglycerides.<ref name="BED secondary outcomes" /><ref name="BED systematic review" /> Lisdexamfetamine, like all pharmaceutical amphetamines, has direct appetite suppressant effects that may be therapeutically useful in both BED and its comorbidities.<ref name="BED rapid review" /><ref name="BED systematic review" /> Based on reviews of [[neuroimaging]] studies involving BED-diagnosed participants, therapeautic [[neuroplasticity]] in [[neurotransmitter#Neurotransmitter systems|dopaminergic and noradrenergic pathways]] from long-term use of lisdexamfetamine may be implicated in lasting improvements in the regulation of eating behaviors that are observed.<ref name="BED rapid review" /><ref name="BED neuroplasticity" /><ref name="BED systematic review" />
<!-- Section end:BED -->
<!-- Section begin: Narcolepsy -->

=====Narcolepsy=====
Narcolepsy is a chronic sleep-wake disorder that is associated with excessive daytime sleepiness, [[cataplexy]], and [[sleep paralysis]].<ref name="Autoimmune basis review">{{cite journal | vauthors = Mahlios J, De la Herrán-Arita AK, Mignot E | title = The autoimmune basis of narcolepsy | journal = Current Opinion in Neurobiology | volume = 23 | issue = 5 | pages = 767–773 | date = October 2013 | pmid = 23725858 | pmc = 3848424 | doi = 10.1016/j.conb.2013.04.013 }}</ref> Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms.<ref name="Barateau_2022">{{cite journal |vauthors=Barateau L, Pizza F, Plazzi G, Dauvilliers Y |date=August 2022 |title=Narcolepsy |journal=Journal of Sleep Research |volume=31 |issue=4 |pages=e13631 |doi=10.1111/jsr.13631 |pmid=35624073 |quote=Narcolepsy type 1 was called “narcolepsy with cataplexy” before 2014 (AASM, 2005), but was renamed NT1 in the third and last international classification of sleep disorders (AASM, 2014).&nbsp;... A low level of Hcrt-1 in the CSF is very sensitive and specific for the diagnosis of NT1.&nbsp;...<br /> All patients with low CSF Hcrt-1 levels are considered as NT1 patients, even if they report no cataplexy (in about 10–20% of cases), and all patients with normal CSF Hcrt-1 levels (or without cataplexy when the lumbar puncture is not performed) as NT2 patients (Baumann et al., 2014).&nbsp;...<br /> In patients with NT1, the absence of Hcrt leads to the inhibition of regions that suppress REM sleep, thus allowing the activation of descending pathways inhibiting motoneurons, leading to cataplexy.}}</ref> Type 1 narcolepsy results from the loss of approximately 70,000 [[orexin]]-releasing neurons in the [[lateral hypothalamus]], leading to significantly reduced [[Cerebrospinal fluid|cerebrospinal]] orexin levels;<ref name="Narcolepsy guide">{{cite journal |vauthors=Mignot EJ |date=October 2012 |title=A practical guide to the therapy of narcolepsy and hypersomnia syndromes |journal=Neurotherapeutics |volume=9 |issue=4 |pages=739–752 |doi=10.1007/s13311-012-0150-9 |pmc=3480574 |pmid=23065655 |quote=At the pathophysiological level, it is now clear that most narcolepsy cases with cataplexy, and a minority of cases (5–30 %) without cataplexy or with atypical cataplexy-like symptoms, are caused by a lack of hypocretin (orexin) of likely an autoimmune origin. In these cases, once the disease is established, the majority of the 70,000 hypocretin-producing cells have been destroyed, and the disorder is irreversible.&nbsp;...<br /> Amphetamines are exceptionally wake-promoting, and at high doses also reduce cataplexy in narcoleptic patients, an effect best explained by its action on adrenergic and serotoninergic synapses.&nbsp;...<br /> The D-isomer is more specific for DA transmission and is a better stimulant compound. Some effects on cataplexy (especially for the L-isomer), secondary to adrenergic effects, occur at higher doses.&nbsp;...<br /> Numerous studies have shown that increased dopamine release is the main property explaining wake-promotion, although norepinephrine effects also contribute.}}</ref><ref name="Malenka_2015b">{{Cite book |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE, Holtzman DM |publisher=McGraw-Hill Medical |year=2015 |isbn=9780071827706 |edition=3rd |location=New York |pages=456–457 |chapter=Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu |quote=More recently, the lateral hypothalamus was also found to play a central role in arousal. Neurons in this region contain cell bodies that produce the orexin (also called hypocretin) peptides (Chapter 6). These neurons project widely throughout the brain and are involved in sleep, arousal, feeding, reward, aspects of emotion, and learning. In fact, orexin is thought to promote feeding primarily by promoting arousal. Mutations in orexin receptors are responsible for narcolepsy in a canine model, knockout of the orexin gene produces narcolepsy in mice, and humans with narcolepsy have low or absent levels of orexin peptides in cerebrospinal fluid (Chapter 13). Lateral hypothalamus neurons have reciprocal connections with neurons that produce monoamine neurotransmitters (Chapter 6).}}</ref> this reduction is a [[Biomarker (medicine)|diagnostic biomarker]] for type 1 narcolepsy.<ref name="Barateau_2022" /> Lateral hypothalamic orexin neurons innervate every component of the [[ascending reticular activating system]] (ARAS), which includes [[Norepinephrine|noradrenergic]], [[dopamine]]rgic, [[histamine]]rgic, and [[Serotonin|serotonergic]] nuclei that promote [[wakefulness]].<ref name="Malenka_2015b" /><ref name="Malenka_2015a">{{Cite book |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE, Holtzman DM |publisher=McGraw-Hill Medical |year=2015 |isbn=9780071827706 |edition=3rd |pages=521 |chapter=Chapter 13: Sleep and Arousal |quote=The ARAS consists of several different circuits including the four main monoaminergic pathways discussed in Chapter 6. The norepinephrine pathway originates from the LC and related brainstem nuclei; the serotonergic neurons originate from the RN within the brainstem as well; the dopaminergic neurons originate in the ventral tegmental area (VTA); and the histaminergic pathway originates from neurons in the tuberomammillary nucleus (TMN) of the posterior hypothalamus. As discussed in Chapter 6, these neurons project widely throughout the brain from restricted collections of cell bodies. Norepinephrine, serotonin, dopamine, and histamine have complex modulatory functions and, in general, promote wakefulness. The PT in the brainstem is also an important component of the ARAS. Activity of PT cholinergic neurons (REM-on cells) promotes REM sleep, as noted earlier. During waking, REM-on cells are inhibited by a subset of ARAS norepinephrine and serotonin neurons called REM-off cells.}}</ref>

Amphetamine’s therapeutic mode of action in narcolepsy primarily involves increasing [[Monoamine neurotransmitter|monoamine]] neurotransmitter activity in the ARAS.<ref name="Narcolepsy guide" /><ref name="Amphetamine ARAS textbook">{{cite book |url=https://books.google.com/books?id=kWxWEdqvue4C&pg=PA81 |title=Sleep medicine a guide to sleep and its disorders |vauthors=Shneerson JM |date=2009 |publisher=John Wiley & Sons |isbn=9781405178518 |edition=2nd |page=81 |quote=All the amphetamines enhance activity at dopamine, noradrenaline and 5HT synapses. They cause presynaptic release of preformed transmitters, and also inhibit the re-uptake of dopamine and noradrenaline. These actions are most prominent in the brainstem ascending reticular activating system and the cerebral cortex.}}</ref><ref name="Narcolepsy - Amphetamine and the ARAS" /> This includes noradrenergic neurons in the [[locus coeruleus]], dopaminergic neurons in the [[ventral tegmental area]], histaminergic neurons in the [[tuberomammillary nucleus]], and serotonergic neurons in the [[dorsal raphe nucleus]].<ref name="Malenka_2015a" /><ref name="Narcolepsy - Amphetamine and the ARAS">{{cite journal |vauthors=Schwartz JR, Roth T |year=2008 |title=Neurophysiology of sleep and wakefulness: basic science and clinical implications |journal=Current Neuropharmacology |volume=6 |issue=4 |pages=367–378 |doi=10.2174/157015908787386050 |pmc=2701283 |pmid=19587857 |quote=Alertness and associated forebrain and cortical arousal are mediated by several ascending pathways with distinct neuronal components that project from the upper brain stem near the junction of the pons and the midbrain.&nbsp;...<br /> Key cell populations of the ascending arousal pathway include cholinergic, noradrenergic, serotoninergic, dopaminergic, and histaminergic neurons located in the pedunculopontine and laterodorsal tegmental nucleus (PPT/LDT), locus coeruleus, dorsal and median raphe nucleus, and tuberomammillary nucleus (TMN), respectively.&nbsp;...<br /> The mechanism of action of sympathomimetic alerting drugs (eg, dextro- and methamphetamine, methylphenidate) is direct or indirect stimulation of dopaminergic and noradrenergic nuclei, which in turn heightens the efficacy of the ventral periaqueductal grey area and locus coeruleus, both components of the secondary branch of the ascending arousal system.&nbsp;...<br />Sympathomimetic drugs have long been used to treat narcolepsy}}</ref> Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines.<ref name="Narcolepsy guide" /> In contrast, levoamphetamine may have a greater effect on cataplexy, a symptom more sensitive to the effects of norepinephrine and serotonin.<ref name="Narcolepsy guide" /> Noradrenergic and serotonergic nuclei in the ARAS are involved in the regulation of the [[Rapid eye movement sleep|REM]] sleep cycle and function as "REM-off" cells, with amphetamine's effect on norepinephrine and serotonin contributing to the suppression of REM sleep and a possible reduction of cataplexy at high doses.<ref name="Narcolepsy guide" /><ref name="Barateau_2022" /><ref name="Malenka_2015a" />

The [[American Academy of Sleep Medicine]] (AASM) 2021 [[clinical practice guideline]] conditionally recommends dextroamphetamine for the treatment of both type 1 and type 2 narcolepsy.<ref name="narcolepsy efficacy">{{cite journal | vauthors = Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD, Watson NF | title = Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline | journal = Journal of Clinical Sleep Medicine | volume = 17 | issue = 9 | pages = 1881–1893 | date = September 2021 | pmid = 34743789 | pmc = 8636351 | doi = 10.5664/jcsm.9328 | quote = The TF identified 1 double-blind RCT, 1 single-blind RCT, and 1 retrospective observational long-term self-reported case series assessing the efficacy of dextroamphetamine in patients with narcolepsy type 1 and narcolepsy type 2. These studies demonstrated clinically significant improvements in excessive daytime sleepiness and cataplexy. }}</ref> Treatment with pharmaceutical amphetamines is generally less preferred relative to other stimulants (e.g., [[modafinil]]) and is considered a [[Therapy#Lines of therapy|third-line treatment]] option.<ref name="narcolepsy addiction">{{cite journal |vauthors=Barateau L, Lopez R, Dauvilliers Y |date=October 2016 |title=Management of Narcolepsy |journal=Current Treatment Options in Neurology |volume=18 |issue=10 |pages=43 |doi=10.1007/s11940-016-0429-y |pmid=27549768 |quote=The usefulness of amphetamines is limited by a potential risk of abuse, and their cardiovascular adverse effects (Table 1). That is why, even though they are cheaper than other drugs, and efficient, they remain third-line therapy in narcolepsy. Three class II studies showed an improvement of EDS in that disease.&nbsp;...<br /> Despite the potential for drug abuse or tolerance using stimulants, patients with narcolepsy rarely exhibit addiction to their medication.&nbsp;...<br /> Some stimulants, such as mazindol, amphetamines, and pitolisant, may also have some anticataplectic effects.}}</ref><ref>{{cite journal | vauthors = Dauvilliers Y, Barateau L | title = Narcolepsy and Other Central Hypersomnias | journal = Continuum | volume = 23 | issue = 4, Sleep Neurology | pages = 989–1004 | date = August 2017 | pmid = 28777172 | doi = 10.1212/CON.0000000000000492 | quote = Recent clinical trials and practice guidelines have confirmed that stimulants such as modafinil, armodafinil, or sodium oxybate (as first line); methylphenidate and pitolisant (as second line [pitolisant is currently only available in Europe]); and amphetamines (as third line) are appropriate medications for excessive daytime sleepiness. }}</ref><ref>{{cite journal | vauthors = Thorpy MJ, Bogan RK | title = Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications | journal = Sleep Medicine | volume = 68 | pages = 97–109 | date = April 2020 | pmid = 32032921 | doi = 10.1016/j.sleep.2019.09.001 | quote = The first agents used to treat EDS (ie, amphetamines, methylphenidate) are now considered second- or third-line options because newer medications have been developed with improved tolerability and lower abuse potential (eg, modafinil/armodafinil, solriamfetol, pitolisant) }}</ref> Medical reviews indicate that amphetamine is safe and effective for the treatment of narcolepsy.<ref name="Narcolepsy guide" /><ref name="narcolepsy addiction" /><ref name="narcolepsy efficacy" /> Amphetamine appears to be most effective at improving symptoms associated with [[Excessive daytime sleepiness|hypersomnolence]], with three reviews finding clinically significant reductions in [[Somnolence|daytime sleepiness]] in patients with narcolepsy.<ref name="Narcolepsy guide" /><ref name="narcolepsy addiction" /><ref name="narcolepsy efficacy" /> Additionally, these reviews suggest that amphetamine may dose-dependently improve cataplexy symptoms.<ref name="Narcolepsy guide" /><ref name="narcolepsy addiction" /><ref name="narcolepsy efficacy" /> However, the quality of evidence for these findings is low and is consequently reflected in the AASM's conditional recommendation for dextroamphetamine as a treatment option for narcolepsy.<ref name="narcolepsy efficacy" />
<!-- Section end: Narcolepsy -->
<!-- ====Obesity====
Topics to cover:

Amphetamine's MoA in the periphery:
* cover amphetamine-triggered induction of lipolysis via peripheral (nor-)adrenergic signaling in adipose fat cells which induces the release of triglycerides into blood plasma
* cover amphetamine-induced TAAR1 signaling in peripheral organs (i.e., cover "File:TAAR1 organ-specific expression and function.jpg" in the context of amphetamine's MoA for treating obesity), provided that I can find a review mentioning amphetamine+TAAR1+obesity at some point

Amphetamine's MoA in the CNS:
* indicate that every monoamine neurotransmitter is involved in energy homeostasis, specify how, and mention which DA/NE-ergic projections are involved [cite PMID 22547886 and the refs I added to the "energy homeostasis" article]
** cover the systems neurobiology of monoaminergic regulation of feeding behavior
* amphetamine-induced hypothalamic CART induction probably plays some role in the mechanism of action, but would need to find a source once its GPCR has been IDed
**quotes on CART's physiological/cognitive effects: "CART promotes physical activity and wakefulness" [PMID 22547886] and markedly inhibits hunger [pubchem amphetamine entry] (pubchem quote: "this anorectic peptide inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated by leptin in the hypothalamus")
:Note: PMID 22547886 contains material relevant to both narcolepsy and obesity as well as covers CART; doesn't mention amphetamine though

-->