神經增強：修订间差异

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[[膳食]]中的[[葡萄糖]]（及其[[糖原]]形態）是[[大脑]]的主要能量来源，尽管直接摄入[[葡萄糖]]会影响健康，但一些研究人员认为葡萄糖是種「生化增强剂」，需要持續補充，但以單醣補充，会使血糖飙升，且其提供的葡萄糖供应，也不会持续太久。与快速吸收或高[[升糖指數|GI]]食物相比，吸收缓慢的含[[碳水化合物]]食物或低[[升糖指數|GI]]食物释放[[葡萄糖]]的速度较慢。<ref>{{cite journal |last1=Philippou |first1=Elena |last2=Constantinou |first2=Marios |title=The Influence of Glycemic Index on Cognitive Functioning: A Systematic Review of the Evidence |journal=Advances in Nutrition |date=1 March 2014 |volume=5 |issue=2 |pages=119–130 |doi=10.3945/an.113.004960 |pmid=24618754 |pmc=3951795 |language=en |issn=2161-8313}}</ref><ref name="10.1123/ijsnem.2017-0314">{{cite journal |last1=Meeusen |first1=Romain |last2=Decroix |first2=Lieselot |title=Nutritional Supplements and the Brain |journal=International Journal of Sport Nutrition and Exercise Metabolism |date=1 March 2018 |volume=28 |issue=2 |pages=200–211 |doi=10.1123/ijsnem.2017-0314 |pmid=29252056 |s2cid=4582295 |language=en |issn=1543-2742}}</ref><ref name="10.1021/acschemneuro.8b00571"/><ref name="joshi"/>尽管脑葡萄糖代谢与[[神经退行性疾病]]有关，但有关脑葡萄糖代谢与认知能力之间联系的研究却很少。<ref>{{cite journal |last1=Rebelos |first1=Eleni |last2=Rinne |first2=Juha O. |last3=Nuutila |first3=Pirjo |last4=Ekblad |first4=Laura L. |title=Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review |journal=Journal of Clinical Medicine |date=January 2021 |volume=10 |issue=7 |pages=1532 |doi=10.3390/jcm10071532 |pmid=33917464 |pmc=8038699 |language=en |issn=2077-0383|doi-access=free }}</ref>[[乳酸]]（尤其是在特定类型的运动中释放）也可能与认知能力的提高有关。<ref>{{cite journal |last1=Gubert |first1=Carolina |last2=Hannan |first2=Anthony J. |title=Exercise mimetics: harnessing the therapeutic effects of physical activity |journal=Nature Reviews Drug Discovery |date=November 2021 |volume=20 |issue=11 |pages=862–879 |doi=10.1038/s41573-021-00217-1 |pmid=34103713 |s2cid=235379365 |language=en |issn=1474-1784}}</ref><ref>{{cite journal |last1=Yamada |first1=Yujiro |last2=Frith |first2=Emily M. |last3=Wong |first3=Vickie |last4=Spitz |first4=Robert W. |last5=Bell |first5=Zachary W. |last6=Chatakondi |first6=Raksha N. |last7=Abe |first7=Takashi |last8=Loenneke |first8=Jeremy P. |title=Acute exercise and cognition: A review with testable questions for future research into cognitive enhancement with blood flow restriction |journal=Medical Hypotheses |date=1 June 2021 |volume=151 |pages=110586 |doi=10.1016/j.mehy.2021.110586 |pmid=33848917 |s2cid=233233538 |language=en |issn=0306-9877}}</ref><ref>{{cite journal |last1=Taubert |first1=Marco |last2=Villringer |first2=Arno |last3=Lehmann |first3=Nico |title=Endurance Exercise as an "Endogenous" Neuro-enhancement Strategy to Facilitate Motor Learning |journal=Frontiers in Human Neuroscience |date=2015 |volume=9 |page=692 |doi=10.3389/fnhum.2015.00692 |pmid=26834602 |pmc=4714627 |issn=1662-5161|doi-access=free }}</ref>
[[膳食]]中的[[葡萄糖]]（及其[[糖原]]形態）是[[大脑]]的主要能量来源，尽管直接摄入[[葡萄糖]]会影响健康，但一些研究人员认为葡萄糖是種「生化增强剂」，需要持續補充，但以單醣補充，会使血糖飙升，且其提供的葡萄糖供应，也不会持续太久。与快速吸收或高[[升糖指數|GI]]食物相比，吸收缓慢的含[[碳水化合物]]食物或低[[升糖指數|GI]]食物释放[[葡萄糖]]的速度较慢。<ref>{{cite journal |last1=Philippou |first1=Elena |last2=Constantinou |first2=Marios |title=The Influence of Glycemic Index on Cognitive Functioning: A Systematic Review of the Evidence |journal=Advances in Nutrition |date=1 March 2014 |volume=5 |issue=2 |pages=119–130 |doi=10.3945/an.113.004960 |pmid=24618754 |pmc=3951795 |language=en |issn=2161-8313}}</ref><ref name="10.1123/ijsnem.2017-0314">{{cite journal |last1=Meeusen |first1=Romain |last2=Decroix |first2=Lieselot |title=Nutritional Supplements and the Brain |journal=International Journal of Sport Nutrition and Exercise Metabolism |date=1 March 2018 |volume=28 |issue=2 |pages=200–211 |doi=10.1123/ijsnem.2017-0314 |pmid=29252056 |s2cid=4582295 |language=en |issn=1543-2742}}</ref><ref name="10.1021/acschemneuro.8b00571"/><ref name="joshi"/>尽管脑葡萄糖代谢与[[神经退行性疾病]]有关，但有关脑葡萄糖代谢与认知能力之间联系的研究却很少。<ref>{{cite journal |last1=Rebelos |first1=Eleni |last2=Rinne |first2=Juha O. |last3=Nuutila |first3=Pirjo |last4=Ekblad |first4=Laura L. |title=Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review |journal=Journal of Clinical Medicine |date=January 2021 |volume=10 |issue=7 |pages=1532 |doi=10.3390/jcm10071532 |pmid=33917464 |pmc=8038699 |language=en |issn=2077-0383|doi-access=free }}</ref>[[乳酸]]（尤其是在特定类型的运动中释放）也可能与认知能力的提高有关。<ref>{{cite journal |last1=Gubert |first1=Carolina |last2=Hannan |first2=Anthony J. |title=Exercise mimetics: harnessing the therapeutic effects of physical activity |journal=Nature Reviews Drug Discovery |date=November 2021 |volume=20 |issue=11 |pages=862–879 |doi=10.1038/s41573-021-00217-1 |pmid=34103713 |s2cid=235379365 |language=en |issn=1474-1784}}</ref><ref>{{cite journal |last1=Yamada |first1=Yujiro |last2=Frith |first2=Emily M. |last3=Wong |first3=Vickie |last4=Spitz |first4=Robert W. |last5=Bell |first5=Zachary W. |last6=Chatakondi |first6=Raksha N. |last7=Abe |first7=Takashi |last8=Loenneke |first8=Jeremy P. |title=Acute exercise and cognition: A review with testable questions for future research into cognitive enhancement with blood flow restriction |journal=Medical Hypotheses |date=1 June 2021 |volume=151 |pages=110586 |doi=10.1016/j.mehy.2021.110586 |pmid=33848917 |s2cid=233233538 |language=en |issn=0306-9877}}</ref><ref>{{cite journal |last1=Taubert |first1=Marco |last2=Villringer |first2=Arno |last3=Lehmann |first3=Nico |title=Endurance Exercise as an "Endogenous" Neuro-enhancement Strategy to Facilitate Motor Learning |journal=Frontiers in Human Neuroscience |date=2015 |volume=9 |page=692 |doi=10.3389/fnhum.2015.00692 |pmid=26834602 |pmc=4714627 |issn=1662-5161|doi-access=free }}</ref>

====Medications====
Notable potentially viable pharmacological agents – as final products or as prototypes for similar ones – [[Lists of investigational drugs|under early-stage research]] with potential for substantial effect sizes for specific purposes in specific situations (such as learning periods) also in healthy non-old humans but, in at least most cases, largely unknown effects in humans and safety profiles (and consequently not widely used or not used at all): [[orexin-A]],<ref name="10.1371/journal.pbio.1001289">{{cite journal |last1=Tennison |first1=Michael N. |last2=Moreno |first2=Jonathan D. |title=Neuroscience, Ethics, and National Security: The State of the Art |journal=PLOS Biology |date=20 March 2012 |volume=10 |issue=3 |pages=e1001289 |doi=10.1371/journal.pbio.1001289 |pmid=22448146 |pmc=3308927 |language=en |issn=1545-7885}}</ref> [[Fibroblast growth loop peptide|FGL]], [[PTEN-PDZ]], and [[Phosphoinositide 3-kinase#Learning and memory|PI3K-activator]] PTD4-PI3KAc,<ref>{{cite journal |last1=Asua |first1=Diego |last2=Bougamra |first2=Ghassen |last3=Calleja-Felipe |first3=María |last4=Morales |first4=Miguel |last5=Knafo |first5=Shira |title=Peptides Acting as Cognitive Enhancers |journal=Neuroscience |date=1 February 2018 |volume=370 |pages=81–87 |doi=10.1016/j.neuroscience.2017.10.002 |pmid=29030286 |s2cid=10269993 |language=en |issn=0306-4522}}</ref> [[dihexa]],<ref>{{cite journal |last1=Wright |first1=John W. |last2=Harding |first2=Joseph W. |title=The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease |journal=Journal of Alzheimer's Disease |date=1 January 2015 |volume=45 |issue=4 |pages=985–1000 |doi=10.3233/JAD-142814 |pmid=25649658 |language=en |issn=1387-2877}}</ref><ref>{{cite journal |last1=Ho |first1=Jean K. |last2=Nation |first2=Daniel A. |title=Cognitive benefits of angiotensin IV and angiotensin-(1–7): A systematic review of experimental studies |journal=Neuroscience & Biobehavioral Reviews |date=1 September 2018 |volume=92 |pages=209–225 |doi=10.1016/j.neubiorev.2018.05.005 |pmid=29733881 |pmc=8916541 |language=en |issn=0149-7634}}</ref><ref>{{cite journal |last1=Hallberg |first1=Mathias |last2=Larhed |first2=Mats |title=From Angiotensin IV to Small Peptidemimetics Inhibiting Insulin-Regulated Aminopeptidase |journal=Frontiers in Pharmacology |date=2020 |volume=11 |page=590855 |doi=10.3389/fphar.2020.590855 |pmid=33178027 |pmc=7593869 |issn=1663-9812|doi-access=free }}</ref> [[d-cycloserine]],<ref>{{cite journal |last1=Stern |first1=Sarah A. |last2=Alberini |first2=Cristina M. |title=Mechanisms of memory enhancement |journal=WIREs Systems Biology and Medicine |date=January 2013 |volume=5 |issue=1 |pages=37–53 |doi=10.1002/wsbm.1196 |pmid=23151999 |pmc=3527655 |language=en |issn=1939-5094}}</ref><ref>{{cite journal |last1=Hofmann |first1=Stefan G. |last2=Fang |first2=Angela |last3=Gutner |first3=Cassidy A. |title=Cognitive enhancers for the treatment of anxiety disorders |journal=Restorative Neurology and Neuroscience |date=1 January 2014 |volume=32 |issue=1 |pages=183–195 |doi=10.3233/RNN-139002 |pmid=23542909 |language=en |issn=0922-6028}}</ref><ref name="10.3389/fnsys.2014.00046">{{cite journal |last1=Diekelmann |first1=Susanne |title=Sleep for cognitive enhancement |journal=Frontiers in Systems Neuroscience |date=2014 |volume=8 |page=46 |doi=10.3389/fnsys.2014.00046 |pmid=24765066 |pmc=3980112 |issn=1662-5137|doi-access=free }}</ref><ref name="10.1016/j.neubiorev.2007.12.001"/><ref>{{cite journal |last1=Merlo |first1=Emiliano |last2=Milton |first2=Amy L |last3=Everitt |first3=Barry J |title=Enhancing cognition by affecting memory reconsolidation |journal=Current Opinion in Behavioral Sciences |date=1 August 2015 |volume=4 |pages=41–47 |doi=10.1016/j.cobeha.2015.02.003 |s2cid=53170506 |language=en |issn=2352-1546|url=http://sro.sussex.ac.uk/id/eprint/81983/1/__smbhome.uscs.susx.ac.uk_sc328_Desktop_Papers%20for%20SRO_MERLO_Current_Opinion_in_Behavioral_Sciences_Jan_2015_author_copy.pdf }}</ref> [[Dopamine reuptake inhibitor|DAT blockers]] [[CE-123]] and CE-158,<ref>{{cite journal |last1=Desibhatla |first1=Mukund |title=The Development and Evaluation of Novel DA Transport Inhibitors and their Effects on Effort-Related Motivation: A Review |journal=Honors Scholar Theses |date=1 May 2021 |url=https://opencommons.uconn.edu/srhonors_theses/787/}}</ref> [[ampakine]]s like [[IDRA-21]] and [[CX717]],<ref name="10.3233/JAD-2012-121186">{{cite journal |last1=Froestl |first1=Wolfgang |last2=Muhs |first2=Andreas |last3=Pfeifer |first3=Andrea |title=Cognitive Enhancers (Nootropics). Part 1: Drugs Interacting with Receptors |journal=Journal of Alzheimer's Disease |date=1 January 2012 |volume=32 |issue=4 |pages=793–887 |doi=10.3233/JAD-2012-121186 |pmid=22886028 |language=en |issn=1387-2877}}</ref><ref>{{cite journal |last1=Partin |first1=Kathryn M |title=AMPA receptor potentiators: from drug design to cognitive enhancement |journal=Current Opinion in Pharmacology |date=1 February 2015 |volume=20 |pages=46–53 |doi=10.1016/j.coph.2014.11.002 |pmid=25462292 |pmc=4318786 |language=en |issn=1471-4892}}</ref><ref name="10.1016/j.neubiorev.2007.12.001"/><ref name="joshi">{{cite journal |last1=Pranav |first1=Joshi C. |title=A review on natural memory enhancers (nootropics) |journal=Unique Journal of Engineering and Advanced Sciences |date=2013 |url=http://www.ujconline.net/wp-content/uploads/2013/09/3-UJEAS-1314-Rv.pdf |language=en}}</ref><ref name="10.2174/1874620900902010048">{{cite journal |last1=Þorsteinsson |first1=Haraldur |last2=Karlsson |first2=KarlÆgir |title=Is Sleep Beyond Our Control? |journal=The Open Sleep Journal |date=12 August 2009 |volume=2 |issue=1 |pages=48–55 |doi=10.2174/1874620900902010048}}</ref> [[rapastinel]],<ref>{{cite journal |last1=Kato |first1=Taro |last2=Duman |first2=Ronald S. |title=Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: Convergent mechanisms |journal=Pharmacology Biochemistry and Behavior |date=1 January 2020 |volume=188 |pages=172827 |doi=10.1016/j.pbb.2019.172827 |pmid=31733218 |s2cid=207976034 |language=en |issn=0091-3057}}</ref><ref>{{cite journal |last1=Burgdorf |first1=Jeffrey |last2=Zhang |first2=Xiao-lei |last3=Weiss |first3=Craig |last4=Matthews |first4=Elizabeth |last5=Disterhoft |first5=John F. |last6=Stanton |first6=Patric K. |last7=Moskal |first7=Joseph R. |title=The N-methyl-d-aspartate receptor modulator GLYX-13 enhances learning and memory, in young adult and learning impaired aging rats |journal=Neurobiology of Aging |date=1 April 2011 |volume=32 |issue=4 |pages=698–706 |doi=10.1016/j.neurobiolaging.2009.04.012 |pmid=19446371 |pmc=3035742 |language=en |issn=0197-4580}}</ref><ref>{{cite journal |last1=R. Moskal |first1=Joseph |last2=S. Burgdorf |first2=Jeffrey |last3=K. Stanton |first3=Patric |last4=A. Kroes |first4=Roger |last5=F. Disterhoft |first5=John |last6=M. Burch |first6=Ronald |last7=Amin Khan |first7=M. |title=The Development of Rapastinel (Formerly GLYX-13); A Rapid Acting and Long Lasting Antidepressant |journal=Current Neuropharmacology |date=2017 |volume=15 |issue=1 |pages=47–56 |doi=10.2174/1570159X14666160321122703 |pmid=26997507 |pmc=5327451 |url=https://www.ingentaconnect.com/content/ben/cn/2017/00000015/00000001/art00008 |language=en}}</ref> [[ISRIB]],<ref>{{cite journal |last1=Costa-Mattioli |first1=Mauro |last2=Walter |first2=Peter |title=The integrated stress response: From mechanism to disease |journal=Science |date=24 April 2020 |volume=368 |issue=6489 |pages=eaat5314 |doi=10.1126/science.aat5314 |pmid=32327570 |pmc=8997189 |language=en |issn=0036-8075}}</ref><ref>{{cite journal |last1=Jin |first1=Yang |last2=Saatcioglu |first2=Fahri |title=Targeting the Unfolded Protein Response in Hormone-Regulated Cancers |journal=Trends in Cancer |date=1 February 2020 |volume=6 |issue=2 |pages=160–171 |doi=10.1016/j.trecan.2019.12.001 |pmid=32061305 |s2cid=211136354 |language=en |issn=2405-8033}}</ref> [[citicoline]],<ref>{{Cite web|last=Tardner|first=P.|date=2020-08-30|title=The use of citicoline for the treatment of cognitive decline and cognitive impairment: A meta-analysis of pharmacological literature • International Journal of Environmental Science & Technology|url=https://www.ijest.org/citicoline-cognitive-decline-ptardner-0820/|access-date=2020-08-31|website=International Journal of Environmental Science & Technology|language=en-US}}</ref> [[selective receptor modulator|selective]] [[receptor modulator]]s such as [[MRK-016]] which targets subtypes of GABA<sub>A</sub> receptors,<ref>{{cite journal |last1=Atack |first1=John R. |title=GABAA Receptor Subtype-Selective Modulators. II. α5-Selective Inverse Agonists for Cognition Enhancement |journal=Current Topics in Medicinal Chemistry |year=2011 |volume=11 |issue=9 |pages=1203–1214 |doi=10.2174/156802611795371314 |pmid=21050171 |language=en}}</ref> {{anchor|Modafinil analogs}}modafinil-analogs [[CRL-40,940]] and {{tooltip|modafiendz|N-Methylbisfluoromodafinil}},<ref name="10.1080/08897077.2019.1700584">{{cite journal |last1=Sousa |first1=Ana |last2=Dinis-Oliveira |first2=Ricardo Jorge |title=Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects |journal=Substance Abuse |date=2 April 2020 |volume=41 |issue=2 |pages=155–173 |doi=10.1080/08897077.2019.1700584 |pmid=31951804 |s2cid=210709160 |issn=0889-7077}}</ref> modafinil-inspired/hybrid [[Triple reuptake inhibitor|TRIs]] [[JZ-IV-10]] and JZAD-IV-22,<ref>{{cite journal |last1=Kleczkowska |first1=Patrycja |title=Chimeric Structures in Mental Illnesses&mdash;"Magic" Molecules Specified for Complex Disorders |journal=International Journal of Molecular Sciences |date=January 2022 |volume=23 |issue=7 |pages=3739 |doi=10.3390/ijms23073739 |pmid=35409098 |pmc=8998808 |language=en |issn=1422-0067|doi-access=free }}</ref><ref>{{cite journal |last1=Sharma |first1=Horrick |last2=Santra |first2=Soumava |last3=Dutta |first3=Aloke |title=Triple reuptake inhibitors as potential next-generation antidepressants: a new hope? |journal=Future Medicinal Chemistry |date=November 2015 |volume=7 |issue=17 |pages=2385–2406 |doi=10.4155/fmc.15.134|pmid=26619226 |pmc=4976848 }}</ref><ref>{{cite journal |last1=Subbaiah |first1=Murugaiah A. M. |title=Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges |journal=Journal of Medicinal Chemistry |date=22 March 2018 |volume=61 |issue=6 |pages=2133–2165 |doi=10.1021/acs.jmedchem.6b01827 |pmid=28731336 |language=en |issn=0022-2623}}</ref> [[Danavorexton|TAK-925]] ([[Orexin receptor#Agonists|orexin agonist]] that promotes wakefulness in ways similar to modafinil),<ref>{{cite journal |last1=Jacobson |first1=Laura H. |last2=Hoyer |first2=Daniel |last3=Lecea |first3=Luis |title=Hypocretins (orexins): The ultimate translational neuropeptides |journal=Journal of Internal Medicine |date=May 2022 |volume=291 |issue=5 |pages=533–556 |doi=10.1111/joim.13406 |pmid=35043499 |s2cid=248119793 |language=en |issn=0954-6820}}</ref><ref>{{cite journal |last1=Seigneur |first1=Erica |last2=de Lecea |first2=Luis |title=Hypocretin (Orexin) Replacement Therapies |journal=Medicine in Drug Discovery |date=1 December 2020 |volume=8 |pages=100070 |doi=10.1016/j.medidd.2020.100070 |s2cid=225129746 |language=en |issn=2590-0986}}</ref> wakefulness-inducing or procognitive [[Narcolepsy#Medications|narcolepsy medication]] candidates like [[samelisant]],<ref name="10.3389/fphar.2022.861094"/><ref>{{cite journal |last1=Shinde |first1=Anil |last2=Subramanian |first2=Ramkumar |last3=Palacharla |first3=Raghava |last4=Benade |first4=Vijay |last5=Abraham |first5=Renny |last6=Kamuju |first6=Venkatesh |last7=Pandey |first7=Santosh |last8=Badange |first8=Rajesh |last9=Achanta |first9=Pramod Kumar |last10=Nirogi |first10=Ramakrishna |title=004 Samelisant (SUVN-G3031), Differentiating features over current treatments of narcolepsy |journal=Sleep |date=1 May 2021 |volume=44 |issue=Supplement_2 |pages=A2 |doi=10.1093/sleep/zsab072.003 |issn=0161-8105 |quote=Recent research has described a procognitive effect of samelisant, an inverse agonist of H3 receptors, in animal models of schizophrenia [157]. Nevertheless, more studies are required.}}</ref> [[pterostilbene]],<ref>{{cite journal |last1=Poulose |first1=Shibu M. |last2=Thangthaeng |first2=Nopporn |last3=Miller |first3=Marshall G. |last4=Shukitt-Hale |first4=Barbara |title=Effects of pterostilbene and resveratrol on brain and behavior |journal=Neurochemistry International |date=1 October 2015 |volume=89 |pages=227–233 |doi=10.1016/j.neuint.2015.07.017 |pmid=26212523 |s2cid=33577543 |language=en |issn=0197-0186}}</ref><ref>{{cite journal |last1=McCormack |first1=Denise |last2=McFadden |first2=David |title=A Review of Pterostilbene Antioxidant Activity and Disease Modification |journal=Oxidative Medicine and Cellular Longevity |date=4 April 2013 |volume=2013 |pages=e575482 |doi=10.1155/2013/575482 |pmid=23691264 |pmc=3649683 |language=en |issn=1942-0900|doi-access=free }}</ref> [[Caloric restriction mimetic|CRM]] acyl-[[ghrelin]] mimetics and agonists like [[ibutamoren]],<ref>{{cite journal |last1=Buntwal |first1=Luke |last2=Sassi |first2=Martina |last3=Morgan |first3=Alwena H. |last4=Andrews |first4=Zane B. |last5=Davies |first5=Jeffrey S. |title=Ghrelin-Mediated Hippocampal Neurogenesis: Implications for Health and Disease |journal=Trends in Endocrinology & Metabolism |date=1 November 2019 |volume=30 |issue=11 |pages=844–859 |doi=10.1016/j.tem.2019.07.001 |pmid=31445747 |s2cid=201126380 |language=en |issn=1043-2760|url=https://cronfa.swan.ac.uk/Record/cronfa52032 }}</ref><ref>{{cite journal |last1=Morgan |first1=A. H. |last2=Andrews |first2=Z. B. |last3=Davies |first3=J. S. |title=Less is more: Caloric regulation of neurogenesis and adult brain function |journal=Journal of Neuroendocrinology |date=October 2017 |volume=29 |issue=10 |pages=e12512 |doi=10.1111/jne.12512 |pmid=28771924 |s2cid=3070497 |url=https://research.monash.edu/en/publications/d666c1b2-d88f-46ba-ac78-1248c0b7d0fe |language=en}}</ref> and [[H3 receptor antagonist|H<sub>3</sub> receptor antagonist]] [[pitolisant]].<ref>{{cite journal |last1=Harwell |first1=Victoria |last2=Fasinu |first2=Pius |title=Pitolisant and Other Histamine-3 Receptor Antagonists—An Update on Therapeutic Potentials and Clinical Prospects |journal=Medicines |date=1 September 2020 |volume=7 |issue=9 |pages=55 |doi=10.3390/medicines7090055|pmid=32882898 |pmc=7554886 |doi-access=free }}</ref><ref name="10.3389/fphar.2022.861094">{{cite journal |last1=Alhusaini |first1=Mera |last2=Eissa |first2=Nermin |last3=Saad |first3=Ali K. |last4=Beiram |first4=Rami |last5=Sadek |first5=Bassem |title=Revisiting Preclinical Observations of Several Histamine H3 Receptor Antagonists/Inverse Agonists in Cognitive Impairment, Anxiety, Depression, and Sleep–Wake Cycle Disorder |journal=Frontiers in Pharmacology |date=2022 |volume=13 |page=861094 |doi=10.3389/fphar.2022.861094 |pmid=35721194 |pmc=9198498 |issn=1663-9812|doi-access=free }}</ref><ref>{{cite book |last1=Schlicker |first1=Eberhard |last2=Kathmann |first2=Markus |title=Histamine and Histamine Receptors in Health and Disease |date=2017 |publisher=Springer International Publishing |isbn=978-3-319-58194-1 |pages=277–299 |language=en |chapter=Role of the Histamine H3 Receptor in the Central Nervous System}}</ref>


==參考文獻==
==參考文獻==

2023年8月16日 (三) 13:59的版本

神经增强（英語：Neuroenhancement）或认知增强（英語：cognitive enhancement），是指對已知無任何精神疾病的健康人身上，通過應用神經生物學研究成果，有針對性地增強或擴展其認知與情感能力，算是個概括性的術語。[1][2][3][4][5][6][7]通過藥物或非藥物方法來改善神經功能，或是超出了维持或恢复健康所必需的范围，而旨在改善人类形态或機能的干预措施，以及伴随这些目标和做法的神經倫理學（英语：Neuroethics）討論。[8][9]

尽管广义上的認知增強剂，還包括使用被认为不健康或有严重副作用的精神活性物质，但神经增強剂仍能几乎不会产生副作用的可靠地为健康人带来超出正常功能的大量认知、社交、心理、情绪或运动方面的益处。[9][7]促智藥包括莫达非尼[13]、假馬齒莧[19]、磷脂酰丝氨酸[6]和咖啡因[27]等已被证实有健脑功效的药物，與用于治疗神经系统疾病的其他药物。

通过非药物措施来改善认知能力的方法，包括行为方法[28]（活动、技巧和改变）、非侵入性脑刺激技术（已被用于改善各种认知和情感功能）和脑机接口（在扩展运动和认知能力方面具有很大潜力）。[29]

药物方法

在PubMed上搜索title或abstract中包含 “nootropic”或“smart drug”的研究和摘要的搜索结果指标；[30]许多有关促智药的研究未被收录到PubMed，而有些被收录的研究也并非主要针对这类主题

有许多包括智能药物与膳食补充剂在内的促智药，与神经或认知增强有关，但许多营养剂在健康人身上起效小，副作用大。最常见、最流行[31][32]或最起效最显著的神经增强剂包括莫达菲尼和哌醋甲酯（利他林），此类药或可能产生显著的促智效果（或至少与咖啡因效果相同或相似）。[33][12][9][9]

一般的兴奋剂[20][22]和各种抗失智药（英语：Dementia#Medications）[20][22][34][35]、抗焦虑药[34]、神入感激發劑（英语：Empathogen–entactogen）[36]、各种微量用剂（英语：microdosing）（主要用微剂量迷幻剂（英语：Psychedelic microdosing））[36][37][38][39]、及抗抑郁药[20][22]，尽管或不被认为是属促智药之范围，但或从属于神经增强的范畴。

尽管神经增强剂通常是在临床或技术领域取得成功后才被考虑投入使用，但其也常被用于帮助缺乏如社交技能与共情能力在内的，正常认知、运动和情感能力的个体。此种情况下，神经增强药物试图增加催产素，降低皮质醇水平，以帮助个体提高沟通与社交能力。[5][40]

神经增强不仅涉及强化短期和长期的智力（通常由各种类型的评估确定）、学习能力（如记忆强化）、专注或沉浸能力[9][41][42][43][40]，及通过各类心理测量所体现的指标，而且还涉及：

增强剂有生化、物理和行为层面上不同的增强策略。[64]乙醯半胱氨酸，一种低副作用的认知增强剂，与改善不健康的物质使用[51][52][65]或稳定情绪都有关系[66][67][68][69][70]。

莫達非尼

主条目：莫達非尼
莫达非尼的3D结构
在PubMed使用title或abstract筛选检索“Modafinil”的检索结果指标[71]

莫达非尼是觉醒促进剂（英语：Wakefulness-promoting agent）之一，能减轻疲劳、提高警惕、减少白天过度嗜睡（英语：Excessive daytime sleepiness）症状与改善情绪。[4][5][10]莫达非尼目前获准用于治疗嗜睡症、睡眠呼吸暂停和轮班工作睡眠紊乱等疾病，[2][5]目前也正被美国空军采用，以用于减轻机组人员执行长时间任务所带来的疲劳。莫达非尼在普通大众中也越来越受欢迎，在《自然》杂志进行的一次在线调查中，1400名读者中就有8.8%承认出于非医疗原因使用莫达非尼。他们使用莫达非尼的理由是为了提高注意力和对特定任务的专注度，或者是为了抵御睡眠不足和倒时差。[2]若将莫达非尼销售量与患者人数进行比较发现，两者的比例失调，表明对莫达非尼的滥用现象严重。[2]

莫达非尼被报告出，可以改善非有失眠症状的健康个体的执行能力，或改善注意力、学习能力与记忆力。[1]而莫达非尼对睡眠不足者的作用更为显著：单一剂量就已能提高清醒度、执行能力与记忆力。[10]在持续睡眠不足的情况下，重复服用莫达非尼有助于保持比安慰剂更高的清醒水平，但对改善注意力和执行能力没有帮助。[2][10]由于此类试验大多针对军人进行，因而还需进一步研究莫达非尼对普通人群的影响。莫达非尼或会损害人的自我监控能力，研究发现的常见趋势之一是：参与者对自己在认知测试中的表现评价高于实际水平，这表明存在「自负」效应。[2]

莫达非尼在普通人群中也越来越受欢迎，[8]除了希望借此改善自身神经系统性能，给药厂带来的经济利益也是原因之一。每年，莫达非尼的市场份额就超过7亿美元，表明除医用外的份额很高。[4]莫达非尼也是目前市场上，比较容易买到的神经增强药物之一。莫达非尼可以从许多网站（大多产自亚洲国家）或暗网市场上买到。[4][72][73]莫达非尼首次引起公众注意是在2003年田径世锦赛上，世界冠军长跑运动员凯莉·怀特因非法服用莫达非尼，被检测出阳性反应，因此也失去了两枚金牌。[4]

派醋甲酯

主条目：派醋甲酯
派醋甲酯的3D结构

哌醋甲酯（MPH）又名利他林，是兴奋剂，用于治疗注意力缺陷多动障碍（ADHD）。但众所周知，哌醋甲酯在普通人群——尤其是在大学生中被大量滥用。[2][4]在《自然》杂志开展的一次在线调查中，1400名读者中有12.4%承认出于非医疗原因使用哌醋甲酯，使用MPH的理由是为了提高注意力、改善睡眠不足和倒时差。[2]

将MPH销售量与患者人数进行比较后发现，两者的比例失调，表明滥用现象严重。[2]MPH被认为对巩固记忆有积极作用，尽管研究未能最终证实此说法。[2][10]流行观点认为MPH能增强注意力，但这一观点同样未能得到证实。[2][10]MPH的研究报告指出，MPH能提高解题能力。然而，当重复研究以期复现结果时，安慰剂组的得分更高，这表明MPH甚至会损害成绩。[4]这些不确定的、普遍负面的记忆力改善研究结果，不足以解释出于非医疗用途使用MPH的原因。除了用于改善神经机能外，用药者还可能有其他动机，如主观和娱乐效果等，而这推动了其在无处方的情况下用药。[2]

美金剛胺

主条目：美金剛胺

美金剛胺，一种NMDA受体拮抗剂，用于治疗中至重度阿尔茨海默病患者，但也被用作神经增强药物。[3]由于此类研究，大多是对美金刚的单剂量测试，而因此类药物，只有在持续摄入后才会显示出某些无论积极或消极的效果。因而，在此之前，单剂量美金刚研究不足以揭示该药物的实际潜力。[3]

多奈哌齊

主条目：多奈哌齊

多奈哌齐，一种乙酰胆碱酯酶抑制剂（AChEI），用于治疗轻至中度阿尔茨海默病患者。虽然，许多乙酰胆碱酯酶抑制剂都可能是潜在的神经增强物质，但因多奈哌齐被广泛用于治疗阿尔茨海默病，因而在普通人群中是属最常用的乙酰胆碱酯酶抑制剂。[3]

关于多奈哌齐的大多数研究都无法最终验证该药物具有神经增强的能力，[3]尽管这些研究中，服用多奈哌齐的参与者组得分高于服用安慰剂的参与者组。多奈哌齐能帮助患者保持训练任务、言语记忆和外显记忆。[3]在睡眠剥夺研究中，虽然多奈哌齐对休息良好的个体没有影响，但对被睡眠剥夺24小时的个体有积极影响，记忆力和注意力都得到了提高；若非如此，在如此睡眠不足的境地下，其记忆力和注意力就会出现缺陷。[3]不过，值得注意的是，此种效果仅出现在因睡眠不足，而成绩明显下降的人身上。[3]

研究和潜力药物

有关神经增强的研究数量指标（PubMed检索结果，通过titles与abstracts检索）[74]

有相关研究探索了现有认知增强剂的衍生物，这些衍生物具有或可能具有更高的生物利用度，如乙醯半胱胺酸的衍生物N-乙酰-L-胱氨酸（英语：Acetylcysteinamide），和其他生物利用度增强策略。[75][76]另一种增强药效、效力或选择性（selectivity）的方法是改进给药方式，[77][78]开辟更多给药途径，如通过奈米乳液（英语：nanoemulsion）鼻内给药（英语：Drug delivery to the brain）（"nose-to-brain" drug deliver），[79]或假设通过脑部植入给药。[80]

半衰期或也是研发课题之一。如，尽管莫达非尼能显著提高人的警觉性，但其半衰期长达约13小时，[81]会延迟或影响入睡时间与睡眠，[82][21]而目前市面上，也还没有短效的莫达非尼。根据2009年的两项研究，阿莫达非尼的消除速度，比外消旋莫达非尼的S-异构体慢约三倍。[83][81]

研究还可能围绕以下问题进行（英语：Research question）：

腦內生物工程

参见：神經工程和納米生物技術#應用（英语：Nanobiotechnology#Applications）

短期内，无法用于人类的高级认知增强技术，可以建立在设计受体的研究基础上，並通过蛋白质激活或抑制神经元，如使用药物遗传学技术（英语：Receptor activated solely by a synthetic ligand）。[105] 经过基因改造的神经元可将外部元件与神经连接。[106]2020年，研究人員報告稱，通过生物工程對秀麗隱桿線蟲進行了改造，使其能够在脑细胞中合成、制造和组装生物電子材料（英语：Bioelectronics），实现了对特定神经元群膜特性的调控，以及操纵活体动物的行为。[107][108][109]

如果有机神经形态设备达到一定程度，并具有生物相容性，就有可能實現新型大腦植入物。[110]还有有關潜在的可植入式物理人工神经元的研究。[111][112]基因工程或干细胞培育的神经组织的生物移植也有可能实现，[113]另种方法是透過濕件計算機（英语：Wetware computer）達成。

膳食成分和补充剂

参见：營養神經科學（英语：Nutritional neuroscience）和營養對認知的影響（英语：Nutrition and cognition）

健腦食品所含各種化合物，以草藥或分離物形式攝入，如：桂皮、[114]可可粉、[115][44][116][117][91] 花色素苷（如於 山桑子和西洋接骨木之中）、[118]硝酸盐（如於紅菜頭之中）、[91]蜂蜜、[119]多酚（存在於許多水果和蔬菜之中）、[91][120][121][122]儿茶素、[123][124] L-多巴[42]苯丙氨酸[125][126]和酪氨酸,[127][87]苯乙胺、[128]類胡蘿蔔素如番茄紅素（於番茄醬中）[128]茶氨酸、[129][89][90]芹菜素（和洋甘菊）、[130][131]薑、[132][117][126]草本茶（尤為香蜂花、迷迭香、辣薄荷和含咖啡因的飲料（英语：Caffeinated drink））、[133][134][135][136][26][126]红景天、[77][85][126][137][138]肌酸、[139][140][141]Ω-3脂肪酸（如，藻類提取物（英语：Algaculture））[146]以及纠正普遍存有的微量营养素缺乏症[147][148][149][150][126][151]研究其對健康年輕人認知能力，可能产生的微小，但显著的影响或叠加影响。

膳食中的葡萄糖（及其糖原形態）是大脑的主要能量来源，尽管直接摄入葡萄糖会影响健康，但一些研究人员认为葡萄糖是種「生化增强剂」，需要持續補充，但以單醣補充，会使血糖飙升，且其提供的葡萄糖供应，也不会持续太久。与快速吸收或高GI食物相比，吸收缓慢的含碳水化合物食物或低GI食物释放葡萄糖的速度较慢。[152][91][64][126]尽管脑葡萄糖代谢与神经退行性疾病有关，但有关脑葡萄糖代谢与认知能力之间联系的研究却很少。[153]乳酸（尤其是在特定类型的运动中释放）也可能与认知能力的提高有关。[154][155][156]

Medications

Notable potentially viable pharmacological agents – as final products or as prototypes for similar ones – under early-stage research with potential for substantial effect sizes for specific purposes in specific situations (such as learning periods) also in healthy non-old humans but, in at least most cases, largely unknown effects in humans and safety profiles (and consequently not widely used or not used at all): orexin-A,[157] FGL, PTEN-PDZ, and PI3K-activator PTD4-PI3KAc,[158] dihexa,[159][160][161] d-cycloserine,[162][163][164][40][165] DAT blockers CE-123 and CE-158,[166] ampakines like IDRA-21 and CX717,[167][168][40][126][169] rapastinel,[170][171][172] ISRIB,[173][174] citicoline,[175] selective receptor modulators such as MRK-016 which targets subtypes of GABAA receptors,[176] modafinil-analogs CRL-40,940 and modafiendz,[100] modafinil-inspired/hybrid TRIs JZ-IV-10 and JZAD-IV-22,[177][178][179] TAK-925 (orexin agonist that promotes wakefulness in ways similar to modafinil),[180][181] wakefulness-inducing or procognitive narcolepsy medication candidates like samelisant,[182][183] pterostilbene,[184][185] CRM acyl-ghrelin mimetics and agonists like ibutamoren,[186][187] and H3 receptor antagonist pitolisant.[188][182][189]

參考文獻

引用

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  2. ^ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 Repantis, Dimitris; Schlattmann, Peter. Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacological Research. 2010, 62 (3): 187–206. PMID 20416377. doi:10.1016/j.phrs.2010.04.002. 
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