Serenic

{{Short description|Type of drug that reduces aggression}} {{Infobox drug class | Name = | Image = | ImageClass = | Alt = | Caption = | Pronounce = | Synonyms = Anti-aggressive drug; Anti-aggressive agent; Anti-aggressive medication; Antiaggressive drug; Antiaggressive agent; Antiaggressive medication

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A '''serenic''', or '''anti-aggressive drug''', is a type of drug which reduces the capacity for aggression.<ref name="OlivierMos1986">{{cite journal |url=https://onlinelibrary.wiley.com/doi/10.1002/smi.2460020305 |title=Serenics and aggression | vauthors = Olivier B, Mos J |volume=2 |issue=3 |pages=197–209 |issn=1532-2998 |doi=10.1002/smi.2460020305 |publisher=Wiley |journal=Stress & Health | veditors = Chan DK |publication-place=Arlington, Virginia, United States of America |date=10 July 1986 |url-access=subscription }}</ref> Known drugs with antiaggressive effects include various serotonergic agents, antidopaminergic drugs like antipsychotics, anticonvulsants and mood stabilizers, beta blockers, nicotine, cannabinoids, oxytocin- and vasopressin-related drugs, and testosterone-suppressing drugs.

==Examples== ===Serotonergic agents=== The recreational drug MDMA ("ecstasy") and a variety of related drugs have been described as ''empathogen-entactogens'', or simply as ''entactogens''.<ref name="pmid20947066">{{cite journal | vauthors = Bedi G, Hyman D, de Wit H | title = Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others | journal = Biological Psychiatry | volume = 68 | issue = 12 | pages = 1134–1140 | date = December 2010 | pmid = 20947066 | pmc = 2997873 | doi = 10.1016/j.biopsych.2010.08.003 | publisher = Society of Biological Psychiatry | publication-place = Brentwood, Tennessee, United States of America | lccn = 78009779 | veditors = Krystal JH | oclc = 424038458 }}</ref> These agents possess serenic and empathy-increasing properties in addition to their euphoriant effects, and have been associated with increased sociability, friendliness, and feelings of closeness to others as well as emotional empathy and prosocial behavior.<ref name="pmid24097374">{{cite journal | vauthors = Hysek CM, Schmid Y, Simmler LD, Domes G, Heinrichs M, Eisenegger C, Preller KH, Quednow BB, Liechti ME | display-authors = 6 | title = MDMA enhances emotional empathy and prosocial behavior | journal = Social Cognitive and Affective Neuroscience | volume = 9 | issue = 11 | pages = 1645–1652 | date = November 2014 | pmid = 24097374 | pmc = 4221206 | doi = 10.1093/scan/nst161 | publisher = Oxford University Press | veditors = Lieberman MD }}</ref><ref name="pmid10917407">{{cite journal | vauthors = Cami J, Farré M, Mas M, Roset PN, Poudevida S, Mas A, San L, de la Torre R | display-authors = 6 | title = Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects | journal = Journal of Clinical Psychopharmacology | volume = 20 | issue = 4 | pages = 455–466 | date = August 2000 | pmid = 10917407 | doi = 10.1097/00004714-200008000-00010 }}</ref> The entactogenic effects of these drugs are thought to be related to their ability to temporarily increase the levels of certain brain chemicals, including serotonin,<ref name="pmid17609680">{{cite journal | vauthors = Piper BJ, Fraiman JB, Owens CB, Ali SF, Meyer JS | title = Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram | journal = Neuropsychopharmacology | volume = 33 | issue = 5 | pages = 1192–1205 | date = April 2008 | pmid = 17609680 | doi = 10.1038/sj.npp.1301491 | publication-place = Brentwood, Tennessee, United States of America | veditors = Carlezon WA, George TP, Neumaier JF | publisher = American College of Neuropsychopharmacology (ACNP) | doi-access = free }}</ref> dopamine, and, particularly, oxytocin.<ref name="pmid24097374" /><ref name="pmid19562632">{{cite journal | vauthors = Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, van Gerven JM, Buitelaar JK, Verkes RJ | display-authors = 6 | title = Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration | journal = Social Neuroscience | volume = 4 | issue = 4 | pages = 359–366 | year = 2009 | pmid = 19562632 | doi = 10.1080/17470910802649470 | s2cid = 12310995 | veditors = Eslinger P, Boggio PS, Young L, Zahn R | oclc = 69984013 | publication-place = London, United Kingdom of Great Britain | publisher = Society for Social Neuroscience/Taylor & Francis | lccn = 2006244001 }}</ref><ref name="pmid23872370">{{cite journal | vauthors = Broadbear JH, Kabel D, Tracy L, Mak P | title = Oxytocinergic regulation of endogenous as well as drug-induced mood | journal = Pharmacology, Biochemistry, and Behavior | volume = 119 | issue = 1 | pages = 61–71 | date = April 2014 | pmid = 23872370 | doi = 10.1016/j.pbb.2013.07.002 | veditors = Koob JF, Schulteis G, Kantak KM, Arends M, Buisman-Pijlman FT, Broadbear JH, Zoltán S | oclc = 1787728 | publication-place = Amsterdam, Netherlands | publisher = Elsevier | s2cid = 19772247 | lccn = 73644949 }}</ref>

Certain other serotonergic drugs, such as 5-HT1A receptor agonists, also increase oxytocin levels and may possess serenic properties as well.<ref name="pmid16310183">{{cite journal | vauthors = de Boer SF, Koolhaas JM | title = 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis | journal = European Journal of Pharmacology | volume = 526 | issue = 1–3 | pages = 125–139 | date = December 2005 | pmid = 16310183 | doi = 10.1016/j.ejphar.2005.09.065 | publisher = Elsevier | veditors = Redegeld FA, Verri WA, Burk J | publication-place = Amsterdam, Netherlands | lccn = sf97001017 | oclc = 01568459 }}</ref> The phenylpiperazine mixed 5-HT1A and 5-HT1B receptor agonists eltoprazine, fluprazine, and batoprazine have been described based on animal research as serenics.<ref name="Olivier2006">{{cite journal | vauthors = Olivier B | title = Serotonin and aggression | journal = Annals of the New York Academy of Sciences | volume = 1036 | issue = 1 | pages = 382–392 | date = December 2004 | pmid = 15817750 | doi = 10.1196/annals.1330.022 | publisher = New York Academy of Sciences | publication-place = New York City, New York, United States of America | s2cid = 45595253 | lccn = 12037287 | bibcode = 2004NYASA1036..382O | oclc = 01306678 }}</ref> The selective 5-HT1A biased full agonist F-15,599 (NLX-101) has shown antiaggressive effects in rodents as well.<ref name="SałaciakPytka2021">{{cite journal | vauthors = Sałaciak K, Pytka K | title = Biased agonism in drug discovery: Is there a future for biased 5-HT1A receptor agonists in the treatment of neuropsychiatric diseases? | journal = Pharmacol Ther | volume = 227 | issue = | article-number = 107872 | date = November 2021 | pmid = 33905796 | doi = 10.1016/j.pharmthera.2021.107872 | url = | doi-access = free }}</ref>

The serotonin 5-HT2C receptor agonist lorcaserin has been found to reduce impulsive aggression in people with intermittent explosive disorder (IED).<ref name="PopovaTsybkoNaumenko2022">{{cite journal | vauthors = Popova NK, Tsybko AS, Naumenko VS | title = The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference | journal = Int J Mol Sci | volume = 23 | issue = 15 | date = August 2022 | page = 8814 | pmid = 35955946 | pmc = 9369404 | doi = 10.3390/ijms23158814 | doi-access = free | url = | quote = There are some pharmacological data indicating a link between aggressive behavior and 5-HT2A receptor activity. In animals, 5-HT2A agonists, such as DOI, reduced aggressive behavior in flies, amphibians, mice and rats [34]. However, accumulated data also revealed a pro-aggressive effect of the 5-HT2A agonist DOI [119,120], whereas 5-HT2A antagonists effectively suppressed aggressive behavior [119,121,122]. In humans, a number of atypical antipsychotics, which act as antagonists of 5-HT2A receptors, had antiaggressive effects in clinical trials reviewed by Comai and co-authors [123]. [...] There are a few currently available data in support of the antiaggressive role of 5-HT2C receptors: (1) the activation of 5-HT2C receptors enhanced the display of defeat submissive and defensive behavior in golden hamsters [172]. (2) 5-HT2C receptor agonist/alpha 2 receptor antagonist S32212 suppressed aggressive behavior in mice [173]. (3) Mice expressing only the VGV isoform of 5-HT2C receptors displayed a high level of conspecific aggression [174]. (4) The association between Htr2c gene polymorphism and criminal behavior in humans was demonstrated [175]. (5) Recently, a novel 5-HT2C agonist, lorcaserin, has been demonstrated to have antiaggressive properties in human subjects with impulsive aggressive behavior. Lorcaserin attenuated provoked, but not unprovoked, aggression in impulsively aggressive individuals indicating that 5-HT2C receptor may be a putative target for the treatment of impulsive aggressive behavior in human subjects [176]. }}</ref><ref name="DesilvaHollander2023">{{cite book | last1=Desilva | first1=Nilifa | last2=Hollander | first2=Eric | title=Tasman's Psychiatry | chapter=Impulse Control Disorders: Intermittent Explosive Disorder, Kleptomania, Pyromania | publisher=Springer International Publishing | publication-place=Cham | date=2023 | isbn=978-3-030-42825-9 | doi=10.1007/978-3-030-42825-9_165-1 | page=1–49 | quote=Based on evidence from a recent pilot study, lorcaserin, a selective 5-HT2c agonist, was found to have anti-aggressive effects in humans with high levels of impulsive aggression like in those diagnosed with IED. }}</ref><ref name="TahirWongMaaz2022">{{cite journal | vauthors = Tahir T, Wong MM, Maaz M, Naufal R, Tahir R, Naidoo Y | title = Pharmacotherapy of impulse control disorders: A systematic review | journal = Psychiatry Res | volume = 311 | issue = | article-number = 114499 | date = May 2022 | pmid = 35305343 | doi = 10.1016/j.psychres.2022.114499 | url = }}</ref><ref name="CoccaroLee2019">{{cite journal | vauthors = Coccaro EF, Lee RJ | title = 5-HT2c agonist, lorcaserin, reduces aggressive responding in intermittent explosive disorder: A pilot study | journal = Hum Psychopharmacol | volume = 34 | issue = 6 | article-number = e2714 | date = November 2019 | pmid = 31774584 | doi = 10.1002/hup.2714 | url = }}</ref> Serotonin 5-HT2C receptor agonists have also been found to produce antiaggressive effects in rodents.<ref name="PopovaTsybkoNaumenko2022" />

The serotonergic psychedelics DOB and DOI, which act as serotonin 5-HT2 receptor agonists, show antiaggressive effects in rodents.<ref name="PopovaTsybkoNaumenko2022" /><ref name="MorrisonMelloni2014">{{cite book | vauthors = Morrison TR, Melloni RH | title = Neuroscience of Aggression | chapter = The role of serotonin, vasopressin, and serotonin/vasopressin interactions in aggressive behavior | series = Curr Top Behav Neurosci | volume = 17 | pages = 189–228 | date = 2014 | pmid = 24496652 | doi = 10.1007/7854_2014_283 | isbn = 978-3-662-44280-7 | chapter-url = | quote = Another 5HT2A receptor partial agonist, DOB, has a marginally higher affinity for the 5HT2A receptor (in its low affinity state) than DOI (Roth et al. 1997), and in the water competition (WC) test it has been shown to block defensive aggression in rats. Interestingly, DOI also reduced the number of offensive aggressive behaviors (i.e., attacks, greater latency to first attack, shorter attack duration) in the same animals that exhibited DOI-induced reductions in defensive behaviors during the WC test (Muehlenkamp et al. 1995).}}</ref><ref name="MuehlenkampLucionVogel1995">{{cite journal | vauthors = Muehlenkamp F, Lucion A, Vogel WH | title = Effects of selective serotonergic agonists on aggressive behavior in rats | journal = Pharmacology Biochemistry and Behavior | volume = 50 | issue = 4 | pages = 671–674 | date = April 1995 | pmid = 7617717 | doi = 10.1016/0091-3057(95)00351-7 | s2cid = 12774131 }}</ref><ref name="SakaueAgoSowa2002">{{cite journal | vauthors = Sakaue M, Ago Y, Sowa C, Sakamoto Y, Nishihara B, Koyama Y, Baba A, Matsuda T | title = Modulation by 5-hT2A receptors of aggressive behavior in isolated mice | journal = Jpn J Pharmacol | volume = 89 | issue = 1 | pages = 89–92 | date = May 2002 | pmid = 12083749 | doi = 10.1254/jjp.89.89 | url = | doi-access = free }}</ref> However, DOI has also been found to have pro-aggressive effects.<ref name="PopovaTsybkoNaumenko2022" /> In older literature, other psychedelics, including LSD, psilocin, dimethyltryptamine (DMT), and mescaline, have been found to reduce aggression in monkeys, but have also been found to increase aggression in animals in other contexts.<ref name="MartinSloan1977">{{cite book | last1=Martin | first1=W. R. | last2=Sloan | first2=J. W. | title=Drug Addiction II: Amphetamine, Psychotogen, and Marihuana Dependence | chapter=Pharmacology and Classification of LSD-like Hallucinogens | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | date=1977 | isbn=978-3-642-66711-4 | doi=10.1007/978-3-642-66709-1_3 | chapter-url=https://books.google.com/books?id=gb_uCAAAQBAJ&pg=PA305 | pages=305–368}}</ref> Serotonin 5-HT2A receptor antagonists have been found to reduce aggression in animals.<ref name="PopovaTsybkoNaumenko2022" /> Atypical antipsychotics, which act in part as serotonin 5-HT2A receptor antagonists, have antiaggressive effects in humans.<ref name="PopovaTsybkoNaumenko2022" /> The selective serotonin reuptake inhibitors (SSRIs) sertraline, fluvoxamine, and fluoxetine inhibited aggression in rodents, whereas the SSRIs citalopram and paroxetine were ineffective.<ref name="MiczekFishDeBold2002">{{cite journal | vauthors = Miczek KA, Fish EW, De Bold JF, De Almeida RM | title = Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gamma-aminobutyric acid systems | journal = Psychopharmacology (Berl) | volume = 163 | issue = 3–4 | pages = 434–458 | date = October 2002 | pmid = 12373445 | doi = 10.1007/s00213-002-1139-6 | url = }}</ref><ref name="SánchezMeier1997">{{cite journal | vauthors = Sánchez C, Meier E | title = Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike? | journal = Psychopharmacology (Berl) | volume = 129 | issue = 3 | pages = 197–205 | date = February 1997 | pmid = 9084057 | doi = 10.1007/s002130050181 | url = }}</ref>

===Antidopaminergic agents=== Antipsychotics, which are dopamine D2 receptor antagonists, are well-known as reducing aggression in humans and have been clinically employed for this purpose.<ref name="ItilWadud1975">{{cite journal | vauthors = Itil TM, Wadud A | title = Treatment of human aggression with major tranquilizers, antidepressants, and newer psychotropic drugs | journal = J Nerv Ment Dis | volume = 160 | issue = 2–1 | pages = 83–99 | date = February 1975 | pmid = 235010 | doi = 10.1097/00005053-197502000-00003 | url = }}</ref> Molindone is under development for the treatment of impulsive aggression in children and adolescents with attention deficit hyperactivity disorder (ADHD).<ref name="AdisInsight">{{cite web | title=Molindone - Supernus Pharmaceuticals | website=AdisInsight | date=29 May 2024 | url=https://adisinsight.springer.com/drugs/800029611 | access-date=18 October 2024}}</ref><ref name="RobbSchwabeCeresoli-Borroni2019">{{cite journal | vauthors = Robb AS, Schwabe S, Ceresoli-Borroni G, Nasser A, Yu C, Marcus R, Candler SA, Findling RL | title = A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression | journal = Postgrad Med | volume = 131 | issue = 2 | pages = 129–137 | date = March 2019 | pmid = 30678534 | doi = 10.1080/00325481.2019.1574401 | url = | doi-access = free }}</ref>

===Anticonvulsants and mood stabilizers=== Certain anticonvulsants and mood stabilizers, including valproic acid/divalproex sodium, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, and lithium, have been found to be effective in the treatment of aggression.<ref name="StanfordAndersonLake2009">{{cite journal | vauthors = Stanford MS, Anderson NE, Lake SL, Baldridge RM | title = Pharmacologic treatment of impulsive aggression with antiepileptic drugs | journal = Curr Treat Options Neurol | volume = 11 | issue = 5 | pages = 383–390 | date = September 2009 | pmid = 19744405 | doi = 10.1007/s11940-009-0043-3 | url = }}</ref><ref name="HubandFerriterNathan2010">{{cite journal | vauthors = Huband N, Ferriter M, Nathan R, Jones H | title = Antiepileptics for aggression and associated impulsivity | journal = Cochrane Database Syst Rev | volume = 2010 | issue = 2 | article-number = CD003499 | date = February 2010 | pmid = 20166067 | pmc = 4163499 | doi = 10.1002/14651858.CD003499.pub3 | url = }}</ref><ref name="ComaiTauPavlovic2012">{{cite journal | vauthors = Comai S, Tau M, Pavlovic Z, Gobbi G | title = The psychopharmacology of aggressive behavior: a translational approach: part 2: clinical studies using atypical antipsychotics, anticonvulsants, and lithium | journal = J Clin Psychopharmacol | volume = 32 | issue = 2 | pages = 237–260 | date = April 2012 | pmid = 22367663 | doi = 10.1097/JCP.0b013e31824929d6 | url = }}</ref><ref name="Guay2007">{{cite journal | vauthors = Guay DR | title = Newer antiepileptic drugs in the management of agitation/aggression in patients with dementia or developmental disability | journal = Consult Pharm | volume = 22 | issue = 12 | pages = 1004–1034 | date = December 2007 | pmid = 18198960 | doi = 10.4140/tcp.n.2007.1004 | url = }}</ref><ref name="GallagherHerrmann2014">{{cite journal | vauthors = Gallagher D, Herrmann N | title = Antiepileptic drugs for the treatment of agitation and aggression in dementia: do they have a place in therapy? | journal = Drugs | volume = 74 | issue = 15 | pages = 1747–1755 | date = October 2014 | pmid = 25239267 | doi = 10.1007/s40265-014-0293-6 | url = }}</ref> Certain others, including gabapentin and tiagabine, may also have antiaggressive effects.<ref name="StanfordAndersonLake2009" /><ref name="ComaiTauPavlovic2012" /><ref name="GallagherHerrmann2014" /> Conversely, levetiracetam has been found to be ineffective.<ref name="StanfordAndersonLake2009" /><ref name="GallagherHerrmann2014" /> Although anticonvulsants have been found to be effective for treating aggression, it has been reported that many of the same drugs might also produce anger, aggression, and irritability in people with epilepsy.<ref name="BrodieBesagEttinger2016">{{cite journal | vauthors = Brodie MJ, Besag F, Ettinger AB, Mula M, Gobbi G, Comai S, Aldenkamp AP, Steinhoff BJ | title = Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review | journal = Pharmacol Rev | volume = 68 | issue = 3 | pages = 563–602 | date = July 2016 | pmid = 27255267 | pmc = 4931873 | doi = 10.1124/pr.115.012021 | url = }}</ref><ref name="HansenLjungBrodtkorb2018">{{cite journal | vauthors = Hansen CC, Ljung H, Brodtkorb E, Reimers A | title = Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel | journal = Behav Neurol | volume = 2018 | issue = | article-number = 2064027 | date = 2018 | pmid = 30581496 | pmc = 6276511 | doi = 10.1155/2018/2064027 | doi-access = free | url = }}</ref>

===Beta blockers=== Beta blockers, or β-adrenergic receptor antagonists, have been used to treat aggression and agitation.<ref name="BoyceBalloneCerta2021">{{cite journal | vauthors = Boyce TG, Ballone NT, Certa KM, Becker MA | title = The Use of β-Adrenergic Receptor Antagonists in Psychiatry: A Review | journal = J Acad Consult Liaison Psychiatry | volume = 62 | issue = 4 | pages = 404–412 | date = 2021 | pmid = 34210401 | doi = 10.1016/j.jaclp.2020.12.009 | url = }}</ref> Beta blockers that have been used for such purposes include propranolol, pindolol, and nadolol.<ref name="BoyceBalloneCerta2021" />

===Psychostimulants=== Psychostimulants like methylphenidate and amphetamines as well as the atypical antipsychotic risperidone are useful in reducing aggression and oppositionality in children and adolescents with attention-deficit hyperactivity disorder (ADHD), antisocial personality disorder, and autism spectrum disorder with moderate to large effect sizes and greater effectiveness than other studied medications.<ref>{{cite journal | vauthors = Pringsheim T, Hirsch L, Gardner D, Gorman DA | title = The pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder: a systematic review and meta-analysis. Part 1: psychostimulants, alpha-2 agonists, and atomoxetine | journal = Can J Psychiatry | volume = 60 | issue = 2 | pages = 42–51 | date = February 2015 | pmid = 25886655 | pmc = 4344946 | doi = 10.1177/070674371506000202 | url = }}</ref><ref>{{cite journal | vauthors = Pringsheim T, Hirsch L, Gardner D, Gorman DA | title = The pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder: a systematic review and meta-analysis. Part 2: antipsychotics and traditional mood stabilizers | journal = Can J Psychiatry | volume = 60 | issue = 2 | pages = 52–61 | date = February 2015 | pmid = 25886656 | pmc = 4344947 | doi = 10.1177/070674371506000203 | url = }}</ref> Another meta-analysis found that methylphenidate slightly reduced irritability while amphetamines increased the risk of irritability several-fold in children with ADHD however.<ref>{{cite journal | vauthors = Stuckelman ZD, Mulqueen JM, Ferracioli-Oda E, Cohen SC, Coughlin CG, Leckman JF, Bloch MH | title = Risk of Irritability With Psychostimulant Treatment in Children With ADHD: A Meta-Analysis | journal = J Clin Psychiatry | volume = 78 | issue = 6 | pages = e648–e655 | date = June 2017 | pmid = 28682529 | doi = 10.4088/JCP.15r10601 | url = }}</ref> Other research has found no impact of amphetamine or methamphetamine on aggression in humans.<ref name="OMalleyHartCasey2022">{{cite journal | vauthors = O'Malley KY, Hart CL, Casey S, Downey LA | title = Methamphetamine, amphetamine, and aggression in humans: A systematic review of drug administration studies | journal = Neurosci Biobehav Rev | volume = 141 | issue = | article-number = 104805 | date = October 2022 | pmid = 35926727 | doi = 10.1016/j.neubiorev.2022.104805 | url = | hdl = 10072/422156 | hdl-access = free }}</ref>

===Cholinergic agents=== Nicotinic acetylcholine receptors within the CNS, specifically α7 homopentameric receptors, are implicated in the regulation of aggression. The serenic effect of nicotine is well documented both in laboratory animals and humans, and, conversely, nicotinic receptor antagonists and nicotine withdrawal are associated with irritability and aggression.<ref>{{cite journal | vauthors = Lewis AS, Picciotto MR | title = Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies | journal = Neuropharmacology | volume = 167 | article-number = 107929 | date = May 2020 | pmid = 32058178 | pmc = 7080580 | doi = 10.1016/j.neuropharm.2019.107929 }}</ref><ref>{{cite journal | vauthors = Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR | title = Modulation of aggressive behavior in mice by nicotinic receptor subtypes | journal = Biochemical Pharmacology | volume = 97 | issue = 4 | pages = 488–497 | date = October 2015 | pmid = 26212554 | pmc = 4600457 | doi = 10.1016/j.bcp.2015.07.019 | series = Nicotinic Acetylcholine Receptors as Therapeutic Targets: Emerging Frontiers in Basic Research and Clinical Science (Satellite to the 2015 Meeting of the Society for Neuroscience) Oct 14-15, Chicago, IL USA }}</ref><ref>{{cite journal | vauthors = Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS | title = Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states | journal = Neuropharmacology | volume = 96 | issue = Pt B | pages = 235–243 | date = September 2015 | pmid = 25582289 | pmc = 4486625 | doi = 10.1016/j.neuropharm.2014.12.028 | series = The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition }}</ref> Additionally, nicotinic receptors are required for rabies virus entry into a neuron, and the dysfunction of these neurons is implicated in the rabies-associated aggression.<ref>{{cite journal | vauthors = Hueffer K, Khatri S, Rideout S, Harris MB, Papke RL, Stokes C, Schulte MK | title = Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS | journal = Scientific Reports | volume = 7 | issue = 1 | article-number = 12818 | date = October 2017 | pmid = 28993633 | pmc = 5634495 | doi = 10.1038/s41598-017-12726-4 | bibcode = 2017NatSR...712818H }}</ref>

===Cannabinoids=== Cannabinoids like nabilone have been studied and reported effective for management of severe aggression in people with profound autism and other intellectual and developmental disabilities.<ref name="LinAbi-JaoudeDesarkar2025">{{cite journal | last1=Lin | first1=Hsiang-Yuan | last2=Abi-Jaoude | first2=Elia | last3=Desarkar | first3=Pushpal | last4=Wang | first4=Wei | last5=Ameis | first5=Stephanie H. | last6=Lai | first6=Meng-Chuan | last7=Lunsky | first7=Yona | last8=Rajji | first8=Tarek | title=364. Nabilone for Severe Aggression in Adults With Profound Autism or Intellectual and Developmental Disabilities: A Phase I Open-Label Clinical Trial | journal=Biological Psychiatry | volume=97 | issue=9 | date=2025 | doi=10.1016/j.biopsych.2025.02.602 | page=S246 | url=https://linkinghub.elsevier.com/retrieve/pii/S0006322325007000 | access-date=6 May 2025| url-access=subscription }}</ref>

===Hormonal and related agents=== Agonists and antagonists of the receptors for the endogenous hormones oxytocin and vasopressin, respectively, have been shown to decrease aggressive behavior in scientific research, implicating them in the normal regulation of pathways involving aggressive behavior in the brain.<ref name="pmid23624810">{{cite journal | vauthors = Calcagnoli F, de Boer SF, Althaus M, den Boer JA, Koolhaas JM | title = Antiaggressive activity of central oxytocin in male rats | journal = Psychopharmacology | volume = 229 | issue = 4 | pages = 639–651 | date = October 2013 | pmid = 23624810 | doi = 10.1007/s00213-013-3124-7 | s2cid = 481042 | veditors = de Witt H, Curran VH, Morrow AL, Hashimoto K, Howes O, Floresco SB, D'Souza D | publication-place = Geneva, Switzerland | publisher = European Behavioural Pharmacology Society (EBPS)/Springer | url = https://research.rug.nl/en/publications/9c823e23-6545-4295-8340-12457a2b1567 | hdl = 11370/9c823e23-6545-4295-8340-12457a2b1567 | hdl-access = free }}</ref><ref name="pmid16504276">{{cite journal | vauthors = Ferris CF, Lu SF, Messenger T, Guillon CD, Heindel N, Miller M, Koppel G, Robert Bruns F, Simon NG | display-authors = 6 | title = Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior | journal = Pharmacology, Biochemistry, and Behavior | volume = 83 | issue = 2 | pages = 169–174 | date = February 2006 | pmid = 16504276 | doi = 10.1016/j.pbb.2006.01.001 | veditors = Griebel G, Arends MA, Izenwasser S | publication-place = Amsterdam, Netherlands | s2cid = 24199104 | oclc = 67271683 }}</ref> The small-molecule indirect oxytocin-like drugs KNX-100 (SOC-1) and KNX-101, which have since been found to act as 15-lipoxygenase (15-LOX; ALOX15) inhibitors, have been found to produce antiaggressive effects in animals.<ref name="SalthouseAsserehLee2025">{{cite journal | vauthors = Salthouse T, Assereh N, Lee T, Wilson B, Tan O, Badolato C, Freeborn C, Bowen M | title=696. Whole Brain Activity Mapping of the Effects of a Novel Small Molecule on Chronic Social Isolation Induced Aggression in Mice | journal=International Journal of Neuropsychopharmacology | volume=28 | issue=Supplement_2 | date=18 August 2025 | issn=1461-1457 | pmc=12359352 | doi=10.1093/ijnp/pyaf052.113 | pages=ii56–ii57 | url=https://academic.oup.com/ijnp/article/28/Supplement_2/ii56/8237030 | quote=KNX100 is a novel, prosocial compound that has been shown to reduce aggression in preclinical models. [...]}}</ref><ref name="Bowen2026">{{cite conference | author = Michael Bowen, Kinoxis Therapeutics | title = Developing Novel ALOX15 Inhibitors for Dementia and Pain, High-Need CNS Indications | conference = Sachs Associates 9th Annual Neuroscience Innovation Forum for Business Development, Licensing & Investment, 11th January 2026, Marines' Memorial Club, San Francisco, USA | date = 11 January 2026 | conference-url = https://www.sachsforum.com/9nif-about.html | url = https://www.youtube.com/watch?v=bOqOipQDjHg}}</ref> Certain neurosteroids, such as allopregnanolone, also appear to play a role in the regulation of aggression, including, notably, sexually-dimorphic aggressive behavior.<ref name="pmid18473173">{{cite journal | vauthors = Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E | title = Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice | journal = Neurochemical Research | volume = 33 | issue = 10 | pages = 1990–2007 | date = October 2008 | pmid = 18473173 | doi = 10.1007/s11064-008-9718-5 | publisher = Springer | publication-place = Geneva, Switzerland | veditors = Schousboe A | s2cid = 19338424 }}</ref> The sex hormones testosterone and estradiol regulate aggression as well.<ref name="CunninghamLumiaMcGinnis2012">{{cite journal | vauthors = Cunningham RL, Lumia AR, McGinnis MY | title = Androgen receptors, sex behavior, and aggression | journal = Neuroendocrinology | volume = 96 | issue = 2 | pages = 131–140 | date = 2012 | pmid = 22414851 | pmc = 3474193 | doi = 10.1159/000337663 | url = }}</ref><ref name="GiammancoTabacchiGiammanco2005">{{cite journal | vauthors = Giammanco M, Tabacchi G, Giammanco S, Di Majo D, La Guardia M | title = Testosterone and aggressiveness | journal = Med Sci Monit | volume = 11 | issue = 4 | pages = RA136–45 | date = April 2005 | pmid = 15795710 | doi = | url = }}</ref><ref name="AlbertJonikWalsh1992">{{cite journal | vauthors = Albert DJ, Jonik RH, Walsh ML | title = Hormone-dependent aggression in male and female rats: experiential, hormonal, and neural foundations | journal = Neurosci Biobehav Rev | volume = 16 | issue = 2 | pages = 177–192 | date = 1992 | pmid = 1630729 | doi = 10.1016/s0149-7634(05)80179-4 | url = }}</ref>

== References == {{Reflist}}

Category:Antiaggressive drugs