Editing Entactogen (section)

{{Short description|Class of psychoactive drugs that produce empathic experiences}}

{{redirect|empathogen|the album by [[Willow Smith]]|Empathogen (album){{!}}''Empathogen'' (album)}}
{{Infobox drug class
| Name                = Entactogen
| Image               = File:Ecstasy monogram.jpg
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| Caption             = A selection of [[MDMA]] pills, which are often nicknamed "Ecstasy" or "E".
| Width               = 200px
| Pronounce           = 
| Synonyms            = Entactogen; Empathogen; Connectogen<ref name="Nichols2022" /><ref name="StockerLiechti2024" /><ref name="NicholsYensenMetzner1993">{{cite journal | vauthors = Nichols D, Yensen R, Metzner R, Shakespeare W | title = The Great Entactogen-Empathogen Debate | journal = Newsletter of the Multidisciplinary Association for Psychedelic Studies | volume = 4 | issue = 2 | date = 1993 | pages = 47–49 | url = https://maps.org/wp-content/uploads/1993/07/v4n2_47.pdf}}</ref><ref name="Nichols1986" />
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| Use                 = [[Recreational drug use|Recreational]], [[entheogen|spiritual]], [[medicine|medical]], [[microdosing]]
| ATC_prefix          = 
| Mode_of_action      = 
| Mechanism_of_action = [[Serotonin–norepinephrine–dopamine releasing agent]]; [[Serotonin]] [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] [[agonism]]
| Biological_target   = [[Serotonin transporter]]; [[Norepinephrine transporter]]; [[Dopamine transporter]]; [[Serotonin]] [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]s
| Chemical_class      = [[Substituted amphetamine|Amphetamine]]s, [[MDxx]], [[substituted cathinone|cathinone]]s, [[substituted benzofuran|benzofuran]]s, [[α-alkyltryptamine]]s, [[2-aminoindane]]s, others
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| Drugs.com           = <!-- {{Drugs.com|drug-class|?}} -->
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| medicinenet         = 
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| MeshID              = 
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| legal_status        = Variable
}}
{{Psychedelic sidebar}}

'''Entactogens''', also known as '''empathogens''' or '''connectogens''', are a class of [[psychoactive drug]]s that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, [[empathy]]—as particularly observed and reported for experiences with [[MDMA]].<ref name="Nichols2022" /><ref name="StockerLiechti2024" /><ref name="Oeri2021" /><ref name="NicholsYensenMetzner1993" /><ref name="Nichols1986" /> This class of drug is distinguished from the classes of [[hallucinogens|hallucinogen]]s or [[psychedelic_drug|psychedelic]]s and [[stimulant]]s, although entactogens, for instance MDMA, can also have these properties.<ref name="Nichols2022" /><ref name="Nichols1986" /><ref name="NicholsHoffmanOberlender1986">{{cite journal | vauthors = Nichols DE, Hoffman AJ, Oberlender RA, Jacob P, Shulgin AT | title = Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class | journal = J Med Chem | volume = 29 | issue = 10 | pages = 2009–2015 | date = October 1986 | pmid = 3761319 | doi = 10.1021/jm00160a035 | url = }}</ref><ref name="McGregorThompsonCallaghan2010">{{cite book|title=Encyclopedia of Psychopharmacology|last1=McGregor|first1=Iain S.|last2=Thompson|first2=Murray R.|last3=Callaghan|first3=Paul D.|date=2010-01-01|publisher=Springer Berlin Heidelberg|isbn=9783540686989|editor-last=Stolerman|editor-first=Ian P.|pages=758–762|language=en|doi=10.1007/978-3-540-68706-1_154}}</ref> Entactogens are used both as [[recreational drug]]s<ref name="HillThomas2011" /> and are being investigated for [[medicine|medical use]] in the treatment of [[psychiatric disorder]]s, for instance [[MDMA-assisted therapy]] for [[post-traumatic stress disorder]] (PTSD).<ref name="Baldo2024" /><ref name="Singh2025" /><ref name="WolfgangFonzoGray2025" />

Notable members of this class include MDMA, [[3,4-Methylenedioxyamphetamine|MDA]], [[Methylenedioxyethylamphetamine|MDEA]], [[Methylenedioxyhydroxyamphetamine|MDOH]], [[MBDB]], [[5-APB]], [[5-MAPB]], [[6-APB]], [[6-MAPB]], [[methylone]], [[mephedrone]], [[α-Methyltryptamine|αMT]], [[α-Ethyltryptamine|αET]], and [[MDAI]], among others.<ref name="Nichols2022" /><ref name="Oeri2021" /> Most entactogens are [[substituted phenethylamine|phenethylamine]]s and [[amphetamines]], although several, such as αMT and αET, are [[substituted tryptamine|tryptamine]]s.<ref name="Nichols2022" /><ref name="Oeri2021" /> When referring to MDMA and its counterparts, the term ''[[MDxx]]'' is often used (with the exception of certain non-entactogen drugs like [[MDPV]]).

Entactogens act as [[serotonin releasing agent]]s (SRAs) as their key action.<ref name="Kamilar-BrittBedi2015" /><ref name="HalberstadtNichols2020" /><ref name="Oeri2021" /><ref name="Baggott2023" /><ref name="Baggott2024" /> However, entactogens also frequently have additional actions, such as induction of [[dopamine]] and [[norepinephrine]] and [[serotonin]] [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] [[agonism]], which contributes to their effects as well.<ref name="Kamilar-BrittBedi2015" /><ref name="HalberstadtNichols2020" /><ref name="Oeri2021" /><ref name="Baggott2023" /><ref name="Baggott2024" /> It is thought that dopamine and norepinephrine release provide additional [[stimulant]], [[euphoriant]], and [[cardiovascular]] or [[sympathomimetic]] effects, serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] agonism produces [[psychedelic drug|psychedelic]] effects of variable intensity, and both dopamine release and serotonin 5-HT<sub>2</sub> receptor agonism may enhance the entactogenic effects and be critically involved in allowing for the qualitative "magic" of these drugs.<ref name="Kamilar-BrittBedi2015" /><ref name="HalberstadtNichols2020" /><ref name="Oeri2021" /><ref name="Baggott2023" /><ref name="Baggott2024" /> Entactogens that simultaneously induce serotonin and dopamine release, for instance MDMA, are known to produce long-lasting [[serotonergic neurotoxicity]]<ref name="BaggottMendelson2001">{{cite book | author1-last=Baggott | author1-first=Matthew | author2-last= Mendelson | author2-first=John | chapter=Does MDMA Cause Brain Damage? | pages=110–145, 396–404 | editor1-last=Holland | editor1-first=J. | title=Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA | publisher=Inner Traditions/Bear | year=2001 | isbn=978-0-89281-857-0 | chapter-url=https://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml | url=https://books.google.com/books?id=CUCcyklcO00C}}</ref><ref name="SpragueEvermanNichols1998">{{cite journal | vauthors = Sprague JE, Everman SL, Nichols DE | title = An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine | journal = Neurotoxicology | volume = 19 | issue = 3 | pages = 427–441 | date = June 1998 | pmid = 9621349 | doi = | url = https://www.researchgate.net/publication/13663847}}</ref><ref name="Oeri2021" /> with associated [[cognitive deficit|cognitive]] and [[memory deficit]]s as well as [[psychiatric disorder|psychiatric changes]].<ref name="Parrott2002">{{cite journal | vauthors = Parrott AC | title = Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity | journal = Pharmacol Biochem Behav | volume = 71 | issue = 4 | pages = 837–844 | date = April 2002 | pmid = 11888574 | doi = 10.1016/s0091-3057(01)00711-0 | url = }}</ref><ref name="Parrott2013">{{cite journal | vauthors = Parrott AC | title = MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users | journal = Neurosci Biobehav Rev | volume = 37 | issue = 8 | pages = 1466–1484 | date = September 2013 | pmid = 23660456 | doi = 10.1016/j.neubiorev.2013.04.016 | url = }}</ref><ref name="AguilarGarcía-PardoParrott2020">{{cite journal | vauthors = Aguilar MA, García-Pardo MP, Parrott AC | title = Of mice and men on MDMA: A translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy') | journal = Brain Res | volume = 1727 | issue = | pages = 146556 | date = January 2020 | pmid = 31734398 | doi = 10.1016/j.brainres.2019.146556 | url = }}</ref><ref name="MontgomeryRoberts2022">{{cite journal | vauthors = Montgomery C, Roberts CA | title = Neurological and cognitive alterations induced by MDMA in humans | journal = Exp Neurol | volume = 347 | issue = | pages = 113888 | date = January 2022 | pmid = 34624331 | doi = 10.1016/j.expneurol.2021.113888 | url = https://researchonline.ljmu.ac.uk/id/eprint/15629/3/Montgomery_Roberts_2021%20Review.pdf}}</ref>

MDA and MDMA were both first [[chemical synthesis|synthesized]] independently in the early 1910s.<ref name="Passie2023" /> The [[psychoactive drug|psychoactive]] effects of MDA were discovered in 1930 but were not described until the 1950s, MDA and MDMA emerged as [[recreational drug]]s in the 1960s, and the unique entactogenic effects of MDMA were first described in the 1970s.<ref name="Passie2023">{{cite book | last=Passie | first=Torsten | title=The History of MDMA | publisher=Oxford University Press | date=29 June 2023 | isbn=978-0-19-886736-4 | doi=10.1093/oso/9780198867364.001.0001 | url=https://books.google.com/books?id=KSvCEAAAQBAJ}}</ref><ref name="Bernschneider-ReifOxlerFreudenmann2006">{{cite journal | vauthors = Bernschneider-Reif S, Oxler F, Freudenmann RW | title = The origin of MDMA ("ecstasy")--separating the facts from the myth | journal = Pharmazie | volume = 61 | issue = 11 | pages = 966–972 | date = November 2006 | pmid = 17152992 | doi = | url = }}</ref><ref name="BenzenhöferPassie2010">{{cite journal | vauthors = Benzenhöfer U, Passie T | title = Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin | journal = Addiction | volume = 105 | issue = 8 | pages = 1355–61 | date = August 2010 | pmid = 20653618 | doi = 10.1111/j.1360-0443.2010.02948.x | url = }}</ref><ref name="Alles1959a">{{cite book | author=[[Gordon A. Alles]] | chapter = Some Relations Between Chemical Structure and Physiological Action of Mescaline and Related Compounds / Structure and Action of Phenethylamines | veditors = Abramson HA | title = Neuropharmacology: Transactions of the Fourth Conference, September 25, 26, and 27, 1957, Princeton, N. J. | location = New York | publisher = Josiah Macy Foundation | date = 1959 | pages = 181–268 | oclc = 9802642 | url = https://books.google.com/books?id=sDQLAQAAMAAJ&q=%22Some+relations+between+chemical+structure+and+physiological+action+of+mescaline+and+related+compounds%22 | chapter-url = https://bitnest.netfirms.com/external/Books/NeuropharmacologyTrans.4.181#page=5 | archive-url = https://web.archive.org/web/20250321230359/https://bitnest.netfirms.com/external/Books/NeuropharmacologyTrans.4.181#page=5 | archive-date = 21 March 2025 }}</ref><ref name="Alles1959b">{{cite book | author = [[Gordon A. Alles]] | chapter = Subjective Reactions to Phenethylamine Hallucinogens | title = A Pharmacologic Approach to the Study of the Mind | date = 1959 | publisher = CC Thomas | location = Springfield | pages = 238–250 (241–246) | isbn = 978-0-398-04254-7 | url = https://books.google.com/books?id=x45rAAAAMAAJ | chapter-url = https://archive.org/details/pharmacologicapp0000univ/page/238/mode/1up}}</ref> Entactogens as a unique pharmacological class depending on induction of serotonin release was established in the mid-1980s and novel entactogens such as MBDB were developed at this time and after.<ref name="Nichols2022" /><ref name="Nichols1986" /><ref name="NicholsHoffmanOberlender1986" /> [[Gordon Alles]] discovered the psychoactive effects of MDA,<ref name="Alles1959a" /><ref name="Alles1959b" /> [[Alexander Shulgin]] played a key role in bringing awareness to MDMA and its unique effects,<ref name="BenzenhöferPassie2010" /> and [[Ralph Metzner]]<ref name="Eisner1989">{{cite book | last=Eisner | first=Bruce | chapter=Chapter II. What is an Empathogen? | pages=33–50 | title=Ecstasy: The MDMA Story | publisher=Ronin Pub. | location=Berkeley, California | date=1989 | isbn=978-0-914171-25-6 | ol = OL2222596M | oclc = 27935523 | url=https://books.google.com/books?id=oIM4AQAAIAAJ | archive-url=https://archive.org/details/ecstasymdmastory0000eisn_a4n2/ | archive-date=8 June 2023 | access-date=25 April 2025}}</ref><ref name="MetznerAdamson2001">{{cite book | author1-last=Metzner | author1-first=Ralph | author2-last=Adamson | author2-first=Sophia | chapter=Using MDMA in Healing, Psychotherapy, and Spiritual Practice | pages=182–207 | editor1-last=Holland | editor1-first=J. | title=Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA | publisher=Inner Traditions/Bear | year=2001 | isbn=978-0-89281-857-0 | url=https://books.google.com/books?id=CUCcyklcO00C | quote=The term "empathogenic," meaning "generating a state of empathy," was independently proposed for these substances in 1983—84 by Ralph Metzner, a psychologist and psychopharmacologist, and David Nichols, a professor of medicinal chemistry at Purdue University. Nichols subsequently rejected the term and now prefers "entactogenic," meaning "touching within," for MDMA. We continue to use the term "empathogenic."}}</ref><ref name="Metzner1983">{{cite conference | author = [[Ralph Metzner]] | title = [Lecture presented at the Psychedelics and Spirituality Conference] | conference = Psychedelics and Spirituality, University of California, Santa Babara, May 13–14, 1983 | date = May 1983 | url = https://scholar.google.com/scholar?cluster=16938435501563008121 | quote = Another group of drugs are the phenethylamines, of which MDA [and MDMA] is an example. Instead of calling these "psychedelic drugs," I'd like to suggest the name "empathogenic." Empathogenic means "empathy generating." Everyone I've mentioned this name to thinks it is a good one. These drugs don't produce visions as LSD does. They don't produce multileveled thinking or objectivity toward your mind as LSD and the psychedelics do. They generate a profound state of empathy for self and other in the most general and profound terms. A state of empathy where the feeling is that the self, the other, and the world is basically good, is all right. This state can be referred to as the ground of being, the core of our being, a still point of our being. Then individuals using these substances in therapy can look at their own problems from the standpoint of stillness and empathy. They are able to do changework on themselves very rapidly, compared to ordinary therapy.}}</ref> and [[David E. Nichols]] formally defined entactogens and established them as a distinct class of drugs.<ref name="Nichols2022" /><ref name="Nichols1986" /><ref name="NicholsHoffmanOberlender1986" /> Many entactogens like [[MDMA]] are [[controlled substance]]s throughout the world.<ref name="Shulgin1992">{{cite book | last=Shulgin | first=Alexander | title=Controlled Substances: A Chemical and Legal Guide to the Federal Drug Laws | publisher=Ronin Pub. | date=1992 | isbn=978-0-914171-50-8 | url=https://books.google.com/books?id=rO4MAAAACAAJ | access-date=25 April 2025 | page=}}</ref><ref name="ShulginManningDaley2011">{{cite book | last1=Shulgin | first1=A. | last2=Manning | first2=T. | last3=Daley | first3=P.F. | title=The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher=[[Transform Press]] | location=Berkeley | volume=1 | year=2011 | isbn=978-0-9630096-3-0 | url=https://books.google.com/books?id=68-huAAACAAJ}}</ref>