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Entactogen

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Overview

Entactogens (also known as empathogens) are a class of psychoactive substances that produce distinctive emotional and social effects similar to those of MDMA. PW

Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observed and reported for experiences with MDMA (ecstasy). This class of drug is distinguished from the classes of hallucinogens or psychedelics and stimulants, although entactogens, for instance MDMA, can also have these properties. Entactogens are used both as recreational drugs and are being investigated for medical use in the treatment of psychiatric disorders, for instance MDMA-assisted therapy for post-traumatic stress disorder (PTSD).[1–11] WP

Notable members of this class include the methylenedioxyphenethylamines (MDxx) MDMA, MDA, MDEA, MDOH, MBDB, and methylone, the benzofurans 5-APB, 5-MAPB, 6-APB, and 6-MAPB, the cathinone mephedrone, the 2-aminoindane MDAI, and the α-alkyltryptamine αET, among others. Most entactogens are amphetamines, although some, such as αET, are tryptamines. When referring to MDMA and its counterparts, the term MDxx is often used (with the exception of certain non-entactogen drugs like MDPV).[1][3] WP

Entactogens act as serotonin releasing agents (SRAs) as their key action. However, entactogens also frequently have additional actions, such as induction of dopamine and norepinephrine and serotonin 5-HT₂ receptor agonism, which contributes to their effects as well. It is thought that dopamine and norepinephrine release provide additional stimulant, euphoriant, and cardiovascular or sympathomimetic effects, serotonin 5-HT2A receptor agonism produces psychedelic effects of variable intensity, and both dopamine release and serotonin 5-HT₂ receptor agonism may enhance the entactogenic effects and be critically involved in allowing for the qualitative "magic" of these drugs. Entactogens that simultaneously induce serotonin and dopamine release, for instance MDMA, may produce serotonergic neurotoxicity with associated cognitive and memory deficits as well as psychiatric changes. However, these effects are tied to larger and/or more frequent doses of MDMA in humans, while the doses that elicit neurotoxicity and cognitive deficits in animal models are typically larger than those used in clinical settings and by most recreational users.[3][12–23] WP

MDA and MDMA were both first synthesized independently in the early 1910s. The psychoactive effects of MDA were discovered in 1930 but were not described until the 1950s, MDA and MDMA emerged as recreational drugs in the 1960s, and the unique entactogenic effects of MDMA were first described in the 1970s. 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. Gordon Alles discovered the psychoactive effects of MDA, Alexander Shulgin played a key role in bringing awareness to MDMA and its unique effects, and Ralph Metzner and David E. Nichols formally defined entactogens and established them as a distinct class of drugs. Many entactogens like MDMA are controlled substances throughout the world.[1][5][6][16][24–32] WP

Drugs in this class on intoxicant.wiki

Every page on this site that a cited source puts in this class: 91 pages. A drug is listed when PsychonautWiki's "Entactogen" page, revision 162375 lists it, or when its own PsychonautWiki, TripSit or Wikipedia entry names this class. Each name opens our page for that drug; long chemical names are shown by a shorter name the drug is also known by (hover for the full name).

Tags show who puts each drug in this class (hover for the exact wording): PW list = listed on PsychonautWiki's page for this class; PW = the drug's PsychonautWiki entry; TS = the drug's TripSit entry (drug category); WP = the drug infobox of the drug's Wikipedia article. These are classifications only, not dosage guidance.

References

  1. Journal / agency Nichols DE. Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated. Front Psychiatry. 2022. doi:10.3389/fpsyt.2022.863088 · PMID 35401275 · PMC8990025
  2. Journal / agency Stocker K, Liechti ME. Methylenedioxymethamphetamine is a connectogen with empathogenic, entactogenic, and still further connective properties: It is time to reconcile "the great entactogen-empathogen debate". J Psychopharmacol. August 2024. doi:10.1177/02698811241265352 · PMID 39068642 · PMC11311894
  3. Journal / agency Oeri HE. Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy. J Psychopharmacol. May 2021. doi:10.1177/0269881120920420 · PMID 32909493 · PMC8155739
  4. Journal / agency Nichols D, Yensen R, Metzner R, Shakespeare W. The Great Entactogen-Empathogen Debate. Newsletter of the Multidisciplinary Association for Psychedelic Studies. 1993
  5. Journal / agency Nichols, D. Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens. Journal of Psychoactive Drugs. 1986. doi:10.1080/02791072.1986.10472362 · PMID 2880944
  6. Journal / agency Nichols DE, Hoffman AJ, Oberlender RA, Jacob P, Shulgin AT. Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class. J Med Chem. October 1986. doi:10.1021/jm00160a035 · PMID 3761319
  7. Journal / agency McGregor, Iain S.; Thompson, Murray R.; Callaghan, Paul D. Encyclopedia of Psychopharmacology. 2010-01-01. doi:10.1007/978-3-540-68706-1_154
  8. Journal / agency Hill SL, Thomas SH. Clinical toxicology of newer recreational drugs. Clin Toxicol (Phila). October 2011. doi:10.3109/15563650.2011.615318 · PMID 21970769
  9. Journal / agency Baldo BA. The entactogen 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) as a treatment aid in psychotherapy and its safety concerns. Arch Toxicol. August 2024. doi:10.1007/s00204-024-03765-8 · PMID 38743292
  10. Journal / agency Singh B. MDMA-Assisted Therapy for Post-Traumatic Stress Disorder: Regulatory Challenges and a Path Forward. CNS Drugs. April 2025. doi:10.1007/s40263-025-01162-y · PMID 39955464 · PMC11910333
  11. Journal / agency Wolfgang AS, Fonzo GA, Gray JC, Krystal JH, Grzenda A, Widge AS, Kraguljac NV, McDonald WM, Rodriguez CI, Nemeroff CB. MDMA and MDMA-Assisted Therapy. Am J Psychiatry. January 2025. doi:10.1176/appi.ajp.20230681 · PMID 39741438
  12. Journal / agency Kamilar-Britt P, Bedi G. The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals. Neurosci Biobehav Rev. October 2015. doi:10.1016/j.neubiorev.2015.08.016 · PMID 26408071 · PMC4678620
  13. Journal / agency Halberstadt, Adam L.; Nichols, David E. Handbook of Behavioral Neuroscience. 2020. doi:10.1016/b978-0-444-64125-0.00043-8
  14. Other Baggott M. Beyond Ecstasy: Progress in Developing and Understanding a Novel Class of Therapeutic Medicine. 23 June 2023
  15. Other Better Than Ecstasy: Progress in Developing a Novel Class of Therapeutic with Matthew Baggott, PhD. 6 March 2024
  16. Other Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA. 2001
  17. Journal / agency Sprague JE, Everman SL, Nichols DE. An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine. Neurotoxicology. June 1998. PMID 9621349
  18. Journal / agency Parrott AC. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. April 2002. doi:10.1016/s0091-3057(01)00711-0 · PMID 11888574
  19. Journal / agency Parrott AC. MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users. Neurosci Biobehav Rev. September 2013. doi:10.1016/j.neubiorev.2013.04.016 · PMID 23660456
  20. Journal / agency Aguilar MA, García-Pardo MP, Parrott AC. Of mice and men on MDMA: A translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Res. January 2020. doi:10.1016/j.brainres.2019.146556 · PMID 31734398
  21. Journal / agency Montgomery C, Roberts CA. Neurological and cognitive alterations induced by MDMA in humans. Exp Neurol. January 2022. doi:10.1016/j.expneurol.2021.113888 · PMID 34624331
  22. Journal / agency Müller, Felix; Brändle, Raphael; Liechti, Matthias E.; Borgwardt, Stefan. Neuroimaging of chronic MDMA (“ecstasy”) effects: A meta-analysis. Neuroscience & Biobehavioral Reviews. 2019-01-01. doi:10.1016/j.neubiorev.2018.11.004
  23. Journal / agency Pantoni, Madeline M.; Anagnostaras, Stephan G. Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose. Pharmacological Reviews. 2019-07-01. doi:10.1124/pr.118.017087 · PMID 31249067 · PMC6607799
  24. Journal / agency Passie, Torsten. The History of MDMA. 29 June 2023. doi:10.1093/oso/9780198867364.001.0001
  25. Journal / agency Bernschneider-Reif S, Oxler F, Freudenmann RW. The origin of MDMA ("ecstasy")--separating the facts from the myth. Pharmazie. November 2006. PMID 17152992
  26. Journal / agency Benzenhöfer U, Passie T. Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin. Addiction. August 2010. doi:10.1111/j.1360-0443.2010.02948.x · PMID 20653618
  27. Other Gordon A. Alles. Neuropharmacology: Transactions of the Fourth Conference, September 25, 26, and 27, 1957, Princeton, N. J. 1959
  28. Other Gordon A. Alles. A Pharmacologic Approach to the Study of the Mind. 1959
  29. Other Eisner, Bruce. Ecstasy: The MDMA Story. 1989
  30. Other Ralph Metzner. Lecture presented at the Psychedelics and Spirituality Conference. May 1983
  31. Other Shulgin, Alexander. Controlled Substances: A Chemical and Legal Guide to the Federal Drug Laws. 1992
  32. Other Shulgin, A.; Manning, T.; Daley, P.F. The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. 2011

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