Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs 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.[1][2][5][3][4] 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.[1][4][6][7] Entactogens are used both as recreational drugs[8] and are being investigated for medical use in the treatment of psychiatric disorders, for instance MDMA-assisted therapy for post-traumatic stress disorder (PTSD).[9][10][11]
Notable members of this class include MDMA, MDA, MDEA, MDOH, MBDB, 5-APB, 5-MAPB, 6-APB, 6-MAPB, methylone, mephedrone, αMT, αET, and MDAI, among others.[1][5] Most entactogens are phenethylamines and amphetamines, although several, such as αMT and αET, are tryptamines.[1][5] 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 agents (SRAs) as their key action.[12][13][5][14][15] 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.[12][13][5][14][15] 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.[12][13][5][14][15] Entactogens that simultaneously induce serotonin and dopamine release, for instance MDMA, are known to produce long-lasting serotonergic neurotoxicity[16][17][5] with associated cognitive and memory deficits as well as psychiatric changes.[18][19][20][21]
The term empathogen, meaning "generating a state of empathy", was independently coined by Ralph Metzner in 1983 and David E. Nichols in 1984 as a term to denote a class of drugs that includes MDMA and other agents with similar effects.[27][28][29] Subsequently, in 1986, Nichols rejected this initial terminology and adopted, instead, the term entactogen, meaning "producing a touching within", to denote this class of drugs, asserting a concern with the potential for improper association of the term empathogen with negative connotations related to the Greek root πάθος páthos ("suffering; passion").[1][4][6] Additionally, Nichols wanted to avoid any association with the term pathogenesis.[66]
Nichols also thought the original term was limiting, and did not cover other therapeutic uses for the drugs that go beyond instilling feelings of empathy.[3] The hybrid word entactogen is derived from the roots en (Greek: within), tactus (Latin: touch) and -gen (Greek: produce).[4] Entactogen is not becoming dominant in usage, and, despite their difference in connotation, they are essentially interchangeable, as they refer to precisely the same chemicals.
In 2024, an additional alternative term, connectogen, was proposed and introduced by Kurt Stocker and Matthias Liechti.[2]
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