Entactogen

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. 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).

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. Most entactogens are phenethylamines and amphetamines, although several, such as αMT and 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).

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-HT_2A 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, are known to produce long-lasting serotonergic neurotoxicity with associated cognitive and memory deficits as well as psychiatric changes.

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.