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Empathogens or entactogens are a class of
psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. ...
s that produce experiences of emotional communion, oneness, relatedness, emotional openness—that is, empathy or sympathy—as particularly observed and reported for experiences with 3,4-methylenedioxymethamphetamine (
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
). This class of drug is distinguished from the classes of
hallucinogen Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...
or psychedelic, and
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
or
stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
. Major members of this class include
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
,
MDA MDA, mda, or ''variation'', may refer to: Places * Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics * Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...
, MDEA,
MDOH 3,4-Methylenedioxy-''N''-hydroxyamphetamine (MDOH, MDH, N-hydroxytenamphetamine) is an entactogen, psychedelic, and stimulant of the phenethylamine and amphetamine chemical classes. It is the ''N''- hydroxy homologue of MDA, and the ''N' ...
,
MBDB 1,3-Benzodioxolyl-''N''-methylbutanamine (''N''-methyl-1,3-benzodioxolylbutanamine, MBDB, 3,4-methylenedioxy-''N''-methyl-α-ethylphenylethylamine) is an entactogen of the phenethylamine chemical class. It is known by the street names Eden and ...
, 5-APB, 5-MAPB,
6-APB 6-APB (6-(2-aminopropyl)benzofuran) is an empathogenic psychoactive compound of the substituted benzofuran and substituted phenethylamine classes. 6-APB and other compounds are sometimes informally called "Benzofury" in newspaper reports. It is ...
,
6-MAPB 6-MAPB (1-(benzofuran-6-yl)-''N''-methylpropan-2-amine) is a psychedelic and entactogenic drug which is structurally related to 6-APB and MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crysta ...
,
methylone Methylone (also known as "3,4-methylenedioxy-''N''-methylcathinone", "MDMC", "βk-MDMA" and by the slang term "M1") is an empathogen and stimulant psychoactive drug. It is a member of the substituted amphetamine, substituted cathinone and s ...
,
mephedrone Mephedrone, also known as , , and , is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone, , White Magic, meow meow, bubble, ''txomin'' and yurrpt. It is chemically similar to the cathinone compounds ...
,
GHB ''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...
, αMT, and αET,
MDAI MDAI (5,6-methylenedioxy-2-aminoindane) is a drug developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic and highly selective serotonin releasing agent (SSRA) ''in vitro'' and produces entact ...
among others. Most entactogens are phenethylamines and
amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...
, although several, such as αMT and αET, are
tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...
s. When referring to MDMA and its counterparts, the term '' MDxx'' is often used (with the exception of
MDPV Methylenedioxypyrovalerone (MDPV) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. Its activity at the dopamine tra ...
). Entactogens are sometimes incorrectly referred to as hallucinogens or stimulants, although many entactogens such as ecstasy exhibit psychedelic or stimulant properties as well.


Etymology

The term ''empathogen'', meaning "generating a state of
empathy Empathy is the capacity to understand or feel what another person is experiencing from within their frame of reference, that is, the capacity to place oneself in another's position. Definitions of empathy encompass a broad range of social, co ...
", was coined in 1983–84 by
Ralph Metzner Ralph Metzner (May 18, 1936 – March 14, 2019) was a German-born American psychologist, writer and researcher, who participated in psychedelic research at Harvard University in the early 1960s with Timothy Leary and Richard Alpert (later named ...
as a term to denote a therapeutic class of drugs that includes
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
and phenethylamine relatives.
David E. Nichols David Earl Nichols (born December 23, 1944, Covington, Kentucky) is an Americans, American pharmacologist and medicinal chemist. Previously the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University, Nichol ...
later 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"). Additionally, Nichols wanted to avoid any association with the term
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
. 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. The
hybrid word A hybrid word or hybridism is a word that etymologically derives from at least two languages. Common hybrids The most common form of hybrid word in English combines Latin and Greek parts. Since many prefixes and suffixes in English are of Latin ...
''entactogen'' is derived from the roots ''en'' ( el, within), ''tactus'' ( la, touch) and ''-gen'' ( el, produce). Entactogen is becoming dominant in usage, and, despite their difference in connotation, they are essentially interchangeable, as they refer to precisely the same chemicals.


Psychological effects

Both terms adopted and used in naming the class of therapeutic drugs for
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
and related compounds were chosen with the intention of providing some reflection of the reported psychological effects associated with drugs in the classification and distinguishing these compounds from classical
psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...
s such as
LSD Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
,
mescaline Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin. Biological sou ...
, and
psilocybin Psilocybin ( , ) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus ''Psilocybe'', such as '' P. azurescens'', '' P. semilanceata'', and '' P.&nbs ...
and major
stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
, such as methamphetamine and
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
. Chemically, MDMA is classified as a substituted amphetamine (which includes stimulants like dextroamphetamine and psychedelics like 2,5-dimethoxy-4-methylamphetamine), which makes MDMA a
substituted phenethylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by ...
(which includes other stimulants like
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...
and other psychedelics like
mescaline Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin. Biological sou ...
) by the definition of amphetamine. While chemically related both to psychedelics and stimulants, the psychological effects experienced with MDMA were reported to provide obvious and striking aspects of personal relatedness, feelings of connectedness, communion with others, and ability to feel what others feel—in short an empathic resonance is consistently evoked. While psychedelics like LSD may sometimes yield effects of empathic resonance, these effects tend to be momentary and likely passed over on the way to some other dimension or interest. In contrast, the main characteristic that distinguishes MDMA from LSD-type experiences is the consistency of the effects of emotional communion, relatedness, emotional openness—in short, empathy and sympathy.


Examples

The chemicals below have a varying degree of entactogenic effects; some of them induce additional effects, including
serenic A serenic, or antiaggressive agent, is a type of drug which reduces the capacity for irritability and aggression. Examples The recreational drug MDMA ("ecstasy") and a variety of related drugs have been described as '' empathogen-entactogens'', or ...
effects,
stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
effects,
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
effects,
anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...
effects, and psychedelic effects.


Phenethylamines

* (2,5-dimethoxy-4-bromophenethylamine) (2C-B)


Substituted amphetamines

* 5-(2-Aminopropyl)-2,3-dihydro-1H-indene (5-APDI, IAP) * 6-(2-Aminopropyl)benzofuran (6-APB) (benzofury) * 5-(2-aminopropyl)benzofuran (5-APB) * 5-(2-methylaminopropyl)benzofuran ( 5-MAPB) *
Methylbenzodioxolylbutanamine 1,3-Benzodioxolyl-''N''-methylbutanamine (''N''-methyl-1,3-benzodioxolylbutanamine, MBDB, 3,4-methylenedioxy-''N''-methyl-α-ethylphenylethylamine) is an entactogen of the phenethylamine chemical class. It is known by the street names Eden an ...
(MBDB) *
Methylenedioxyamphetamine 3,4-Methylenedioxyamphetamine (also known as MDA and sass) is an empathogen-entactogen, psychostimulant, and psychedelic drug of the amphetamine family that is encountered mainly as a recreational drug. In terms of pharmacology, MDA acts ...
(MDA) *
Methylenedioxyethylamphetamine 3,4-Methylenedioxy-''N''-ethylamphetamine (MDEA; also called MDE and colloquially, Eve) is an empathogenic psychoactive drug. MDEA is a substituted amphetamine and a substituted methylenedioxyphenethylamine. MDEA acts as a serotonin, norepine ...
(MDEA) *
Methylenedioxymethamphetamine 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desired ...
(MDMA) *
Methylenedioxyhydroxyamphetamine 3,4-Methylenedioxy-''N''-hydroxyamphetamine (MDOH, MDH, N-hydroxytenamphetamine) is an entactogen, psychedelic, and stimulant of the phenethylamine and amphetamine chemical classes. It is the ''N''- hydroxy homologue of MDA, and the ''N''-de ...
(MDOH) * 4-Fluoroamphetamine (4-FA) Substituted aminorexes *
4,4'-Dimethylaminorex 4,4'-Dimethylaminorex (abbreviated as 4,4'-DMAR), sometimes referred to by the street name "Serotoni", is a psychostimulant and entactogen designer drug related to aminorex, 4-methylaminorex, and pemoline. It was first detected in the Netherla ...
(4,4'-DMAR) * Methylenedioxy-4-methylaminorex (MDMAR) Cathinones *
Mephedrone Mephedrone, also known as , , and , is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone, , White Magic, meow meow, bubble, ''txomin'' and yurrpt. It is chemically similar to the cathinone compounds ...
(4-MMC) * 3-Methylmethcathinone (3-MMC, metaphedrone) *
Methylone Methylone (also known as "3,4-methylenedioxy-''N''-methylcathinone", "MDMC", "βk-MDMA" and by the slang term "M1") is an empathogen and stimulant psychoactive drug. It is a member of the substituted amphetamine, substituted cathinone and s ...
(βk-MDMA) * Butylone (βk-MBDB) * Flephedrone (4-FMC)


Tryptamines

* α-Ethyltryptamine (αET) * α-Methyltryptamine (αMT)


Aminoindanes

* 5-Iodo-2-aminoindane (5-IAI) * Methylenedioxyaminoindane (MDAI)


Therapeutic uses

Psychiatrists began using entactogens as psychotherapy tools in the 1970s despite the lack of clinical trials. In recent years, the scientific community has been revisiting the possible therapeutic uses of entactogens. Therapeutic models using MDMA have been studied because of its entactogenic properties. This type of therapy would be applicable for treating a patient who was experiencing psychological trauma such as PTSD. Traumatic memories can be linked to fear in the patients which makes engaging with these memories difficult. Administration of an entactogen such as MDMA allows the patient to disconnect from the fear associated with the traumatic memories and engage in therapy. MDMA acts by targeting the body's stress response in order to cause this therapeutic effect. In addition to reducing anxiety and a conditioned fear response, MDMA also reduces the avoidance of feelings. Patients are then able to trust themselves and their therapist and engage with traumatic memories under the influence of MDMA. Although the therapeutic effects of entactogens may be promising, drugs such as MDMA have the potential for negative effects that are counter productive in a therapy setting. For example, MDMA may make negative cognition worse. This means that a positive experience is not a guarantee and can be contingent on aspects like the setting and the patient's expectations. Additionally there is no clear model of the
psychopharmacological Psychopharmacology (from Ancient Greek, Greek grc, wiktionary:ψῡχή, ψῡχή, psȳkhē, breath, life, soul, label=none; grc, wiktionary:φάρμακον, φάρμακον, pharmakon, drug, label=none; and grc, wiktionary:-λογία, - ...
means for a positive or negative experience. There is also a potential concern for the
neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
effects of MDMA on the fiber density of
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
neurons in the
neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
. High doses of MDMA may cause potential depletion of serotonergic axons. The same effects may not be caused by lower doses of MDMA required for treatment, however.


References


Bibliography

* Nichols, D.E., Hoffman, A.J., Oberlender, R.A., Jacob P 3rd & Shulgin A.T. ''Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class'' 1986 J Med Chem 29 2009-15 * Nichols, D.E. ''Entactogens: How the Name for A novel Class of Psychoactive Agents Originated'' ''Frontiers in Psychiatry 2022'', 3, Online March 25, (2022), DOI: 10.3389/fpsyt.2022.863088


External links

* {{DEFAULTSORT:Empathogen-Entactogen