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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. T ...
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 form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desired ...
). 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 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 ...
, 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 form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desired ...
, MDA, MDEA, MDOH, MBDB,
5-APB 5-APB (abbreviation of "5-(2-aminopropyl)benzofuran"; see infobox for the correct IUPAC name) is an empathogenic psychoactive compound of the substituted benzofuran, substituted amphetamine and substituted phenethylamine classes. 5-APB and oth ...
,
5-MAPB 5-MAPB (1-(benzofuran-5-yl)-''N''-methylpropan-2-amine) is an entactogenic designer drug similar to MDMA in its structure and effects. Legal Status Canada 5-MAPB is not listed itself in the CDSA but since it is structurally related to MDMA it ...
, 6-APB, 6-MAPB,
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, αMT, and αET, MDAI among others. Most entactogens are
phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace am ...
s 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 su ...
, 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 Substituted methylenedioxy- phenethylamines (MDxx) are a large chemical class of derivatives of the phenethylamines, which includes many psychoactive drugs that act as entactogens, psychedelics, and/or stimulants, as well as entheogens. These a ...
'' 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, cog ...
", was coined in 1983–84 by Ralph Metzner as a term to denote a therapeutic class of drugs that includes
MDMA 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 ...
and phenethylamine relatives. David E. Nichols 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 ''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 form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desired ...
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 ...
s such as LSD,
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 ...
, 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.&n ...
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 Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Meth ...
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 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 s ...
(which includes stimulants like dextroamphetamine and psychedelics like
2,5-dimethoxy-4-methylamphetamine 2,5-Dimethoxy-4-methylamphetamine (DOM; known as STP, standing for "Serenity, Tranquility and Peace") is a psychedelic and a substituted amphetamine. It was first synthesized by Alexander Shulgin, and later reported in his book '' PiHKAL: A Chem ...
), 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 extent ...
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 ...
) 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 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 ...
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 anxie ...
effects, and
psychedelic 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 ...
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 (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-APB) (benzofury) *
5-(2-aminopropyl)benzofuran 5-APB (abbreviation of "5-(2-aminopropyl)benzofuran"; see infobox for the correct IUPAC name) is an empathogenic psychoactive compound of the substituted benzofuran, substituted amphetamine and substituted phenethylamine classes. 5-APB and oth ...
(5-APB) * 5-(2-methylaminopropyl)benzofuran (
5-MAPB 5-MAPB (1-(benzofuran-5-yl)-''N''-methylpropan-2-amine) is an entactogenic designer drug similar to MDMA in its structure and effects. Legal Status Canada 5-MAPB is not listed itself in the CDSA but since it is structurally related to MDMA it ...
) *
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 and ...
(MBDB) * Methylenedioxyamphetamine (MDA) * Methylenedioxyethylamphetamine (MDEA) * Methylenedioxymethamphetamine (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''-des ...
(MDOH) *
4-Fluoroamphetamine 4-Fluoroamphetamine (4-FA; 4-FMP; PAL-303; "Flux"), also known as ''para''-fluoroamphetamine (PFA) is a psychoactive research chemical of the phenethylamine and substituted amphetamine chemical classes. It produces stimulant and entactogenic ef ...
(4-FA) Substituted aminorexes * 4,4'-Dimethylaminorex (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-Methylmethcathinone, also known as 3-MMC and metaphedrone, is a designer drug from the substituted cathinone family. 3-MMC is closely related in structure to the more commonly known illicit drug mephedrone (4-MMC), and is also illegal in most ...
(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 Flephedrone, also known as 4-fluoromethcathinone (4-FMC), is a stimulant drug of the cathinone chemical class that has been sold online as a designer drug starting in 2008. Toxicity Flephedrone has only a short history of human use and its tox ...
(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 Greek grc, ψῡχή, psȳkhē, breath, life, soul, label=none; grc, φάρμακον, pharmakon, drug, label=none; and grc, -λογία, -logia, label=none) is the scientific study of the effects drugs have on moo ...
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 – specifical ...
effects of MDMA on the fiber density of serotonin 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, ...
. 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