| Entactogen | |
|---|---|
| Drug class | |
 A selection ofMDMA pills, which are often nicknamed "Ecstasy" or "X" | |
| Class identifiers | |
| Synonyms | Entactogen; Empathogen; Connectogen[1][2][3][4] |
| Use | Recreational,spiritual,medical,microdosing |
| Mechanism of action | Serotonin–norepinephrine–dopamine releasing agent;Serotonin5-HT2 receptoragonism |
| Biological target | Serotonin transporter;Norepinephrine transporter;Dopamine transporter;Serotonin5-HT2 receptors |
| Chemical class | Amphetamines,MDxx,cathinones,benzofurans,α-alkyltryptamines,2-aminoindanes, others |
| Legal status | |
| Legal status |
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| In Wikidata | |
| Part ofa series on |
| Psychedelia |
|---|
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Entactogens, also known asempathogens orconnectogens, are a class ofpsychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is,empathy—as particularly observed and reported for experiences withMDMA.[1][2][5][3][4] This class of drug is distinguished from the classes ofhallucinogens orpsychedelics andstimulants, although entactogens, for instance MDMA, can also have these properties.[1][4][6][7] Entactogens are used both asrecreational drugs[8] and are being investigated formedical use in the treatment ofpsychiatric disorders, for instanceMDMA-assisted therapy forpost-traumatic stress disorder (PTSD).[9][10][11]
Notable members of this class include themethylenedioxyphenethylamines (MDxx) MDMA,MDA,MDEA,MDOH,MBDB, andmethylone, thebenzofurans5-APB,5-MAPB,6-APB, and6-MAPB, thecathinonemephedrone, the2-aminoindaneMDAI, and theα-alkyltryptaminesαMT andαET, among others.[1][5] Most entactogens areamphetamines, although several, such as αMT and αET, aretryptamines.[1][5] When referring to MDMA and its counterparts, the termMDxx is often used (with the exception of certain non-entactogen drugs likeMDPV).
Entactogens act asserotonin releasing agents (SRAs) as their key action.[12][13][5][14][15] However, entactogens also frequently have additional actions, such as induction ofdopamine andnorepinephrine andserotonin5-HT2 receptoragonism, which contributes to their effects as well.[12][13][5][14][15] It is thought that dopamine and norepinephrine release provide additionalstimulant,euphoriant, andcardiovascular orsympathomimetic effects, serotonin5-HT2A receptor agonism producespsychedelic 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-lastingserotonergic neurotoxicity[16][17][5] with associatedcognitive andmemory deficits as well aspsychiatric changes.[18][19][20][21]
MDA and MDMA were both firstsynthesized independently in the early 1910s.[22] Thepsychoactive effects of MDA were discovered in 1930 but were not described until the 1950s, MDA and MDMA emerged asrecreational drugs in the 1960s, and the unique entactogenic effects of MDMA were first described in the 1970s.[22][23][24][25][26] 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.[1][4][6]Gordon Alles discovered the psychoactive effects of MDA,[25][26]Alexander Shulgin played a key role in bringing awareness to MDMA and its unique effects,[24] andRalph Metzner[27][28][29] andDavid E. Nichols formally defined entactogens and established them as a distinct class of drugs.[1][4][6] Many entactogens likeMDMA arecontrolled substances throughout the world.[30][31]
Entactogens are used asrecreational drugs, including notably atraves.[8]
Psychiatrists began using entactogens as psychotherapy tools in the 1970s despite the lack of clinical trials.[32] 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.[33] 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.[33] 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.[33] 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.[34] Additionally there is no clear model of thepsychopharmacological means for a positive or negative experience.[34] There is also a potential concern for theneurotoxic effects of MDMA on the fiber density ofserotonin neurons in theneocortex. 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.[35]
MDMA-assisted psychotherapy (MDMA-AT) is in late-stageclinical trials to treat PTSD as of 2025.[9][10][11]
| Compound | Class | Dose | Duration | |
|---|---|---|---|---|
| MDA (Sally, Sassafras) | Amphetamine | 80–160 mg (20–200 mg+) | 4–8 hours | |
| (S)-MDA | Amphetamine | 160–225 mg | 3 hours | |
| (R)-MDA | Amphetamine | 70–200 mg | 4–8 hours | |
| MDMA (Ecstasy; Molly; Adam) | Amphetamine | 80–150 mg (25–200 mg+) | 3–6 hours | |
| (S)-MDMA | Amphetamine | 60–125 mg | 5 hours | |
| (R)-MDMA | Amphetamine | 250–300 mg | 4–5 hours | |
| MDEA (MDE; Eve) | Amphetamine | 100–200 mg (30–225 mg+) | 3–5 hours | |
| MDOH (MDHA) | Amphetamine | 100–160 mg | 3–6 hours | |
| FLEA (MDMOH, MDHMA) | Amphetamine | 100–160 mg | 4–8 hours | |
| Lys-MDA | Amphetamine | ~164 mg | ~6 hours | |
| MMDA (5-methoxy-MDA) | Amphetamine | 100–250 mg | "Moderate" | |
| BDB (J) | Phenylisobutylamine | 150–230 mg | 4–8 hours | |
| MBDB (methyl-J; Eden) | Phenylisobutylamine | 180–210 mg (150–250 mg+) | 4–6 hours | |
| Methylone (βk-MDMA) | Cathinone | 100–250 mg (60–325 mg+) | 2–5 hours | |
| Ethylone (βk-MDEA) | Cathinone | 150–250 mg (80–400 mg) | 2–6 hours | |
| Butylone (βk-MBDB) | Cathinone | 100–250 mg (20–250 mg) | 2–5 hours | |
| Mephedrone (4-MMC) | Cathinone | 100–200 mg (15–300 mg+) | 2–5 hours | |
| 5-APB | Benzofuran | 60–80 mg (20–100 mg+) | 3–8 hours | |
| 5-MAPB | Benzofuran | 30–70 mg | 5–6 hours | |
| 6-APB | Benzofuran | 80–100 mg (15–125 mg+) | 6–9 hours | |
| 6-MAPB | Benzofuran | 50–100 mg | 6–8 hours | |
| 5-APDB | Dihydrobenzofuran | 50–200 mg+ | Unknown | |
| 5-MAPDB | Dihydrobenzofuran | 50–150 mg+ | Unknown | |
| 6-APDB | Dihydrobenzofuran | 20–130 mg+ | Unknown | |
| MDAI | 2-Aminoindane | 100–200 mg (20–300 mg+) | 2–5 hours | |
| MMAI | 2-Aminoindane | Unknown | Unknown | |
| MEAI (5-MeO-AI) | 2-Aminoindane | Unknown | Unknown | |
| 5-IAI | 2-Aminoindane | 100–200 mg | 2–4 hours | |
| AMT | Tryptamine | 15–30 mg | 12–16 hours | |
| AET | Tryptamine | 100–150 mg | 6–8 hours | |
| BK-NM-AMT (βk-NM-AMT) | Tryptamine | Unknown | Unknown | |
| Borax combob | Multipleb | Variable | Variable | |
| Footnotes:a = Some of these drugs also act as robustpsychedelics and/orstimulants. Examples of psychedelics includeMDA,MMDA, andAMT, while examples of stimulants includemephedrone.b = TheBorax combo is acombination of5-MAPB orMDAI,2-FMA, and5-MeO-MiPT or4-HO-MET and is said to closely mimic the effects and unique "magic" ofMDMA.Refs:[36][37][5][31][38][39][40][41][42][43][44]Individual:[45][46][47][48][49][50][51][52][53][54][55] | ||||
The above table does not include atypical agents with some reported entactogen-like effects, such as thephenethylamineserotonergic psychedelic2C-B[44][56][57][5] and the atypicaltryptamine serotonergic psychedelics5-MeO-DiPT[54][58][59][5] and5-MeO-MiPT.[54][60][59]
Both terms adopted and used in naming the class of therapeutic drugs forMDMA 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 classicalpsychedelic drugs such asLSD,mescaline, andpsilocybin and majorstimulants, such asmethamphetamine andamphetamine.[3] Chemically, MDMA is classified as asubstituted amphetamine (which includes stimulants like dextroamphetamine and psychedelics like2,5-dimethoxy-4-methylamphetamine), which makes MDMA asubstituted phenethylamine (which includes other stimulants likemethylphenidate and other psychedelics likemescaline) 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.[61] 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.[3]
Side effects of entactogens like MDMA includemydriasis,nystagmus,jaw clenching,bruxism,insomnia,appetite loss,tachycardia,hypertension, andhyperthermia, among others.[5][9] Severeadverse effects of entactogens like MDMA can includedehydration, hyperthermia,seizures,rhabdomyolysis,disseminated intravascular coagulation,hyponatremia,acute renal failure,liver injury,serotonin syndrome, andvalvular heart disease.[9][44] Entactogens can produce long-lastingserotonergic neurotoxicity[16][17][5] and associatedcognitive andmemory deficits as well aspsychiatric changes.[18][19][20][21]
Entactogens like MDMA show a much narrower margin ofsafety and greatertoxicity inoverdose thanserotonergic psychedelics.[62] Whereas LSD and psilocybin have extrapolated human lethal doses relative to typical recreational doses of approximately 1,000-fold and 200-fold, respectively,[63] a reasonable estimated fatal dose of MDMA is only about 15 or 16 times a single typical recreational dose.[62]
Entactogens like MDMA pose high risks of severe and potentially fatalserotonin syndrome andhypertensive crisis in people onmonoamine oxidase inhibitors (MAOIs) due to synergistic elevations ofmonoamines likeserotonin andnorepinephrine.[64][65] MDMA also has the potential to interact with various other drugs.[66][67][68]
Entactogens like MDMA areserotonin releasing agents and hence are indirectagonists ofserotonin receptors.[69][70][71] They produce entactogenic effects in animals such as increasedprosocial behavior like adjacent lying, enhancedempathy-like behavior, andantiaggressive effects.[69][72][12] Likewise, MDMA increasessociability, prosociality, andemotional empathy in humans.[12]
In animals, MDMA induced prosocial behavior and elevations in circulatingoxytocin levels and these effects were abolished by pretreatment with the serotonin5-HT1A receptorantagonistWAY-100635.[69][73][74][75][76] Conversely, the serotonin 5-HT1A receptor agonist8-OH-DPAT produced prosocial behavior and increased oxytocin levels similarly to MDMA.[69][74][77] In addition, MDMA has been shown to activate oxytocinergicneurons in thehypothalamus and this too is reversed by serotonin 5-HT1A receptor antagonism.[69][74][78] Subsequent research found that direct injection of the serotonin 5-HT1A receptor WAY-100635 locally into thebasolateral amygdala (BLA) suppressed MDMA-induced prosocial behavior and that direct injection of MDMA locally into the BLA significantly increased sociability.[79][75]
The serotonin5-HT2B and5-HT2C receptor antagonistSB-206553 has also been found to block MDMA-induced prosocial behavior, although it produced potentiallyconfoundingthigmotaxis (hyperactivity at periphery of testing chamber) as well.[73][76] Conversely, the serotonin5-HT1B receptor antagonistGR-55562 and the serotonin5-HT2A receptor antagonistketanserin were both ineffective.[73][75][76] Likewise, another study found thatselective antagonists of the serotonin 5-HT1B, 5-HT2A, 5-HT2C, and5-HT4 receptors (SB-216641),volinanserin (MDL-100907),SB-242084, andSB-204070, respectively) were all ineffective in suppressing MDMA-induced prosocial activity.[79][75] Other research has found that serotonin 5-HT2B receptor inactivation abolishes the serotonin release induced by MDMA and attenuates many of its effects.[70][71][80] In addition to the preceding findings, induction of serotonin release by MDMA in thenucleus accumbens and consequent activation of serotonin 5-HT1B receptors in this area is implicated in its enhancement of prosocial behaviors, whereas consequent activation of yet-to-be-determined serotonin receptors in this area is implicated in its enhancement of empathy-like behaviors.[1][72][81][82] Injection of the serotonin 5-HT1B receptor antagonistNAS-181 directly into the nucleus accumbens blocked the prosocial behaviors of MDMA.[81]
On the basis of the serotonin 5-HT1A receptor-mediated oxytocin release with MDMA, it has been proposed that increased oxytocinergic signaling may mediate the prosocial effects of MDMA in animals.[69][74] Accordingly,intracerebroventricular injection of thepeptideoxytocin receptor antagonisttocinoic acid blocked MDMA- and 8-OH-DPAT-induced prosocial effects.[69][74][83] However, in a subsequent study,systemically administered C25, a non-peptide oxytocin receptor antagonist, failed to affect MDMA-induced prosocial behavior, whereas thevasopressinV1A receptor antagonistrelcovaptan (SR-49059) was able to block MDMA-induced prosocial activity.[69][83] It might be that tocinoic acid isnon-selective and also blocks the vasopressin V1A receptor or that C25 isperipherally selective and is unable to blockoxytocin receptors in the brain.[69][83] More research is needed to clarify this.[83][69] In any case, in another study, the non-peptide andcentrally active selective oxytocin receptor antagonistL-368899 abolished MDMA-induced prosocial behavior.[83][84] Conversely, in other studies, different oxytocin receptor antagonists were ineffective.[81]
As in animals, MDMA greatly increases circulating oxytocin levels in humans.[69]Serotonin reuptake inhibitors andnorepinephrine reuptake inhibitors reduced the subjective effects of MDMA in humans, for instance increasedextroversion,self-confidence,closeness,openness, andtalkativeness.[12] The 5-HT2A receptor antagonistketanserin reduced MDMA-induced increases in friendliness.[12] MDMA-induced emotional empathy was not affected by the serotonin 5-HT1A receptor antagonistpindolol or byintranasaloxytocin.[85] Similarly, MDMA-induced emotional empathy and prosocial behavior have not been associated with circulating oxytocin levels.[85][69] As such, the role of oxytocin in the entactogenic effects of MDMA in humans is controversial.[69]
Other serotonin releasing agents, likefenfluramine, show prosocial effects in animals similar to those of MDMA.[86][81] Fenfluramine has likewise been reported to improvesocial deficits in children withautism.[81][87] Selective agonists of the serotonin 5-HT1A and 5-HT1B receptors and of the oxytocin receptors have been or are being investigated for the potential treatment of social deficits andaggression.[88][89][90][91] Examples includebatoprazine,eltoprazine (DU-28853),fluprazine (DU-27716),F-15,599 (NLX-01),zolmitriptan (ML-004), andLIT-001.[90][91][92]Serotonergic psychedelics, for instancelysergic acid diethylamide (LSD) andpsilocybin, which act as non-selective serotonin receptor agonists including of the serotonin5-HT1 and5-HT2 receptors, have shown prosocial and empathy-enhancing effects in animals and/or humans as well, both acutely and long-term.[93][94][95]
The serotonin release of MDMA appears to be the key pharmacological action mediating the entactogenic, prosocial, and empathy-enhancing effects of the drug.[12][13][5] However, in addition to serotonin release, MDMA is also apotentreleasing agent ofnorepinephrine anddopamine, and hence acts as a well-balancedserotonin–norepinephrine–dopamine releasing agent.[13][5] Additionally, MDMA is a direct agonist of several serotonin receptors, including of the serotonin 5-HT2 receptors, with moderateaffinity.[13][5] These actions are thought to play an important role in the effects of MDMA, including in itspsychostimulant,euphoriant, and mildpsychedelic effects, as well as in its unique and difficult-to-replicate "magic".[13][14][5][96] It has been said byMatthew Baggott that few to no MDMAanalogues, includingMBDB,methylone,6-APDB,5-APDB,6-APB,5-APB,MDAT, andMDAI among others, reproduce the full quality and "magic" of MDMA.[14][15] Exceptions mayanecdotally include5-MAPB, particularly in specificenantiomer ratios, and theBorax combo.[14][15][97] The unique properties of MDMA are believed to be dependent on a very specific mixture and ratio of pharmacological activities, including combined serotonin, norepinephrine, and dopamine release and direct serotonin receptor agonism.[14][15]
Some entactogens, such as thebenzofurans5-MAPB,6-MAPB,BK-5-MAPB, andBK-6-MAPB, have unexpectedly been found to be potent serotonin 5-HT1B receptor agonists.[98] In addition to serotonin release and other actions, this property may be involved in their entactogenic effects.[98] Conversely, MDMA is much less potent as an agonist of the serotonin 5-HT1B receptor.[98]
Ariadne, the α-ethylanalogue of the serotonergic psychedelicDOM, fully substitutes for MDMA in rodentdrug discrimination tests, suggesting that it may have entactogen-like effects.[99][100] This property is unusual among psychedelics, and is in notable contrast to DOM, which at best partially substitutes for MDMA.[100][101] Besides Ariadne, theNBOMe drugs such as25I-NBOMe and25B-NBOMe also partially to fully substitute for MDMA in rodents.[102][103][104][105] Unlike conventional entactogens, Ariadne shows no activity at the monoamine transporters, and instead acts as a selective serotonin 5-HT2 receptor partial agonist, including as a lower-efficacy agonist of the serotonin 5-HT2A receptor.[99] Certain other psychedelics and related compounds, like low doses of2C-B, are also selective serotonin 5-HT2 receptor partial agonists that have likewise been implicated as having entactogenic effects.[44][56][57] MDMA itself is notable in being a lower-efficacy partial agonist of the serotonin 5-HT2A receptor as well.[106][107][5] The stimulus effects of MDMA in thedrug discrimination paradigm are partially blocked by the selective serotonin 5-HT2A receptor antagonist volinanserin in rodents.[108] Similarly, the psychoactive effects of MDMA are partially blocked by the relatively selective serotonin 5-HT2A receptor antagonist ketanserin in humans.[13][109][110][111]
Entactogens belong to a few chemical families, includingphenethylamines oramphetamines,cyclized phenethylamines, andtryptamines. Phenethylamine entactogens can be divided intomethylenedioxyphenethylamines (MDxx) likeMDA andMDMA,benzofurans like5-APB and6-APB, anddihydrobenzofurans like5-APDB and6-APDB. They can also be further divided into additional subgroups such ascathinones likemethyloneBK-5-MAPB andphenylisobutylamines likeMBDB. Cyclized phenethylamine entactogens include2-aminoindanes likeMDAI and2-aminotetralins likeMDAT. Tryptamine entactogens areα-alkyltryptamines and includeα-methyltryptamine (AMT) andα-ethyltryptamine (AET) as well asβ-keto-α-alkyltryptamines likeBK-NM-AMT. Other possible structural families also exist, such asbenzothiophenes and otherbioisosteres likeODMA,TDMA, andSeDMA.
The history of MDMA and other entactogens has been reviewed.[22][23][112][24][113][1]
The termempathogen, meaning "generating a state ofempathy", was coined byRalph Metzner in 1983 as a term to denote a class of drugs that includesMDMA and other agents with similar effects.[27][28][29] Subsequently, in 1986, Nichols introduced the termentactogen, meaning "producing a touching within", to denote this class of drugs, asserting a concern with the potential for improper association of the termempathogen with negative connotations related to the Greek root πάθοςpáthos ("suffering; passion").[1][4][6] Additionally, Nichols wanted to avoid any association with the termpathogenesis.[114]
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] Thehybrid wordentactogen is derived from the rootsen (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 andMatthias Liechti.[2]
While an argument can be made that compounds like 4-bromo-2,5-dimethoxyphenethylamine (2CB) or N,N-diisopropyl-5-methoxytryptamine (5-MeO-DiPT) are also entactogenic, and they have been described as such in the past (González et al., 2015; Palamar and Acosta, 2020; Schifano et al., 2019), they were also excluded due to their high affinity as agonists at post-synaptic 5-HT2 and 5-HT1A receptors (Fantegrossi et al., 2006; Nugteren-van Lonkhuyzen et al., 2015; Taylor et al., 1986; Villalobos et al., 2004), which would indicate that their effects also include a marked psychedelic component.
{{cite book}}:ISBN / Date incompatibility (help)The term "empathogenic," meaning "generating a state of empathy," was independently proposed for these substances in 1983—84 by Ralph Metzner, a psychologist and psychopharmacologist, and David Nichols, a professor of medicinal chemistry at Purdue University. Nichols subsequently rejected the term and now prefers "entactogenic," meaning "touching within," for MDMA. We continue to use the term "empathogenic."
Another group of drugs are the phenethylamines, of which MDA [and MDMA] is an example. Instead of calling these "psychedelic drugs," I'd like to suggest the name "empathogenic." Empathogenic means "empathy generating." Everyone I've mentioned this name to thinks it is a good one. These drugs don't produce visions as LSD does. They don't produce multileveled thinking or objectivity toward your mind as LSD and the psychedelics do. They generate a profound state of empathy for self and other in the most general and profound terms. A state of empathy where the feeling is that the self, the other, and the world is basically good, is all right. This state can be referred to as the ground of being, the core of our being, a still point of our being. Then individuals using these substances in therapy can look at their own problems from the standpoint of stillness and empathy. They are able to do changework on themselves very rapidly, compared to ordinary therapy.
{{cite book}}: CS1 maint: multiple names: authors list (link){{cite book}}: CS1 maint: multiple names: authors list (link){{cite book}}: CS1 maint: multiple names: authors list (link)In one of the few clinical studies of a designer drug, 4-bromo-2,5-dimethoxyphenylethylamine (2C-B) was shown to induce euphoria, well-being, and changes in perception, and to have mild stimulant properties (Gonzalez et al. 2015). 2C-B may thus be classified as a psychedelic with entactogenic properties, an effect profile that is similar to various other phenethylamine psychedelics (Shulgin and Shulgin 1995).
The normal routes of mephedrone administration in recreational users are reported to be oral and insufflation. Extrapolation from dosing to plasma levels is difficult as there are no detailed dose–concentration curves available and pharmacokinetic studies on the drug in humans have yet to be performed. However, it is suggested that a 'normal' recreational oral dose is 100–200 mg, while somewhat lower doses are used when the drug is insufflated (EROWID, 2013). This oral dose is similar to the usual oral MDMA dose typically resulting from ingestion of two tablets (140–180 mg), but an important difference with mephedrone is that the reported short duration of the psychoactive response often leads to rapid repeat dosing (Schifano et al., 2012).
Mephedrone oral dosage ranges from 15 to 300 mg, whereas nasal insufflation dosage is somewhat lower and ranges from 5 to 200 mg. Intravenous/intramuscular injection has been reported at approximately half or one-third of oral dosage, whilst 100 mg is described as a usual rectal dose [26, 38]. The initial impact is felt by recreational users approximately 30 min after oral ingestion, with effects lasting for 2–5 h [39]; in contrast, intravenous and rectal administration produce earlier onset of action and shorter duration [40].
Doses range from 70–300 mg; typical doses appear to be 150–200 mg of active ingredient (equivalent to half of a 300 mg capsule or a whole 200 mg capsule). A 'low' dose of 70–80 mg produces subtle but noticeable effects; a strong dose is considered to be 250–300 mg. Redosing often occurs; typically a 'booster' of 100–150 mg is administered after the initial positive effects have worn off (Drugs-Forum, 2009a; Bluelight, 2010a; Herbalhighs, 2012a; Partyvibe, 2012).
DOSE EFFECT: Anecdotal data suggests that recreational doses of 2C-B range from 4—30 mg with lower doses (4—10 mg) producing entactogenic effects, whereas high doses (10— 20 mg) cause psychedelic and sympathomimetic effects.
[...] These increased sensations of touch [with 5-methoxytryptamines like 5-MeO-DiPT and 5-MeO-MiPT] are likely why some users compared the "body high" with the high associated with MDMA use. [...] I would actually say that it is closer to MDMA in its effects. The whole series of 5-MeO and 4-MeO … they're both very closely related in their effects so it tends to be a body high kind of thing. At higher doses it can get more psychedelic, but it's not that psychedelic. [...]
Baggott says his team regularly uses one of the compounds on the list in his lab. "When my team synthesizes and characterizes a new compound, we need to compare it to compounds with known effects. We use 5-MeO-MiPT as one of these known comparison compounds," he says. "It is scientifically interesting to my team because, although it has classical psychedelic effects at higher doses, it has some MDMA-like effects at low doses."
{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)In rat drug discrimination assays, Ariadne substituted responding in LSD trained animals in one study, in another showed full substitution for MDMA stimulus.14,15 [...] 15). Glennon RA MDMA-like Stimulus Effects of α-Ethyltryptamine and the α-Ethyl Homolog of Dom. Pharmacology Biochemistry and Behavior 1993, 46 (2), 459–462. [PubMed: 7903460]
The results of initial studies (Nichols et al., 1986) generally demonstrated the lack of LSD-Iike discriminative stimulus properties for the members of the entactogen drug class. This was confirmed and extended to other hallucinogens in tests with rats trained on entactogens. These results are summarized in Table 12. Table 12. Results of DD tests comparing entactogens and hallucinogens. [...] It seems clear that entactogen activity is distinct from that of hallucinogens. [...]
For a better understanding of the actions of different NBOMes resulting from their molecular structure and receptor binding affinity, drug discrimination studies were performed. Animals trained with 4-methyl-2,5-dimethoxyamphetamine (DOM) and 3,4-methylenedioxymethamphetamine (MDMA) were used in the drug discrimination paradigm. 25B- and 25CNBOMe completely (80%) substituted DOM, while 25INBOMe produced 74% drug-appropriate responding (Gatch et al. 2017). On the other hand, only 25B-NBOMe fully substituted for MDMA, suggesting that this compound could be used as both a hallucinogen and an entactogen.
Gatch et al. (2017) tested 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe for discriminative stimulus effects similar to a prototypical psychedelic/hallucinogen DOM and to an empathogen, 3,4-methylenedioxymethamphetamine (MDMA). In DOM-trained rats 25B-NBOMe and 25C-NBOMe, but not 25I-NBOMe, fully substituted for this drug. 25B-NBOMe also fully substituted for MDMA. In both tests, the dose-effect curves for 25B-NBOMe had an inverted U-shape. It is suggested that 25B-NBOMe and 25C-NBOMe are most likely used as recreational psychedelics, although 25B-NBOMe may also be used as an empathogenic compound (Gatch et al., 2017). However, the latter assumption should be taken with caution, as some compounds (e.g., fenfluramine) that substitute for MDMA in rats do not produce MDMA-like empathogenic effects in humans (Schechter, 1988).
Recent studies employing drug discrimination in rats show that novel psychedelics including 25I-, 25B-, and 25C-NBOMe, and 5-MeO-DALT fully substitute for DOM; interestingly, the NBOMe drugs also substitute for MDMA, but 5-MeO-DALT does not (Gatch et al. 2017).
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