3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, and molly, is an empathogen–entactogenic drug with stimulant and minor psychedelic properties. In studies, it has been used alongside psychotherapy in the treatment of post-traumatic stress disorder (PTSD) and social anxiety in autism spectrum disorder. The purported pharmacological effects that may be prosocial include altered sensations, increased energy, empathy, and pleasure. When taken by mouth, effects begin in 30 to 45 minutes and last three to six hours.
Empathogens or entactogens are a class of psychoactive drugs that induce the production of 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). This class of drug is distinguished from the classes of hallucinogen or psychedelic, and amphetamine or stimulants. Major members of this class include MDMA, MDA, MDEA, MDOH, MBDB, 5-APB, 5-MAPB, 6-APB, 6-MAPB, methylone, mephedrone, GHB, αMT, and αET, 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. Entactogens are sometimes incorrectly referred to as hallucinogens or stimulants, although many entactogens such as ecstasy exhibit psychedelic or stimulant properties as well.
3,4-Methylenedioxyamphetamine (MDA), sometimes referred to as sass, is an empathogen-entactogen, stimulant, and psychedelic drug of the amphetamine family that is encountered mainly as a recreational drug. In its pharmacology, MDA is a serotonin–norepinephrine–dopamine releasing agent (SNDRA). In most countries, the drug is a controlled substance and its possession and sale are illegal.
para-Methoxyamphetamine (PMA), also known as 4-methoxyamphetamine (4-MA), is a designer drug of the amphetamine class with serotonergic effects. Unlike other similar drugs of this family, PMA does not produce stimulant, euphoriant, or entactogen effects, and behaves more like an antidepressant in comparison, though it does have some psychedelic properties.
Methylone, also known as 3,4-methylenedioxy-N-methylcathinone (MDMC), is an empathogen and stimulant psychoactive drug. It is a member of the amphetamine, cathinone and methylenedioxyphenethylamine classes.
Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family and a major active metabolite of the appetite suppressants fenfluramine and benfluorex. The compound is a racemic mixture of two enantiomers with differing activities, dexnorfenfluramine and levonorfenfluramine.
MDAI, also known as 5,6-methylenedioxy-2-aminoindane, is an entactogen drug of the 2-aminoindane group which is related to MDMA and produces similar subjective effects.
A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; MRAs can induce the release of one or more of these neurotransmitters.
5-Methoxy-6-methyl-2-aminoindane (MMAI) is a drug of the 2-aminoindane group developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a less neurotoxic and highly selective serotonin releasing agent (SSRA) and produces entactogenic effects in humans. It has been sold as a designer drug and research chemical online since 2010.
5-Iodo-2-aminoindane (5-IAI) is an entactogen drug of the 2-aminoindane group. Human anecdotal reports suggest that it is entactogenic but produces little euphoria or stimulation.
A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.
α-Methyldopamine (α-Me-DA), also known as 3,4-dihydroxyamphetamine or as catecholamphetamine, is a research chemical of the catecholamine and amphetamine families. It is a monoamine releasing agent and a metabolite of MDMA and MDA. The bis-glutathionyl metabolite of α-methyldopamine is slightly neurotoxic when directly injected into the brain's ventricles.
3,4-Dimethoxy-N-methylamphetamine (DMMA) is a psychoactive drug and research chemical of the phenethylamine and amphetamine chemical classes. It appears to act as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), although it is significantly less potent than MDMA.
UWA-101 is a phenethylamine derivative researched as a potential treatment for Parkinson's disease. Its chemical structure is very similar to that of the illegal drug MDMA, the only difference being the replacement of the α-methyl group with an α-cyclopropyl group. MDMA has been found in animal studies and reported in unauthorised human self-experiments to be effective in the short-term relief of side-effects of Parkinson's disease therapy, most notably levodopa-induced dyskinesia. However the illegal status of MDMA and concerns about its potential for recreational use, neurotoxicity and potentially dangerous side effects mean that it is unlikely to be investigated for medical use in this application, and so alternative analogues were investigated.
4-Hydroxy-3-methoxymethamphetamine (HMMA) is an active metabolite of 3,4-methylenedioxymethamphetamine (MDMA). It is a slightly more potent stimulant than MDMA in rodents. The drug is substantially less potent than MDMA as a monoamine releasing agent in vitro. Nonetheless, HMMA has been found to induce the release of serotonin, norepinephrine, and dopamine with EC50Tooltip half-maximal effective concentration values of 589 nM, 625 nM, and 607–2884 nM, respectively, and hence acts as a lower-potency serotonin–norepinephrine–dopamine releasing agent (SNDRA). The predicted log P of HMMA is 1.2.
Serotonin (5-hydroxytryptamine) is a monoamine neurotransmitter that plays a role in mood, eating, sleeping, arousal and potentially visual orientation processing. To investigate its function in visual orientation, researchers have utilised MDMA, or as it is commonly referred to, Ecstasy (3,4-methylenedioxymethamphetamine). MDMA is known to affect serotonin neurons in the brain and cause neurotoxicity. Serotonin has been hypothesised to be involved in visual orientation because individuals who use MDMA exhibit an increase in the magnitude of the tilt aftereffect (TAE). The TAE is a visual illusion where viewing lines in one direction, for an extended period of time, produces the perception of a tilt in the opposite direction to vertical lines subsequently viewed. This effect is proposed to occur due to lateral inhibition to orientation sensitive neurons in the occipital lobe. Lateral inhibition is where neurons that become activated to a particular orientation send inhibitory signals to their neighbouring neurons. The degree of orientation that each neuron becomes maximally excited to is referred to as the tuning bandwidth. Lateral inhibition consequently plays a pivotal role in each neuron's tuning bandwidth, such that if lateral inhibition no longer occurs, a greater number of neurons will become stimulated to the same orientation. This results in the activated neurons becoming adapted to the same orientation stimulus, if the stimulus is viewed for a period of time. As a consequence, if those neurons are subsequently 'shown' another stimulus that differs slightly in its orientation, those neurons are no longer able to achieve the same level of response as compared to other non-adapted neurons.
3,4-Dihydroxymethamphetamine, or 3,4-dihydroxy-N-methylamphetamine, also known as α-methylepinine or α,N-dimethyldopamine, is the major metabolite of 3,4-methylenedioxy-N-methylamphetamine (MDMA). It is formed from MDMA by O-demethylation via cytochrome P450 enzymes including CYP2D6 as well as CYP1A2 and CYP3A4. Like MDMA, HHMA is a monoamine releasing agent.
(R)-3,4-Methylenedioxy-N-methylamphetamine ((R)-MDMA), also known as (R)-midomafetamine or as levo-MDMA, is the (R)- or levorotatory (l-) enantiomer of 3,4-methylenedioxy-N-methylamphetamine (MDMA; midomafetamine; "ecstasy"), a racemic mixture of (R)-MDMA and (S)-MDMA. Like MDMA, (R)-MDMA is an entactogen or empathogen. It is taken by mouth.
4-Hydroxy-3-methoxyamphetamine (HMA), also known as 3-O-methyl-α-methyldopamine, is an active metabolite of 3,4-methylenedioxymethamphetamine (MDMA). It is substantially less potent than MDMA or 3,4-methylenedioxyamphetamine (MDA) as a monoamine releasing agent in vitro. Nonetheless, HMA has been found to induce the release of serotonin, norepinephrine, and dopamine with EC50Tooltip half-maximal effective concentration values of 897 nM, 694 nM, and 1450–3423 nM, respectively, and hence acts as a lower-potency serotonin–norepinephrine–dopamine releasing agent (SNDRA). The predicted log P of HMA is 0.6.
3,4-Isopropylidenedioxyamphetamine (IDA) is a monoamine releasing agent (MRA) of the amphetamine family related to 3,4-methylenedioxyamphetamine (MDA). It is considerably less potent than MDA as an MRA in vitro. IDA fully substituted for MDMA and LSD in animal drug discrimination tests, albeit with 5- to 7-fold lower potency than MDA.
