3,4-methylenedioxymethamphetamine

メチレンジオキシメタンフェタミン

WordNet

1. a stimulant drug that is chemically related to mescaline and amphetamine and is used illicitly for its euphoric and hallucinogenic effects; it was formerly used in psychotherapy but in 1985 it was declared illegal in the United States; "MDMA is often used at parties because it enables partygoers to remain active for long periods of time" (同)MDMA

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/06 13:49:52」(JST)

wiki en

[Wiki en表示]

Not to be confused with other meanings of the word Ecstasy.

MDMA

Systematic (IUPAC) name
(RS)-1-(Benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine
Clinical data
AHFS/Drugs.com	entry
Legal status	AU: Prohibited (S9) CA: Schedule I UK: Class A US: Schedule I UN: Schedule I
Dependence liability	Physical: None Psychological: Moderate
Addiction liability	Moderate
Routes	Oral, sublingual, insufflation, inhalation (vaporization), injection, rectal
Pharmacokinetic data
Metabolism	Hepatic, CYP450 extensively involved, including CYP2D6
Onset of action	Immediate
Half-life	(R)-MDMA: 5.8 ± 2.2 hours (S)-MDMA: 3.6 ± 0.9 hours
Excretion	Renal
Identifiers
CAS number	42542-10-9 Y[TOXNET]
ATC code	None
PubChem	CID 1615
IUPHAR ligand	4574
DrugBank	DB01454
ChemSpider	1556 Y
UNII	KE1SEN21RM Y
KEGG	C07577 Y
ChEBI	CHEBI:1391 Y
ChEMBL	CHEMBL43048 Y
Synonyms	3,4-MDMA, Ecstasy, Molly
PDB ligand ID	B41 (PDBe, RCSB PDB)
Chemical data
Formula	C11H15NO2
Molecular mass	193.24 g/mol
SMILES CC(NC)CC1=CC=C(OCO2)C2=C1
InChI InChI=1S/C11H15NO2/c1-8(12-2)5-9-3-4-10-11(6-9)14-7-13-10/h3-4,6,8,12H,5,7H2,1-2H3 Y Key:SHXWCVYOXRDMCX-UHFFFAOYSA-N Y
Physical data
Boiling point	105 °C (221 °F) at 0.4 mmHg (experimental)
Y (what is this?)  (verify)

MDMA (contracted from 3,4-methylenedioxy-methamphetamine) is a psychoactive drug of the substituted methylenedioxyphenethylamine and substituted amphetamine classes of drugs that is consumed primarily for its euphoric and empathogenic effects. Pharmacologically, MDMA acts as a serotonin-norepinephrine-dopamine releasing agent and reuptake inhibitor.

MDMA has become widely known as "ecstasy" (shortened to "E", "X", or "XTC"), usually referring to its tablet street form, although this term may also include the presence of possible adulterants. The UK term "Mandy" and the US term "Molly" colloquially refer to MDMA in a crystalline powder form that is relatively free of adulterants. "Molly" can sometimes also refer to the related drugs methylone, MDPV, mephedrone or any other of the pharmacological group of compounds commonly known as bath salts.

Possession of MDMA is illegal in most countries. Some limited exceptions exist for scientific and medical research. For 2012, the UNODC estimated between 9.4 and 28.24 million people globally used MDMA at least once in the past year. This was broadly similar to the number of cocaine, amphetamine, and opioid users, but far fewer than the global number of cannabis users. It is taken in a variety of contexts far removed from its roots in psychotherapeutic settings, and is commonly associated with dance parties (or "raves") and electronic dance music.

Medical reviews have noted that MDMA has some limited therapeutic benefits in certain mental health disorders, but has potential adverse effects, such as neurotoxicity and addiction, associated with its use. More research is needed in order to determine if its potential usefulness in posttraumatic stress disorder (PTSD) treatment outweighs the risk of persistent neuropsychological harm to a patient.

§Uses

§Medical

MDMA currently has no accepted medical uses.

§Recreational

Ecstasy is commonly consumed at raves. Above, a rave in Austria in 2005.

MDMA is often considered the drug of choice within the rave culture and is also used at clubs, festivals and house parties. In the rave environment, the sensory effects from the music and lighting are often highly synergistic with the drug. The psychedelic amphetamine quality of MDMA offers multiple reasons for its appeals to users in the "rave" setting. Some users enjoy the feeling of mass communion from the inhibition-reducing effects of the drug, while others use it as party fuel because of the drug's stimulatory effects.

MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as LSD or psilocybin mushrooms, or even common drugs such as cannabis. As this practice has become more prevalent, most of the more common combinations have been given nicknames, such as “candy flipping” for MDMA combined with LSD, “hippie flipping” for MDMA with psilocybin mushrooms, or “kitty flipping” for MDMA with ketamine. The term “flipping” may come from the subjective effects of using MDMA with a psychedelic in which the user may shift rapidly between a more lucid state and a more psychedelic state several times during their experiences. Many users use mentholated products while taking MDMA for its cooling sensation while experiencing the drug’s effects. Examples include menthol cigarettes, Vicks VapoRub, NyQuil, and lozenges.

§Recreational effects

In general, MDMA users begin reporting subjective effects within 30 to 60 minutes of consumption, hitting a peak at about 75 to 120 minutes which plateaus for about 3.5 hours.

The desired short-term psychoactive effects of MDMA include:

• Euphoria – a sense of general well-being and happiness
• Increased sociability and feelings of communication being easy or simple
• Entactogenic effects – increased empathy or feelings of closeness with others
• A sense of inner peace
• Mild hallucination (e.g., colors and sounds are enhanced and mild closed-eye visuals)
• Enhanced sensation, perception, or sexuality

§Purity and adulterants

The average tablet contains 60–70 mg (base equivalent) of MDMA, usually as the hydrochloride salt. Powdered MDMA is typically 30–40% pure, due to bulking agents (e.g., lactose) and binding agents. Tablets sold as ecstasy sometimes only contain 3,4-methylenedioxyamphetamine (MDA) instead of MDMA; the proportion of seized ecstasy tablets with MDMA-like impurities has varied annually and by country.

Ecstasy tablets which allegedly contain MDMA, but may contain adulterants

A salt of MDMA (typically white) with impurities, resulting in a tan discoloration

§Adverse effects

§Immediate effects

The most serious short-term physical health risks of MDMA are hyperthermia and dehydration. Cases of life-threatening or fatal hyponatremia (excessively low sodium concentration in the blood) have developed in MDMA users attempting to prevent dehydration by consuming excessive amounts of water without replenishing electrolytes.

The immediate adverse effects of MDMA use can include:

• Dehydration
• Hyperthermia
• Bruxism (grinding and clenching of the teeth)
• Increased wakefulness or insomnia
• Increased perspiration and sweating
• Increased heart rate and blood pressure

• Loss of appetite
• Nausea and vomiting
• Diarrhea
• Erectile dysfunction
• Mydriasis

§After-effects

The effects that last up to a week following cessation of moderate MDMA use include:

Physical

• Trismus
• Loss of appetite
• Insomnia

Psychological

• Anxiety or paranoia
• Depression
• Irritability
• Impulsiveness
• Restlessness
• Memory impairment
• Anhedonia

§Long-term effects

MDMA use has been shown to produce brain lesions, a form of brain damage, in the serotonergic neural pathways of humans and other animals. In addition, long-term exposure to MDMA in humans has been shown to produce marked neurotoxicity in serotonergic axon terminals. Neurotoxic damage to axon terminals has been shown to persist for more than two years. Brain temperature during MDMA use is positively correlated with MDMA-induced neurotoxicity in animals. Adverse neuroplastic changes to brain microvasculature and white matter also seem to occur in humans using low doses of MDMA. Reduced gray matter density in certain brain structures has also been noted in human MDMA users. In addition, MDMA has immunosuppressive effects in the peripheral nervous system, but pro-inflammatory effects in the central nervous system. Babies of mothers who used MDMA during pregnancy exhibit impaired motor function at 4 months of age, which may reflect either a delay in development or a persistent neurological deficit.

MDMA also produces persistent cognitive impairments in human users. Impairments in multiple aspects of cognition, including memory, visual processing, and sleep have been noted in humans; the magnitude of these impairments is correlated with lifetime ecstasy or MDMA usage. Memory is significantly impacted by ecstasy use, which is associated with marked impairments in all forms of memory (e.g., long-term, short-term, working).

§Dependence and withdrawal

Some studies indicate repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug. Other meta analyses have reported possibility of impairment of executive functioning. Approximately 60% of MDMA users experience withdrawal symptoms, including, but not limited to: fatigue, loss of appetite, depression, and trouble concentrating. Tolerance is expected to occur with consistent MDMA use.

§Overdose

Overdose symptoms vary widely with MDMA; they can include:

Overdose symptoms by system

System	Symptom
Cardiovascular	Disseminated intravascular coagulation Intracranial hemorrhage Severe hypertension or hypotension
Central nervous system	Abnormally fast reflexes Agitation Cognitive and memory impairment potentially to the point of retrograde or anterograde amnesia Coma Convulsions Hallucinations Loss of consciousness Mental confusion Paranoia Serotonin syndrome Stimulant psychosis
Musculoskeletal	Muscle rigidity Rhabdomyolysis (i.e., rapid muscle breakdown)
Respiratory	Acute respiratory distress syndrome
Urinary	Renal failure
Other	Cerebral edema Hepatitis Hyperpyrexia (a life-threatening elevation of body temperature) Hyponatremia (Syndrome of inappropriate antidiuretic hormone)

§Chronic use and addiction

Main article: ΔFosB

Signaling cascade in the nucleus accumbens that results in psychostimulant addiction

Note: colored text contains article links.

Nuclear pore

Nuclear membrane

Plasma membrane

Ca_v1.2

NMDAR

AMPAR

DRD1

DRD5

DRD2

DRD3

DRD4

G_s

G_i/o

cAMP

cAMP

PKA

CaM

CaMKII

DARPP-32

PP1

PP2B

CREB

ΔFosB

JunD

c-Fos

SIRT1

HDAC1

This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methylphenidate, and phenethylamine. Following presynaptic dopamine and glutamate co-release by such psychostimulants, postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP pathway and calcium-dependent pathway that ultimately result in increased CREB phosphorylation. Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-fos gene with the help of corepressors; c-fos repression acts as a molecular switch that enables the accumulation of ΔFosB in the neuron. A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for one or two months, slowly accumulates following repeated exposure to stimulants through this process. ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.

MDMA has been shown to induce ΔFosB in the nucleus accumbens. Since MDMA releases dopamine in the mesocorticolimbic projection, the mechanisms by which it induces ΔFosB in the nucleus accumbens are analogous to other psychostimulants. Therefore, chronic use of MDMA at high doses can result in altered brain structure and drug addiction, which occur as a consequence of ΔFosB overexpression in the nucleus accumbens.

§Interactions

A number of drug interactions can occur between MDMA and other drugs, including serotonergic drugs. MDMA also interacts with drugs which inhibit CYP450 enzymes, like ritonavir (Norvir), particularly CYP2D6 inhibitors. Concurrent use of MDMA with another serotonergic drug can result in a life-threatening condition called serotonin syndrome. Severe overdose resulting in death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitors, such as phenelzine (Nardil), tranylcypromine (Parnate), or moclobemide (Aurorix, Manerix).

§Pharmacology

§Pharmacodynamics

MDMA acts primarily as a presynaptic releasing agent of serotonin, norepinephrine, and dopamine, which arises from its activity at trace amine-associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2). MDMA is a monoamine transporter substrate (i.e., a substrate for DAT, NET, and SERT), so it enters monoamine neurons via these neuronal membrane transport proteins; by acting as a monoamine transporter substrate, MDMA produces competitive reuptake inhibition at the neuronal membrane transporters (i.e., it competes with endogenous monoamines for reuptake). MDMA inhibits both vesicular monoamine transporters (VMATs), the second of which (VMAT2) is highly expressed within monoamine neurons at vesicular membranes. Once inside a monoamine neuron, MDMA acts as a VMAT2 inhibitor and a TAAR1 agonist. Inhibition of VMAT2 by MDMA results in increased concentrations of the associated neurotransmitter (serotonin, norepinephrine, or dopamine) in the cytosol of a monoamine neuron. Activation of TAAR1 by MDMA triggers protein kinase A and protein kinase C signaling events which then phosphorylates the associated monoamine transporters – DAT, NET, or SERT – of the neuron. In turn, these phosphorylated monoamine transporters either reverse transport direction – i.e., move neurotransmitters from the cytosol to the synaptic cleft – or withdraw into the neuron, respectively producing neurotransmitter efflux and noncompetitive reuptake inhibition at the neuronal membrane transporters.

In summary, MDMA enters monoamine neurons by acting as a monoamine transporter substrate. MDMA activity at VMAT2 moves neurotransmitters out from synaptic vesicles and into the cytosol; MDMA activity at TAAR1 moves neurotransmitters out of the cytosol and into the synaptic cleft.

MDMA also has weak agonist activity at postsynaptic serotonin receptors 5-HT₁ and 5-HT₂ receptors, and its more efficacious metabolite MDA likely augments this action. A placebo-controlled study in 15 human volunteers found 100 mg MDMA increased blood levels of oxytocin, and the amount of oxytocin increase was correlated with the subjective prosocial effects of MDMA.(S)-MDMA is more effective in eliciting 5-HT, NE, and DA release, while (D)-MDMA is overall less effective, and more selective for 5-HT and NE release (having only a very faint efficacy on DA release).

MDMA is a ligand at both sigma receptor subtypes, though its efficacies at the receptors have not yet been elucidated.

§Pharmacokinetics

(R)/(–)-enantiomer of MDMA (top)

(S)/(+)-enantiomer of MDMA (bottom)

MDMA reaches maximal concentrations in the blood stream between 1.5 and 3 hr after ingestion. It is then slowly metabolized and excreted, with levels of MDMA and its metabolites decreasing to half their peak concentration over the next several hours.

Metabolites of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-dihydroxyamphetamine (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone (MDP2P), and 3,4-Methylenedioxy-N-hydroxyamphetamine (MDOH). The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. Sixty-five percent of MDMA is excreted unchanged in the urine (in addition, 7% is metabolized into MDA) during the 24 hours after ingestion.

MDMA is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. The metabolism may be primarily by cytochrome P450 (CYP450) enzymes CYP2D6 and CYP3A4 and COMT. Complex, nonlinear pharmacokinetics arise via autoinhibition of CYP2D6 and CYP2D8, resulting in zeroth order kinetics at higher doses. It is thought that this can result in sustained and higher concentrations of MDMA if the user takes consecutive doses of the drug.

MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides. MDMA is a chiral compound and has been almost exclusively administered as a racemate. However, the two enantiomers have been shown to exhibit different kinetics. The disposition of MDMA may also be stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. Evidence suggests that the area under the blood plasma concentration versus time curve (AUC) was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after a 40 mg oral dose in human volunteers. Likewise, the plasma half-life of (R)-MDMA was significantly longer than that of the (S)-enantiomer (5.8 ± 2.2 hours vs 3.6 ± 0.9 hours). However, because MDMA excretion and metabolism have nonlinear kinetics, the half-lives would be higher at more typical doses (100 mg is sometimes considered a typical dose).

§Physical and chemical properties

A powdered salt of MDMA

Reactors used to synthesize MDMA on an industrial scale in a chemical factory in Cikande, Indonesia

The free base of MDMA is a colorless oil that is insoluble in water. The most common salt of MDMA is the hydrochloride salt; pure MDMA hydrochloride is water soluble and appears as a white or off-white powder or crystal.

§Synthesis

There are numerous methods available in the literature to synthesize MDMA via different intermediates. The MDMA synthesis described in Merck's patent involves brominating safrole to 1-(3,4-methylenedioxyphenyl)-2-bromopropane and then reacting this adduct with methylamine. Most illicit MDMA is synthesized using MDP2P (3,4-methylenedioxyphenyl-2-propanone) as a precursor. MDP2P in turn is generally synthesized from piperonal, safrole or isosafrole. One method is to isomerize safrole to isosafrole in the presence of a strong base, and then oxidize isosafrole to MDP2P. Another method uses the Wacker process to oxidize safrole directly to the MDP2P intermediate with a palladium catalyst. Once the MDP2P intermediate has been prepared, a reductive amination leads to racemic MDMA (an equal parts mixture of (R)-MDMA and (S)-MDMA).

§Yield

Relatively small quantities of essential oil are required to make large amounts of MDMA. The essential oil of Ocotea cymbarum typically contains between 80 and 94% safrole. This allows 500 ml of the oil to produce between 150 and 340 grams of MDMA.

§Detection in body fluids

MDMA and MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug.

§History

§Early research

German patent for MDMA (methylsafrylamin) synthesis filed by Merck in 1912 and issued in 1914.

MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to avoid an existing patent held by Bayer for one such compound: hydrastinine. Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine, at the request of his coworkers, Walther Beckh and Otto Wolfes. MDMA was an intermediate compound in the synthesis of methylhydrastinine and Merck was not interested in its properties at the time. On 24 December 1912, Merck filed two patent applications that described the synthesis of MDMA and its subsequent conversion to methylhydrastinine.

Merck records indicate that its researchers returned to the compound sporadically. In 1927, Max Oberlin studied the pharmacology of MDMA and observed that its effects on blood sugar and smooth muscles were similar to those of ephedrine. Research was stopped "particularly due to a strong price increase of safrylmethylamine". Albert van Schoor performed simple toxicological tests with the drug in 1952, most likely while researching new stimulants or circulatory medications. While researching stimulants in 1959, Wolfgang Fruhstorfer also synthesized MDMA.

Outside of Merck, other researchers began to investigate MDMA. In 1953 and 1954, the United States Army commissioned a study of toxicity and behavioral effects in animals injected with mescaline and several analogues, including MDMA. Conducted at the University of Michigan in Ann Arbor, these investigations were declassified in October 1969 and published in 1973. A 1960 Polish paper describing the synthesis of MDMA was the first published scientific paper on the substance.

§Shulgin's research

Alexander Shulgin in March 2010

Chemist Alexander Shulgin reported that he synthesized MDMA in 1965 while researching methylenedioxy compounds at Dow Chemical Company, but did not test the psychoactivity of the compound at this time. Around 1970, Shulgin sent instructions for N-methylated MDA (MDMA) synthesis to the founder of a Los Angeles chemical company who had requested them. This individual later provided these instructions to a client in the Midwest. MDMA was being used recreationally in Illinois and Indiana by May 1970.

Shulgin first heard of the effects of N-methylated MDA in 1975 from a student who reported "amphetamine-like content". Around late May 1976, Shulgin again heard about the effects of N-methylated MDA, this time from a graduate student in a medicinal chemistry group he advised at San Francisco State University. Intrigued by her positive report, Shulgin synthesized MDMA and tried it himself in September and October 1976. Shulgin also noted the trials of a colleague who had tried the substance before him. Shulgin first reported on MDMA in a presentation at a conference in Bethesda, Maryland in December 1976. Two years later, he and David E. Nichols published a report on the drug's psychotropic effect in humans. They described MDMA as inducing "an easily controlled altered state of consciousness with emotional and sensual overtones" comparable "to marijuana, to psilocybin devoid of the hallucinatory component, or to low levels of MDA". Believing MDMA allowed users to strip away habits and perceive the world clearly, Shulgin called the drug "window".

Shulgin took to occasionally using MDMA for relaxation, referring to it as "my low-calorie martini", and giving the drug to his friends, researchers, and other people whom he thought could benefit from it. One such person was psychotherapist Leo Zeff, who had been known to use psychedelics in his practice. When he tried the drug in 1977, Zeff was so impressed with the effects of MDMA that he came out of his semi-retirement to proselytize for it. Over the following years, Zeff traveled around the U.S. and occasionally to Europe, eventually introducing roughly four thousand psychotherapists to the use of MDMA in therapy. Zeff named the drug "Adam", believing it put users in a state of primordial innocence.

§Rising popularity and criminalization

In the late seventies and early eighties, MDMA spread through personal networks of psychotherapists, psychiatrists, users of psychedelics, and yuppies. Hoping MDMA could avoid criminalization like LSD and mescaline, psychotherapists and experimenters attempted to limit the spread of MDMA and information about it while conducting informal research. By the time MDMA was criminalized in 1985, this network of MDMA users consumed an estimated 500,000 doses.

A small recreational market for MDMA had developed by the late 1970s. Into the early 1980s, production of MDMA was dominated by a small group of Boston chemists known as the "Boston group". Composed of tenured professors from Harvard and MIT, the group began distributing MDMA in New York City clubs as part of a social experiment to replace cocaine. With demand for MDMA growing, the Southwest distributor for the "Boston group" started the "Texas group" supported by several former cocaine dealers who had experienced MDMA. The "Texas group" mass-produced MDMA in a Texas lab or imported it from California and marketed tablets using pyramid sales structures and toll-free numbers with credit card purchase options. Under the brand name "Sassyfras", MDMA was sold in brown bottles and advertised as a "fun drug" and "good to dance to". MDMA was openly distributed in Dallas area bars and nightclubs and became popular with yuppies, college students, and gays. "Ecstasy" was recognized as slang for MDMA by 1981, named by "Texas group" leader Michael Clegg over the alternative "empathy" for broader marketing appeal.

The Drug Enforcement Administration (DEA) began collecting information about MDMA in 1982 with the intention of banning the drug if enough evidence for abuse could be found. By mid-1984, MDMA use was becoming more noticed. Bill Mandel reported on "Adam" in a June 10 San Francisco Chronicle article, but misidentified the drug as methyloxymethylenedioxyamphetamine (MMDA). In the next month, the World Health Organization identified MDMA as the only substance out of twenty phenethylamines to be seized a significant number of times. The drug was first proposed for scheduling by the DEA on 27 July 1984 with a request for comments and objections. The DEA was surprised when a number of physicians, therapists, and researchers objected to the proposed scheduling and requested a hearing. In a Newsweek article published the next year, a DEA pharmacologist stated that the agency had been unaware of its use among psychiatrists.

MDMA was classified as a Schedule I controlled substance in the U.S. on 31 May 1985 on an emergency basis. No double blind studies had yet been conducted as to the efficacy of MDMA for psychotherapy. In 1985 the World Health Organization's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the 1971 Convention on Psychotropic Substances, which is its current status.

§Post-criminalization

In the late 1980s, MDMA began to be widely used in Ibiza, the UK and other parts of Europe, becoming an integral element of rave culture and other psychedelic-influenced music scenes. Spreading along with rave culture, illicit MDMA use became increasingly widespread among young adults in universities and later, in high schools. MDMA became one of the four most widely used illicit drugs in the U.S., along with cocaine, heroin, and cannabis. According to some estimates as of 2004, only marijuana attracts more first time users in the U.S.

After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later, Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent legally-approved MDMA studies in humans have taken place in the U.S. in Detroit (Wayne State University), Chicago (University of Chicago), San Francisco (UCSF and California Pacific Medical Center), Baltimore (NIDA–NIH Intramural Program), and South Carolina, as well as in Switzerland (University Hospital of Psychiatry, Zürich), the Netherlands (Maastricht University), and Spain (Universitat Autònoma de Barcelona).

"Molly", short for 'molecule', was recognized as a slang term for crystalline or powder MDMA in the 2000s.

In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This may be due to increased seizures during use and decreased production of the precursor chemicals used to manufacture MDMA. Unwitting substitution with other drugs, such as mephedrone and methamphetamine, as well as legal alternatives to MDMA, such as BZP, MDPV, and methylone, are also thought to have contributed to its decrease in popularity.

§Society and culture

Global estimates of illicit drug users in 2012
(in millions of users)

Substance	Mean estimate	Low estimate	High estimate
Cannabis	177.63	125.30	227.27
Cocaine	17.24	13.99	20.92
MDMA	18.75	9.4	28.24
Opiates	16.37	12.80	20.23
Opioids	33.04	28.63	38.16
Substituted amphetamines	34.40	13.94	54.81

§Legal status

MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances and other international agreements, although exceptions exist for research and limited medical use. In general, the unlicensed use, sale or manufacture of MDMA are all criminal offences.

In Australia, MDMA was declared illegal in 1986 because of its harmful effects and potential for abuse. It is classed as a Schedule 9 Prohibited Substance in the country, meaning it is available for scientific research purposes only. Any other type of sale, use or manufacture is strictly prohibited by law. Permits for research uses on humans must be approved by a recognized ethics committee on human research.

In the United Kingdom, MDMA was made illegal in 1977 by a modification order to the existing Misuse of Drugs Act 1971. Although MDMA was not named explicitly in this legislation, the order extended the definition of Class A drugs to include various ring-substituted phenethylamines, thereby making it illegal to sell, buy, or possess the drug without a licence. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking.

In the United States, MDMA is currently placed in Schedule I of the Controlled Substances Act. In a 2011 federal court hearing the American Civil Liberties Union successfully argued that the sentencing guideline for MDMA/ecstasy is based on outdated science, leading to excessive prison sentences. Other courts have upheld the sentencing guidelines. The United States District Court for the Eastern District of Tennessee explained its ruling by noting that "an individual federal district court judge simply cannot marshal resources akin to those available to the Commission for tackling the manifold issues involved with determining a proper drug equivalency."

In the Netherlands, the Expert Committee on the List (Expertcommissie Lijstensystematiek Opiumwet) issued a report in June 2011 which discussed the evidence for harm and the legal status of MDMA, arguing in favor of maintaining it on List I.

In Canada, MDMA is listed as a Schedule 1 as it is an analogue of amphetamine. The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule III to Schedule I in March 2012.

§Economics

Worldwide consumption of ecstasy by country in 2012 according to the UNODC 2014 World Drugs Report

§Europe

In 2008 the European Monitoring Centre for Drugs and Drug Addiction noted that although there were some reports of tablets being sold for as little as €1, most countries in Europe then reported typical retail prices in the range of €3 to €9 per tablet, typically containing 25–65 mg of MDMA. By 2014 the EMCDDA reported that the range was more usually between €5 and €10 per tablet, typically containing 57–102 mg of MDMA, although MDMA in powder form was becoming more common.

§North America

The United Nations Office on Drugs and Crime stated in its 2014 World Drug Report that U.S. ecstasy retail prices range from US$1 to $70 per pill, or from $15,000 to $32,000 per kilogram. A new research area named Drug Intelligence aims to automatically monitor distribution networks based on image processing and machine learning techniques, in which an Ecstasy pill picture is analyzed to detect correlations among different production batches. These novel techniques allow police scientists to facilitate the monitoring of illicit distribution networks.

§Australia

MDMA is particularly expensive in Australia, costing A$15–A$30 per tablet. In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%. The majority of tablets contain 70–85 mg of MDMA. Most MDMA enters Australia from the Netherlands, the UK, Asia, and the U.S.

§Controversy

Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Ecstasy was ranked 16th in addictiveness, harmfulness, and social harm.

§Harm assessment

Some scientists such as David Nutt have disagreed with the categorization of MDMA with other drugs they view as more harmful. A 2007 UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. They did not evaluate or rate the negative impact of 'ecstasy' on the cognitive health of ecstasy users, e.g., impaired memory and concentration. Based on these factors, the study ranked MDMA 18th in harmfulness out of 20 recreational drugs. A later 2010 study which took into account impairment of cognitive functioning placed MDMA at number 17 out of 20 recreational drugs.

§Research

MAPS is currently funding pilot studies investigating the use of MDMA in PTSD therapy.

A review of the safety and efficacy of MDMA as a treatment for various disorders, particularly PTSD, indicated that MDMA has therapeutic efficacy in some patients; however, it emphasized that MDMA is not a safe medical treatment due to lasting neurotoxic and cognition impairing effects in humans. The author noted that oxytocin and D-cycloserine are potentially safer co-drugs in PTSD treatment, albeit with limited evidence of efficacy. This review and a second corroborating review by a different author both concluded that, because of MDMA's demonstrated potential to cause lasting harm in humans (e.g., serotonergic neurotoxicity and persistent memory impairment), "considerably more research must be performed" on its efficacy in PTSD treatment to determine if the potential treatment benefits outweigh its potential to cause long-term harm to a patient.

§References

§External links

• MDMA Facts and Statistics

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. MDMA（エクスタシー）中毒 mdma ecstasy intoxication
• 2. 成人における低ナトリウム血症の原因 causes of hyponatremia in adults
• 3. 薬剤誘発性の弁膜症 valvular heart disease induced by drugs
• 4. 薬物乱用検査（DOA） testing for drugs of abuse doa
• 5. アンフェタミンおよび合成カチノン（「バスソルト」）による急性中毒 acute amphetamine and synthetic cathinone bath salt intoxication

English Journal

• Direct and long-lasting effects elicited by repeated drug administration on 50-kHz ultrasonic vocalizations are regulated differently: implications for the study of the affective properties of drugs of abuse.

• Simola N1, Frau L1, Plumitallo A2, Morelli M1.Author information 1Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy.2Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.AbstractSeveral studies suggest that 50-kHz ultrasonic vocalizations (USVs) may indicate a positive affective state in rats, and these vocalizations are increasingly being used to investigate the properties of psychoactive drugs. Previous studies, however, have focused on dopaminergic psychostimulants and morphine, whereas little is known about how other drugs modulate 50-kHz USVs. To further elucidate the neuropharmacology of 50-kHz USVs, the present study characterized the direct and long-lasting effects of different drugs of abuse, by measuring the number of 50-kHz USVs and their 'trill' subtype emitted by adult male rats. Rats received repeated administrations of amphetamine (2 mg/kg, i.p.), 3,4-methylenedioxymethamphetamine (MDMA, 7.5 mg/kg, i.p.), morphine (7.5 mg/kg, s.c.), or nicotine (0.4 mg/kg, s.c.), on either consecutive or alternate days (five administrations in total) in a novel environment. Seven days later, rats were re-exposed to the drug-paired environment, subjected to USVs recording, and then challenged with the same drug. Finally, 7 d after the challenge, rats were repeatedly exposed to the drug-paired environment and vocalizations were measured. Amphetamine was the only drug to stimulate 50-kHz USVs and 'trill' subtype emission during administration and challenge. Conversely, all rats emitted 50-kHz USVs when re-exposed to the test cage, and this effect was most marked in morphine-treated rats, and less evident in nicotine-treated rats. This study demonstrates that the direct and long-lasting effects of drugs on 50-kHz USVs are regulated differently, providing a better understanding of the usefulness of these vocalizations in the study of psychoactive drugs.
• The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP).Int J Neuropsychopharmacol.2014 Mar;17(3):429-41. doi: 10.1017/S1461145713001235. Epub 2013 Oct 21.
• Several studies suggest that 50-kHz ultrasonic vocalizations (USVs) may indicate a positive affective state in rats, and these vocalizations are increasingly being used to investigate the properties of psychoactive drugs. Previous studies, however, have focused on dopaminergic psychostimulants and m
• PMID 24138707

• Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.

• Hysek CM1, Simmler LD1, Schillinger N1, Meyer N1, Schmid Y1, Donzelli M1, Grouzmann E2, Liechti ME1.Author information 1Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.2Biomedicine Service, University Hospital Lausanne, Lausanne, Switzerland.AbstractMethylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).
• The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP).Int J Neuropsychopharmacol.2014 Mar;17(3):371-81. doi: 10.1017/S1461145713001132. Epub 2013 Oct 8.
• Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same t
• PMID 24103254

• How MDMA's Pharmacology and Pharmacokinetics Drive Desired Effects and Harms.

• Michael White C.Author information University of Connecticut and Hartford Hospital, Hartford, CT, USA.Abstract3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin syndrome, multiorgan failure, cardiovascular events, arrhythmias, and death are possible adverse effects. These desirable and adverse effects of MDMA are extensions of its fascinating pharmacologic and pharmacokinetic profile. In addition to methamphatemine like effects, MDMA also has mescaline like effects and increases the release of cortisol, oxytocin, and antidiuretic hormone. The desirable effects of MDMA are accentuated by the rave or electronic dance music scene where warm temperatures, vigorous dancing, loud music, and light shows accentuate some of the responses. However, the same environment increases the risk of certain harms. Knowledge of the constellation of these factors is needed for education, prevention of harm, and treatment.
• Journal of clinical pharmacology.J Clin Pharmacol.2014 Mar;54(3):245-52. doi: 10.1002/jcph.266. Epub 2014 Jan 22.
• 3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin synd
• PMID 24431106

Japanese Journal

• Discriminative Stimulus Effects of Hallucinogenic Drugs: a Possible Relation to Reinforcing and Aversive Effects

• Mori Tomohisa,Yoshizawa Kazumi,Shibasaki Masahiro,Suzuki Tsutomu
• Journal of Pharmacological Sciences 120(2), 70-76, 2012
• … Over the past two decades, the patterns of drug abuse have changed, so that club/recreational drugs such as phencyclidine (PCP), 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and ketamine, which induce perceptual distortions, like hallucinations, are now more commonly abused, especially in younger generations. …
• NAID 130001889167

• Method of simultaneous stir bar sorptive extraction of phenethylamines and THC metabolite from urine

• GOTO Yoshiyuki,TAKEDA Shiho,ARAKI Toshinori,FUCHIGAMI Takayuki
• Journal of toxicological sciences 36(5), 523-529, 2011-10-01
• … In this study, we developed a method for simultaneous detection of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, and a Δ9-tetrahydrocannabiniol (THC) metabolite in human urine. …
• NAID 10029481085

• Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on extracellular dopamine and serotonin in the rat brain.

• Ikeda Rie,Igari Yoshiko,Fuchigami Yuki,Wada Mitsuhiro,Kuroda Naotaka,Nakashima Kenichiro
• European Journal of Pharmacology 660(2-3), 318-325, 2011-06-25
• … 3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive stimulant abused by young people as the recreational drug ecstasy. … Baseline levels of dopamine and 5-HT in the striatum were 16.5±7.7 and 3.5±1.7 nM (mean±standard deviation), respectively. … After a single administration of MDMA (10 mg/kg, i.p.), a dramatic increase in extracellular dopamine (Cmax: 36.1-fold vs. baseline) and 5-HT levels (Cmax: 9.3-fold vs. baseline) was observed. …
• NAID 120003220735

Related Links

• 3,4-methylenedioxymethamphetamine - definition of 3,4 ...

3,4-methylenedioxymethamphetamine /3,4-meth·y·lene·di·oxy·meth·am·phet·amine/ (-meth″am-fet´ah-mēn) MDMA; a compound chemically related to amphetamine and having hallucinogenic properties; it is widely abused. Popularly ...

• 3,4-methylenedioxymethamphetamine (MDMA): current ...

Ecstasy is a widely used recreational drug that usually consists primarily of 3,4-methylenedioxymethamphetamine (MDMA). Most ecstasy users consume other substances as well, which complicates the interpretation of ...

Related Pictures

---

★リンクテーブル★

リンク元	「メチレンジオキシメタンフェタミン」
関連記事	「methylenedioxymethamphetamine」

「メチレンジオキシメタンフェタミン」

　　[★]

英

methylenedioxymethamphetamine、MDMA

同

エクスタシー ecstasy、N-メチル-3,4-メチレンジオキシアンフェタミン N-methyl-3,4-methylenedioxyamphetamine 3,4-methylenedioxymethamphetamine

「methylenedioxymethamphetamine」

　　[★] メチレンジオキシメタンフェタミン