|Systematic (IUPAC) name|
|Routes||Oral, sublingual, insufflation, inhalation (vaporization), injection, rectal|
|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
|Synonyms||3,4-MDMA, Ecstasy, Molly|
|PDB ligand ID||B41 (, )|
|Molecular mass||193.24 g/mol|
|Boiling point||105 °C (221 °F) at 0.4 mmHg (experimental)|
|(what is this?)|
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.
- 1 Effects
- 2 Uses
- 3 Adverse effects
- 4 Overdose
- 5 Chronic use and addiction
- 6 Interactions
- 7 Pharmacology
- 8 Physical and chemical properties
- 9 History
- 10 Society and culture
- 11 References
- 12 External links
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
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.
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-depressing 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.
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.
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 periphery, 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).
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:
Overdose symptoms vary widely with MDMA; they include:
Chronic use and addiction
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. 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.
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.
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).
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 withdrawal 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 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 (in humans, but CYP2D1 in mice), 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.[medical citation needed]
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
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.
The primary precursor of MDMA is MDP2P (3,4-methylenedioxyphenyl-2-propanone, also known as piperonyl methylketone), which is generally synthesized from piperonal or safrole. There are numerous synthetic methods available in the literature to convert safrole into MDMA via different intermediates. 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 (3,4-methylenedioxy phenyl-2-propanone) 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). Racemic MDMA can be synthesized directly from safrole by adding hydrogen bromide to safrole and reacting the adduct with methylamine.
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.
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 scientific paper on the substance.
Chemist Alexander Shulgin synthesized MDMA in 1965 while researching methylenedioxy compounds at Dow Chemical Company, however Shulgin 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. The few early chemists who supplied MDMA were more interested in contributing to psychological health than in making money. 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. Unaware of the therapeutic use of MDMA, the DEA was surprised when a number of physicians, therapists, and researchers objected to the proposed scheduling and requested a hearing. 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 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,[when?] 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).
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
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 3 to Schedule I in March 2012.
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.
Despite its illegal status, some therapists continue to use MDMA in treatment for PTSD.
A 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 placed MDMA at number 18 in the list of 20 harmful drugs.
Usage, cost and distribution
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.
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.
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.
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/EPIDEMIOLOGY STUDIES/ /Investigators/ compared the prevalence of Diagnostic and Statistical Manual version IV (DSM-IV) mental disorders in 30 current and 29 former ecstasy users, 29 polydrug and 30 drug-naive controls. Groups were approximately matched by age, gender and level of education. The current ecstasy users reported a life-time dose of an average of 821 and the former ecstasy users of 768 ecstasy tablets. Ecstasy users did not significantly differ from controls in the prevalence of mental disorders, except those related to substance use. Substance-induced affective, anxiety and cognitive disorders occurred more frequently among ecstasy users than polydrug controls. The life-time prevalence of ecstasy dependence amounted to 73% in the ecstasy user groups. More than half of the former ecstasy users and nearly half of the current ecstasy users met the criteria of substance-induced cognitive disorders at the time of testing. Logistic regression analyses showed the estimated life-time doses of ecstasy to be predictive of cognitive disorders, both current and life-time. ... Cognitive disorders still present after over 5 months of ecstasy abstinence may well be functional consequences of serotonergic neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) [Thomasius R et al; Addiction 100(9):1310-9 (2005)] **PEER REVIEWED** PubMed Abstract
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MDMA has been proven to produce lesions of serotonin neurons in animals and humans.
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Human Psychopharmacology recently published my review into the increase in empirical knowledge about the human psychobiology of MDMA over the past 25 years (Parrott, 2013a). Deficits have been demonstrated in retrospective memory, prospective memory, higher cognition, complex visual processing, sleep architecture, sleep apnoea, pain, neurohormonal activity, and psychiatric status. Neuroimaging studies have shown serotonergic deficits, which are associated with lifetime Ecstasy/MDMA usage, and degree of neurocognitive impairment. Basic psychological skills remain intact. Ecstasy/MDMA use by pregnant mothers leads to psychomotor impairments in the children. Hence, the damaging effects of Ecstasy/MDMA were far more widespread than was realized a few years ago. ... Rogers et al. (2009) concluded that recreational ecstasy/MDMA is associated with memory deficits, and other reviews have come to similar conclusions. Nulsen et al. (2010) concluded that ‘ecstasy users performed worse in all memory domains’. Laws and Kokkalis (2007) concluded that abstinent Ecstasy/MDMA users showed deficits in both short-term and long-term memory, with moderate to large effects sizes. Neither of these latter reviews suggested that the empirical literature they were reviewing was of poor quality (Laws and Kokkalis, 2007; Nulsen et al., 2010).
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Clinical manifestation ...
hypertension, aortic dissection, arrhythmias, vasospasm, acute coronary syndrome, hypotension ... Agitation, paranoia, euphoria, hallucinations, bruxism, hyperreflexia, intracerebral haemorrhage ... pulmonary oedema/ARDS ... Hepatitis, nausea, vomiting, diarrhoea, gastrointestinal ischaemia ... Hyponatraemia (dilutional/SIADH), acidosis ... Muscle rigidity, rhabdomyolysis
[entactogen] – euphoria, inner peace, social facilitation, ‘heightens sexuality and expands consciousness’, mild hallucinogenic effects ...
Bruxism, hyperthermia, ataxia, confusion, hyponatraemia (SIADH), hepatitis, muscular rigidity, rhabdomyolysis, DIC, renal failure, hypotension, serotonin syndrome, chronic mood/memory disturbances ... human data have shown that long-term exposure to MDMA is toxic to serotonergic neurones.75,76
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MDMA has become a popular recreational drug of abuse at nightclubs and rave or techno parties, where it is combined with intense physical activity (‘‘all-night dancing’’), crowded conditions (aggregation), high ambient temperature, poor hydration, loud noise, and is commonly taken together with other stimulant ‘‘club drugs’’ and/or alcohol (Parrott 2006; Von Huben et al. 2007; Walubo and Seger 1999). This combination is probably the main reason why it is generally seen an increase in toxicity events at rave parties since all these factors are thought to induce or enhance the toxicity (particularly the hyperthermic response) of MDMA. ... Another report showed that MDMA users displayed multiple regions of grey matter reduction in the neocortical, bilateral cerebellum, and midline brainstem brain regions, potentially accounting for previously reported neuropsychiatric impairments in MDMA users (Cowan et al. 2003). Neuroimaging techniques, like PET, were used in combination with a 5-HTT ligand in human ‘‘ecstasy’’ users, showing lower density of brain 5-HTT sites (McCann et al. 1998, 2005, 2008). Other authors correlate the 5-HTT reductions with the memory deficits seen in humans with a history of recreational MDMA use (McCann et al. 2008). A recent study prospectively assessed the sustained effects of ‘‘ecstasy’’ use on the brain in novel MDMA users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. The authors concluded that low MDMA dosages can produce sustained effects on brain microvasculature, white matter maturation, and possibly axonal damage (de Win et al. 2008).
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In contrast, MDMA produces damage to serotonergic, but not dopaminergic axon terminals in the striatum, hippocampus, and prefrontal cortex (Battaglia et al., 1987, O'Hearn et al., 1988). The damage associated with Meth and MDMA has been shown to persist for at least 2 years in rodents, non-human primates and humans (Seiden et al., 1988, Woolverton et al., 1989, McCann et al., 1998, Volkow et al., 2001a, McCann et al., 2005)
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Hyponatremia can occur from free water uptake in the collecting tubules secondary to the ADH effects and from over consumption of water to prevent dehydration and overheating. ... Hyperpyrexia resulting in rhabdomyolysis or heat stroke has occurred due to serotonin syndrome or enhanced physical activity without recognizing clinical clues of overexertion, warm temperatures in the clubs, and dehydration.1,4,9 ... Hepatic injury can also occur secondary to hyperpyrexia with centrilobular necrosis and microvascular steatosis.
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Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch—from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure—cited earlier (Renthal et al. in press).
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