History Effects Recreational Use Supply Use in Psychotherapy Synthesis Legal Issues Health Concerns Poly-Substance Use
MDMA is sometimes rumored to have been first synthesized by German chemist Fritz Haber in 1891; however, this is considered unlikely.
The patent for MDMA—referred to as methylsafrylamin—which is not under dispute, was originally filed on December 24 1912 by the German pharmaceutical company Merck, after being first synthesised for them by German chemist Anton Köllisch at Darmstadt earlier that year. The patent was granted in 1914; Köllisch died in 1916 unaware of the impact his synthesis would have.
At the time, MDMA was not known to be a drug in its own right; rather, it was patented as an intermediate chemical used in the synthesis of a hydrastinine (a drug intended to control bleeding from wounds) analogs . During 1927, Max Oberlin used MDMA as a mimic for adrenaline as the compound has a similar chemical structure. At this time the first animal studies were performed to demonstrate the effects of MDMA on blood glucose levels and vascular tissue.
This study was discontinued due to the high costs of the chemical synthesis. Interest was revived in the compound as a possible human stimulant by Wolfgang Fruhstorfer in 1959, although it is unclear if tests were actually performed on humans. The synthesis of the compound first appeared in 1960.
The U.S. Army did, however, carry out lethal dose studies of MDMA and several other compounds on animals in the mid-1950s. It was given the name EA-1475, with the EA standing for either (accounts vary) "Experimental Agent" or "Edgewood Arsenal. The results of these studies were not declassified until 1969.
MDMA appeared sporadically as a street drug in the late 1960s (when it was known as the "love drug").
MDMA began to be used therapeutically in the late-1970s after the chemist Alexander Shulgin tried it himself, in 1977, then introduced it to psychotherapist Leo Zeff. As Zeff and others spread word about MDMA, it developed a reputation for enhancing communication, reducing psychological defenses, and increasing capacity for introspection. However, no formal measures of these putative effects were made and blinded or placebo-controlled trials were not conducted. A small number of therapists—including George Greer, Joseph Downing, and Philip Wolfson—used it in their practices until it was made illegal.
Due to the wording of the existing Misuse of Drugs Act 1971, MDMA was automatically classified as a Class A drug in 1977 in the UK.
In early 1980s USA, MDMA rose to prominence in certain trendy nightclubs in the Dallas area, then in gay dance clubs. From there use spread to rave clubs, and then to mainstream society. The street name of "ecstasy" was coined in California in 1984. The drug was first proposed for scheduling by the DEA in July 1984, and was classified as a Schedule I controlled substance in the United States from May 31, 1985.
In the late 1980s and early 1990s, ecstasy was widely used in the United Kingdom and other parts of Europe, becoming an integral element of rave culture and other psychedelic/dancefloor-influenced music scenes, such as Madchester and Acid House. Spreading along with rave culture, illegal MDMA use became increasingly widespread among young adults in universities and later in high schools. It rapidly became one of the four most widely used illegal drugs in the U.S., along with cocaine, heroin and cannabis.
MDMA's unique effects can be attributed to an array of pharmacological changes which occur in the brain which are yet to be fully understood. One of the primary components in producing effects is the drug's higher affinity for SERTs than serotonin itself. SERTs are the part of the serotonergic neuron which removes serotonin from the synapse to be recycled or stored for later use. Not only does MDMA inhibit the reuptake of serotonin, but it reverses the action of the transporter so that it begins pumping serotonin into the synapse from inside the cell. This usually causes the serotonin storage vesicles to be emptied after only a few hours with a standard recreational dose. In addition, MDMA has a partial affinity for blocking the reuptake of norepinephrine as well as an affinity for blocking that of dopamine.
MDMA's unique empathic/entactogenic effects have recently been attributed to the release of oxytocin, a hormone usually released in large quantities following such events as orgasm and childbirth. Essential in facilitating bonding and the establishment of trust, absent the release of this hormone, the subjective "loved-up" feelings of closeness and connectedness with others would be significantly less pronounced.
Other effects may include:
Serious complications increasing in likelihood with dose, environmental severity, degree of physical activity, and/or certain drug interactions include:
MDMA use has increased markedly since the late 1980s, and spread beyond its original subcultures to mainstream use, with prices generally falling, although there is still wide geographical variance, both regionally and between countries.
Pills come in a variety of "brands", usually identified by the icons stamped on the pills. Many popular icons are appropriated for this use; an example would be "Red Mercedes", which gets its name because of its red color and Mercedes-Benz logo imprinted on it. However the brands do not consistently designate the actual active compound within the pill, as it is possible for "copycat" manufacturers to make their own pills which replicate the features of a well-known brand.
MDMA powder, usually the hydrochloride, is often simply called 'crystal' or 'molly', and 'mandy', and in the UK 'Muds', 'Mud' or 'madman' (a play on words- MaDMAn), a mutation of 'madman' 'mandy', and 'MD'. This powder is produced in MDMA labs and provided to the pill-manufacturers to press the tablets at a different place. In many parts of the world the usage of plain MDMA powder instead of pills is popular. One of the reasons for this might be the control over dosage and purity. MDMA is less likely to be cut as it would be more easy to notice compared to pressed pills. Also, because its taste is so strong, distinctive and (many would argue) unpleasant that it would be relatively easy for an experienced user to tell if it were impure. Dealers are more likely to simply sell an amount that is smaller than they claim. When pressed into pill tablets, MDMA powder is always mixed with pill binders because pure MDMA cannot be pressed. Powder or crystal MDMA can be snorted, which makes the effect begin and end quicker. Some users claim that snorting it results in a more intense effect. Snorting however is painful compared to drugs such as cocaine and ketamine, and many users prefer oral administration either by applying a 'dab' to the tongue and washing it down with water, or mixing it into a drink. Some people also 'bomb' or 'parachute' pure MDMA, whereby a dose is wrapped in cigarette papers or a small piece of toilet paper and then swallowed. This is the preferred method of ingestion for many users as the taste is quite unpleasant and can be exacerbated by the heightened sense of taste which can be a feature of MDMA use.
In 1980, psychiatrist George Greer synthesized MDMA in the lab of Alexander Shulgin and administered it to about 80 of his clients over the course of the remaining years preceding MDMA's Schedule I placement in 1985. In a published summary of the effects, subjects reported improvements in various, mild psychiatric disorders and other personal benefits, especially improved intimate communication with their significant others. In a subsequent publication on the treatment method, one patient with severe pain from terminal cancer reported definitive and lasting pain relief and improved quality of life.
An ongoing study being conducted by the Multidisciplinary Association for Psychedelic Studies is evaluating the efficacy of treating those diagnosed with posttraumatic stress disorder with MDMA. Some of the criteria for the study are that the patients had to have had the disorder for a number of years and tried other treatments without success. Some of the patients demonstrated a significant long-term reduction in the degree of manifestation of the disorder after having undergone a single MDMA psychotherapy session, sometimes to the degree of no longer meeting the diagnostic criteria any longer.
According to DEA Microgram newsletters very little safrole is actually required to make MDMA. "Ocotea cymbarum is an essential oil... that typically contains between 80 and 94 percent safrole," "a 500-milliliter bottle of Ocotea cymbarum sells for $20 to more than $100," "An MDMA producer with access to the proper chemicals can use a 500-milliliter quantity of Ocotea cymbarum to produce an estimated 1,300 to 2,800 tablets containing 120 milligrams of MDMA."
That same year, the World Health Organization's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the Convention on Psychotropic Substances. Unlike the Controlled Substances Act, the Convention has a provision in Article 7(a) that allows use of Schedule I drugs for "scientific and very limited medical purposes." The committee's report stated:
In the United Kingdom, MDMA is a Class A drug under the Misuse of Drugs Act 1971, making it illegal to sell, buy, or possess without a license. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. A mandatory seven year sentence is now the penalty for a third conviction for trafficking.
While the short term side effects and contraindications of MDMA are fairly well known, there is significant debate within the scientific and medical community over the long term effects and the possibility for physical harm arising from MDMA use.
MDMA affects the regulation of the body's internal systems. Continuous dancing without sufficient breaks or drinks can lead to dangerous overheating and dehydration, and serves to significantly enhance the drug's neurotoxic action. Drinking too much water without adequate salt can cause hyponatremia or water intoxication, although this is less common than overheating.
Hypertension is a risk in some users due to the increase in heart rate and blood pressure. This risk increases as dose increases which can lead to overstimulation of the heart and ultimately death.
Although oxidative stress (see neurotoxicity theory below) may cause SERTs to degrade faster than they are able to be replaced, the serotonin axon itself seems to have been spared, which indicates that neurotoxicity may not be the means by which SERT count was reduced. It is possible that excess serotonin in the synapse due to MDMA, especially if uses occur within a short period, causes the serotonin cells to produce fewer SERTs, a phenomenon which has already been demonstrated with other serotonin-depleting drugs. MDMA use may also cause a decrease in the number of serotonin receptors on the dendrite of the neuron. (See down-regulation theory below.)
For a detailed and comprehensive explanation of this topic, see TheDea.org's evaluation of studies.
One theory of SERT-depletion arising out of long-term MDMA use is receptor down-regulation which is one form of synaptic plasticity. When any neurotransmitter is present in excess for prolonged periods of time, the brain responds in an attempt to reestablish its own natural neuro-electrical balance. Weekly use of MDMA over a prolonged period may actually cause serotonin receptors to retreat into the dendrite of serotonin nerve cells, in addition to enticing serotonin cells lower its own SERT count. The change in synaptic serotonin concentration due to recreational MDMA use is at the extreme end of what is even possible in the brain and therefore, down-regulation could occur fairly easily with regular use.
This process causes the brain to become desensitized to the neurotransmitters present in the synapses and therefore also to the effects of MDMA itself. Therefore, in addition to a generally decreased quality of mood between doses, greater amounts of MDMA are required to achieve the same level of desired effects. It is this cycle that is often believed to be the cause of long-term emotional problems among regular ecstasy users.
Normally, the brain is able to protect itself from oxidative stress, but it is believed that the aforementioned damage can be attributed to MDMA's unique interaction with serotonin transporters. Not only does MDMA reverse the normal functioning of the transporter in which case serotonin is pumped out of the cell, but once the stored serotonin has been depleted, the transporter begins to take up dopamine which has been shown to be toxic to serotonin cells by itself. Once MAO oxidizes dopamine inside the serotonin cell, the damage is greatly magnified. Several studies have demonstrated that such damage in the brain is reversible after prolonged abstinence from the drug. In severe cases, however, the possibility for recovery of cognitive functions may be much more limited.
Neurotoxicity of serotonergic neurons would occur in selective areas of the human brain as serotonin cells are highly concentrated in certain areas such as the neocortex and hippocampus. Although some studies have demonstrated this, the rate at which this damage occurs is disputed. U.S. government-funded studies performed by George Ricaurte at Johns Hopkins University, which have demonstrated catastrophic brain damage occurring due to MDMA exposure, have been widely discredited by the scientific community. The second study on the subject, which claimed that a single recreational dose of MDMA could cause Parkinson's Disease in later life due to severe dopaminergic stress, was actually retracted by Ricaurte himself after he discovered his lab had administered methamphetamine, a known neurotoxin, and not MDMA.
Antioxidants have been shown to prevent the neurotoxicity of MDMA in rats. In one study, intravenous administration of alpha lipoic acid completely blocked the neurotoxic effects of MDMA. No scientific experiment has been performed to date with human subjects, although some users report that taking various combinations of antioxidants before, during, and after using MDMA serves to moderate the subsequent mood-dip and improve recovery time.
The administration of an SSRI in rats prior to the administration of MDMA has been shown to completely block neurotoxicity. This is due to the binding of such medications with SERTs. However, administering an SSRI prior to administration of MDMA also completely or partially blocks the desired effects of the latter, something a large number of users prescribed an SSRI have reported. As a compromise it has been shown that administration of an SSRI 3-4 hours after MDMA, at which time the primary effects will have tapered off significantly, markedly limits neurotoxicity overall despite some axonal damage having already occurred. Once again, no such scientific experiment has been performed on human test subjects, and potential complications may still exist.
It should also be noted that the production and introduction into the active brain of serotonin is a much lengthier process than is that of dopamine. Therefore, users who redose once the serotonergically-induced effects of MDMA have mostly diminished are likely not stimulating the release of serotonin at all as a single recreational dose of MDMA is likely to have depleted these rather limited reserves. The subsequent effects of redosing are therefore due almost entirely to the action of increased dopamine in the brain, and therefore, once again, neurotoxicity is significantly enhanced.
"Redosing" in an attempt to extend MDMA's desired effects has been shown to substantially increase neurotoxicity as well as the undesired physical side effects associated with MDMA use such as trisma and bruxia. The longer MDMA is active and being metabolized in the brain, the greater the neurotoxic damage and the greater the risk of exacerbating pre-existing emotional problems. The more occasions MDMA is used, the greater the chances of long-term problems. Deficits in memory have been shown in long term MDMA users.
A recent University of Louisiana study found no significant relationship between depression and recreational ecstasy use. The preliminary results from an ongoing Dutch study also indicate that the very moderate use of Ecstasy alleviates symptoms of depression by 28% and improved users' overall mental state. These users also appear to be free of neurological injury of any kind.
Most people who die while under the influence of Ecstasy have also consumed significant quantities of at least one other drug. The risk of MDMA-induced death overall is very low.
The use of MDMA can be dangerous when combined with other drugs (particularly monoamine oxidase inhibitors (MAOIs) and antiretroviral drugs, in particular ritonavir). Combining MDMA with MAOIs can precipitate hypertensive crisis, as well as serotonin syndrome which can be fatal. MAO-B inhibitors such as deprenyl do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats.
Pills often contain other active substances meant to stimulate in a way similar to MDMA. These substances commonly include amphetamine, methamphetamine, ephedrine, and caffeine, all of which may be comparatively cheap to produce and can help to boost profit overall. Due to many users' inability to discern subtle pharmacological differences between substances, this practice is widely ignored by the market. In some cases, tablets sold as Ecstasy do not even contain any MDMA, chemicals in the Ecstasy Family, or even any kind of stimulant drug. Instead they may contain an assortment of presumably undesirable drugs such as paracetamol, ibuprofen, or ketamine amongst others.
Scientific surveys of seized Ecstasy pills in the United Kingdom and Europe indicate that purity levels are generally high, and that adulterants are rare. Although the US government's Office of National Drug Control Policy reports that over 55% of ecstasy pills seized in the United States in 2007 were laced with methamphetamine, it is unknown what percentage of a tablet on average the drug constitutes. It should also be noted that as a general rule, tablets seized do not necessarily represent the entire market accurately, as it is impossible to know how many of each tablet are being consumed and what each contains.
A full and proper characterization of ecstasy pills requires advanced lab techniques, such as high performance liquid chromatography-mass spectrometry (usually referred to as HPLC-MS), gas chromatography-mass spectrometry (usually referred to as GC-MS) and gas chromatography-infrared spectroscopy (usually referred to as GC-IRD). Ecstasydata.org, an American non-profit organization, uses such techniques to analyze MDMA pills for a fee.
In the Netherlands, testing of pills has been available free of charge and funded by the government at festivals and parties for almost 2 decades, but government funding has seized in recent years, and testing of pills at festivals and parties has been banned. Testing of pills as well as other common partydrugs is still possible at several testing facilities spread throughout the country, and free of charge. Both GC/MS and HPLC/MS analysis are used to determine the active constituents of the drugs being tested, and quantative analysis is performed on some drugs including Ecstacy pills and LSD blotter paper to analyse the quantities of active consituent(s) in the pills or blotters tested. Results of the quantative analysis are given in milligrams of (each) active constituent(s) in pills, and in micrograms for the constituents of tested blotter papers. Testing results are passed on to a EU monitoring program on new drugs trends. This way early warning reports can been given when possibly dangerous adulterated substances appear on the market, like cocaine adulterated with atropine, or Ecstacy pills adulterated with or containing solely PMA. The latter has never appeared in Dutch pills but is used as an example to explain the aim of the monitoring program.
DanceSafe, among other companies, provides home testing kits to verify the contents of MDMA pills. PillReports.com and Trancesafe.com each provide the results of home testing kits in addition to the suspected contents when a test has not been performed.
There have been a number of deaths in which PMA, a potent and highly neurotoxic hallucinogenic amphetamine, has been sold as Ecstasy. PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, a user who believes he is consuming 2 120mg pills of MDMA is actually consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin, but also acts as an MAO-A inhibitor. When combined with an ecstasy-like substance, serotonin syndrome can result.
While both PMA and MDMA are currently Schedule I in the U.S, PMA was scheduled more than 10 years before MDMA. Additionally, both drugs were rescued from obscurity by the same man, Alexander Shulgin, who at the time was synthesizing new psychoactive chemicals having been granted a license by the DEA to conduct autonomous research.
Between the late 1970s and early 1990s, virtually no PMA-related deaths were reported worldwide. It was not until safrole, one of the key ingredients in the original method of MDMA synthesis, was made more difficult to acquire that PMA began to be seen in batches of ecstasy pills in any notable quantity.
PMA is almost never sought after as a drug of choice, and this would not be practical to assume for several reasons. One reason is because it is so rare, another is that those who are aware of its existence are usually equally familiar with its unique hazards. The psychological effects of PMA as compared to MDMA are also quite different. PMA lacks the empathogenic qualities of MDMA, and depending on the analogue ingested, may only produce physical stimulation absent of any notable euphoria.
MDMA is known for being taken in conjunction with other recreational drugs. It is said to complement psychedelics such as LSD and hallucinogenic mushrooms. The two drugs are not taken simultaneously, but rather one is taken as the peak effects of the first are diminishing. A psychedelic such as LSD is usually the first drug taken but this is not always so. Because this practice has become more prevalent, most of the more common combinations have been given nicknames. Some examples include "candy flipping", MDMA combined with LSD, also known as trolling (tripping and rolling) , hippie flipping or flower flipping, which is MDMA combined with mushrooms, or triple flipping, which is MDMA with mushrooms and LSD.
Pills sold as 'ecstasy' very often contain amphetamine as well as MDMA. In the UK this is so common that pills containing amphetamine are not seen as adulterated, and it is taken for granted that ecstasy pills 'keep you going' for longer than crystal MDMA, due to the 'speed' content of many pills. Clubbers may also take speed during MDMA use to intensify the effects, or after MDMA use to stay awake and energised once tolerance and serotonin depletion has prevented them from gaining any more effect from MDMA. Using MDMA and amphetamine together makes both substances more neurotoxic than using them separately.
Clubbers in Europe are increasingly using ketamine during or after MDMA use. Using smaller amounts while on MDMA has little pronounced effect, as the stimulation from the MDMA balances out the depressant qualities of the ketamine. This may however increase the hallucinogenic effects of the MDMA. Clubbers more often use ketamine after the primary effects MDMA have worn off to make the comedown less dysphoric.
Many users use mentholated products while taking MDMA, as it is believed to heighten the drug's effects. Examples include menthol cigarettes, Vicks lozenges, etc. This sometimes has deleterious results on the upper respiratory tract.
Find out more about the truth about marijuana's therapeutic value by reading the recent position paper released by The American College of Physicians.
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