Methylenedioxymethamphetamine
From Wikipedia, the free encyclopedia
| Methylenedioxymethamphetamine | |
| Systematic (IUPAC) name | |
| 1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine | |
| Identifiers | |
| CAS number | ? [2] [3] [4] |
| ATC code | ? |
| PubChem | |
| Chemical data | |
| Formula | C11H15NO2 |
| Mol. mass | 193.25 g/mol |
| SMILES | search in , |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | Hepatic, CYP extensively involved |
| Half life | The half-life of MDMA is dose dependent, increasing with higher doses, but is around 6–10 hours at doses of 40–125 mg |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. | C [5] |
| Legal status | Prohibited (S9)(AU) Schedule III(CA) Class A(UK) Schedule I(US) |
| Routes | Sublingual salla |
MDMA (3,4-methylenedioxy-N-methylamphetamine), most commonly known today by the street name ecstasy, (often abbreviated to E, X, or XTC) is a semisynthetic psychedelic entactogen of the phenethylamine family. It is considered a recreational drug, and has long had a strong association with the rave culture. MDMA is illegal in most countries, and its possession, manufacture or sale may result in criminal prosecution.
Contents
|
[edit] History
The origin of MDMA is often rumored to be an invention by the famous German chemist Fritz Haber in 1891. 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.[1][2] 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 [citation needed]. 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.[1]
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.[3]
The U.S. Army did, however, carry out lethal dose studies on animals of MDMA and several other compounds in the mid-1950s. It was given the name EA-1475, with the EA standing for either (accounts vary) "Experimental Agent" or "Edgewood Arsenal."[4] The results of these studies were not declassified until 1969.
Due to the wording of the existing Misuse of Drugs Act 1971, MDMA was automatically classified as a Class A drug in 1977 in UK and was classified as a Schedule I controlled substance in the United States from May 31, 1985.[5] Before then, it was used both as an adjunct to psychotherapy and as a recreational drug.
MDMA began to be used therapeutically in the mid-1970s after the chemist Alexander Shulgin 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. There have even been accounts that the military also used this for interrogating enemy spies due to these effects. 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.
MDMA appeared sporadically as a street drug in the late 1960s (when it was known as the "love drug"), but it rose to prominence in the early 1980s in certain trendy nightclubs in the Dallas area, then in gay dance clubs.[6] 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.[3]
During the 1990s, along with the growing popularity of the rave subculture, 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.
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.
[edit] Effects
- For more details on this topic, see Effects of MDMA on the human body.
[edit] Subjective effects
The primary effects of MDMA include an increased awareness of the senses, feelings of openness, euphoria, empathy, love, heightened self-awareness, feeling of mental clarity and an increased appreciation of music and movement. Tactile sensations are enhanced for some users, making physical contact with others more pleasurable.[7] Other side effects, such as jaw clenching and elevated pulse, are common. Some users report effects similar to those of softer stimulants such as caffeine, and a few report effects comparable to harder stimulants such as cocaine. Alexander Shulgin stated that the single best use of MDMA was to facilitate more direct communication between people involved in significant emotional relationships.[citation needed] Psychiatrist George Greer came to the same conclusion in his report on the first 29 subjects administered MDMA in his practice, with the MDMA having been synthesized in Shulgin's lab.[8] This is why the most profound experiences are usually had between close friends, family, or partners in a serene setting.[citation needed]
[edit] Recreational use
Recreational uses:
| |
Other putative uses:
| |
Contraindications:
| |
| Side effects: | |
|---|---|
Endocrine:
| |
Eye:
| |
Psychological:
| |
Skin:
| |
Miscellaneous:
|
MDMA use has increased markedly since the late 1980s, and spread beyond its original subcultures to mainstream use. Prices have also fallen since the 1980s. In countries where distribution is more extensive, such as the Netherlands, prices can sometimes be as low as €0.50 per tablet, but elsewhere in Europe it is common to pay €3-6 each. In Ireland their general price is €3.50-€4 and its use has grown rapidly, leading to reports of children as young as 10 using the drug on a regular basis. It is easily available in Ireland, and is often given for free as a "goodwill gesture" at raves or social functions. In countries where distribution is more difficult, such as the U.S., New Zealand, Australia, and Japan, prices are accordingly higher at up to US$10–40, NZ$50-80, AUD$20–40, and 3000-5000¥ respectively per tablet. In the United Kingdom it is common to pay around £2 to £3 for one tablet on average, and around £1 a tablet when purchased in larger quantities. Prices have been driven very low in Canada due to large supply: CAD$5 to CAD$10 is the average price per tablet, while prices decrease with quantity, such as two for CAD$5 or three for CAD$10 depending on quality. Prices are also usually higher when the drug is purchased in a club or at a rave.
[edit] Supply
Worldwide, almost all MDMA is supplied via clandestine routes. The synthesis of MDMA is more complex than that of analogues such as methamphetamine, but still well within the grasp of a university-level chemistry student. Arguably the most difficult part of the synthesis is obtaining the necessary chemical precursors: some have few legitimate uses outside of clandestine drug production, and purchases of them are often illegal or heavily monitored by government agencies like the DEA.
[edit] Purity
Because of its legal status, the typical recreational user is unable to verify the purity of a substance sold as MDMA. A small percentage of MDMA pills have been found to be cut with various substances; typical substances include caffeine, methamphetamine and ephedrine, all of which have similar stimulant effects to MDMA. Recent surveys of seized Ecstasy pills indicate that purity levels are generally high, and that adulterants are rare.[9]
Although 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), it is also possible to use a less accurate presumptive alkaloid test known as the Marquis reagent. Many organizations sell pill testing kits containing this reagent. DanceSafe is one such company, and it includes an extensive database of photographs of different pills, along with the results of a laboratory analysis of their contents. EcstasyData.org[10] is a non-profit site that tests the purity of street pills and compiles results. PillReports.com[11] also enables users to post reports on pills they have purchased, to share the experiences, pictures, and testing results; other users can then post what they think about the pill in question or even rate the report on the pill.
[edit] Administration
MDMA is typically ingested orally, although insufflation, and taking as a suppository is possible as well. The drug is commonly found in pressed pills, or in capsules containing it in powder or crystal form. The typical recreational dose of 100-150 mg creates a "high", which takes effect within 30-60 minutes and lasts 4-6 hours. Some users take additional doses to prolong the high.
Insufflated MDMA acts quicker and stronger, and wears off faster. Rectal administration produces about the same effects as ingesting, but if the user vomits, the remainder of the dose is not wasted.[citation needed]
[edit] Ecstasy-pills
Pills come in a variety of "brands", usually identified by the icons stamped on the pills. An example would be "Red Mercedes", which gets its name because of its red color and Mercedes-Benz logo imprinted on it. Most are named after famous persons or places such as "D&G's" (Dolce & Gabbana). 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.
[edit] MDMA powder/crystals
MDMA powder, usually the hydrochloride, is often simply called 'crystal' or 'molly'. 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. When pressed into pill tablets, MDMA powder is always mixed with pill binders because pure MDMA cannot be pressed.
[edit] Use in psychotherapy
Some scientists have suggested that MDMA may facilitate self-examination with reduced fear, which may prove useful in some therapeutic settings. In 1980, psychiatrist George Greer synthesized MDMA in the lab of Alexander Shulgin, then administered it to about 80 of his clients over the next five years, until MDMA was scheduled in 1985. In a published summary of the effects,[12] 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.[13]
In 2001, the FDA granted permission for experimental administration of MDMA to patients suffering from post-traumatic stress disorder. This research is being sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS). For further information on this, see MAPS's MDMA Research Information and the recent article from MSNBC/Newsweek. This research in patients builds on studies in which MDMA was given to healthy volunteers. The first of these healthy volunteer studies was conducted by Dr. Charles Grob, with other studies done by Dr. Franz Vollenweider in Switzerland, Drs. John Mendelson and Reese Jones at the University of California San Francisco, and Drs. Magi Faree and Rafael de la Torre in Spain.
A parallel similar study is currently underway in Switzerland which should finish in 2008.[14] MDMA has been classed in an entirely new category of drug action as an "empathogen" and/or an "entactogen."[15][16]
[edit] Synthesis
Safrole, a colorless or slightly yellow oil, extracted from the root-bark or the fruit of sassafras plants is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert Safrole into MDMA via different intermediates. One common route is via the MDP2P (3,4-methylenedioxyphenyl-2-propanone, also known as piperonyl acetone) intermediate. This intermediate can be produced in at least two different ways. One method is to isomerize Safrole in the presence of a strong base to isosafrole and then oxidize isosafrole to MDP2P. Another, reportedly better method, is to make use of the Wacker process to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate. This can be done with a palladium catalyst. Once the MDP2P intermediate has been produced it is then consumed via a reductive amination to form MDMA as the product.
According to DEA Microgram newsletters very little safrole is actually required to make MDMA. [17]"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."
[edit] Legal issues
Use, supply and trafficking of ecstasy are currently illegal in most countries. In the United States, MDMA was legal and unregulated until May 31, 1985, at which time it was added to DEA Schedule I, for drugs deemed to have no medical uses and a high potential for abuse. During DEA hearings to criminalize MDMA, most experts recommended DEA Schedule III prescription status for the drug, due to its beneficial usage in psychotherapy. The judge overseeing the hearings, Francis Young, also made this recommendation. Nonetheless, the DEA classified it as Schedule I.[18]
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:
- The Expert Committee held extensive discussions concerning therapeutic usefulness of 3,4 Methylenedioxymethamphetamine. While the Expert Committee found the reports intriguing, it felt that the studies lacked the appropriate methodological design necessary to ascertain the reliability of the observations. There was, however, sufficient interest expressed to recommend that investigations be encouraged to follow up these preliminary findings. To that end, the Expert Committee urged countries to use the provisions of article 7 of the Convention on Psychotropic Substances to facilitate research on this interesting substance.
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.
[edit] Health Risks
| This article may require cleanup to meet Wikipedia's quality standards. Please improve this article if you can. |
The short-term health risks of taking MDMA include hypertension, dehydration and hyperthermia, with the last two particularly notable in the rave context of dancing for long periods of time, as the drug's stimulatory effects can mask the body's normal sense of exhaustion and thirst. The risk of hyperthermia may be increased by a high fat diet, and the mechanism the activation of uncoupling protein (UCP) in mitochondria. [6] Because the lethal dose is many times higher than the typical recreational dose of 100-150 mg, overdoses are rare, but about 100 people die each year in the US with MDMA in the blood samples.[citation needed]
There exists a significant risk for physical harm arising from excessive and irresponsible MDMA use. The chief executive of the UK Medical Research Council stated MDMA was "on the bottom of the scale of harm", and the Science & Technology Committee rated it of lower concern than for alcohol, tobacco, and cannabis, when examining the harmfulness of any given drug, the 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-- MDMA scores relatively low on these dimensions of harm, this is why it has an overall harm score lower than even alcohol.[19][20] Nevertheless, there is evidence that[21] MDMA might lead to damage to the cortex and hippocampus of the human brain [21] In these areas, serotonin is known to be associated with the regulation of emotion and the retrieval of memory. Neurotoxicity from MDMA only occurs when antioxidant supplies are inadequate[7] or from Hyperthermia itself.
Deficits of memory have been shown in long term MDMA users. [22] This however should not be unexpected from long term depletion of a vital neurotransmitter involved in memory function. It is not, as many have suggested, conclusive proof of neurotoxicity and may be the result of neuroadaptation. [23] For the most current scientific understanding of the toxicity of MDMA see the January 2007 issue of Psychopharmacology entitled "A contemporary view of MDMA" [24]
Some safety considerations when using MDMA:
- Antioxidants have been shown to prevent the neurotoxicity of MDMA and should always be taken as a preventative. Vitamin C suplements are readily available. Detailed information on this subject is available at thedea.org [8].
- Redosing has been shown to substantially increase the neurotoxicity of MDMA. The longer the user is on MDMA, the greater the serotonin depletion and potential for neurotoxicity. "Rolling" for longer than 12 hours should be considered extremely dangerous.
- At least one month should be given between taking MDMA to allow the brain to recover its stores of serotonin and from any potential damage. The more frequently MDMA is used, the greater the serotonin depletion and potential for neurotoxicity.
- The MDMA content of Ecstasy tablets varies widely. They usually contain other substances - especially caffeine, amphetamine and methamphetamine. In some cases, tablets sold as Ecstasy do not even contain MDMA or even the chemically related substances MDEA or MDA, but instead are substituted with various other drugs including benzylpiperazine and 2C-B. Some users purchase pill testing kits to verify that the tablets actually contain MDMA. Organizations such as DanceSafe provide pill testing kits.[25]
- Hypertension is a risk in some, given the increased cardiac load.[26]
- 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, which can be fatal. [9]
- MDMA affects the regulation of the body's internal systems. Continuous dancing without sufficient breaks or drinks can lead to dangerous overheating and dehydration. Drinking too much water without adequate salt can cause hyponatremia or water intoxication.
- MDMA use commonly results in a rebound depression known as a "comedown", the length and severity of this period depends on the user, the dose and the length of the period spent on MDMA. It may also precipitate lasting depression and anxiety in vulnerable users.[27]
- A small percentage of users may be highly sensitive to MDMA; this may make first-time use especially hazardous. This includes, but is not limited to, people with congenital heart defects. (Some scientists have suggested that a small percentage of people lack the proper enzymes to break down the drug. One enzyme involved in MDMA's breakdown is CYP2D6, which is deficient or totally absent in 5-10% of the Caucasian population and those of African descent, and in 1-2% of Asians.[28] However, there is no clear evidence linking lack of this enzyme to problems in users, and the connection remains theoretical.)
[edit] Poly substance use
MDMA is known for being taken in conjunction with other recreational drugs. It is said to complement psychedelics such as LSD and hallucinogenic mushrooms by preventing difficult experiences and bad trips. Use is so prevalent, most of the more common combinations have been given nicknames that are well known throughout the drug culture. Examples include "candy flipping", MDMA combined with LSD[29], also known as trolling (tripping and rolling) , hippie flipping or flower flipping, which is MDMA combined with mushrooms,[citation needed] or triple flipping, which is MDMA with mushrooms and LSD.[citation needed]
Many users use mentholated products while taking MDMA, as it is believed to heighten the drug's effects. Examples include menthol cigarettes, Vicks[30] lozenges, etc. This sometimes has deleterious results on the upper respiratory tract.[31]