MDMA (3,4-methylenedioxy-N-methamphetamine) is commonly known as “Ecstasy,” “E,” “X,” or “XTC.” It is a drug used to generate a “feel good” emotion. It is a hallucinogen that has stimulant effects. Specifically, the structure of MDMA is chemically similar to the drug methamphetamine, where it gets it "stimulant" characteristics. A stimulant is a psychoactive substance that can provoke a change in the mind and body through increased sensitivity. For example, a user may feel increased happiness or pleasure for things that may seem normal for someone not under the influence. Their bodies will feel more sensitive to touch and texture, while they feel hyper or energized. MDMA is also chemically similar to the mescaline, which is of the psychedelic branch of hallucinogens. Psychedelic drugs tend to alter the mind in ways that affect thinking, perception and consciousness. MDMA is is a very popular drug that is used today.
In 1912, Merck Pharmaceuticals synthesized MDMA, which was originally used as an appetite suppressant. As the years went on, in the 1970s, MDMA was used to enhance communication skills it was also said to have been tested by the US government as a possible "truth serum". In 1987, MDMA became an illegal drug under the suspicion that it causes damage to the brain of the user which was the case with the animal models used in research experiments with this drug . Although it is an illegal drug, many people all over the world have been using MDMA. It is commonly used at a rave, club, or gatherings. As the years have progressed, it has become a very mainstream drug.
MDMA mainly affects neurotransmitters in the brain, specifically serotonin, dopamine, and norepinephrine. MDMA increases the release of serotonin, a neurotransmitter that regulates mood, sleep, pain, emotion, appetite, and other behaviors. MDMA is said to increase the activity of serotonin and also decrease the release of dopamine. The increase in serotonin is caused by the fact that MDMA inhibits serotonin to enter the reuptake site, causing and excess flow of serotonin.
MDMA has many psychological effects on the human mind. Some side effects include euphoria, decreased aggression, loss of self consciousness, enhanced senses, and enhanced empathy towards others. MDMA also has many physical side effects
Since MDMA increases the activity of serotonin, the brain becomes depleted of serotonin. MDMA users can undergo many side effects from using the drug. Some physical side effects include nausea, excessive sweating, teeth grinding, increased heart rate, papillary dilation, increased blood pressure, and increased body temperature.
After the drug is used and the user is "coming down" from the high, they may feel acute after effects such as:
- Tiredness 
- Depression 
- Anxiety 
- Impaired attention, focus and concentration 
- Residual feelings of empathy and closeness 
- Dizziness or lightheadedness 
- Shift in mood for several days after use 
- Tiredness 
- Depression 
MDMA is notoriously known for its recreational use at electronic dance music (EDM) events, more specifically scenes called "raves." However many users like to take Ecstasy many other music events such as concerts, dance and party scenes where it may seem to enhance the perception of music. MDMA is usually taken in a pill form, although it can be crushed and snorted, and which the purity of the pill is usually unknown. There are many types of pills that contain different concentrations of MDMA and are sometimes mixed with other drugs such as caffeine and methamphetamine  which alters the types of drug effects the user have. After being digested the pill usually comes into effect in 30-40 minutes, typically following the user's metabolism pattern and the "peak" effect is typically about 60-90 minutes after digestion. The user typically experiences the effects of MDMA for a total 3-4 hours , excluding the after-effects.
Medicinal Use & Potential Therapeutic Effects
Despite how MDMA is infamously known for its recreational use, few people know the prospects of MDMA as a medicinal drug. Emphasizing its psychadelic properties as well as its mental and mood uplifting abilities, MDMA has been tested on patients with mild psychiatric disorders, those who suffer from Post-traumatic Stress Disorder (PTSD), cancer patients, and even those who need assistance with communication to their partners . Furthermore, a study on MDMA with patients that suffer from PTSD by Michael C. Mithoefer, Mark T. Wagner, Ann T. Mithoefer, Lisa Jerome and Rick Doblin concluded that "MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments" .
Before MDMA became illegalized by the government, it was in popular usage by psychiatrists for research in therapeutic medicine, specifically for opening up the mind for investigation. In the Army’s Chemical Center, MDMA was used to reduce the fear of veterans who suffered from post-traumatic stress disorder. The MDMA supposedly “reduced the fear response to emotional threats… many respondents reported on the therapeutic benefits of MDMA. They had used it to uncover painful childhood memories and experiences that had been repressed; to decrease fear and defensiveness; to increase communication and empathy with one's spouse; to get through traumatic experiences such as rape and incest; to live with the pain of cancer; to resolve oneself to dying13.” This newfound sense of security was intended to enable psychiatrists to communicate with their patients with ease and without the emotional tension. According to the Studies in Crime, Law and Justice Vol. 7 by Rosenbaum and Doblin, “Trauma victims were treated with MDMA-assisted psychotherapy to help them delve into the source of their problems, experience a healing catharsis, and subsequently function more effectively.” However, this positive, therapeutic side of MDMA was lost after the DEA added it to “Schedule I” due to a “potential” of it being abused, although the favor of it being used as a recreational drug was not affected. That being said, many researchers lost the interest of continuing research on therapeutic effects of MDMA due to the negative connotation that the drug now had after being added to Schedule I despite how there were 200 physicians using MDMA for psychotherapy during the time of its banning15. Also, since MDMA was made illegal, the ability to obtain MDMA is harder and much more expensive, two other reasons why research on MDMA slowed down.
Formal IUPAC name: N-methyl-1-(3,4-methylenedioxyphenyl)propan-2-amine
Other names: 3,4-methylenedioxymethamphetamine, methylenedioxy-methylamphetamine, or N-methyl-1-(1,3-benzodioxol-5-yl)-2-propanamine
MDMA can exist in a racemic mixture with an R and S form.
MDMA is part of the phenethylamine family which is also known as “designer drug” and is also closely related to amphetamines. Phenethylamines are known for their hallucinogenic effects which originate from the compound’s ability to release serotonin in the brain as well as the ability to stimulate the central nervous system, giving users “more” energy. There are also many homologous forms of MDMA which consist of: MDA, MDEA, and MBDB. MDMA predominates as a salt in physical form; either a hydrochloride or phosphate salt which are found in tablet form. It can also exist as a powder or capsule16. As a base MDMA is a clear oil.
MDMA is manufactured by safrole, a liquid extract from sassafras trees. The most popular way to convert safrole into MDMA is by synthesizing the 3,4-methylenedioxyphenyl-2-propanone (MDP2P) intermediate via the Wacker process or by isomerizing safrole into isosafrole by a strong base. Both processes oxidize either safrole or isosafrole into the MDP2P intermediate which then undergoes reductive animation to make a racemic mixture of MDMA.
MDMA is manufactured by safrole, a liquid extract from sassafras trees. The most popular way to convert safrole into MDMA is by synthesizing the 3,4-methylenedioxyphenyl-2-propanone (MDP2P or PMK) intermediate via the Wacker process (which is the oxidation of ethylene to acetaldehyde by oxygen in water with a tetracholoropalladate catalyst) or by isomerizing (changing the arrangement of the atoms in the compound) safrole into isosafrole by a strong base. Both processes oxidize either safrole or isosafrole into the MDP2P intermediate which then undergoes reductive animation to make a racemic mixture of MDMA. In the Merck patent, safrole was added to HBr to form a bromosafrole, which was then added to methylamine to produce racemic MDMA16. Other methods of synthesis start with 3,4-methylenedioxyphenyl-2-propanone and use the Leuckart route, aluminum foil method or other reductive aminations. The Leuckart route converts ketones into amine groups using formic acid, ammonium formate or formamide/methylformamide. The aluminum foil method uses ethanol, aluminum metal pieces, an amine and a mercuric chloride catalyst to react with a ketone. The aluminum foil method is a type of reductive amination (reductive alkylation) which is the conversion of a carbonyl group to an amine group with an imine intermediate.
The main way MDMA interacts with the human body is through the brain. As previously mentioned, MDMA induces higher serotonin levels, but can also release dopamine and nonepinephrine. The structure of MDMA makes it an indirect agonist of serotonin, inducing the production of the neurotransmitter as well as inhibiting the re-uptake19. In fact, MDMA seems to act as a re-uptake inhibitor of all these neurotransmitters. MDMA is metabolized through two main 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 reactivity of the CYP2D6 enzyme is an important step in the O-demethylenation pathway because it regulates the degradation of MDMA and the efficiency of this enzyme as coded by genes, may increase a user’s risk of contracting acute toxicity. Furthermore the metabolism of MDMA also has potential involvement in mid to long-term neurotoxicity due to the neurodegeneration of the neurotransmission system.
Generally, pharmacokinetics is a subdivision of pharmacology that deals with timing of the different stages of drug interaction with the body. The term bioavailability is defined as the biochemical interactions with the drug which is used to predict how much of the drug that the body will take in. The bioavailability of MDMA can be measured by the concentration of the substance in plasma, in the urine and even in the concentration of the hormone cortisol in the plasma because MDMA induces its appearance. Research done by M. Farré et al. (2004) maps out a very intricate pathway that MDMA follows as well as how much of the drug is actually take up in the body after two doses in an interval of 24 hours. In the corresponding publication: “Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics” reveals that the results of experimentation indicate that there is a dramatic increase of MDMA concentration and pharmacological effects, suggesting that the second dose has an inhibiting effect on metabolism. The “accumulation” of MDMA could also be explained by looking at the methylenedioxy group present in the structure which is postulated to be able to have an “auto-inhibition” of MDMA’s metabolism . It is postulated that MDMA inhibits its metabolism by the CYP2D6 enzyme. The CYP2D6 enzyme is an important factor in metabolizing many substances that enter the body, vitamins and drugs alike. CYP2D6 enzyme metabolizes substances via oxidation in the liver. However, research on substances with similar structures to MDMA shows that MDMA may be able to inhibit the CYP2D6 enzyme catalysis with the methelenedioxy group by creating an enzyme-metabolite complex . These “accumulative” and inhibitive effects of MDMA prove that it exhibits non-linear pharmacokinetics which can have extremely detrimental pharmacological effects as well as toxicity because of the body’s inability to rid itself of the substance at an efficient rate .
Pharmacogenetics is a subdivision of pharmacology which focuses on the genetics behind the enzymes and other mechanisms behind the metabolism of substances. This area of focus is important for determining the effects of MDMA on users. The genetics of the CYP2D6 enzyme responsible for the metabolism of MDMA is being investigated to determine the body’s efficiency in the metabolization of MDMA. Analyzing the body’s ability to take in and process MDMA is incredibly important because it can give answers to questions about susceptibility to fatality, intensities of pharmacological effects, intensities of toxicity, and susceptibility of dependence. Since recent studies suggest that MDMA has non-linear pharmacokinetics, the rate of metabolizing MDMA in the body is crucial to understanding toxicity, fatality and pharmacological effects.
One example of genetics being a factor in the metabolism of substances is shown in an Interesting study by Y. Ramamoorthy et. Al (2001) in which the metabolistic rate of CYP2D6 substrates is lower in Asians than in Caucasians because the genes that are responsible for the synthesis of CYP2D6 have a variation different from the typical wild type gene which codes for enzymes with slower functionalities . Again taking into consideration that MDMA may acts as an accumulator and an inhibitor, then if the CYP2D6 enzyme has a slower functionality as observed in Asians then users with this genotype have a higher risk of acute toxicity and fatality. However, for Caucasians who have the wild-type genotype that produces a CYP2D6 enzyme with normal-fast functionality, then their susceptibility to fatality and the intensity of pharmacological effects are lower than that of Asians. It is important to remember when looking at data that the genetic populations are still averages of the population and that every individual has different genetic makeup which affects the pharmacokinetics of the drug on an individual basis.
14. Studies in Crime, Law and Justice Vol. 7 by Rosenbaum and Doblin
15. Glen R. Hanson, Peter J. Venturelli, Annette E. Fleckenstein (2005-11-03). "Drugs and society (Ninth Edition)". Jones and Bartlett Publishers. ISBN 978-0-7637-3732-0. Retrieved 2011-04-19.
18. de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Camí J. “Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition”. NCIB
19. R. De La Torre, M. Farré, J. Ortuño, M. Mas, R. Brenneisen, P. N. Roset, et al.(February 2000). " Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics". Springer-Verlag 2004.
20. R. De La Torre, M. Farré, J. Ortuño, M. Mas, R. Brenneisen, P. N. Roset, et al.(February 2000). "Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans". Annals of the New York Academy of Sciences 49 (2): 104–109.
21. Ramamoorthy,Y., Tyndale,R.F., and Sellers, E.M.(2001).Cytochrome P450 2D6.1andcytochrome P450 2D6.10differincatalyticactivityformultiplesubstrates.Pharmacogenetics 11, 477–487.