MDMA

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    MDMA Guide

    General Information

    MDMA, also known as ecstasy or Molly, is a psychoactive substance that has garnered significant attention for its unique effects on mood and perception. Chemically classified as 3,4-methylenedioxymethamphetamine, MDMA belongs to the Amphetamine class of drugs and was first synthesized in 1912 by the German pharmaceutical company Merck. Initially developed for potential therapeutic applications, its psychoactive properties were not explored until the 1970s when it emerged as a popular recreational drug.

    MDMA Hydrochloride Crystals

    The rise of MDMA in the 1980s and 1990s coincided with its adoption by the rave and nightclub culture, where it became renowned for its ability to enhance sensory experiences, promote feelings of empathy, and facilitate interpersonal connections. However, alongside its recreational use, MDMA was also studied for its potential therapeutic benefits, particularly in psychotherapy settings due to its ability to reduce fear and promote trust and intimacy.

    Despite its potential therapeutic uses, MDMA's recreational popularity led to increased regulatory scrutiny, resulting in its classification as a Schedule I controlled substance in many countries, including the United States. This classification reflects its high potential for abuse, lack of accepted medical use, and associated safety concerns. Nevertheless, ongoing research continues to explore MDMA's therapeutic potential, particularly in the treatment of post-traumatic stress disorder (PTSD) and other mental health conditions.

    MDMA Chemical Properties

    MDMA, scientifically referred to as 3,4-methylenedioxymethamphetamine, boasts a distinctive chemical structure that dictates its pharmacological effects and interactions within the body.

    At its core, MDMA is classified as a substituted Amphetamine, sharing structural similarities with both amphetamines and phenethylamines. Its molecular structure features a phenethylamine backbone with a methylenedioxy ring substitution, rendering it unique among psychoactive compounds.

    Chemical Structure of MDMA

    Chemically, MDMA acts primarily as a serotonergic agent, exerting its effects through interactions with serotonin receptors in the brain. This mechanism involves the inhibition of serotonin reuptake and the facilitation of serotonin release, leading to an increase in extracellular serotonin levels. This surge in serotonin activity underlies many of MDMA's psychoactive effects, including heightened mood, emotional empathy, and sensory perception.

    In addition to its serotonergic effects, MDMA also modulates other neurotransmitter systems, such as dopamine and norepinephrine. By promoting the release of dopamine and norepinephrine, MDMA elicits feelings of euphoria, increased energy, and heightened arousal. These interactions contribute to the reinforcing properties of MDMA and its potential for abuse.

    MDMA Physical Properties

    MDMA possesses distinct physical properties that aid in its identification and characterization, including its melting point and solubility.

    In its pure form, MDMA typically appears as a crystalline hydrochloride salt white powder with a melting point ranging between 147 to 153°C (297 to 307°F). MDMA phosphate has 184-185°C melting point. This melting point represents the temperature at which MDMA transitions from a solid to a liquid state. However, variations in purity and crystalline structure may slightly alter this temperature range. 

    Regarding solubility, MDMA demonstrates limited solubility in water but is highly soluble in organic solvents such as ethanol, methanol, and chloroform.

    • CAS No.: 42542-10-9;
    • Formal Name: 3,4-Methylenedioxymethamphetamine;
    • Synonyms: 3,4-MDMA; Ecstasy (E, X, XTC); midomafetamine; Molly; Mandy; Pingers; Pingas;

    MDMA Synthesis Ways

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

    So far as MDP2P became more avalible by getting from PMK glycidates, the following methods reach popularity around cladestine chemists.

    For instance, MDMA synthesis via its N-methylformamide (NMF) adduct. This method allows to avoid Methylamine precursor, which can be in a poor access.

    There is also an option to carry out this synthesis via LAH reduction:

    The NaBH4 reductive amination of MDP2P actually is superior to all other common routes used in clandestine chemistry and this method allows to scale MDMA synthesis unlike aluminum amalgam reduction. The method is quite simple, it doesn't take expensive equipment. Procedures with the reaction mixture are simple and efficient. This method is very useful for big scale production of MDMA and gives high yields (90%+).

    There is a relatively fast formation of the imine and the imine is reduced rapidly. There's no reduction of the ketone to the secondary alcohol. In similar reactions, the water that is produced during the forming of the imine (Schiff Base) is removed from the reaction before the imine is reduced with drying salt, or molecular sieves, or by using toluene as the solvent, so the water and the toluene form an azeotrope.

    Reagent Qualitative Tests of MDMA

    Marquis reagent gives purple to black colour with MDMA.

    MDMA Effects and Dosage

    MDMA use starts a couple days prior to the act of oral administration. First of all, you should be in a state of complete physical and mental well-being, you shouldn't be in acute or critical state. It is not recommended using while having experienced recent psychological trauma. You shouldn't (ideally) be taking any course of treatment. 4-5 days before use, you should start taking drugs of the proton pump inhibitor group in preventive doses (usually 20 mg of omeprazole per day); alpha-lipic acid at a dose of 600 mg per day; start a course of multivitamins (with mandatory inclusion of vitamins B and C); omega−3 fatty acids according to the instructions; or you can purchase special mixtures that contain the above substances (including acetyl L Carnitine, CoEnzyme Q10, Vitamin C, Vitamin E); pre-stock up with enough water (preferably chloride-bicarbonate-sodium like Gatorade and so on). Meals should be eaten no later than two hours in advance; the qualitative component of the food should be moderate, without a large amount of meat and fat (for preventive purposes, it is recommended to take exogenous enzymes' amylase, protease and lipase) in order to avoid problems with the pancreas. In most cases, it is recommended to follow the algorithm of “premedication before MDMA use”: 4 h before MDMA ingestion: 2 g ginger; 3 h before 500 mg ALCAR (Acetyl-L-carnitine), 500 mg Vitamin C; 2h before nothing; 1h before 2 g ginger and optional - 1 tablet (100 mg) magnesium with MDMA, 300 mg ALA (alpha-lipoic ccid), 500 mg vitamin C; 1 h after MDMA ingestion: 300 mg ALA, 500 mg ALCAR; 2 h after 300 mg ALA, Optional - 1 tablet (100 mg) Magnesium; 3 h after 300 mg ALA, 500 mg Vitamin C; 4 h after 300 mg ALA; 5h after 300 mg ALA, 500 mg ALCAR; 6 h after 300 mg ALA, 500 mg Vitamin C; 7 h after 300 mg ALA. There are anecdotal reports that taking 5-HTP in the nights following MDMA use may help reduce a comedown. There are also anecdotal reports that taking EGCG with the 5-HTP makes it more effective at reducing the comedown. There’s no strong evidence supporting either of these recommendations. There’s some evidence that a precursor to 5-HTP may be beneficial in memory related tasks in ex-MDMA users, so if you’re a heavy user or following less safe practices (e.g. re-doses, frequent use, higher dosages) it may be worth considering taking 5-HTP for a week after using MDMA, starting the night after your MDMA session. Adding green tea catechins (i.e. EGCG and EGC) should help. For safety purposes, recommends avoiding 5-HTP within 24 hours of MDMA consumption. Only consume MDMA in a positive environment to minimize the chance of a negative experience. Being at home can be more enjoyable than being out. You can be as weird as you want without judgement, you can control the music, you can dance and then stop and sit around and talk because it’s not too loud, there are no aggressive people around to make you feel uncomfortable, etc. As a bonus, MDMA is generally safer in a house instead of a club: being at home allows you to take frequent cool off breaks, to take your supplements easily, and means you can get electrolyte-containing fluids easily. Don’t be with people that make you uncomfortable, and consider avoiding sober people that you don’t know. It can also be more enjoyable to avoid drunk people, even if you know them.

     

    Of course, it is not recommended to use MDMA with other substances; however, it is still necessary to study the substance interaction table. MDMA dose, in case of joint use with other psychoactive substance, should be 25-50% less than the initial. Dose calculation of MDMA should exclusively be carried out using this formula: 1.54 mg/kg, depending on the dose there can be different desirable, and undesirable effects of different severity, risk of serotonin syndrome and other complications. Minimal dose of MDMA ranges from 50-90 mg which is associated with minimum risk. Medium recommended dose for most users ranges from 75 to 125 mg. A high dose ranges from 150 to 200 mg, doses exceeding 200 mg are considered dangerous. If finger dipping powder: ideally switch to weighed doses, but if not that, use “crush, dab, wait.” If using tablets and you haven’t taken a tablet from this exact batch before, start with half, or less. Low doses may be particularly important for your first few uses, as you might unknowingly have a health condition like malignant hyperthermia that makes MDMA more dangerous. A study found that MDMA desirable effects are maximized, and undesirable effects minimized, at doses between 81-100 mg. If you’re unwilling to use these dosage guidelines, please make extra sure your friends are aware of the signs of heat stroke and heat exhaustion, and pay extra attention to keeping cool. The onset of effects after oral administration of ecstasy is within the range of 20 to 40 minutes (depending on type of ecstasy, amount of food that you ate before use and other factors). The duration of effects ranges from 3 to 5 hours, post effects can remain within 24 hours. When MDMA crystals are used intranasally, the onset of effects can occur after 5-10 minutes and reach its peak at 2 hours since use, the duration of effects is about 3 hours with a tendency to decrease after 60 minutes. While it is necessary to enjoy MDMA effects during use, you also shouldn't forget about monitoring your condition (but don't get hung up on it). During use, you should drink enough chloride-bicarbonate-sodium water, the volume should correspond to 250 ml per hour (you can drink, for example, Gatorade). In case of active physical activity, the volume of oral water intake should be about 500 ml per hour (but in no more!). However, physical activity is strictly not recommended because it significantly increases the risk of side effects and acute conditions. Take into account that the volume of oral consumption decreases after 5 hours and will be 150 ml per hour. Large amount of water can also negatively affect your general somatic condition. Your body will need rest after use. To reduce the undesirable post effects you can take low doses of tranquilizers (e.g. 1 mg of alprazolam in absence of contraindications) and low therapeutic doses of beta-blockers; it is necessary to sleep (ideally – for 8 hours at night); the other part of the day should be taken to rest, to restore and “return” to the world; it is not recommended driving a car and work both during the trip and the day after; it is not recommended consuming large amounts of food the day after, it is recommended to have light meals. While research hasn’t definitively answered whether MDMA is addictive, there are certainly still people who may be concerned about their own use of MDMA or a loved one’s use of MDMA. This may be especially relevant for MDMA use that is particularly suboptimal - e.g. high doses, using more often than 3x per month, using in particularly unsafe or hot environments, etc. It is not recommended to use MDMA more than 3 times a month (ideally no more than once in 6 months) because considering the mechanism of MDMA action it causes depletion of neurotransmitters (mostly serotonin), associated with depression symptoms and other long-term post effects. You should save ecstasy for special occasions and use it sparingly. Frequent use of this substance lowers its efficacy and can cause tolerance.

    Pharmacology of MDMA

    MDMA acts primarily as a releasing agent of the three principal monoamine neurotransmitters serotonin, norepinephrine, and dopamine through its action at trace amine-associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2). MDMA is a monoamine transporter substrate (i.e. a substrate for the transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT)), enabling it to enter monoaminergic neurons via these neuronal membrane transport proteins. By acting as a monoamine transporter substrate, MDMA produces competitive reuptake inhibition at the neuronal membrane transporters, competing for endogenous monoamines for reuptake.

    MDMA inhibits both vesicular monoamine transporters (VMATs), the second of which (VMAT2) is highly expressed within monoamine neurons vesicular membranes. Once inside a monoamine neuron, MDMA acts as a VMAT2 inhibitor and a TAAR1 agonist. The inhibition of VMAT2 by MDMA results in increased concentrations of the aforementioned monoamine neurotransmitters in the cytosol of the neuron. Activation of TAAR1 by MDMA triggers protein kinase signaling events which then phosphorylates the associated monoamine transporters of the neuron.

    Subsequently, these phosphorylated monoamine transporters either reverse transport direction – i.e. move neurotransmitters from inside the cell to the synaptic cleft – or withdraw into the neuron, respectively producing the inflow of neurotransmitters and noncompetitive reuptake inhibition at the neuronal membrane transporters.MDMA has ten times more affinity for uptake at serotonin transporters compared to dopamine and norepinephrine transporters and consequently has mainly serotonergic effects.

    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. Cortisol, prolactin, and oxytocin quantities in serum are increased by MDMA.

    Additionally, MDMA is a ligand at both sigma receptor subtypes, though its efficacies at these receptors and the role that they play have yet to be elucidated.

    MDMA Storage

    Proper storage of MDMA is essential to maintain its potency and prevent degradation. It should be stored in a cool (5-8°C), dry place away from direct sunlight and moisture. Additionally, it should be kept out of reach of children and pets to prevent accidental ingestion.

    Conclusion

    In conclusion, MDMA's chemical properties, including its molecular structure and pharmacological effects, contribute to its psychoactive properties and physiological interactions. Despite its potential therapeutic benefits, its recreational use led to regulatory scrutiny and classification as a Schedule I controlled substance in many countries. Ongoing research explores its therapeutic potential, particularly in PTSD treatment. Knowledge of MDMA's synthesis, physical and chemical properties, effects, and pharmacology informs interventions, harm reduction strategies, and regulatory measures.

    Bibliography

    • Coates, J., and Reffner, J., "Visualization of Micro-ATR Infrared Spectroscopy," Spectroscopy, Vol. 14, #4, April 1999.
    • Clarke, E.G.C., Isolation and Identification of Drugs, 2nd Edition, The Pharmaceutical Press, 1986.
    • Galichat, Laurent Y., Clarke’s Analysis of Drugs and Poisons, Volume 2, p. 1256, Pharmaceutical Press, 2004.
    • Budavari, S., The Merck Index, 13th Edition, Merck and Co., Inc., 2001.
    • http://en.wikipedia.org/wiki/3,4-methylenedioxymethamphetamine
    • https://psychonautwiki.org
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