ミドマフェタミン

DEA Schedule I Controlled Substance -> Hallucinogenic substances

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals -> Illicit drugs

144.9 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

144.2 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated]

145.77 Ų [M+H]+

Not Classified

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). 3,4-Methylenedioxymethamphetamine (MDMA) (DEA Code Number: 7405) is included on this list.

Kuhn C et al; Buzzed. The Straight Facts About The Most Used and Abused Drugs From Alcohol to Ecstasy 4th ed (2014); Handbook features the most recent discoveries about drugs, including new information about biological and behavioral changes in addiction, the prescription-drug abuse epidemic, distinctive drug effects on the adolescent brain, and a perspective on legal trends.

National Institute on Drug Abuse (NIDA) DrugFacts on MDMA (Ecstasy/Molly)[Available from, as of October 7, 2017: http://www.nida.nih.gov/Infofax/ecstasy.html]

Ghuran A, Nolan J; Heart 83 (6): 627-33 (2000). Recreational drug misuse: issues for the cardiologist.

DHHS/NIH; NIDA Research Report Series on MDMA (Ecstasy) Abuse (2006)[Available from, as of October 6, 2017: http://www.nida.nih.gov/PDF/RRmdma.pdf]

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

Skin protection: Handle with gloves. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /(+/-)-3,4-Methylenedioxymethamphetamine hydrochloride/

3,4-Methylenedioxymethamphetamine has been measured in sweat at 42.4-1326 ng/patch/day accumulated after a single 100 mg oral dose (first observed 1.5 hour after dose)(1). Approximately 20% of 3,4-methylenedioxymethamphetamine passes through the body unchanged(2).

The effects of injection of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and N-ethyl-3,4-methylenedioxyamphetamine (MDEA) (all 20 mg/kg) on blood pressure, heart rate, core body temperature and locomotor activity in conscious rats were investigated using radiotelemetry. MDMA and MDA produced a prolonged increase in both systolic and diastolic pressures, with MDA causing the most marked rise. MDEA produced a transient but nonsignificant fall in diastolic pressure. The pressor response produced by MDA was accompanied by bradycardia. All three amphetamine derivatives caused an initial hypothermic response; however, MDA also produced a subsequent hyperthermia, and the speed of recovery from hypothermia was MDA>MDMA>MDEA. The alpha-2A-adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (BRL 44408) (1 mg/kg) prolonged the hypothermic response to MDMA. Only MDA induced locomotor activity when given alone, but in the presence of BRL 44408, MDMA produced increased locomotor activity. The order of potency for producing isometric contractions of rat aorta (alpha1D) and vas deferens (alpha1A) was MDA>MDMA>MDEA, with MDEA acting as an alpha1-adrenoceptor antagonist with a pKB of 4.79 +/- 0.12 (n=4) in aorta. The order of potency for prejunctional inhibition of stimulation-evoked contractions in rat vas deferens (alpha2A-adrenoceptor mediated) was MDA>MDMA>MDEA. Blood pressure actions of the three amphetamine derivatives may be at least partly due to alpha1-adrenoceptor agonism or antagonism. The reversal of the hypothermic actions are at least partly due to alpha2A-adrenoceptor agonism since the hypothermic response was more prolonged with MDEA which exhibits low alpha2A-adrenoceptor potency, and effects of MDMA after alpha2A-adrenoceptor antagonism were similar to those of MDEA.

Ethanol and 3, 4-Methylenedioxymethamphetamine (MDMA) are popular recreational drugs widely abused by adolescents that may induce neurotoxic processes associated with behavioral alterations. Adolescent CD1 mice were subjected to ethanol intake using the drinking in the dark (DID) procedure, acute MDMA or a combination. Considering that both drugs of abuse cause oxidative stress in the brain, protein oxidative damage in different brain areas was analyzed 72 hr after treatment using a proteomic approach. Damage to specific proteins in treated animals was significant in the hippocampus but not in the prefrontal cortex. The damaged hippocampus proteins were then identified by mass spectrometry, revealing their involvement in energy metabolism, structural function, axonal outgrowth and stability, and neurotransmitter release. Mice treated with MDMA displayed higher oxidative damage than ethanol-treated mice. To determine whether this oxidative damage was affecting hippocampus activity, declarative memory was evaluated at 72 hr after treatment using the object recognition assay and the radial arm maze. Although acquisition in the radial arm maze was not impaired by ethanol intake, MDMA treatment impaired long-term memory in both tests. Therefore, oxidative damage to specific proteins observed under MDMA treatment affects important cellular function on the hippocampus that may contribute to declarative memory deficits.

We have recently shown that chronic exposure to 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") of adolescent mice exacerbates dopamine neurotoxicity and neuroinflammatory effects elicited by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the substantia nigra and striatum at adulthood. The present study investigated whether the amplification of MPTP effects by previous treatment with MDMA extends to the limbic and cortical regions and consequently affects cognitive performance. Mice received MDMA (10 mg/kg, twice a day/twice a week) for 9 weeks, followed by MPTP (20 mg/kg x 4 administrations), starting 2 weeks after MDMA discontinuation. Complement type 3 receptor (CD11b) and glial fibrillary acidic protein (GFAP) were evaluated by immunohistochemistry in both the hippocampus and the medial prefrontal cortex (mPFC) to measure microglia and astroglia activation. These neurochemical evaluations were paired with an assessment of cognitive performance by means of the novel object recognition (NOR) and spontaneous alternation tasks. MPTP administration to MDMA-pretreated mice elicited a stronger activation of CD11b and GFAP in both the hippocampus and the mPFC compared with either substance administered alone. Furthermore, NOR performance was lower in MDMA-pretreated mice administered MPTP compared with mice that received either substance alone. These results demonstrate that MDMA-MPTP negative interactions extend to the limbic and cortical regions and may result in cognitive impairment, providing further evidence that exposure to MDMA may amplify the effects of later neurotoxic insults.

Evidence is accumulating to suggest that 3,4-methylenedioxymethamphetamine (MDMA) has neurotoxic and neuroinflammatory properties. MDMA is composed of two enantiomers with different biological activities. In this study, we evaluated the in vivo effects of S(+)-MDMA, R(-)-MDMA, and S(+)-MDMA in combination with R(-)-MDMA on microglial and astroglial activation compared with racemic MDMA, by assessment of complement type 3 receptor (CD11b) and glial fibrillary acidic protein (GFAP) immunoreactivity in the mouse striatum, nucleus accumbens, motor cortex, and substantia nigra. Motor activity and body temperature were also measured, to elucidate the physiological modifications paired with the observed glial changes. Similar to racemic MDMA (4 x 20 mg/kg), S(+)-MDMA(4 x 10 mg/kg) increased both CD11b and GFAP in the striatum, although to a lower degree, whereas R(-)-MDMA (4 x 10 mg/kg) did not induce any significant glial activation. Combined administration of S(+) plus R(-)-MDMA did not induce any further activation compared with S(+)-MDMA. In all other areas, only racemic MDMA was able to slightly activate the microglia, but not the astroglia, whereas enantiomers had no effect, either alone or in combination. Racemic MDMA and S(+)-MDMA similarly increased motor activity and raised body temperature, whereas R(-)-MDMA affected neither body temperature nor motor activity. Interestingly, the increase in body temperature was correlated with glial activation. The results show that no synergism, but only additivity of effects, is caused by the combined administration of S(+)- and R(-)-MDMA, and underline the importance of investigating the biochemical and behavioral properties of the two MDMA enantiomers to understand their relative contribution to the neuroinflammatory and neurotoxic effects of MDMA.

For more Interactions (Complete) data for 3,4-Methylenedioxymethamphetamine (29 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), a log Koc value of 2.68(2), indicates that 3,4-methylenedioxymethamphetamine is expected to have moderate mobility in soil(SRC). However, hydrolysis may attenuate adsorption(SRC). The pKa of 3,4-methylenedioxymethamphetamine is 9.9(3), indicating that this compound will exist almost entirely in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the cation from moist soil is not expected because cations do not volatilize(SRC). 3,4-Methylenedioxymethamphetamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.3X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), a log Koc of 2.68(2), indicates that 3,4-methylenedioxymethamphetamine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 9.9(3) indicates 3,4-methylenedioxymethamphetamine will exist entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). 3,4-Methylenedioxymethamphetamine is expected to undergo hydrolysis in the environment due to functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(5), an estimated BCF of 15(SRC), from its log Kow of 2.15(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low. Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3,4-methylenedioxymethamphetamine, which has an estimated vapor pressure of 2.3X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 3,4-methylenedioxymethamphetamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3 hours(SRC), calculated from its rate constant of 1.4X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). 3,4-Methylenedioxymethamphetamine does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: 3,4-Methylenedioxymethamphetamine (MDMA) is a schedule I controlled substance. Ecstasy is the popular name for the illicit drug MDMA and is widely used at dance parties. It is usually consumed orally in tablet or capsule form. MDMA acts as both a stimulant and psychedelic, producing an energizing effect, as well as distortions in time and perception and enhanced enjoyment from tactile experiences. HUMAN STUDIES: Acute toxic effects of MDMA include hyperthermia, muscle rigidity, metabolic acidosis, disseminated intravascular coagulation, and rhabdomyolysis. These effects can lead to multiorgan failure and death. The level of hyperthermia predicts the potential for survival. MDMA produces cardiovascular effects similar to those seen with methamphetamine, including an increase in blood pressure and heart rate. Serious sequelae can occur from electrolyte abnormalities seen in MDMA abuse and overdose. Hyponatremia from inappropriate antidiuretic hormone production and increased free water intake has been described in several case reports of significant cerebral edema and subsequent death. Acute hepatotoxicity has been described as a consequence of MDMA use. An acute hepatitis pattern with lymphocytic infiltration of hepatic parenchyma is seen. Over the course of a week following moderate use of the drug, many MDMA users report feeling a range of emotions, including anxiety, restlessness, irritability, and sadness that in some individuals can be as severe as true clinical depression. Similarly, elevated anxiety, impulsiveness, and aggression, as well as sleep disturbances, lack of appetite, and reduced interest in and pleasure from sex have been observed in regular MDMA users. MDMA has been implicated as a cause of amnesic syndrome associated with severe ataxia. Chronic use of MDMA has been implicated in sleep disorders and mood changes. Cognitive deficits such as memory recall were also seen in users of MDMA even after 6 months of abstinence. Eye pathology, including retinal hemorrhage with blurred vision, has been described with the use of MDMA. Prospective follow up of 136 babies exposed to ecstasy in utero showed that the drug may be associated with a significantly increased risk of congenital defects. Cardiovascular anomalies and musculoskeletal anomalies were predominant. ANIMAL STUDIES: A variety of animal models have shown MDMA to be a selective serotonin neurotoxin. Acutely MDMA exposure elicits a classical serotonin syndrome. In the long-term, exposure results in serotonin neurotoxicity and a lasting cognitive impairment. Direct injection of MDMA into the brain fails to reproduce the serotonergic neurotoxicity seen following peripheral administration. The serotonergic neurotoxicity of MDMA therefore appears to be dependent upon the generation of a neurotoxic metabolite, or metabolites, the identity of which remains unclear. ECOTOXICITY STUDIES: Environmentally relevant MDMA concentrations did not induce deleterious effects to the zebra mussel (Dreissena polymorpha).

/AQUATIC SPECIES/ Recent monitoring studies showed measurable levels of the 3,4-methylenedioxymethamphetamine (MDMA) in aquatic environments. However, no information is currently available on its potential hazard to aquatic non-target organisms. The aim of this study was to investigate the potential sub-lethal effects induced by 14-day exposures to low MDMA concentrations (0.05 and 0.5 ug/L) to zebra mussel (Dreissena polymorpha) specimens through the application of a biomarker suite. The trypan blue exclusion method and the neutral red retention assay (NRRA) were used to assess MDMA cytotoxicity. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST), as well as the lipid peroxidation (LPO) and protein carbonyl content (PCC), were measured as oxidative stress indexes. The single cell gel electrophoresis (SCGE) assay, the DNA diffusion assay, and the micronucleus test (MN test) were applied to investigate DNA damage, while filtration rate was measured as physiological parameter. Despite significant decrease in lysosome membrane stability, hemocyte viability and imbalances in CAT and GST activities pointed out at the end of the exposure to 0.5 ug/L, no significant variations for the other end points were noticed at both the treatments, suggesting that environmentally relevant MDMA concentrations did not induce deleterious effects to the zebra mussel.

Influent and effluent samples collected from 7 sewage treatment plants in from Oct 2007 to Jul 2008, located along Ebro River basin in Spain, contained 3,4-methylenedioxymethamphetamine at 3.5-180.0 and 3.3-120.0 ng/L, respectively(1). In wastewater treatment plant samples collected Feb and Mar 2010 from Miami Gardens, FL, 3,4-methylenedioxymethamphetamine loading rates were 97-106 and 23-30 g/day in the influent and effluent, respectively(2).

The log Koc for 3,4-methylenedioxymethamphetamine was reported as 2.68 using an agricultural soil from Correstown, County Dublin Ireland(1). According to a classification scheme(2), this reported Koc value suggests that 3,4-methylenedioxymethamphetamine is expected to have moderate mobility in soil. However, hydrolysis may attenuate adsorption(SRC). The pKa of 3,4-methylenedioxymethamphetamine is 9.9(3), indicating that this compound will exist entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ A comprehensive cognitive test battery was administered to 28 abstinent ecstasy users with concomitant use of cannabis only and to two equally sized matched groups of cannabis users and non-users. The sample consisted of ecstasy users with a typical recreational use pattern and did not include very heavy users. Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not differ significantly in their performance from the non-users.

/HUMAN EXPOSURE STUDIES/ 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100 mg doses of MDMA separated by 4 hr. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4 hr interval there exists a phenomenon of acute tolerance to its effects.

/HUMAN EXPOSURE STUDIES/ The synthetic psychostimulant MDMA (+/- 3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT). This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women) healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6). A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75-100 mg) which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers) or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles). Female subjects displayed more intense physiological (heart rate, and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determined greater cardiovascular effects, and with low functionality (met/* or s/s) negative subjective effects (dizziness, anxiety, sedation). In conclusion, the contribution of MDMA pharmacokinetics following 1.4 mg/kg MDMA to the gender differences observed in drug effects appears to be negligible or even null. In contrast, 5-HTTLPR and COMT val158met genotypes play a major role.

/HUMAN EXPOSURE STUDIES/ 3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N=36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called "Cyberball" during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

For more Human Toxicity Excerpts (Complete) data for 3,4-Methylenedioxymethamphetamine (64 total), please visit the HSDB record page.

An estimated BCF of 15 was calculated in fish for 3,4-methylenedioxymethamphetamine(SRC), using a log Kow of 2.15(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low.

A pKa of 9.9(1) indicates 3,4-methylenedioxymethamphetamine will exist entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). 3,4-Methylenedioxymethamphetamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.3X10-4 mm Hg(SRC), determined from a fragment constant method(2).

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). 3,4-Methylenedioxymethamphetamine (MDMA) (DEA Code Number: 7405) is included on this list.

It enters neurons via carriage by the monoamine transporters. Once inside, MDMA inhibits the vesicular monoamine transporter, which results in increased concentrations of serotonin, norepinephrine, and dopamine into the cytoplasm, and induces their release by reversing their respective transporters through a process known as phosphorylation. It also acts as a weak 5-HT1 and 5-HT2 receptor agonist. MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin secretion via activation of the serotonin system. Oxytocin is a hormone released following events like hugging, orgasm, and childbirth, and is thought to facilitate bonding and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin 5-HT1A receptor.

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca(2+) homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10uM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury.

The aim of the present study was to identify the neural substrate underlying memory impairment due to a single dose of MDMA (3,4-methylenedioxymethamphetamine) by means of pharmaco-MRI. Based on previous behavioral results it was hypothesized that this deficit could be attributed to a specific influence of MDMA on encoding. Fourteen Ecstasy users participated in this double-blind, placebo-controlled, within-subject study with two treatment conditions: MDMA (75 mg) and placebo. Memory performance was tested by means of a word learning task including two words lists, one addressing reading processes (control task, CWL) and a second (experimental task, EWL) addressing encoding and reading processes. Behavioral data showed that under the influence of MDMA, EWL performance was worse than placebo. Imaging data showed that Encoding was situated mainly in (pre)frontal, temporal and parietal areas. MDMA by Encoding interaction was situated in three areas: the left middle frontal gyrus (BA10), the right fusiform gyrus (BA19), and the left cuneus (BA18). Behavioral and functional data only correlated in BA10. It appeared that EWL performance caused BOLD signal change in BA10 during placebo treatment but not during MDMA intoxication. It is concluded that MDMA influences middle frontal gyrus processes resulting in impoverished memory encoding.

The recreational drug 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') produces a neuro-inflammatory response in rats characterized by an increase in microglial activation and IL-1beta levels. The integrity of the blood-brain barrier (BBB) is important in preserving the homeostasis of the brain and has been shown to be affected by neuro-inflammatory processes. We aimed to study the effect of a single dose of MDMA on the activity of metalloproteinases (MMPs), expression of extracellular matrix proteins, BBB leakage and the role of the ionotropic purinergic receptor P2X7 (P2X7R) in the changes induced by the drug. Adult male Dark Agouti rats were treated with MDMA (10 mg/kg, i.p.) and killed at several time-points in order to evaluate MMP-9 and MMP-3 activity in the hippocampus and laminin and collagen-IV expression and IgG extravasation in the dentate gyrus. Microglial activation, P2X7R expression and localization were also determined in the dentate gyrus. Separate groups were treated with MDMA and the P2X7R antagonists Brilliant Blue G (BBG; 50 mg/kg, i.p.) or A-438079 (30 mg/kg, i.p.). MDMA increased MMP-3 and MMP-9 activity, reduced laminin and collagen-IV expression and increased IgG immunoreactivity. In addition, MDMA increased microglial activation and P2X7R immunoreactivity in these cells. BBG suppressed the increase in MMP-9 and MMP-3 activity, prevented basal lamina degradation and IgG extravasation into the brain parenchyma. A-438079 also prevented the MDMA-induced reduction in laminin and collagen-IV immunoreactivity. These results indicate that MDMA alters BBB permeability through an early P2X7R-mediated event, which in turn leads to enhancement of MMP-9 and MMP-3 activity and degradation of extracellular matrix.

3,4-Methylenedioxymethamphetamine (MDMA) produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1beta) and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra) levels and IL-1 receptor type I (IL-1RI) expression and the effects of JWH-015. The cellular location of IL-1beta and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI) and neurotoxic effects examined. Dark Agouti rats received MDMA (12.5 mg/kg, i.p.) and levels of IL-1ra and expression of IL-1RI measured 1 hr, 3 hr or 6 hr later. JWH-015 (2.4 mg/kg, i.p.) was injected 48 hr, 24 hr and 0.5 hr before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 hr or 3 hr following MDMA and stained for IL-1beta or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 ug/animal; i.c.v.) was administered 5 min before MDMA and 3 hr later. 5-HT transporter density was determined 7 days after MDMA injection. MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1beta expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1beta may play a partial role in MDMA-induced neurotoxicity.

For more Mechanism of Action (Complete) data for 3,4-Methylenedioxymethamphetamine (9 total), please visit the HSDB record page.

6–10 (though duration of effects is typically actually 3–5 hours)

The present study compared the disposition and metabolism of the recreational drug (+/-) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. ... The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). ...

... In this study, we examine MDMA pharmacokinetics in rats given low (2 mg/kg) and high (10 mg/kg) doses of racemic MDMA via intraperitoneal, subcutaneous, and oral routes. Repeated blood specimens were collected from venous catheters, and plasma was assayed for MDMA and its metabolites, 4-hydroxy-3-methoxymethamphetamine (HMMA) and 3,4-methylenedioxyamphetamine (MDA), by gas chromatography-mass spectrometry. ... MDMA plasma half-lives were <1 hr for low-dose groups, whereas HMMA and MDA half-lives were >2 hr. ...

... Elimination half-life was 8.6 hr /(75 mg)/ and 7.7 hr /(125 mg)/ for low and high dose 3,4-methylenedioxymethamphetamine /in eight men with experience in the recreational use of 3,4-methylenedioxymethamphetamine/ ...

... /The/ half-life of (R)-3,4-methylenedioxymethamphetamine (5.8 +/- 2.2 hr) was significantly longer than that of the S-enantiomer (3.6 +/- 0.9 hr). ...

Studies to characterize the pharmacokinetics of the enantiomers of MDMA were conducted in rats using the iliac arterial cannulation. Two routes of administration, intravenous and subcutaneous, were evaluated at two dose levels for each route [20 and 40 mg/kg (+/-)-MDMA for subcutaneous, 10 and 20 mg/kg (+/-)-MDMA for intravenous administrations]. The average half-life (+/- SD) for all dosing groups was 2.5 +/- 0.8 hr for (-)-(R)-MDMA and 2.2 +/- 0.8 hr for (+)-(S)-MDMA. ...

Midomafetamine, or MDMA, is reported to undergo extensive CYP-mediated hepatic metabolism, with CYP2D6 playing a major role in humans. Other CYP enzymes contributing to MDMA metabolism are CYP3A4 and COMT. MDMA is metabolized via two primary metabolic pathways. It may undergo O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation. In contrast, it may also undergo N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. Due to autoinhibition of CYP2D6 and CYP2D8, MDMA displays a complex, nonlinear pharmacokinetics profile, with the zeroth order kinetics occurring 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.

MDMA (3,4-methylenedioxymethamphetamine) metabolism is a major cause of MDMA-mediated hepatotoxicity. In this study the effects of MDMA and its metabolites on the glutathione system were evaluated. Glutathione (GSH/GSSG) levels and gene expression of glutamate cysteine ligase catalytic subunit (GCLC), glutathione-S-transferase (GST) and pregnane X receptor (PXR) were compared in the immortalized human liver epithelial cell line THLE-Neo lacking phase I metabolism and primary rat hepatocytes expressing both phase I and II metabolism. Furthermore, we evaluated the potential protective effects of two antioxidants, N-acetyl-cysteine (NAC) and sulforaphane (SFN) in these cell systems. In THLE-Neo cells, the MDMA metabolite 3,4-dihydroxymetamphetamine (HHMA) significantly decreased cell viability and depleted GSH levels, resulting in an increased expression of GCLC and GST up to 3.4- and 2.2-fold, respectively. In primary rat hepatocytes, cell viability or GSH levels were not significantly affected upon MDMA exposure. GCLC expression levels where not significantly altered either, although GST expression was increased 2.3-fold. NAC counteracted MDMA-induced cytotoxicity and restored GSH levels. Phase II enzyme expression was also reverted. Conversely, SFN increased MDMA-induced cytotoxicity and GSH depletion, while GCLC and GST expression were significantly induced. In addition, PXR expression decreased after HHMA and MDMA exposure, while co-exposure to SFN induced it up to 3.6- and 3.9-fold compared to vehicle-control in the THLE-Neo cells and rat hepatocytes, respectively. Taken together, these data indicate that HHMA is a major factor in the MDMA-mediated hepatotoxicity through interaction with the glutathione system. The results of our study show that for MDMA intoxication the treatment with an antioxidant such as NAC may counteract the potentially hepatotoxicity. However, SFN supplementation should be considered with care because of the indications of possible drug-drug interactions.

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6, and is also a potent mechanism-based inhibitor of the enzyme. After assessing the inhibition and recovery of CYP2D6 in a previous study, the aim of this work was to study in humans the activity of CYP1A2 in vivo after CYP2D6 had been inhibited by MDMA, using caffeine as a probe drug. Twelve male and nine female recreational MDMA users were included. In session 1, 100 mg of caffeine was given at 0 hr. In session 2, a 1.5 mg/kg MDMA dose (range 75-100 mg) was given at 0 hr followed by a 100 mg dose of caffeine 4 hr later. Aliquots of plasma were assayed for caffeine (137X) and paraxanthine (17X) and statistically significant differences were assessed with a one-way ANOVA. There were significant gender differences at basal condition, which persisted after MDMA administration. CYP1A2 activity was higher in both genders after drug administration, with an increase in 40% in females and 20% in males. Results show an increase in CYP1A2 activity when CYP2D6 is inhibited by MDMA in both genders, being more pronounced in females.

The R- and S-enantiomers of racemic 3,4-methylenedioxymethamphetamine (MDMA) exhibit different dose-concentration curves. In plasma, S-MDMA was eliminated at a higher rate, most likely due to stereoselective metabolism. Similar data were shown in various in vitro experiments. The aim of the present study was the in vivo investigation of stereoselective elimination of MDMA's phase I and phase II metabolites in human urine following controlled oral MDMA administration. Urine samples from 10 participants receiving 1.0 and 1.6 mg/kg MDMA separated by at least one week were analyzed blind by liquid chromatography-high resolution-mass spectrometry and gas chromatography-mass spectrometry after chiral derivatization with S-heptafluorobutyrylprolyl chloride. R/S ratios at C(max) were comparable after low and high doses with ratios >1 for MDMA, free 3,4-dihydroxymeth-amphetamine (DHMA), and 4-hydroxy-3-methoxymethamphetamine (HMMA) sulfate, and with ratios <1 for 3,4-methylendioxyamphetamine (MDA), free HMMA, DHMA sulfate and HMMA glucuronide. In the five days after the high MDMA dose, a median of 21% of all evaluated compounds were excreted as R-stereoisomers and 17% as S-stereoisomers. Significantly greater MDMA, DHMA, and HMMA sulfate R-enantiomers and HMMA and HMMA glucuronide S-stereoisomers were excreted. No significant differences were observed for MDA and DHMA sulfate stereoisomers. Changes in R/S ratios could be observed over time for all analytes, with steady increases in the first 48 hr. R/S ratios could help to roughly estimate time of MDMA ingestion and therefore, improve interpretation of MDMA and metabolite urinary concentrations in clinical and forensic toxicology.

3,4-Methylenedioxy-amphetamine (MDA) and benzodioxolyl-butanamine (BDB) are chiral designer drugs distributed on the illicit drug market and they are also N-dealkyl metabolites of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy, Adam), 3,4-methylenedioxyethylamphetamine (MDEA, Eve), and N-methyl-benzodioxolyl-butanamine (MBDB, Eden), respectively. MDA and BDB are mainly metabolized via demethylenation to the corresponding catecholamines. The aim of the present work was to elucidate the contribution of the relevant human P450s in the demethylenation of the MDA and BDB enantiomers. They were incubated using heterologously expressed human P450s and the corresponding metabolites dihydroxyamphetamine and 1,2-dihydroxy-4-[2-amino-butyl]benzene were determined. Highest contributions to the demethylenation as calculated from the enzyme kinetic data were obtained for CYP2D6 (MDA and BDB) and additionally CYP3A4 in the case of BDB at substrate concentrations corresponding to plasma concentrations of recreational users. A preferred transformation of the S-enantiomer could be observed for the CYP2D6- and CYP3A4-catalyzed reactions.

For more Metabolism/Metabolites (Complete) data for 3,4-Methylenedioxymethamphetamine (18 total), please visit the HSDB record page.

Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.

Drugs used for their effects on serotonergic systems. Among these are drugs that affect serotonin receptors, the life cycle of serotonin, and the survival of serotonergic neurons.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

renal

3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is excreted as unchanged drug, 3,4-methylenedioxyamphetamine (MDA), and free and glucuronidated/sulfated 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) metabolites. The aim of this paper is to describe the pattern and timeframe of excretion of MDMA and its metabolites in urine. Placebo, 1.0 mg/kg, and 1.6 mg/kg oral MDMA doses were administered double-blind to healthy adult MDMA users on a monitored research unit. All urine was collected, aliquots were hydrolyzed, and analytes quantified by gas chromatography-mass spectrometry. Median C(max), T(max), ratios, first and last detection times, and detection rates were determined. Sixteen participants provided 916 urine specimens. After 1.6 mg/kg, median C(max) were 21,470 (MDMA), 2229 (MDA), 20,793 (HMMA), and 876 ng/mL (HMA) at median T(max) of 13.9, 23.0, 9.2 and 23.3 hr. In the first 24 hr, 30.2-34.3% total urinary excretion occurred. HMMA last detection exceeded MDMA's by more than 33 hr after both doses. Identification of HMMA as well as MDMA increased the ability to identify positive specimens but required hydrolysis. These MDMA, MDA, HMMA, and HMA pharmacokinetic data may be useful for interpreting workplace, drug treatment, criminal justice, and military urine drug tests. Measurement of urinary HMMA provides the longest detection of MDMA exposure yet is not included in routine monitoring procedures.

Based on animal data, there is speculation that (+ or -)-3,4-methylenedioxymethamphetamine (MDMA) is neurotoxic to humans. Extrapolation of MDMA findings from animals to humans requires assessment of pharmacokinetics in various species, and low-dose administration data from rats are lacking. In this study, we examine MDMA pharmacokinetics in rats given low (2 mg/kg) and high (10 mg/kg) doses of racemic MDMA via intraperitoneal, subcutaneous, and oral routes. Repeated blood specimens were collected from venous catheters, and plasma was assayed for MDMA and its metabolites, 4-hydroxy-3-methoxymethamphetamine (HMMA) and 3,4-methylenedioxyamphetamine (MDA), by gas chromatography-mass spectrometry. After 2 mg/kg, maximum MDMA concentrations (C(max)) were approximately 200 ng/mL for intraperitoneal and subcutaneous routes, but less for the oral route. MDMA plasma half-lives were <1 hr for low-dose groups, whereas HMMA and MDA half-lives were >2 hr. After 10 mg/kg, MDMA areas under the curve (AUCs) were 21-fold (intraperitoneal), 10-fold (subcutaneous), and 36-fold (oral) greater than those at 2 mg/kg. In contrast, HMMA AUC values in high-dose groups were <3-fold above those at 2 mg/kg. Several new findings emerge from this report of low-dose MDMA pharmacokinetics in rats. First, 2 mg/kg MDMA in rats can produce MDMA C(max) values similar to those in humans, perhaps explaining why both species discriminate 1.5 mg/kg MDMA in laboratory paradigms. Second, our data provide additional support for nonlinear kinetics of MDMA in rats, and, analogous to humans, this phenomenon appears to involve impaired drug metabolism. Finally, given key similarities between MDMA pharmacokinetics in rats and humans, data from rats may be clinically relevant when appropriate dosing conditions are used.

3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA's safety are needed. We evaluated MDMA's pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (+/-)-3,4-dihydroxymethamphetamine (HHMA), (+/-)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (+/-)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography-tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA Cmax was 164 +/- 47.1 ng/mL, HHMA and HMMA were major metabolites, and <20% of MDMA was metabolized to MDA. After 5- and 10-mg/kg doses, MDMA areas under the curve (AUCs) were 3- and 10-fold greater than those after 2.5 mg/kg; HHMA and HMMA AUC values were relatively constant across doses; and MDA AUC values were greater than dose-proportional. Our data provide decisive in vivo evidence that MDMA and MDA display nonlinear accumulation via metabolic autoinhibition in the rat. Importantly, 5-HT syndrome severity correlated with MDMA concentrations (r = 0.8083; P < 0.0001) and core temperature correlated with MDA concentrations (r = 0.7595; P < 0.0001), suggesting that MDMA's behavioral and hyperthermic effects may involve distinct mechanisms. Given key similarities between MDMA pharmacokinetics in rats and humans, data from rats can be useful when provided at clinically relevant doses.

MDMA is rapidly absorbed into the human bloodstream, but once in the body, MDMA metabolites interfere with the body's ability to metabolize, or break down, the drug. As a result, additional doses of MDMA can produce unexpectedly high blood levels, which could worsen the cardiovascular and other toxic effects of this drug.

For more Absorption, Distribution and Excretion (Complete) data for 3,4-Methylenedioxymethamphetamine (9 total), please visit the HSDB record page.

3,4-Methylenedioxymethamphetamine (MDMA) (DEA Code Number: 7405) is a Schedule I controlled substance.

Schedule I Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has no currently accepted medical use in treatment in the United States; and (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Hallucinogens Serotonin Agents; Adrenergic Uptake Inhibitors

Ecstasy is the popular name for the illicit drug MDMA and is widely used at dance parties or "raves." It is usually consumed orally in tablet or capsule form ... Its primary effect is to produce a positive mood state with euphoria, intimacy, and closeness to others.

For more Uses (Complete) data for 3,4-Methylenedioxymethamphetamine (6 total), please visit the HSDB record page.

There are four principal precursors which can be used in the manufacture of MDMA and related drugs: safrole, isosafrole, piperonal and 3,4-methylenedioxyphenyl-2-propanone (PMK). Safrole is the key starting material in so far as the other three can be synthesised from it. In the original Merck patent of 1914, safrole was reacted with hydrobromic acid to form bromosafrole, which was converted to MDMA using methylamine. Many illicit syntheses start with PMK and use either the Leuckart route or various reductive aminations including the aluminium foil method. All of these methods produce racemic MDMA.

Preparation: Germany patent 274350 (1914 to E. Merck).

Common street names include: Adam, Beans, Clarity, Disco Biscuit, E, Ecstasy, Eve, Go, Hug Drug, Lover's Speed, MDMA, Peace, STP, X, and XTC.

MDMA or ecstasy tablets are sold in many colors with a variety of logos to attract youth.

MDMA is also distributed in capsules, powder, and liquid forms.

(S)-Form possesses more potent CNS activity.

Tablets contain, on average, 60-70 mg (base equivalent) of MDMA either as the hydrochloride salt or, less commonly, as the phosphate salt. Loose powders may range from crushed tablets (typically 30-40 % purity) to almost pure MDMA. The free base constitutes 84 % of the hydrochloride salt. Apart from the active drug, tablets contain a bulking agent such as lactose and smaller quantities of binders. In 2011, average values of 43 (Denmark) to 113 mg (Turkey) MDMA per tablet were reported across Europe. During the last few years, there has been a change in the content of illicit drug tablets in Europe, from a situation where most tablets analysed contained MDMA or another ecstasy-like substance (MDEA, MDA) as the only psychoactive substance, to one where the contents are more diverse, and MDMA-like substances less present. This shift was most pronounced in 2009, when only three countries reported that MDMA-like substances accounted for a large proportion of the tablets analysed. More recently, there is evidence of a return to MDMA in tablets. In 2011, the number of countries reporting a predominance of tablets containing MDMA-like substances increased to eleven.

Pharmaceuticals

Pharmaceuticals -> Illicit drugs and related compounds

No one other drug is quite like MDMA, but MDMA produces both amphetamine-like stimulation and mild mescaline-like hallucinations.

Although MDMA is known among users as Ecstasy, researchers have determined that many Ecstacy tablets contain not only MDMA but also a number of other drugs or drug combinations that can be harmful, such as: methamphetamine, ketamine, cocaine, the over-the-counter cough supressant dextromethorphan, the diet drug ephedrine and caffeine.

Other drugs similar to MDMA, such as MDA or PMA, are often sold as Ecstacy which can lead to overdose and death

MDMA is mainly distributed in tablet form ... with logos, creating brand names ... colorful pills ... MDMA is also distributed in capsules, powder and liquid forms

For more General Manufacturing Information (Complete) data for 3,4-Methylenedioxymethamphetamine (6 total), please visit the HSDB record page.