MDMA (3,4-Methylenedioxymethamphetamine) – colloquially known as ecstasy, often abbreviated "E" or "X" – is an entactogenic drug of the phenethylamine and amphetamine class of drugs. MDMA can induce euphoria, a sense of intimacy with others, and diminished anxiety. Many studies, particularly in the fields of psychology and cognitive therapy, have suggested that MDMA has therapeutic benefits and facilitates therapy sessions in certain individuals, a practice for which it had formally been used in the past.
Keywords
MDMA; Methylenedioxymethamphetamine
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Background
Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy or molly, is a psychoactive drug that belongs to the amphetamine class of substances. The chemical structure of MDMA includes a methylenedioxy group attached to the amphetamine molecule, giving it its distinctive properties. This modification results in a combination of stimulant and hallucinogenic effects. MDMA primarily acts by increasing the release and blocking the reuptake of neurotransmitters such as serotonin, dopamine, and norepinephrine in the brain, leading to altered mood, perception, and cognition. However, excessive consumption of ecstasy may pose several fatal risks, including hyperthermia, serotonin syndrome, acute dehydration or water intoxication, addiction, and neurological damage to serotonin. Clinical manifestations include episodes of anxiety and panic, depression, memory inversion, cognitive dysfunction, memory disorders, and other psychiatric and neurological symptoms. MDMA [BSA] refers to a specific chemical compound created by conjugating (linking) MDMA with bovine serum albumin (BSA). It is primarily used as an immunogen or antigen in the development of antibodies for detecting and quantifying MDMA. By conjugating MDMA to BSA, it allows the immune system to recognize the compound as foreign, leading to the production of specific antibodies against MDMA. These antibodies can then be utilized in various immunoassay techniques, such as enzyme-linked immunosorbent assays (ELISA), to detect and measure the presence of MDMA in samples. In the analytical field, the availability of MDMA [BSA] contributes to the development of reliable methods for identifying and quantifying MDMA in biological samples, such as urine, blood, or saliva. These methods are important for drug testing purposes, clinical toxicology, and research studies related to MDMA metabolism, pharmacokinetics, and illicit drug use patterns.
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References
Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats
Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2-deoxyguanosine, 8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the colocalization between cells positive for the dopamine transporter (DT1) and cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration. MDMA did not affect NOX2, NOX1, and NOX4 immunoreactivity, whereas iNOS expression was enhanced. The number of NT-positive cells was increased in MDMA-exposed animals, whereas no differences were detected in 8OHdG expression among experimental groups. MDMA and NT markers colocalized with DT1 positive cells. DT1 immunostaining was found in NeuN-positive stained cells. Virtually no colocalization was observed with microglia and astrocytes. Moreover, MDMA immunostaining was not found in NOX2-positive cells. Our results suggest that iNOS-derived nitrosative stress, but not NOX enzymes, may have a crucial role in the pathogenesis of MDMA-induced neurotoxicity, highlighting the specificity of different enzymatic systems in the development of neuropathological alterations induced by the abuse of this psychoactive compound.
What is the drug of choice of young festivalgoers?
DRUG AND ALCOHOL DEPENDENCE
Authors: Bade, Richard; White, Jason M.; Nguyen, Lynn; Pandopulos, Aaron J.; Gerber, Cobus
Background: Drug and alcohol consumption are commonplace at festivals including those aimed at younger attendees. However, there is little quantitative information about the extent of this consumption. This work investigates drug use at a school-leaver festival and how it compares to non-festival weeks. Methods: Influent wastewater was collected over three consecutive weeks from a location where a school-leaver festival occurs. Multiple liquid chromatography-mass spectrometry methods were used to analyse the use of illicit drugs, pharmaceuticals with abuse potential, new psychoactive substances (NPS), alcohol and cannabis. A method for human neurotransmitter metabolites was also utilised to show the population change and allow the drugs found to be normalised to a population. Results: A total of 12 compounds were quantifiable: methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), alcohol, cannabis, cocaine, morphine, codeine, fentanyl, buprenorphine, oxycodone and nicotine. The NPS methylone was found solely over the festival weekend but at levels below the limit of quantification of the analytical method. The catecholamine metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA) were found over the entire three weeks, with identical trends - an increase over the festival weekend - indicating a population increase. HVA was used to normalise the drug mass loads to derive a population normalised mass load. Statistical differences using Hedges' g showed large changes in the use of MDMA and MDA over the festival week. Smaller increases were also seen for alcohol and cocaine. Conclusions: The drugs of choice for the attendees of this school-leaver festival were MDMA and MDA.
The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)
The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.
Development of a point-of-care test for the detection of MDMA in latent fingerprints using surface plasmon resonance and lateral flow technology
Drug Testing and Analysis
Authors: Pollard C, Hudson M, McDonnell J M, et al.
To date, a specific point-of-care test (POCT) for 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, 'E') in latent fingerprints (LFPs) has not been explored. Other POCTs identify MDMA in sweat by detecting the drug as a cross-reactant rather than target analyte, thus decreasing the test's sensitivity. The study's aim was to design a sensitive POCT for the detection of MDMA in LFPs using surface plasmon resonance (SPR) and lateral flow immunoassay (LFA) technology. A high-affinity antibody binding pair was identified using the former technique, deeming the pair suitable for a LFA. Titrations of fluorescently labelled antibody and antigen concentrations were tested to identify a sharp drop-in signal upon the addition of MDMA to allow a clear distinction between negative and positive outcomes. We trialled the LFA by producing dose response curves with MDMA and a group of drugs that share a similar chemical structure to MDMA. These were generated through spiking the LFA with increasing levels of drug (0–400 pg/10 μl of MDMA; 0–10,000 pg/10 μl of cross-reactant). Fluorescent test signals were measured using a cartridge reader. The cut-off (threshold) 60 pg/10 μl calculated better cartridge performance (1.00 sensitivity, 0.95 specificity and 0.98 accuracy), when compared with 40 pg/10 μl. The biggest cross-reactant was PMMA (250%), followed by MDEA (183%), MBDB (167%), MDA (16%) and methamphetamine (16%). A sensitive LFP screening tool requiring no sample preparation was successfully designed.
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