[Recent abuse of 3,4-methylenedioxymethamphetamine ("yaoto-wang", "ecstasy")].
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Abstract:
3,4-methylenedioxymethamphetamine ("Yaoto(head shifting)-wang", "Ecstasy"), designer drugs is popular world wide along with rave party, especially from the 1980s. Although there is a significant misconception of MDMA as "a safe drug", recent findings show its serotonin (5-HT) selective neurotoxity with memory disturbance and cognitive disorders, not only during its use but lasting for years. Hyperinnervation of 5-HT neurons has also been reported among non-human primates. Serotonin syndrome, serious dehydration and acute renal failure are reported as serious clinical symptoms and some deaths related to the use of MDMA have been reported. Unlike many stimulant users, MDMA users are likely to be socially adapted and epidemiological research suggests that, in the United States and European countries, 6-8% of students and 0.5-3% of adults have experienced MDMA use. Although criminal cases have been reported in Japan since the 1990s, there has been no empirical study of MDMA abuse, especially among youth. Based on the "Classification of Medicine and Drugs" of the Ministry of Health, Welfare and Labor. MDMA is classified as "compound narcotics: hallucinogens and stimulants" rather than individually. Another problem is that MDMA users are likely to visit emergency rooms rather than psychiatric clinics. The American Psychiatric Association has publicized the misconception of MDMA as a safe drug and informed people of its dangers. The author offers suggestions for Japanese psychiatrists to take steps to cope with this situation and recommends authorities to establish an appropriate drug policy.Keywords:
MDMA
Ecstasy
Serotonin Syndrome
Stimulant
Psychoactive drug
Designer drug
Cite
The drug 3,4 methylenedioxymethamphetamine (MDMA), also known as "ecstasy," is a "designer" drug that is becoming popular with American adolescents at dance halls known as "raves" and on college campuses. An analogue of amphetamine, MDMA shares properties with both amphetamine and hallucinogenic drugs. Now available in many US cities, MDMA has an undeserved reputation for safety and a long duration of action. The drug appeals to young people, who believe that it enhances empathy and closeness to others. Common short-term adverse effects of MDMA include sweating, tachycardia, fatigue, and muscle spasms, including jaw-clenching. Serious adverse effects from MDMA include serious or fatal heat injury, fluid and electrolyte depletion, and central nervous system, cardiac, muscular, renal, and hepatic dysfunction. MDMA has been implicated in at least 53 deaths in the United Kingdom and at least five more deaths in the United States, mainly attributable to profound disturbances in thermoregulation (heatstroke). MDMA is a selective serotonergic neurotoxin. "Herbal ecstasy" containing ephedrine (Herba ephedrae) and other herbs, can be purchased by mail. Several toxicology screening tests for the amphetamine class of drugs of abuse can detect MDMA, but at about 50% reduced sensitivity. Treatment of acute toxic reactions includes rapid cooling and rehydration, monitoring electrolytes, and organ dysfunction. Because current national and state surveys show a significant increase in use of this drug, physicians in primary care, emergency medicine, critical care medicine, and addiction medicine can be expected to manage an occasional patient with acute MDMA toxicity.MDMA (also known as ecstasy, XTC, Adam, or E), a "designer drug," is a 3 ring-substituted, methoxylated analogue of methamphetamine and its closest congeners, 3,4 methylenedioxy-amphetamine (MDA),and 3,4 methylenedioxy-ethamphetamine (MDEA, also known as Eve). MDMA is reputedly safe to take as a "recreational" or "therapeutic" drug in a dose of 1 to 2 mg/kg.1 With the passage of recent referenda in Arizona, that allows the use of Schedule I drugs for medical purposes, the possibility that efforts to legalize MDMA for medical purposes may also succeed. The Multidisciplinary Association for Psychedelic Study, lobbies intensively to legalized MDMA for research purposes. However, a 1996 editorial in the Lancetstated that MDMA has no recognized therapeutic potential, is not a "soft" drug, and has caused a disproportionate amount of harm and death. The author of the editorial recommended that MDMA retain its illegal status.2 Reports of acute1-13 and chronic toxicity1415 associated with ingestion of MDMA continue to mount. Although prevalence data for serious problems from MDMA is unknown, but probably infrequent, misuse has caused at least 53 fatalities in the United Kingdom.2 Serious morbidity and mortality occurred from fulminant hyperthermia, cardiac arrhythmia, disseminated intravascular coagulation, rhabdomyolysis, acute renal failure,1617 and hepatic toxicity.18-20 As early as 1992, at least five deaths associated with MDMA had already been reported in the United States.34 More recent data are not available. For each relatively rare major complication after ingestion of MDMA, many lesser events21 go unrecorded.Data on the use of MDMA by American teenagers is slowly accumulating. A random 1990 survey of illicit drug use by undergraduate students at Tulane University revealed that use of MDMA was reported by 24% of those surveyed, exceeding use of lysergic acid diethylamide (LSD) and cocaine. In that Tulane study, MDMA was more likely than any other drug to have been used first during the student's college years.22 A 1994 comprehensive survey of drug use was reported for 7722 15- and 16 year-old British students. MDMA use was reported by 8% of those surveyed.23 By contrast 5% of American 16-year-olds used MDMA in 1996.24 A Texas study conducted in 1996 found that 9% of high school seniors in that state had used MDMA at least once and the annual National Institute on Drug Abuse High School Student Survey found that 5% of seniors admitted to MDMA use.25Risk-taking youths, in a party setting, are reported to experiment by "stacking" MDMA (ie, taking three or more tablets at once, ingesting look-alike ephedrine-containing tablets called "herbal ecstasy," or mixing MDMA with LSD, alcohol, marijuana, and other drugs of abuse).The purpose of this review is to trace the evolution of the use of MDMA, describe the effects of the drug, explain the role of urine toxicology screening, and outline management of acute toxicity.MDMA was first synthesized in Germany in 191426and used in the United States as adjunct to psychotherapy in the late 1970s and early 1980s. The drug does not hold approval from the Food and Drug Administration for such use. Pharmacologic effects of MDMA include increased psychomotor drive and logorrhea, sympathetic nervous system effects, and muscle spasms. Psychedelic effects include sensory enhancement and distortion and illusions without overt hallucinations. The time for initial effects to occur ranges between 30 to 60 minutes. Peak effects occur at 90 minutes and may persist for 8 hours or more. Tolerance to desirable effects and an increase in adverse effects are reported to develop with regular and frequent use.1 MDMA is known to be metabolized by N-demethylation to MDA. Urinary excretion of the parent drug accounts for 65% of the dose.MDMA is thought to be a safe drug by "recrea-tional" users and by a few psychotherapists27-30 who support its use as an entactogen, (ie, a means of enhancing empathy, introspection, and communication, and inducing positive mood states and feelings of intimacy and tranquility). Greer27 first reported beneficial responses to MDMA-facilitated psychotherapy with 29 subjects, including self-reported decreases in the subjects' use of alcohol and marijuana.MDMA is a selective serotonergic neurotoxin.31-33 In animals, it causes initial release of serotonin (5-HT) followed by the degradation of 5-HT pro-jections. Magnetic resonance imaging of nonhuman primates shows significant anatomical neuro-degeneration.33 There are no human data.Physical signs of sympathetic nerve stimulation from MDMA ingestion are similar to those of low-dose LSD ingestion and include tachycardia and widely dilated pupils for a few hours after ingestion.34 Somewhat unique to MDMA, users often complain of muscle tension and aches, and jaw-clenching.28 Sweating, fatiguability, and difficulty concentrating and retaining newly learned material9 are common. MDMA occasionally causes intense dysphoria (depression, anxiety), confusion, or delirium. High environmental and core body temperature and muscular exertion, such as that which accompanies marathon dancing, seem to lower the threshold for serious MDMA-associated adverse effects, particularly rhabdomyolysis.28 There are increasing reports of ecstasy-associated morbidity and mortality from hyponatremia,35-37 dehydration, hyperthermia, hypertensive crises, and cardiac arrhythmias.The widespread use of MDMA by teenagers can primarily be traced to the British dance hall phenomenon called "raves."38 By 1992, an estimated 20 000 to 30 000 young people were going to raves every weekend in northwest England.39 In large makeshift dance halls, with an affordable admission fee, ravers dance vigorously and continuously, all night, to loud, repetitive, synthesized electronic rock music at 80 to 120 beats per minute, provided by celebrated disk jockeys at clandestine locations kept secret until 1 or 2 days before the event. The vagueness of the actual time and the off-the-beaten-path location, and rave names such as "rave new world" or "save the rave forest", seem to add to the mystique and allure of raves. The cover charge for raves varies between $7 to $15. Although IDs are often requested, underage youth gain admission by the use of altered or counterfeit IDs. Carloads of rave attendees arrive in a caravan of vehicles, often attired in baggy pants and striped polo shirts for the boys and high platform shoes and ghostly makeup for the girls. Rave attendees are divided into committed ravers (somewhat akin to "deadheads" who spend their formative years following the Grateful Dead rock band all over the country) who follow the local rave scenes almost every weekend, occasional ravers, usually college students, who attend raves once a month or so, and curious onlookers, including junior high school students, who want to see what the rave scene is all about. Ravers engaged in marathon, vigorous group dancing with expensive laser light displays illuminating the darkened building.3539-41 A sample of lyrics popular with English ravers indicates the importance of the drug to these events. The lyrics include the following lines: "This is harmony: what you need to live; Everybody's sympathizing, everybody's temperature's rising; Lifting me into the heavens in a state of ecstasy; Such a good feeling is where I want to be, such a good feeling, in totalecstasy.39 As the result of hours of marathon dancing by hundreds of sweaty, gyrating people to the beat of hard rock music, the temperature of the environment and of the ravers, sometimes rose to hyperpyretic levels. Occasionally it caused heat-induced serious morbidity or even death.1351011 Because alcohol may not be served at many raves, the dancers drink "smart drinks" or "power drinks," which are blended concoctions of fruit juices and power agents that help to replenish fluid losses from vigorous dancing. Added to the drinks are mixtures of various B vitamins and powdered amino acids, allegedly to replenish depleted neurotransmitters such as serotonin. Those who are unwilling to stop dancing or who cannot afford the "smart drinks," may become moderately or seriously fluid-depleted and suffer from dehydration with weakness, lightheadedness, and incoordination. Recreational users of MDMA at raves now are advised by "ravers" to include eating something salty and drink frequently and copiously to prevent hyponatremia.Many ravers ingest tablets containing MDMA, its close congener MDEA, or bogus MDMA known as "herbal ecstacy."40-42 However, in one study, much of what is purported to be MDMA at raves is MDMA and not "herbal ecstasy."40When interviewed, many ravers were ignorant of the potential for serious adverse effects of MDMA, believing that it was a totally safe, pure, unadulterated drug.39 Although MDMA itself was often detected, analysis of other tablets purported to contain MDMA revealed adulteration with other drugs, including oriental herbal ephedrine (Ma Huang) and ketamine.41 Raves often have a carnival-like atmosphere including hawkers selling drug paraphernalia or drugs, including brightly-colored, nitrous oxide-filled balloons which sell for about $5, and are used by teenagers as a means of getting high and acting silly in front of friends.In the early 1990s, raves became popular in major coastal American cities such as San Francisco, Baltimore, and New York.43At Stanford University,44 and at raves frequented by high school students in Baltimore and New York City, MDMA, in tablets containing about 100 mg of the drug and costing about $20 each, has become a popular drug of abuse. It is valued for its mild hallucinogenic and stimulant properties, as well as its reputed ability to enhance benevolence and emotional bonding.In addition to admitted or detected abuse of MDMA in the emergency department, it is important to evaluate for acute polydrug abuse and for addiction. Urine toxicology tests for cannabis, hallucinogens, phencyclidine, and stimulant drugs and Breathalyzer or saliva or urine tests for alcohol, are of value. Comprehensive assessment for polydrug use and addiction is advisable to reduce the risk of acute overdose reactions, injuries, suicide attempts, and homicide. The usual toxicology screen fails to detect MDMA unless large doses have been ingested. A positive test shows up as positive for the amphetamine drug class.45 A monoclonal immunoassay for amphetamine/methamphetamine will detect MDMA, although it is about 50% less sensitive compared with detection of d-amphetamine andd-methamphetamine.46 The AxSym (Abbott Laboratories, Abbott Park, IL) manual states that its amphetamine test is approximately equally sensitive for methamphetamine and MDMA. Thin-layer chromatography, the traditional "overdose" toxicology screen, can also detect MDMA metabolites in the urine.Confirmation by means of the toxicology reference standard, gas chromatography/mass spectrometry is strongly recommended whenever amphetamines show up as positive by immunoassay screening tests.Drugs of abuse associated with serious heat-related injury or rhabdomyolysis include amphetamine, methamphetamine, cocaine, phencyclidine, and MDMA. Emergency management of MDMA heat injury include rapid rehydration and core cooling. Anxiety and extreme agitation, panic reactions, and seizures may require short-acting benzodiazepines such as lorazepam, administered intravenously or via the intramuscular route. Frequent observation of vital signs and serial assessment of consciousness by a simple AVPU (A = alertness; V = verbal responsiveness; P = pain responsiveness; U = unresponsive) score, or the Glascow Coma Scale, is often helpful. Inpatient admission with arm restraints may be necessary for those few patients who show complete loss of behavioral control, especially if they indicate an intent to inflict serious self-harm or violence toward others.Management of rhabdomyolysis requires strict attention to restoring depleted fluid and electrolyte balances, alkalinization of the urine, and the administration of furosemide. Dantrolene may be of some value in counteracting MDMA-associated muscle cramping and spasms.47 Cardiac arrhythmias may require β- or calcium-channel blockers or procainamide.What are the risk factors for adolescent drug use? According to several longitudinal studies, adolescents who are close friends with known drug users are at greatest risk. In addition to frequent attendance at raves, sensitive indicators of possible serious involvement with MDMA and other drugs are a steady deterioration in school performance and attendence, early addiction to nicotine cigarettes or frequent use of marijuana, serious and occasionally violent interpersonal quarrels with parents and authority figures, and aggregates of all of the above.Complicating the primary diagnosis of substance abuse and addiction during adolescence are dual diagnosis, including: mood disorders, chronic fatigue syndrome, posttraumatic stress disorder, adoption issues, parent-child conflict, conduct disorders without drug use, and serious attention deficit and late-onset learning disorders. A comprehensive evaluation for drug abuse is best when performed by qualified psychiatrists (trained in addictions) and addiction medicine specialists or by experienced drug counselors. Should the evaluation reveal objective evidence of serious substance abuse, four levels of intensity of drug treatment have been formulated by the American Society of Addiction Medicine. The least intrusive in the life of an adolescent is outpatient afterschool drug treatment and education. Most drug treatment programs recommend abstinence from drugs and alcohol and severing ties with friends that might otherwise tether the young person to the drug-using culture. Self-help groups such as Narcotics Anonymous and Alcoholics Anonymous have been life-saving for many recovering adolescents.48 Periodic and unscheduled monitoring by means of urine toxicology tests for drug use is often an irreplaceable part of rehabilitation. It is particularly important to include a comprehensive assessment of significant additional behavioral and psychiatric problems (comorbidity), which frequently accompany substance abuse.49MDMA, known as "ecstasy," a designer drug, is becoming popular with American adolescents at dance halls known as "raves" and on college campuses. It seems logical that easy availability, affordability, the perception of safety, and peer acceptance and encouragement to initiate use will lead to increased misuse of MDMA. MDMA has been implicated in at least 58 deaths, resulting in a syndrome resembling heatstroke. Look-alike drugs, such as "herbal ecstasy," can easily be confused with MDMA by teenagers. Several toxicology screening tests for the amphetamine class of drugs of abuse can detect MDMA, but at about 50% reduced sensitivity.
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3,4-methylenedioxymethamphetamine ("Yaoto(head shifting)-wang", "Ecstasy"), designer drugs is popular world wide along with rave party, especially from the 1980s. Although there is a significant misconception of MDMA as "a safe drug", recent findings show its serotonin (5-HT) selective neurotoxity with memory disturbance and cognitive disorders, not only during its use but lasting for years. Hyperinnervation of 5-HT neurons has also been reported among non-human primates. Serotonin syndrome, serious dehydration and acute renal failure are reported as serious clinical symptoms and some deaths related to the use of MDMA have been reported. Unlike many stimulant users, MDMA users are likely to be socially adapted and epidemiological research suggests that, in the United States and European countries, 6-8% of students and 0.5-3% of adults have experienced MDMA use. Although criminal cases have been reported in Japan since the 1990s, there has been no empirical study of MDMA abuse, especially among youth. Based on the "Classification of Medicine and Drugs" of the Ministry of Health, Welfare and Labor. MDMA is classified as "compound narcotics: hallucinogens and stimulants" rather than individually. Another problem is that MDMA users are likely to visit emergency rooms rather than psychiatric clinics. The American Psychiatric Association has publicized the misconception of MDMA as a safe drug and informed people of its dangers. The author offers suggestions for Japanese psychiatrists to take steps to cope with this situation and recommends authorities to establish an appropriate drug policy.
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Because illicit drugs are now widely consumed, every doctor needs to know their acute medical consequences and complications. Here, we review the problems associated with the different drugs from a systems-based viewpoint. Apart from the respiratory depressant effect of opioids, crack cocaine is the most common cause of respiratory complications, mainly linked with its mode of use, with airway burns, pneumothorax, pneumomediastinum, and lung syndromes being well-recognised sequelae. Because of its marked cardiovascular effects, cocaine is also a major cause of coronary syndromes and myocardial infarction. Amphetamines may produce similar effects less commonly. Hyperthermia may occur with cocaine toxicity or with 3,4-methylenedioxymethamphetamine (MDMA) due to exertion or from serotonin syndrome. Cerebral haemorrhage may result from the use of amphetamines or cocaine. Hallucinations may follow consumption of LSD, amphetamines, or cocaine. MDMA is a major cause of acute severe hyponatraemia and also has been linked with hepatic syndromes. Collapse, convulsions, or coma may be caused in different circumstances by opioids, MDMA, or gamma hydroxybutyrate and may be aggravated by other sedatives, especially alcohol and benzodiazepines. Recognition of these acute complications is urgent, and treatment must be based on an understanding of the likely underlying problem as well as on basic principles of supportive care.
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Novel psychoactive substances (NPS) are compounds designed to mimic the effects of existing recreational drugs (classical psychoactive substances [CPS]), while eluding established legal frameworks. Little is known about their effects and potential harms, rendering the increasing number of NPS a challenge to policy makers and researchers alike. Quantitative studies on the motives underlying NPS use are limited, though understanding them is crucial for the design of effective harm prevention strategies. The present study therefore aimed to compare motivational patterns for NPS, CPS, and legal psychoactive substance (LPS) use. An online survey including questions about lifetime drug use, demographics, and motives for use was completed by 2,319 participants of which 1,967 consented and were 18 years or older. Data on lifetime use and endorsed motives are presented for 12 psychoactive substances classified into LPS (alcohol, nicotine), CPS (cannabis, MDMA/ecstasy, amphetamines, cocaine, psilocybin, LSD, ayahuasca), and NPS (synthetic cannabinoids, stimulant, and hallucinogenic) and compared between classes. Across substances, the most frequently endorsed motives were to feel euphoric (58.0%), enhance an activity (52.3%), and broaden consciousness (48.1%). Motives for use were found to differ by substance and gender, with coping-related reasons being more frequent among female participants compared to males who indicated to use for a broad range of reasons. Motivational patterns of CPS and NPS use were largely similar to their classical analogues, this was not the case for synthetic cannabinoids, which had as main endorsed motive getting intoxicated, indiscriminate of specific qualities. This information can feed into tailoring of educational campaigns and prevention strategies.
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In recent years, there has been a large increase in the number of synthetic drugs used recreationally. One class of drugs is synthetic cannabinoids, which are sprayed onto herbal preparations and marketed under names such as K2 and spice. Others include amphetaminelike compounds, such as cathinones (eg, bath salts) and methylenedioxymethamphetamine (MDMA) (eg, ecstasy, Molly). New hallucinogens, such as Bromo-Dragonfly, and hallucinogens that have been used for centuries, such as Salvia divinorum, also are gaining popularity. Because these substances are sold labeled as not for human consumption and because the chemicals in them frequently change, they often are unregulated, and many users consider them legal, although they are not. Their use often goes undetected because testing for them is not included in routine drug screening. Nonetheless, these substances can be associated with significant toxicities, often because their concentrations are unpredictable. Adverse effects of synthetic cannabinoids include psychosis and other effects. Amphetaminelike drugs have stimulant effects and can cause hyponatremia and seizures. The new hallucinogens can cause serious vasoconstriction with ischemia. Clinicians, especially those working with adolescents and young adults (ie, the main users of these drugs), should be aware of these new substances and counsel patients about their adverse effects.
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