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Official websites use. Share sensitive information only on official, secure websites. Corresponding author: Feyza Bora. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. Ecstasy MDMA; 3,4-methylenedioxymethylamphetamine is an illicit drug that has been increasingly abused by young people. Its effects include euphoria, enhanced sociability and heightened mental awareness. These come about via the increase of serotonin in both the central nervous system and the sympathetic nervous system. Due to personal pharmacokinetics, effects from the same dosage vary according to the individual. However, it is seldom the case that hyponatremia and hyperthermia co-exist. Hyponatremia is caused by the inappropriate secretion of arginine vasopressin AVP and the excessive intake of hypotonic liquid accompanied by increased hyperthermia. Symptomatic, even deadly hyponatremia is seen more frequently in females, with the effects of oestrogen on arginine vasopressin believed to be the cause. Reasons for acute kidney injury may include rhabdomyolysis, malign hypertension, and necrotizing vasculitis. Synthetic tablet abuse has seen a dramatic worldwide increase. We also suggest treatment methods for these kidney injuries. Ecstasy MDMA; 3,4-methylenedioxymethyl-amphetamine is an illicit drug that has been increa-singly abused by young people. The most well-known of the illicit synthetic tablets, it was introduced to Turkey in the early s — a country which, due to its geographical location and youthful population, has been subject to the negative effects of the international drug trafficking. However, it is still third on the list of most-seized drugs 1. The amounts of ecstasy captured in Turkey between are shown in the Table 1. Although the active component of ecstasy is 3,4-methylenedioxy-methylamphetamine MDMA , users of the drug give the same name to all similar synthetic tables. These tablets, which are illegally manufactured and sold on the streets, contain amphetamine-type stimulants. They may also contain sugar, inorganic chemicals and inorganic salts that do not have any stimulant, sedative or sleeping effects on the human body. Amphetamine-type stimulant substances are illegally produced. As a result, they contain additional chemicals that are created during the production process and which present an added danger to drug users. Ecstasy tablets are made and sold in various colours, with different geometric shapes and logos intended to make them more attractive to young people. The increased attractiveness of synthetic tablets leads to greater curiosity, which in turn leads to higher levels of addiction. Examples of recently captured ecstasy tablets are shown in Figure 1. In , the number of the deaths directly related to illicit drugs in Turkey was , rising to in — a MDMA causes feelings of vibrancy and well-being, loss of anxiety, emotional fluctuations and indecisi-veness 1 , 5 , 8 , 9. Initially, the body experiences hyperthermia and hyperactivity 1 , 5 , There may also be adverse effects such as exhaustion, sleeping disorders, nausea, vomiting, shudders, sweats, chin-lock, gnashing of teeth, blurry sight, dilating pupils, discomfort caused by light, and arrhythmia 1 , 5 , MDMA has a stimulant, hallucinogenic effect, and is also known to enhance mental factors such as energy, empathy and euphoria Generally considered a recreational drug, MDMA produces these effects by preventing the re-uptake of neuroactive hormones such as serotonin, dopamine and noradrenalin in both the central nervous system and the sympathetic nervous system Tablets that include amphetamine-type stimu-lants have a mass of between mg and mg 1. On average, they contain mg of MDMA. The drug begins to take effect after min, peaking at 90 min 14 , In general, its effect may last between hr, occasionally longer. The effects of illicit tablets on humans may depend on the contents and amounts of the tablet consumed. Effects may also differ from case to case depending on the varieties and amounts of the active ingredients in different synthetic tablets 5. MDMA metabolizes in two pathways. In the first, it conjugates with N-dealkylation, deamination, oxidation and glycine, becoming HMA 4-hydroxymethoxyamphetamine. Medicines that are inhibitors of cytochrome P 2D6 isoenzyme ritonavir and antifungal can prevent ecstasy from being metabolized 16 - It has been established that the effect of cytochrome P 2D6 isoenzyme, in addition to inhibiting other medicines, varies from person to person. As the drug stays longer in the body of people who metabolize it slowly, there is a higher risk of acute toxicity Due to the lower enzyme activity in people of Korean, Chinese and Japanese origin, there is an inclination towards hyperthermia, rhabdomyolysis, serotonin syndrome and multi-organ failure 19 , Also, it has been shown that MDMA metabolites might create an inhibitor complex with the cytochrome P 2D6 enzyme, leading to toxicity in repetitive doses. MDMA and metabolites 21 are removed by the kidneys, and variations in the removal process might explain why people taking the same dose of MDMA do not experience the same adverse effects. Although ecstasy usage is relatively common, instances of fatal adverse effects are rare. MDMA has a negative effect on the immune system. IL is an anti-inflammatory or immunosuppressive cytokine that inhibits the production of pro-inflammatory cytokine TNF-alpha, IL, and IFN-gamma, as well as decreasing many macrophage functions. MDMA also has a suppressive effect on catechol aminergic beta-adrenoceptor and nicotinic acetyl-choline receptor-mediated immune function 23 , The drug increases levels of glucocorticoid cortisol, plasma corticosterone, and also the inactive steroid dehydrocorticosterone. MDMA use may negatively affect cancer progression by inhibiting immune regulatory systems and reducing the resistance of host cells to viral infections The effects of ecstasy on the kidneys can be placed into the following sub-groups: effects on fluid and electrolyte metabolism; hyperthermia; and acute kidney injury. These categories are discussed in further detail below. Acute symptomatic hyponatremia heads the list of serious ecstasy-related complications. In terms of physiopathology, inappropriate secretion of AVP is believed to be the cause of hyponatremia. Psychogenic polydipsia resulting from the belief that large amounts of generally hypotonic liquid should be taken to avoid hyperthermia during parties could be of benefit to the physiopathology. In one study, there was a statistically significant increase from 1. Case studies in which AVP levels were not measured have also shown that urine osmolality increases incompatibility in the case of serum hypoosmolality, which is compatible with the inappropriate secretion of AVP MDMA and metabolites have been shown to increase serotonin levels in the central nervous system, and this high level of serotonin causes AVP release due to neurohypophysis It is believed that AVP release could increase with stress, physical activity and the use of nicotine—additional factors that are generally present in situations where ecstasy is used As seen in the case of fluoxetin—a serotonin-specific reuptake inhibitor SSRI —another factor might be increased water absorption in the internal medullar collector channel linked to an increase in the expression of aquaporin 2 channels Hyperthermia, which could be caused by a reduction in MDMA levels and an increase in HMMA, is not frequently seen in cases that are accompanied by hyponatremia Hyponatremia symptoms generally commence between two to twelve hours after ecstasy intake. In patients with Ayus—Arieff syndrome, there may be neurogenic pulmonary oedema. Hyponatremia in patients with this syndrome will cause the development of pulmonary oedema after cytotoxic cerebral oedema. Pulmonary oedema would result in hypoxia, which inhibits the volume regulation of the brain cells, which in turn causes further deterioration to the cerebral and pulmonary oedema The same Na values are more symptomatic in women than in men Some studies affirm that there is a higher risk of symptomatic hyponatremia in women and that the condition may even be fatal 38 , It is more likely for women to experience hyponatremia for the following reasons:. A study involving eight men and eight women found that the levels of copeptin, which is easier to quantify than MDMA, is higher in men. Hyperthermia is a fatal complication of MDMA. However, the condition might lead to non-traumatic rhabdomyolysis, hypotension, disseminated intravas-cular coagulation DIC , acute kidney failure, hepatic failure, cardiovascular collapse, intracranial bleeding and death 48 , Some studies state that hyperthermia originates from sustained heat resulting from the activation of 5-OH tryptamine and dopamine receptor systems 54 - It has been observed that hyperthermia does not originate from a change in heat adjustment in the hypothalamus, and antipyretics are hence not included in the treatment options. It has also been observed that increased muscular activity could contribute to hyperthermia Long-lasting hyperthermia may result in DIC and multi-organ failure 11 , The most significant reason for acute kidney injury is acute tubular necrosis caused by pigment due to non-traumatic rhabdomyolysis necrosis of myocytes caused by a rapid rise in cellular calcium. Acute kidney injury might be caused by hyperthermia, extreme activity, seizures, or by the direct toxic effects of MDMA on muscle cells Volume depletion increases the nephrotoxic effect of rhabdomyolysis. There may also be myoglobinuria, hyperuricemia, hyperkala-emia and hyperphosphatemia. Obvious and long-lasting hyperuricemia in particular may cause renal vasoconstriction, endothelial dysfunction, infla-mmatory response, oxidative stress and failures in autoregulation Reasons for acute kidney injury may include urinary bladder neck obstruction 60 and malign hypertension In a patient who has isole proximal tubule dysfunction, temporary glycosuria, phosphaturia and solute diuresis have all been observed In the literature, there are histopathologic diagnoses of necrotising vasculitis 63 and vascular thrombosis The presence of vascular thrombosis and fibrinoid necrosis 65 have also been seen in the results of renal biopsy performed due to the loss of graft function in two renal kidney transplant patients. A greater number of biopsy results would leave us better placed to establish the relationship between acute kidney injury and MDMA. The underlying cause of tissue damage due to MDMA may be increased oxidative stress or mitochondrial dysfunction The over-expression of antioxidant enzymes such as N-acetylcysteine, ascorbic acid or superoxide dismutase may neutralize the potential toxic effects of MDMA 70 , As there is increased urine osmolality due to the inappropriate secretion of AVP, hypotonic fluids and 0. In cases of acute medium symptomatic hyponat-remia, the transition from hyponatremia to normo-natremia may be achieved by restricting the intake of liquids. The patient should be clinically monitored for urine output, serum Na, urine osmolality and urine Na. AVP antagonists have recently been introduced for clinical use in cases where AVP secretion is inappropriate e. Paralysis and intubation could be performed to reduce muscular thermogenesis, while benzodiazepines can be used for reducing agitation and seizures. Although there are conflicting data on the use of Dantrolene a muscle relaxant in the treatment of hyperthermia caused by MDMA, there are cases in which Dantrolene has been employed successfully 74 , In a study by Hysek et al involving 16 healthy volunteers, Carvedilol helped reduce the low-level hyperthermia and cardiostimulant effects that occurred after a single dose of MDMA. Hyperthermia resulting from MDMA is caused by alpha 1 and beta adrenoceptor, and Carvedilol inhibits alpha 1 and beta 1. The authors therefore support the use of Carvedilol in treating hyperthermia Non-traumatic rhabdomyolysis is caused by long periods of dancing, seizures or hyperthermia. Hyperkalaemia originating from rhabdomyolysis can cause arrhythmias. Treatment requires hydration-force diuresis, monitoring of the fluid and electrolyte situation, including intake and removal, and kidney function tests. For hyperkalaemia, hemodialysis can be used. For hyperuricemia, rasburicase might be used A study by Karami et al has shown that an extract made from the leaves of plant called Feijoa sellowiana acca sellowiana histopathologically showed a protective effect in mice from MDMA-related injury by increasing kidney glutathione CKD presence, kidney function and albuminuria were not found to be related to the use of cocaine, methamphetamine and heroin 80 , despite a study by Vupputturi et al claiming this to be the case However, these studies are not sufficiently large to state with confidence that the use of illicit drugs is not linked to the development of CKD. An increase in the number of young people, coupled with the ease of cross-border transportation, mean that the use and accompanying health effects of MDMA will become more frequent in the future. The adverse effects of ecstasy use include mortality, particularly in young patients with hyperthermia or serious hyponatremia. Fatal hyperthermia is caused by increases in serotonin affecting muscular activity, the treatment for which requires peripheral cooling. Severe hyponatremia is caused by the inappropriate secretion of the antidiuretic hormone psychogenic polydipsia. In order to prevent hyperthermia, a high fluid intake is required. Besides fatal hyperthermia and hyponatre-mia, rhabdomyolysis generally non-traumatic causes acute renal failure. Rhabdomyolysis treatment in this instance is unconventional. Urine alkalization is not recommended, as it would reduce the ability of the kidneys to remove the MDMA We clinicians have an obligation to recognize these deadly side effects of MDMA. Most importantly, young people should be kept away from drugs in order to avoid complications that may result in their deaths. As a library, NLM provides access to scientific literature. Iran J Basic Med Sci. Find articles by Feyza Bora. Find articles by Taner Bora. Received Sep 10; Accepted Apr Open in a new tab. 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Spotlight: Turkey desperate for sustainable solutions to epidemic drug problem

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A police officer sprays gasoline on packages of cocaine, seized from a ship stopped in international waters. Reuters photo. Because of my addiction I was in a severe health condition and had to be hospitalized in the end. I was weighing only 43 kilos when I was admitted,' Seyyide Yoruk told Xinhua in a telephone interview. This year-old repentant drug addict said her family considers drug abuse as 'something ashamed of' in a largely conservative and patriarchal Muslim society, which makes it very difficult for the addicts to look for a clean life and there are few state-sponsored medical facilities that can properly take care of them. There is the real deal which is pure and difficult to reach and the synthetic one that you can buy for 20 liras 5. No one knows what's inside and it can cause deadly overdoses,' Yoruk said. He said his country seizes more drugs than Europe and trafficking of drugs from Iran and Afghanistan usually goes through Turkey. In , Turkish authorities detained 47, people, including foreigners, for drug-related offenses, Akdag said. He was referring to the cheap synthetic drug called bonsai which is holding a large number of youths prisoner of its effects. Operations have led to the seizure of 5,, illegal drugs in the pill-form, including ecstasy, amphetamine and prescriptions, Akdag said. Despite harsh legislation and intense police work, synthetic drug abuse is on the rise among low-income Turkish youths, even in conservative neighborhoods in big cities. Drugs have even made their way to small villages in rural areas where kids aged 9 or 10 are using it,' Fatih Yuzuguler, a former addict, told Xinhua. The year-old Kurdish man said he pretty much used every drug from cannabis to cocaine and methamphetamine to heroin. Yuzuguler now tries to help new addicts and their families to sever ties with narcotics, which is a very hard task in an impoverished and conservative environment. Like a diabetic we struggle to keep away from our kind of sweets,' said Yoruk. He called on the state to establish a comprehensive mechanism for the social problem, and raise awareness of the plight of young addicts. Turkish Interior Minister Suleyman Soylu stirred a controversy last week when he publicly encouraged his police force to use extra judicial methods to deal with drug smugglers. Do it and blame me. Even if it costs five, 10, 20 years in jail, we'll pay,' Soylu was quoted by the local press as saying. He argued that Turkey must fight drug dealers as it fights the Kurdistan Workers' Party PKK which has engaged in a three-decade deadly insurgency against the Turkish state. No one can poison our future,' he said. The interior ministry said last year that the PKK earns million dollars a year from the illegal drug trade since , with cannabis as its main source of funding. The age of drug usage has decreased to 9 in Turkey, according to Ulkumen Rodoplu, the founding president of the Emergency Mede iMessage Association of Turkey. Spotlight: Turkey desperate for sustainable solutions to epidemic drug problem Source: Xinhua Spotlight: Turkey desperate for sustainable solutions to epidemic drug problem. Xinhua Weibo. Sina Weibo. Tencent Weibo. Sohu Weibo. NetEase Weibo. Source: Xinhua Editor: huaxia. Back to Top.

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