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Iran J Pharm Res. The recreational drug ecstasy 3,4-methylenedioxymethamphetamine; MDMA is frequently misused by youths to enhance sexual excitement, intimacy, and energy levels for prolonged dancing sessions. MDMA's psychological effects are akin to those of the stimulant amphetamine family and the hallucinogenic mescaline 1. The increasing use of MDMA in recent decades, driven by its perceived low toxicity, easy availability, and affordability, has led to a rise in reports of multisystem toxicities and fatal complications 1 , 2. AKI is often a complication of acute health issues including malignant hypertension 3 , hyperthermia, multi-organ failure, rhabdomyolysis, and disseminated intravascular coagulation DIC 4 - 8. Additionally, post-mortem findings from a case of chronic renal failure following oral ecstasy ingestion revealed necrotizing vasculitis in a renal biopsy, suggesting a direct nephrotoxic effect of MDMA 9. There is also a case report where MDMA ingestion led to transient proximal tubular injury and hyponatremia 10 , and studies on primary cultures of rat and human renal proximal tubular cells have shown the direct cytotoxic effects of MDMA or its metabolites on renal injury development Although the link between ecstasy use and acute renal failure has been documented in rodent models 11 and several case reports, the underlying mechanisms remain poorly understood Additionally, we assessed the expression rates of the Bcl-2 protein family involved in apoptotic cell death, including mRNA levels of Bax, Bcl-xl, and Bcl-2 in renal tissues. MDMA purity: The dosage and route of administration were chosen based on previous rodent studies 13 - The rats were euthanized under deep anesthesia with an intraperitoneal injection of ketamine and xylazine at 6 or 24 hours after treatment to assess study parameters. This timing was selected because the pharmacological effects of MDMA last 4 - 6 hours 16 , 17 , and previous in vivo and in vitro studies have reported that MDMA induces apoptosis 24 hours following exposure 18 - Blood samples were collected from animals under deep anesthesia. Serum was separated by centrifugation at rpm for 10 minutes and kidney function markers, including serum BUN and creatinine, were measured using a Sapphire auto analyzer Cork, Ireland. Complementary cDNA was synthesized from 0. GAPDH served as the housekeeping gene for normalizing gene expressions. All primer sequences are listed in Table 1. Pathological evaluation was performed using light microscopy by an observer blinded to the sample identities. An independent t -test was used to compare means after verifying data normality with the Shapiro-Wilk test. A P-value of less than 0. There was no significant difference in renal tissue apoptosis between MDMA-treated animals and the control group Figure 3D. The results showed no noticeable histological changes in rat renal tissue 6 and 24 hours after MDMA administration compared to the control group Figure 4. The results of this study demonstrated a decrease in renal function following MDMA administration, evidenced by a reversible increase in serum BUN and creatinine levels. BUN and creatinine levels were found to increase 4 hours post-MDMA treatment, with creatinine returning to baseline within 24 hours 23 , aligning with our findings of MDMA-induced transient renal dysfunction. Kwon et al. Although this indicates direct cytotoxic effects of MDMA or its metabolites on renal tubules, the mechanisms underlying ecstasy-induced damage remain unclear Further, studies on the direct toxic effects of MDMA and its metabolite methylenedioxyamphetamine MDA on primary cultures of renal proximal tubular cells did not reveal any significant decline in cell viability. However, some of MDMA's putative metabolites have been shown to increase cell death in renal proximal tubular cells This inconsistency in the direct cytotoxic effects of MDMA necessitates further experimental research. Some studies have demonstrated the immunosuppressive effects of MDMA 26 , Moreover, there are reports that TNF inhibitor therapy can lead to nephrotoxicity, manifesting as glomerulonephritis and AKI 32 - Supporting this hypothesis, a renal biopsy from a case of fatal renal failure secondary to MDMA use revealed significant changes in small arterioles and arteries with few inflammatory cells 9. Correspondingly, Kassiri et al. Their study showed that blocking either of these cytokines in mice significantly reduces the induction of the other Apoptosis significantly contributes to various renal diseases, particularly in cases of drug-induced nephrotoxicity. Drug-induced renal cell apoptosis predominantly occurs through the intrinsic pathway, which is regulated in part by the pro- and anti-apoptotic members of the Bcl-2 family The anti-apoptotic members, Bcl-2 and Bcl-xL, preserve mitochondrial outer membrane integrity by binding to the pro-apoptotic protein Bax, which prevents mitochondrial cytochrome c release and maintains mitochondrial membrane integrity. Previous studies have demonstrated the role of reduced anti-apoptotic Bcl-xL in MDMA-induced apoptosis in hepatocyte and hepatic stellate cell lines, with no change in Bax protein levels 18 , and in rat neocortical neuronal cell lines without altering mRNA levels of Bax and Bcl-2 These findings align with evidence suggesting that while Bcl-xl and Bcl-2 proteins both serve anti-apoptotic functions, their protein expression is regulated by independent mechanisms, leading to dissociation between their expression changes 49 - This concept is supported by Wei et al. In their model, tubular apoptosis was blocked during ischemic AKI, although tubular necrosis remained unaffected Although it has been previously suggested that events outside the kidney contribute to the renal adverse effects of ecstasy, this study shows that ecstasy induces molecular changes in kidney tissue that could potentially predispose the kidney to malfunction. Alternatively, these molecular alterations could be part of the kidney's compensatory mechanisms against MDMA-induced adverse effects, though further verification of this hypothesis is needed. Since immunological complications were the primary cause of early graft rejection, pre-existing vascular lesions in the grafts due to MDMA consumption were proposed as the possible cause of necrotizing vasculitis that led to the loss of both grafts during the first post-transplant week in the absence of any inflammatory elements. However, the attenuation of Bcl-xl expression as an anti-apoptotic regulator in the induction of MDMA-induced apoptosis is likely prevented by the downregulation of Bax expression. Further studies are needed to assess MDMA-induced renal adverse effects to determine whether these molecular changes are due to its direct effect on the kidney or its effects secondary to immune dysregulation. Cardiovasc Toxicol. MDMA toxicity: management of acute and life-threatening presentations. Br J Nurs. Nephrology Dialysis Transplantation. Acute renal failure after ecstasy. J R Soc Med. Cunningham M. Ecstasy-induced rhabdomyolysis and its role in the development of acute renal failure. Intensive Crit Care Nurs. Mallick A, Bodenham AR. MDMA induced hyperthermia: a survivor with an initial body temperature of J Accid Emerg Med. N-Methyl-3,4-methylendioxymethamphetamine MDMA -related coagulopathy and rhabdomyolysis: A case series and literature review. Res Pract Thromb Haemost. Necrotizing renal vasculopathy resulting in chronic renal failure after ingestion of methamphetamine and 3,4-methylenedioxymethamphetamine 'ecstasy'. Nephrol Dial Transplant. Transient proximal tubular renal injury following Ecstasy ingestion. Pediatr Nephrol. Nephroprotective effects of Feijoa Sellowiana leaves extract on renal injury induced by acute dose of ecstasy MDMA in mice. Iranian journal of basic medical sciences. A case study on MDMA. Two fatal cases involving young adults. Australian Journal of Forensic Sciences. MDMA alone affects sensorimotor and prepulse inhibition responses in mice and rats: tips in the debate on potential MDMA unsafety in human activity. Forensic Toxicology. Curr Pharm Biotechnol. Acute administration of 3,4-methylenedioxymethamphetamine MDMA induces oxidative stress, lipoperoxidation and TNFalpha-mediated apoptosis in rat liver. Pharmacol Res. Acute administration of 3,4-methylenedioxymethamphetamine induces profound hyperthermia, blood-brain barrier disruption, brain edema formation, and cell injury. Ann N Y Acad Sci. Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Ther Drug Monit. Role of reactive oxygen species, glutathione and NF-kappaB in apoptosis induced by 3,4-methylenedioxymethamphetamine 'Ecstasy' on hepatic stellate cells. Biochem Pharmacol. Ecstasy toxicity: a comparison to methamphetamine and traumatic brain injury. J Addict Dis. Ecstasy induces apoptosis via 5-HT 2A -receptor stimulation in cortical neurons. Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals. Attenuation of 3,4-methylenedioxymethamphetamine MDMA, Ecstasy -induced rhabdomyolysis with alpha1- plus beta3-adrenoreceptor antagonists. Br J Pharmacol. Role of metabolites in MDMA ecstasy -induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells. Arch Toxicol. Tumor necrosis factor-alpha: regulation of renal function and blood pressure. Am J Physiol Renal Physiol. Methylenedioxymethamphetamine 'Ecstasy' -induced immunosuppression: a cause for concern? Connor TJ. Acute 3,4-methylenedioxymethamphetamine MDMA administration produces a rapid and sustained suppression of immune function in the rat. Acta Pharmacol Sin. Clin Immunol Immunopathol. Nephrol Ther. Acute kidney injury due to renal sarcoidosis during etanercept therapy: a case report and literature review. Intern Med. Membranous glomerulonephritis with the use of etanercept in ankylosing spondylitis. Ann Pharmacother. Development of glomerulonephritis during anti-TNF-alpha therapy for rheumatoid arthritis. Paroxetine inhibits acute effects of 3,4-methylenedioxymethamphetamine on the immune system in humans. J Pharmacol Exp Ther. Neutralization of tumor necrosis factor-alpha reduces renal fibrosis and hypertension in rats with renal failure. Am J Nephrol. TNF-alpha neutralization ameliorates obstruction-induced renal fibrosis and dysfunction. Simultaneous transforming growth factor beta-tumor necrosis factor activation and cross-talk cause aberrant remodeling response and myocardial fibrosis in Timp3-deficient heart. J Biol Chem. Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int. TGF-beta as a driver of fibrosis: physiological roles and therapeutic opportunities. J Pathol. Effects of transforming growth factor-beta, transforming growth factor-alpha, and other growth factors on renal proximal tubule cells. Laboratory investigation; a journal of technical methods and pathology. Localization of transforming growth factor-beta and latent transforming growth factor-beta binding protein in rat kidney. Expression of transforming growth factor-beta1 limits renal ischemia-reperfusion injury. TGF-beta1 release by volatile anesthetics mediates protection against renal proximal tubule cell necrosis. Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation. Amphetamines induce apoptosis and regulation of bcl-x splice variants in neocortical neurons. Differential expression of Bcl-2, Bcl-XL and p53 in colorectal cancer. J Gastroenterol Hepatol. Mod Pathol. Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models. Early loss of two renal grafts obtained from the same donor: role of ecstasy? We use cookies to provide you with the best possible experience. They also allow us to analyze user behavior in order to constantly improve the website for you. Navigate to IJ Pharmaceutical Research. IJ Pharmaceutical Research: Vol. Abstract The increasing recreational use of ecstasy MDMA poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear. Additionally, apoptosis and histopathological changes in renal tissue were examined. Both pro-apoptotic Bax and anti-apoptotic Bcl-xl gene expressions were significantly reduced, whereas Bcl-2 expression and apoptosis did not show significant changes. No structural alterations were observed in the renal tissues. Background The recreational drug ecstasy 3,4-methylenedioxymethamphetamine; MDMA is frequently misused by youths to enhance sexual excitement, intimacy, and energy levels for prolonged dancing sessions. Methods 3. Measurement of Kidney Function Blood samples were collected from animals under deep anesthesia. Table 1. Figure 1. Figure 2. Figure 3. Figure 4. References 1. This open-access article is available under the Creative Commons Attribution 4. Leave a comment here:. Cookie Setting We use cookies to provide you with the best possible experience.

Profiling of Ecstasy Tablets Seized in Iran

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Official websites use. Share sensitive information only on official, secure websites. To provide prevention programs and educate drug users DUs , the estimation of their population is necessary. This cross-sectional study was performed in summer on people selected through a multistage sampling method based on 14 region of the municipality of Isfahan. The data collection tool was a questionnaire that was previously used in Dr. Banshi's national plan without any changes. The Cronbach's alpha value of the questionnaire was 0. Using correction factors such as transparency of response and the ratio of social network size used in previous national studies, the number of people with high-risk behaviors was estimated. The results were analyzed through NSUM based on survey analysis. Among all kinds of DUs, men were the largest consumers. In both sexes, the prevalence of using opium and its nectar and illegal treatment with methadone and buprenorphine was higher in people of over 30 years of age, while the prevalence of consuming cannabis, ecstasy, tramadol, tobacco products, and stimulants was higher in the age group of 18 to 30 years. The results indicated that the prevalence of different DUs in Isfahan city, especially among men was higher than the reported average especially in young men of years of age. Since the prevalence of drug use varies based on the type of substance used among age groups, targeted preventive planning based on the type of drug used and age group is recommended. To estimate the population size of hidden groups such as drug users DUs is a challenge for researchers and health care practitioners as well as society. The amount and type of drug use differ throughout the world. In a review in , the prevalence of drug injection was estimated to be 0. Despite frequent efforts, for many reasons such as legal prohibition, stigma and discrimination, and lack of social acceptance in many countries of the world including Iran, these groups remain hidden and inaccessible, which makes it difficult to estimate their population size. There are 2 methods for estimating the population size of hidden groups, direct and indirect. Then, considering the social network size in the general population and some other indicators, the size of the hidden population is estimated. This method was used for the first time in to estimate the population size of people lost in the Mexican earthquake. The results of this study can be helpful to provincial policymakers and experts in estimating the extent, direction, and type of preventive activities required, the costs, and required manpower as well as to obtain economic and executive support. The sample size was estimated at about people considering the drug use prevalence of 0. Sampling was performed using non-random multistage sampling; 14 districts of Isfahan municipality were considered as stratified and, based on information obtained from the Health Deputy of Isfahan University of Medical Sciences, the sample size was determined proportionate to the size of each of these districts. Then, a list of crowded areas of the city as clusters was prepared and two clusters were randomly selected from within each district cluster. Within the clusters in the regular days of the week and at busy hours and , a passer-by was randomly selected once every 15 minutes. The study inclusion criteria included residing in Isfahan for at least 2 years, being 18 years of age and older, and having the mental ability to answer the questions. The exclusion criteria included completion of the questionnaire in the previous days and not willing to participate in the study. A standard questionnaire was used for data collection; its validity was evaluated by the experts in the Ministry of Health's Mental Health Bureau and its Cronbach's alpha was 0. Its reliability was evaluated in a pilot study and the kappa coefficient was estimated at 0. Each question is divided into 2 parts based on gender, male and female, and has three age groups: under 18, 18 to 30, and over In each section, if the respondents knew someone, they would report the number of people. The last part included demographic questions i. Four interviewers 2 women and 2 men were selected and trained through a roleplaying method Mr. Tavasoli, Mr. Torkan, Ms. Rezaei, and Ms. Talebi Por. The interviewers were assigned to different districts according to the timetable and based on the age-sex sampling table; they selected the passers-by and asked them for an informed consent. Ethical considerations: All questionnaires were completed anonymously and all information remained confidential. In order to persuade people to answer the questions, the interviewers tried to find a relatively secluded place. Due to the possibility of increasing unwillingness to take part in the study, verbal consent was obtained rather than a written one. In this study, the transparency coefficient varied from 0. The indicators of mean, standard deviation, frequency, and frequency percentage were used to data analysis and independent t-test and chi-squared test were used for data analysis. Thus, participants from each of the 14 regions were weighted based on the population of that area probability weight. The selected clusters from each area were also coded 1 to 4 as primary sampling units. The sex variable was considered as a stratum. A Finite population correlation was used to determine the odds equivalent in selecting the samples. The age of the participants ranged from 18 to 73 years. The mean age SD of the participants was In both genders, most of the participants had a diploma. Most of the participants were married. In all types of drugs, the prevalence of drug use was higher in men than women. Among men, cannabis was the third most used drug after tobacco, and opium and its nectar, while it was the second most used drug among women. In both sexes, the prevalence of opium and Shireh use and illegal treatment with methadone and buprenorphine among people over 30 years of age was higher than that in other age groups. Likewise, the prevalence of cannabis, ecstasy, hallucinogens, tramadol, tobacco, stimulants, and zolpidem among men of years of age was higher than that among the older and younger age groups. In addition, the prevalence of cannabis, stimulants, ecstasy, tramadol, zolpidem, and tobacco, legal treatment with methadone and buprenorphine, and injecting drug use was higher in women of 18 to 30 years of age. Furthermore, the prevalence of injecting drug use and legal treatment with methadone and buprenorphine was 0 in women under 18 years of age Table 2. The results indicated a high prevalence of use of different types of drugs in Isfahan. Tobacco use was had the highest prevalence, followed by opium and cannabis in men, and cannabis and opium among women, respectively. The highest prevalence of drug use in Isfahan was related to tobacco. In a study by Meysamie et al. Evidently, easy and low-cost access to different drug compounds and purity rates are other reasons for increase in drug use. The highest prevalence of the use of ecstasy pills in the city of Isfahan, which was first estimated by the NSUM, was in the sexually active age group of years. Prolonged duration of ejaculation may be one of the reasons for the use of ecstasy pills. The present study estimated the prevalence of zolpidem in Isfahan through NSUM for the first time, and the results indicated that the use of this hypnotic drug was much higher than the expected medical consumption, especially in people of 18 to 30 years of age. There have been reports of zolpidem addiction in athletes, physicians, and students, necessitating attention to this modern addiction and examination of the causes of young people's tendency to take this drug. The prevalence of injecting drug use in Isfahan was lower than estimations in the studies by Baneshi , 2 and Nikfarjam et al. Female sex workers, homosexual men, and injecting drug users IDUs are the 3 most vulnerable groups of a society at risk of developing HIV. In the present study, it was estimated that more than one-third of men who inject drugs had a constant behavioral addiction, while the prevalence of injecting drugs in women was 0. The results of this study indicated that the prevalence of different drug abuse types among men is more likely than women. According to the results of the present study, the highest prevalence of drug use among men and women was observed in the age groups of 18 to 30 and over 30 years, which is in line with the study by Nikfarjam et al. Evidently, it is also important to pay attention to children of less than 18 years of age. A study by Ranjbaran et al. One of the limitations of the present study was the impossibility of household-based random sampling due to the sensitivity of the considered subject, i. Therefore, through multistage sampling and random selection of people at specified intervals, we attempted to approach the sampling systematically. Second, there is likely reporting bias because some refusing people to participate in the study may recognize many DUs in their social network. However, due to the inability to track people, it was not possible to check and compare the characteristics of DUs with those participating in the study. Third, the size of the social network of DUs is smaller than that of the general population, 7 which will cause underestimation. Moreover, the size of the social network of the general population may vary by gender and age, and even by various regions of the country. However, due to the lack of accurate information in this regard, it was decided to use the indices used in earlier studies in Iran. The results of the present study showed that the prevalence of drug use in Isfahan city, especially in men, is significant and in some cases even higher than the average reported in other studies in the country. Since the prevalence of drug use varies by the type of substance used in the age groups of and over 30 years, targeted preventive planning by type of drug and age group is recommended. The authors would like to thank all those who helped us with this project, including the interviewers. They would also like to thank the Social Deputy of the Police Command of Isfahan who assisted in the performance of our citywide survey, Ayandeh Pazhouhi Center associated with Kerman University of Medical Sciences for providing the questionnaires and scientific advice, and Dr. Marjan Meshkati and Dr. Ramin Radfar for their scientific and practical advice. Collected data, analysis, and wrote the original draft: MAJ; statistics advisor- contributed to analysis: MB; contributed to analysis, review, and editing: MN. As a library, NLM provides access to scientific literature. Addict Health. Find articles by Meysam Abshenas-Jami. Find articles by Mohamadreza Baneshi. Find articles by Maryam Nasirian. Received May 17; Accepted Jul Open in a new tab. Conflicts of Interest The Authors have no conflict of interest. Similar articles. Add to Collections. Create a new collection. 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Buy Ecstasy online in Tehran