BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to...BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to result in neuroprotection. OBJECTIVE： To investigate the effects of MDMA on hippocampal neuronal viability, caspase-3 activity, and mRNA expression of the N-methyI-D-aspartate （NMDA） receptor 2B （NR2B） subunit. DESIGN, TIME AND SETTING： A cytological, in vitro experiment was performed at the Department of Anatomy, School of Medicine, and Department of Toxicology-Pharmacology, Faculty of Pharmacy Tehran University of Medical Sciences in 2008. MATERIALS： MDMA was extracted from ecstasy tablets, which were kindly supplied by the Pharmacology-Toxicology Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran. METHODS： Hippocampal neurons were isolated from Wistar rats at gestational day 18. Following primary culture, hippocampal neuronal viability was detected by MTT assay. Varying concentrations of MDMA （100-5 000 μmol/L） were used to determine lethal concentration 50 （LC50）, which was around 1 500 μmol/L. Five concentrations of MDMA below 1 500 μmol/L （100, 200, 400, 800, and 1 050 μmol/L） were used for the remaining experiments. After 24 hours of MDMA treatment, NR2B mRNA expression was detected by RT-PCR, and caspase-3 relative activity was determined by colorimetric assay. MAIN OUTCOME MEASURES： Hippocampal neuronal viability, caspase-3 activity, and NR2B mRNA expression. RESULTS： MDMA-induced neurotoxicity in hippocampal neuronal cultures was dose-dependent. In high concentrations （1 000-5 000μmol/L） of MDMA, neuronal viability was decreased. However, with a 500 μmol/L dose of MDMA, neuronal viability was significantly increased （P 〈 0.01）. Low concentrations of MDMA （200 and 400μmol/L） significantly decreased caspase-3 activity （P 〈 0.01）, whereas high concentrations of MDMA significantly increased caspase-3 acti展开更多
In recent years, the Internet has received increasing recognition as an effective means of facilitating public health interventions. In particular, delivering prevention for substance use to school students via the In...In recent years, the Internet has received increasing recognition as an effective means of facilitating public health interventions. In particular, delivering prevention for substance use to school students via the Internet appears to be an area of great potential. The Climate Schools: Ecstasy and Emerging Drugs Module, a school-based prevention program, facilitated by the Internet, was developed to address the use of ecstasy and new and emerging drugs (Emerging Psychoactive Substances or Novel Psychoactive Substances). This four-lesson course was designed to be delivered to Australian adolescents (aged 15 to 16 years) during their standard health education classes at school, and is based on a harm-minimisation and social influence approach. The program was developed in response to the important public health challenge of new and emerging drugs as well as to address the prevention of ecstasy use among young people. To our knowledge, this will be the first school- and Internet-based prevention program specifically targeting these substances. This paper describes the process involved in developing this new Internet-based substance use prevention program.展开更多
The synthetic hallucinogen 3,4-methylenedioxymet hamphetamine （MDMA） is the main psychoactive constituent of the popular recreational drug ＂ecstasy.＂ Whether its neurotoxic effects are fully reversible is unknown....The synthetic hallucinogen 3,4-methylenedioxymet hamphetamine （MDMA） is the main psychoactive constituent of the popular recreational drug ＂ecstasy.＂ Whether its neurotoxic effects are fully reversible is unknown. Here we report a patient with protracted syndrome induced by ecstasy.展开更多
A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown abou...A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown about the neurobiological consequences of Foxy use. In addition, research into the long-term neuropsychological repercussions associated with these two compounds remains incomplete. The goal of the present research was to explore the effects of MDMA or Foxy on cognitive processes associated with adolescent exposure considered over much of the lifespan. Here we investigated whether the reported effects following adolescent exposure resolved in early adulthood or continued throughout life. The protocol involved repeated doses of either MDMA or Foxy during the period defined as mid-adolescence (postnatal days 34 - 46) in rats, followed by the use of four series of learning and memory tasks repeated at different points in the rodent lifespan. At four time points in adulthood, the animals were trained and tested on a on a series of spatial and non-spatial memory tasks designed to assess the impact and severity of Foxy and MDMA. Oddly, MDMA-treated rats were impaired on a step down passive avoidance task. The performance of the drug-treated rats was markedly inferior to that of the control animals on more demanding water maze tasks, with some results suggesting a lack of flexibility in adapting to changing task demands. MDMA rats were the most impaired. While some persistent cognitive deficits were found, no significant group differences in serotonin or dopamine levels were found in any of the measured regions of the brain changes, cortical or subcortical. These results provide evidence for compromised neurocognition that continues long after drug exposure in the absence of any discernable changes in neurotransmitter levels. Several possible physiological and neurochemical mechanisms associated with these compounds requiring further study are also outlined.展开更多
基金Supported by: the Deputy of Research in Tehran University of Medical Sciences
文摘BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to result in neuroprotection. OBJECTIVE： To investigate the effects of MDMA on hippocampal neuronal viability, caspase-3 activity, and mRNA expression of the N-methyI-D-aspartate （NMDA） receptor 2B （NR2B） subunit. DESIGN, TIME AND SETTING： A cytological, in vitro experiment was performed at the Department of Anatomy, School of Medicine, and Department of Toxicology-Pharmacology, Faculty of Pharmacy Tehran University of Medical Sciences in 2008. MATERIALS： MDMA was extracted from ecstasy tablets, which were kindly supplied by the Pharmacology-Toxicology Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran. METHODS： Hippocampal neurons were isolated from Wistar rats at gestational day 18. Following primary culture, hippocampal neuronal viability was detected by MTT assay. Varying concentrations of MDMA （100-5 000 μmol/L） were used to determine lethal concentration 50 （LC50）, which was around 1 500 μmol/L. Five concentrations of MDMA below 1 500 μmol/L （100, 200, 400, 800, and 1 050 μmol/L） were used for the remaining experiments. After 24 hours of MDMA treatment, NR2B mRNA expression was detected by RT-PCR, and caspase-3 relative activity was determined by colorimetric assay. MAIN OUTCOME MEASURES： Hippocampal neuronal viability, caspase-3 activity, and NR2B mRNA expression. RESULTS： MDMA-induced neurotoxicity in hippocampal neuronal cultures was dose-dependent. In high concentrations （1 000-5 000μmol/L） of MDMA, neuronal viability was decreased. However, with a 500 μmol/L dose of MDMA, neuronal viability was significantly increased （P 〈 0.01）. Low concentrations of MDMA （200 and 400μmol/L） significantly decreased caspase-3 activity （P 〈 0.01）, whereas high concentrations of MDMA significantly increased caspase-3 acti
文摘In recent years, the Internet has received increasing recognition as an effective means of facilitating public health interventions. In particular, delivering prevention for substance use to school students via the Internet appears to be an area of great potential. The Climate Schools: Ecstasy and Emerging Drugs Module, a school-based prevention program, facilitated by the Internet, was developed to address the use of ecstasy and new and emerging drugs (Emerging Psychoactive Substances or Novel Psychoactive Substances). This four-lesson course was designed to be delivered to Australian adolescents (aged 15 to 16 years) during their standard health education classes at school, and is based on a harm-minimisation and social influence approach. The program was developed in response to the important public health challenge of new and emerging drugs as well as to address the prevention of ecstasy use among young people. To our knowledge, this will be the first school- and Internet-based prevention program specifically targeting these substances. This paper describes the process involved in developing this new Internet-based substance use prevention program.
基金This study was supported by the grants from the Science and Technology Bureau of Zhejiang Province Key Science and Technology Innovation Project （No. 2010R50049）, the Education Bureau of Zhejiang Province Grants （No. Y200908102 and No. Y201120182）, the Department of Health Foundation of Zhejiang Province（No. 2013RCB005）, Natural Science Foundation of China （No. 81301158）.Acknowledgements： We are very grateful to the patient for this study.
文摘The synthetic hallucinogen 3,4-methylenedioxymet hamphetamine （MDMA） is the main psychoactive constituent of the popular recreational drug ＂ecstasy.＂ Whether its neurotoxic effects are fully reversible is unknown. Here we report a patient with protracted syndrome induced by ecstasy.
文摘A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown about the neurobiological consequences of Foxy use. In addition, research into the long-term neuropsychological repercussions associated with these two compounds remains incomplete. The goal of the present research was to explore the effects of MDMA or Foxy on cognitive processes associated with adolescent exposure considered over much of the lifespan. Here we investigated whether the reported effects following adolescent exposure resolved in early adulthood or continued throughout life. The protocol involved repeated doses of either MDMA or Foxy during the period defined as mid-adolescence (postnatal days 34 - 46) in rats, followed by the use of four series of learning and memory tasks repeated at different points in the rodent lifespan. At four time points in adulthood, the animals were trained and tested on a on a series of spatial and non-spatial memory tasks designed to assess the impact and severity of Foxy and MDMA. Oddly, MDMA-treated rats were impaired on a step down passive avoidance task. The performance of the drug-treated rats was markedly inferior to that of the control animals on more demanding water maze tasks, with some results suggesting a lack of flexibility in adapting to changing task demands. MDMA rats were the most impaired. While some persistent cognitive deficits were found, no significant group differences in serotonin or dopamine levels were found in any of the measured regions of the brain changes, cortical or subcortical. These results provide evidence for compromised neurocognition that continues long after drug exposure in the absence of any discernable changes in neurotransmitter levels. Several possible physiological and neurochemical mechanisms associated with these compounds requiring further study are also outlined.
