Category: Ecstasy

A new study conducted by researchers at Children's Hospital & Research Center Oakland shows that a century-old drug, methylene blue, may be able to slow or even cure Alzheimer's and Parkinson's disease. Used at a very low concentration – about the equivalent of a few raindrops in four Olympic-sized swimming pools of water – the drug slows cellular aging and enhances mitochondrial function, potentially allowing those with the diseases to live longer, healthier lives.

A paper on the methylene blue study, conducted by Hani Atamna, PhD, and a his team at Children's, was published in the March 2008 issue of the Federation of American Societies for Experimental Biology (FASEB) Journal. Dr. Atamna's research found that methylene blue can prevent or slow the decline of mitochondrial function, specifically an important enzyme called complex IV. Because mitochondria are the principal suppliers of energy to all animal and human cells, their healthy function is critical.

"The results are very encouraging," said Dr. Atamna. "We'd eventually like to try to prevent the physical and cognitive decline associated with aging, with a focus on people with Alzheimer's disease. One of the key aspects of Alzheimer's disease is mitochondrial dysfunction, specifically complex IV dysfunction, which methylene blue improves. Our findings indicate that methylene blue, by enhancing mitochondrial function, expands the mitochondrial reserve of the brain. Adequate mitochondrial reserve is essential for preventing age-related disorders such as Alzheimer's disease."

Also impressed is one of Dr. Atamna's co-authors, Bruce Ames, PhD, a senior scientist at Children's and world-renowned expert in nutrition and aging. "What we potentially have is a wonder drug." said Dr. Ames. "To find that such a common and inexpensive drug can be used to increase and prolong the quality of life by treating such serious diseases is truly exciting."

Methylene blue, first discovered in 1891, is now used to treat methemoglobinemia, a blood disorder. But because high concentrations of methylene blue were known to damage the brain, no one thought to experiment with low concentrations. Also, drugs such as methylene blue do not easily reach the brain.

Dr. Atamna's research is the first to show that low concentrations of the drug have the ability to slow cellular aging in cultured cells in the laboratory and in live mice. He believes methylene blue has the potential to become another commonplace low-cost treatment like aspirin, prescribed as a blood thinner for people with heart disorders.

Dr. Atamna's research, funded by the Bruce and Giovanna Ames Foundation, was conducted at Children's research institute and will continue when Dr. Atamna assumes a position as a professor of Neuroscience at The Commonwealth Medical College in Pennsylvania.

Journal Reference:

1. Atamna et al. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. The FASEB Journal, 2007; 22 (3): 703 DOI: 10.1096/fj.07-9610com

New guidelines have been written which will assist nightclub staff in deciding whether to call ambulances for unwell clubbers. At present, there is a worry that inappropriate management has lead to clubbers only being referred to hospital after significant problems have occurred — leading to increased risk of injury and death.

The proposed guidelines were co-written by medics, police officers and bar owners and are published in BioMed Central's open access journal Substance Abuse Treatment, Prevention, and Policy. Many clubs have designated 'club medic' rooms where individuals with recreational drug toxicity can be assessed and managed.

According to the study's coordinator and consultant physician and clinical toxicologist Dr. David Wood from Guy's and St Thomas' Poisons Unit at Guy's and St Thomas' NHS Foundation Trust, "In the past, club owners and promoters have been reluctant to call an ambulance for clubbers with recreational drug toxicity because of concerns that this could affect their license".

Dr. Wood describes his research as aiming "to work with key stakeholders in the pre-hospital setting to develop strategies to improve pre-hospital care for these clubbers. This includes developing ambulance-transfer guidelines and the training of 'club medic' staff".

The research team visited club medic rooms in various London nightclubs to assess the resources available and the medical training of the club medic staff.

The guidelines were then developed to advise club medics to call an ambulance if the patient meets any of ten defined criteria, including: being unresponsive; chest pain similar to a heart attack; or high blood pressure/heart rate/temperature. 'If in doubt, call an ambulance' is the last point in the guide. The guidelines were audited and revised using feedback from club medic staff. The authors also ran training in the use of the guidelines and in the management of recreational drug toxicity.

Previous studies by these authors have found the main drugs associated with ill health amongst clubbers in the area studied were GHB and stimulants such as ecstasy and cocaine. Typical effects of GHB include significant depression of central nervous function and respiration and effects seen with stimulant use include high temperature, heart-rate, blood pressure.

Dr. Wood added: "The guidelines we have described are designed to ensure that individuals with significant toxicity in these categories are easily identified and that an ambulance is called so that they receive appropriate and timely assessment and management in a hospital environment."

Journal Reference:

1. David M Wood, Shaun L Greene, Graham Alldus, Denise Huggett, Michelle Nicolaou, Kerry Chapman, Fiona Moore, Kim Heather, Nicola Drake and Paul I Dargan. Improvement in the pre-hospital care of recreational drug users through the development of club specific ambulance referral guidelines. Substance Abuse Treatment, Prevention, and Policy, 

 A University of Adelaide study has revealed that effects of the drug ecstasy are compounded when taken in warm environments.

Preclinical research undertaken by Pharmacology PhD student Emily Jaehne shows that ecstasy deaths, which are invariably related to elevated body temperature, may be related to drug users’ failure to recognise their body is abnormally hot.

“The fact that these drugs are often taken in warm nightclubs and at rave parties increases the risk of long- term changes in brain function, or even death,” Emily says.

The 25-year-old student has spent the past three years investigating how ecstasy can increase body temperature, and to understand how drug users respond when this happens.

“Our bodies usually maintain a constant temperature of 37 degrees Celsius, but in some cases ecstasy can elevate this by up to five degrees, leading to severe brain damage.”

Ecstasy is one of the most popular illicit drugs in Australia, according to the Australian Institute of Health and Welfare, with almost 24% of the population aged between 20-29 years admitting to using it in their lifetime. Statistics also show that Australia has one of the highest per capita uses of ecstasy in the world.

“Ecstasy is more readily available here than in the U.S. and Europe and more widely used than heroin or cocaine in Australia. It is crucial, therefore, that we make people more aware of the dangers associated with this drug,” Emily says. “When ecstasy users are taking the drug in nightclubs they tend to blame the surroundings for their elevated body temperature and just ignore the warning signs. That can be fatal.”

Teenagers and young adults across Europe drink and take drugs as part of deliberate sexual strategies. New findings reveal that a third of 16-35 year old males and a quarter of females surveyed are drinking alcohol to increase their chances of sex, while cocaine, ecstasy and cannabis are intentionally used to enhance sexual arousal or prolong sex.

The study was conducted by researchers in public health and social sciences from across Europe. More than 1300 people aged between 16 and 35 and who routinely socialise in nightlife settings completed anonymous questionnaires.

Virtually all of the survey participants had drunk alcohol with most having had their first drink when 14 or 15 years old. Three quarters of the respondents had tried or used cannabis, while around 30 percent had at least tried ecstasy or cocaine.

Overall, alcohol was most likely to be used to facilitate a sexual encounter, while cocaine and cannabis were more likely to be utilised to enhance sexual sensations and arousal.

Despite these perceived sexual "benefits", drunkenness and drug use were strongly associated with an increase in risk taking behaviour and feeling regretful about having sex while under the influence of alcohol or drugs. Thus, participants who had been drunk in the past four weeks were more likely to have had five or more partners, sex without a condom and to have regretted sex after drink or drugs in the past 12 months. Cannabis, cocaine or ecstasy use was linked to similar consequences.

"Trends in recent decades have resulted in recreational drug use and binge drinking becoming routine features of European nightlife," says lead author Mark Bellis, from Liverpool John Moores University. "Millions of young Europeans now take drugs and drink in ways which alter their sexual decisions and increase their chances of unsafe sex or sex that is later regretted. Yet despite the negative consequences, we found many are deliberately taking these substances to achieve quite specific sexual effects."

Individuals were significantly more likely to have had sex under 16 years if they had used alcohol, cannabis, cocaine or ecstasy before that age. Girls in particular were as much as four times as likely to have had sex before the age of 16 if they drank alcohol or used cannabis under 16.

"Sexual activity accompanied by substance use is not just incidental, but often sexually motivated," says co-author, consultant psychiatrist Amador Calafat. "Interventions addressing sexual health are often developed, managed and implemented independently from those addressing substance use, and vice versa. However, young people often see alcohol, drugs and sex all as part of the same social experience and addressing these issues requires an equally joined up approach. "

Journal Reference:

1. Sexual uses of alcohol and drugs and the associated health risks: a cross sectional study of young people in nine European cities Mark A Bellis, Karen Hughes, Amador Calafat, Montse Juan, Anna Ramon, Jose A Rodriguez, Fernando Mendes, Susanne Schnitzer and Penny Phillips-Howard BMC Public Health

 — What do suffering a traumatic brain injury and using club drugs have in common? University of Florida researchers say both may trigger a similar chemical chain reaction in the brain, leading to cell death, memory loss and potentially irreversible brain damage.

A series of studies at UF over the past five years has shown using the popular club drug Ecstasy, also called MDMA, and other forms of methamphetamine lead to the same type of brain changes, cell loss and protein fluctuations in the brain that occur after a person endures a sharp blow to the head, according to recentl findings.

"Using methamphetamine is like inflicting a traumatic brain injury on yourself," said Firas Kobeissy, a postdoctoral associate in the College of Medicine department of psychiatry. "We found that a lot of brain cells are being injured by these drugs. That's alarming to society now. People don't seem to take club drugs as seriously as drugs such as heroin or cocaine."

Working with UF researchers Dr. Mark Gold, chief of the division of addiction medicine at UF's McKnight Brain Institute and one of the country's leading experts on addiction medicine, and Kevin Wang, director of the UF Center for Neuroproteomics and Biomarkers Research, Kobeissy compared what happened in the brains of rats given large doses of methamphetamine with what happened to those that had suffered a traumatic brain injury.

The group's research has already shown how traumatic brain injury affects brain cells in rats. They found similar damage in the rats exposed to methamphetamine. In the brain, club drugs set off a chain of events that injures brain cells. The drugs seem to damage certain proteins in the brain, which causes protein levels to fluctuate. When proteins are damaged, brain cells could die. In addition, as some proteins change under the influence of methamphetamine, they also begin to cause inflammation in the brain, which can be deadly, Kobeissy said.

Kobeissy and other researchers in Gold's lab are using novel protein analysis methods to understand how drug abuse alters the brain. Looking specifically at proteins in the rat cortex, UF researchers discovered that about 12 percent of the proteins in this region of the brain showed the same kinds of changes after either methamphetamine use or traumatic brain injury. There are about 30,000 proteins in the brain so such a significant parallel indicates that a similar mechanism is at work after both traumatic brain injury and methamphetamine abuse, Kobeissy said.

"Sometimes people go to the clubs and take three tablets of Ecstasy or speed," Kobeissy said. "That may be a toxic dose for them. Toxic effects can be seen for methamphetamine, Ecstasy and traumatic injury in different areas of the brain."

About 1.3 million people over the age of 12 reported using methamphetamine in the previous month, according to the 2006 National Survey on Drug Use and Health. In 2004, more than 12 million Americans reported having tried the drug, the survey's findings show.

People often think the effects of drugs of abuse wear off in the body the same way common medications do, but that may not be the case, Gold said.

"These data and the previous four years of data suggest some drugs, especially methamphetamine, cause changes that are not readily reversible," Gold said. "Future research is necessary for us to determine when or if methamphetamine-related brain changes reverse themselves."

Gold and Dennis Steindler, director of UF's McKnight Brain Institute and an expert on stem cells, are planning studies to find out if stem cells can be applied to repair drug-related brain damage.

UF researchers are also trying to uncover all the various ways drugs damage and kill brain cells. During their protein analysis, researchers discovered that oxidation was damaging some proteins, throwing the molecules chemically off balance.

"When proteins are oxidized they are not functional," Kobeissy said. "When proteins are not working, the cell cannot function."

Neurologist Dr. Jean Lud Cadet, chief of the molecular neuropsychiatry branch of the National Institute on Drug Abuse, said analyzing proteins is important to understanding how drugs such as methamphetamine affect the brain.

"I think saying the results of methamphetamine abuse are comparable to the results of a traumatic brain injury is a new idea," Cadet said. "I agree with (the findings). Our own work shows that methamphetamine is pretty toxic to the brains of animals. In humans, imaging studies of patients who use methamphetamine chronically show abnormalities in the brain.

"Abuse of methamphetamine is very dangerous."

This research was presented at a Society for Neuroscience conference held recently in San Diego.

NewsPsychology (Aug. 7, 2007) — There exists a direct relationship between the consumption of MDMA, or Ecstasy, at a high ambient temperature and an increase in the neural damage which this drug provokes. This was the conclusion of the research carried out by Beatriz Goñi at the School of Pharmacy of the University of Navarra.

These results form part of her doctoral dissertation, entitled “A Study of the Neurotoxicity Mechanism of 3.4-methylenedioxy-N-methylamphetamine (MDMA or ‘Ecstasy’) after its Administration in Rats: New Responses to Old Questions.”

By means of this study, the researcher was able to relate for the first time the body temperature of the user with a higher metabolism of this substance. There are two factors which, when they co-occurcan produce malignant hyperthermia, a disorder which can sometimes be fatal.

In order to come to this conclusion, the Pamplonan pharmaceutical specialist administered the drug to rats at ambient temperatures of 15, 21 and 30 degrees centigrade. After performing the pertinent analyses, she demonstrated that metabolism of Ecstasy is accelerated by higher ambient temperatures at the time of administration. In addition, higher ambient temperatures also increase, in the same proportion, the neurochemical deficit that affects the brains of the users of this drug.

Higher Risk in Closed Establishments

According to Beatriz Goñi, the author of the study undertaken at the University of Navarra, the discoveries of this research project acquire more relevance precisely because Ecstasy is typically taken in closed environments, with lots of people and poor ventilation, due to which factors the temperature tends to be quite high.

In addition, she notes that the neural damage provoked by this substance, and which originally was only observed in rats, has already been demonstrated in humans, who appear to suffer severe damage to the serotoninergenic neurons, which are involved in processes as basic as sleep, appetite and mood regulation.

Finally, the pharmaceutical specialist noted that the damage caused by the consumption of MDMA is dependent upon its being metabolized after to its ingestion, since if it were administered directly to the brain, neuronal damage would not occur.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by Basque Research.

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Even low doses of Ecstasy may be associated with a decline in language-related memory, according to a report in the June issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

Ecstasy is an illicit recreational drug popular among young people, according to background information in the article. Research in both humans and animals suggests that the drug can harm the brain. Ecstasy may damage nerve cells that respond to the hormone serotonin, which is involved in mood, thinking, learning and memory.

Thelma Schilt, M.Sc., of the Academic Medical Center of the University of Amsterdam, the Netherlands, and colleagues recruited 188 volunteers (average age 22) who had not used Ecstasy but reported that they were likely to try it soon. Within three years of the initial evaluations, which took place between April 2002 and April 2004, 58 individuals began using Ecstasy.

They were compared with 60 individuals who had the same age, sex and intelligence score but who did not use Ecstasy during the follow-up period. All participants took tests that assessed various types of memory–including attention, verbal memory for words and language, and visual memory for images–at the beginning and end of the study. Verbal memory was tested by memorizing a series of 15 words and repeating them immediately and again 20 minutes later.

"At the initial examination, there were no statistically significant differences in any of the neuropsychological test scores between persistent Ecstasy-naïve subjects and future Ecstasy users," the authors write. "However, at follow-up, change scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-naïve subjects. There were no significant differences on other test scores."

In contrast to other studies, which have suggested that Ecstasy affects women more than men, there was no difference in the drug's effect between the sexes. Overall, test scores remained within the normal range for the general population.

The fact that Ecstasy appeared to affect only verbal memory points to specific brain areas and chemicals that may be affected by the drug, the authors note. "The main underlying factor seems to be a depletion of serotonin in Ecstasy users, a depletion that might be reversible," they write. "Serotonin is involved in several cognitive functions but might be especially relevant to learning and memory."

"In conclusion, our data indicate that low doses of Ecstasy are associated with decreased verbal memory function, which is suggestive for Ecstasy-induced neurotoxicity," the authors conclude. "Further research on the long-term effects of Ecstasy as well as on the possibility of additive effects of Ecstasy use on aging of the brain is needed."

New research from the University of Cincinnati (UC) suggests that the widely abused club drug "ecstasy," or MDMA, can increase the survival of dopamine cells in the brain during fetal development.

Because these cells are critical in the regulation of voluntary movement, the findings, the researchers say, may lead to better therapies for neurological diseases like Parkinson's.

Led by Jack Lipton, PhD, professor of psychiatry, the study was presented today as an abstract at the Society for Neuroscience annual meeting in Atlanta.

"We're certainly not suggesting that this drug be used to treat diseases," said Lipton. "But finding new methods to enhance the survival of dopamine neurons is critical in developing new drugs for diseases such as Parkinson's.

"While MDMA itself isn't likely to be an appropriate therapy for neurodegenerative diseases, it may provide insights for developing new drugs that have similar properties.

"It's exciting to learn that an abused drug may have potential use for developing new therapeutics," he added. "It really makes you rethink your own preconceptions."

Dopamine is a neurotransmitter that has been found to regulate movement, balance, emotion and motivation, and it also affects pleasurable feelings in the brain. Researchers know that a loss of dopamine cells in the brain leads to the development of Parkinson's disease and possibly other movement disorders. Preventing dopamine cells from dying or aiding in the replacement of those cells is key to finding lasting therapies.

Lipton, director of the developmental neuroscience division in UC's psychiatry department, studies the long-term effects of abused drugs on the developing central nervous system. He noticed, during previous laboratory studies in rats, that prenatal exposure to MDMA increased growth of dopamine cells in the brain. His team then decided to study exposure to MDMA in cultured embryonic cells–where they confirmed that this drug was in fact increasing dopamine cell survival.

The findings, Lipton says, aren't consistent with what is known about adult brains, where MDMA has been shown to cause depletion of neurotransmitters–like dopamine–and has been linked to decreased brain activity.

MDMA, chemically known as methylenedioxymethamphetamine and sold and used illegally as "ecstasy," is a synthetic stimulant that prompts the secretion of large amounts of the neurotransmitters serotonin, dopamine and norepinephrine in the brain. This secretion can lead to prolonged periods of activity, hallucinations and euphoria. Before the United States banned it in 1985, MDMA was tested as a possible adjunct in psychotherapy. In 2001, the FDA agreed to allow MDMA to be tested as a possible treatment for post-traumatic stress disorder.

Coauthors include Nicholas Campbell, Timothy Collier, PhD, Katrina Paumier, Caryl Sortwell, PhD, and Emeline Tolod.

The study was funded by the National Institute on Drug Abuse of the National Institutes of Health.

University of Toronto researchers have discovered a new mechanism for the neurodegenerative effects of amphetamines. These drugs are converted in the brain into free radicals, highly reactive molecules that cause neurodegenerative brain damage and whose effects manifest and linger long after the amphetamine has left the body.

"The question of whether amphetamines like ecstasy (MDMA) or methamphetamine (METH) cause neurodegeneration in humans is one of the most controversial areas in science today," says Professor Peter Wells of the Leslie Dan Faculty of Pharmacy, lead author of the study that appears in the April issue of the Journal of the Federation of American Societies for Experimental Biology (FASEB Journal). "The short-term effects of these drugs — hypothermia, electrolyte imbalances and an elevated risk of heart attack — are well understood, but not their long-term consequences."

Wells and doctoral students Winnie Jeng, Annmarie Ramkissoon and Toufan Parman theorized that prostaglandin H synthase (PHS) — an enzyme that synthesizes a range of hormones throughout mammalian life — is the catalyst that transforms amphetamines into free radical products that react with oxygen in the body to enhance the formation of highly toxic reactive oxygen species. These toxic forms of oxygen are implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's because of the increased oxidative stress they place on the body, resulting in irreversible damage to DNA, proteins and lipid membranes. Organs such as the brain, which lack abundant antioxidant protection, are particularly vulnerable to oxidative stress.

To approximate an acute human exposure, the researchers administered four doses of either MDA (the major metabolite of ecstasy) or METH at two-hour intervals to young adult mice. In the case of MDA, before the first drug injection an additional group of mice was given a single dose of aspirin (acetylsalicylic acid), which is known to inhibit PHS and block its ability to convert drugs to free radical products. Over a six-month period, following the single day's treatment of MDA or METH, the mice were observed and had their motor co-ordination tested by walking on a rotating rod. Normally, mice balance easily on the rods for extended periods. Within two weeks of the last treatment, all the mice given MDA or METH without aspirin had trouble with this task and remained disabled for at least six months. These mice also exhibited enhanced molecular damage to the DNA in their brains and a loss of nerve terminals that remained for at least one week after exposure to MDA or METH. The mice pretreated with aspirin had less molecular damage to their DNA and fewer motor disabilities, suggesting that the neurodegenerative effects of MDA are dependent upon its conversion by PHS into a reactive free radical product.

"Our findings reveal how exquisitely susceptible brains are to this kind of damage, at least in mice," Wells says. "The long-term negative effects in the mice treated with MDA or METH all resulted from a single day's dosage that approximated the higher range of human exposures."

Although the team's findings cannot be extrapolated to humans without further study, Wells believes they do suggest a novel mechanism through which amphetamines may contribute to neurodegeneration.

"Our hypothesis about PHS-catalyzed conversation may also be relevant to the neurodegenerative risks associated with aging," he says. "Preliminary results from other studies suggest that PHS may convert other compounds in our brains into free radicals, and there is some evidence in the clinical literature that suggests patients who take high doses of PHS-inhibiting drugs such as aspirin may experience less neurodegeneration. The potential of substances like aspirin to prevent neurodegenerative damage merits more examination, particularly among people who take it chronically for pain."

This study was funded by the Canadian Institutes of Health Research, with support from the National Institute on Drug Abuse (U.S.A) and Health Canada's Healthy Environments and Consumer Safety Branch.

Loud music prolongs the effects of taking ecstasy for up to five days. A study published today in the open access journal BMC Neuroscience shows that the reduction in rats' brain activity induced by 3,4 -Methylenedioxymethamphetamine (MDMA or ecstasy) lasts long after administration of the drug — up to five days — if loud music is played to them simultaneously. The effects wear off within a day when no music is played.

Michelangelo Iannone from the Institute of Neurological Science, Italy, and colleagues from University Magna Graecia in Catanzaro, Italy, injected rats with a low dose (3mg/kg) or a high dose (6mg/kg) of MDMA or, in the control group, with saline. The rats were either left without acoustic stimulation or exposed to white noise – sound at a stable frequency that is used in many types of electronic music. The sound was played at 95dB, the maximum noise intensity permitted in nightclubs by Italian law. The electrocortical activity (EcoG spectrum) of the rats was monitored, using electrodes placed on their skull, from 60 minutes before administration of the drug and start of the music, to up to five days after the music was stopped.

Iannone et al.'s results show that low-dose MDMA did not modify the brain activity of the rats compared with saline, as long as no music was played. However, the EcoG total spectrum of the rats given a low dose of MDMA significantly decreased once loud music was played. The EcoG spectrum of rats in the control group was not modified by loud music. High-dose MDMA induced a reduction in brain activity, compared with both saline and low-dose MDMA. This reduction was enhanced once the loud music was turned on and lasted for up to five days after administration of the drug. In rats that had been given a high dose of MDMA but had not been exposed to music, brain activity returned to normal one day after administration of the drug.

Article:
Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats
Michelangelo Iannone, Immacolata Vecchio, Stefania Bulotta, Donatella Paolino, Maria Cristina Zito, Santo Gratteri, Francesco S Costanzo and Domenicantonio Rotiroti
BMC Neuroscience 2006, 7:12 (16 February 2006) doi:10.1186/1471-2202-7-12