Long-term users of ecstasy risk structural brain damage

April 15, 2011

Science Daily/BMJ-British Medical Journal

Long term users of the popular recreational drug ecstasy (MDMA) risk structural brain damage, suggests preliminary research published online in the Journal of Neurology, Neurosurgery and Psychiatry.

Other research has suggested that people who use ecstasy develop significant memory problems, so the Dutch researchers wanted to find out if there was any clinical evidence of structural changes in the brain to back this up.

They focused on the hippocampus, which is the area of the brain responsible for long term memory.

They measured the volume of the hippocampus using MRI scans in 10 young men in their mid 20s who were long term users of ecstasy and seven of their healthy peers in their early 20s with no history of ecstasy use.

Although the ecstasy group had used more amphetamine and cocaine than their peers, both sets of young men had used similar amounts of recreational drugs, bar ecstasy, and drank alcohol regularly.

The ecstasy group had not been using on average for more than two months before the start of the study, but had taken an average of 281 ecstasy tablets over the preceding six and a half years.

The MRI scans showed that hippocampal volume in this group was 10.5% smaller than that of their peers, and the overall proportion of grey matter was on average 4.6% lower, after adjusting for total brain volume.

This indicates that the effects of ecstasy may not be restricted to the hippocampus alone, say the authors

"Taken together, these data provide preliminary evidence suggesting that ecstasy users may be prone to incurring hippocampal damage, following chronic use of this drug," they write.

They add that their findings echo those of other researchers who have reported acute swelling and subsequent atrophy of hippocampal tissue in long term ecstasy users.

And they point out: "Hippocampal atrophy is a hallmark for diseases of progressive cognitive impairment in older patients, such as Alzheimer's disease."

https://www.sciencedaily.com/releases/2011/04/110406192435.htm

New study finds no cognitive impairment among ecstasy users

February 16, 2011

Science Daily/Wiley-Blackwell

In contrast to many prior studies, ecstasy users in a new study showed no signs of cognitive impairment attributable to drug use: ecstasy use did not decrease mental ability.

The drug known as ecstasy has been used by 12 million people in the United States alone and millions more worldwide. Past research has suggested that ecstasy users perform worse than nonusers on some tests of mental ability. But there are concerns that the methods used to conduct that research were flawed, and the experiments overstated the cognitive differences between ecstasy users and nonusers.

In response to those concerns, a team of researchers has conducted one of the largest studies ever undertaken to re-examine the cognitive effects of ecstasy, funded by a $1.8 million grant from the National Institute on Drug Abuse (NIDA) and published in the journal Addiction. The study was specifically designed to minimize the methodological limitations of earlier research.

In contrast to many prior studies, ecstasy users in the new study showed no signs of cognitive impairment attributable to drug use: ecstasy use did not decrease mental ability.

Lead author John Halpern is quick to point out that this group of researchers is not the first to identify limitations in prior studies of ecstasy users. "Researchers have known for a long time that earlier studies of ecstasy use had problems that later studies should try to correct. When NIDA decided to fund this project, we saw an opportunity to design a better experiment and advance our knowledge of this drug."

The researchers fixed four problems in earlier research on ecstasy. First, the non-users in the experiment were members of the "rave" subculture and thus repeatedly exposed to sleep and fluid deprivation from all-night dancing -- factors that themselves can produce long-lasting cognitive effects.

Second, participants were screened for drug and alcohol use on the day of cognitive testing, to make sure all participants were tested while 'clean'.

Third, the study chose ecstasy users who did not habitually use other drugs that might themselves contribute to cognitive impairment.

Finally, the experiment corrected for the possibility that any cognitive impairment shown by ecstasy users might have been in place before they started using the drug.

The resulting experiment whittled 1500 potential participants down to 52 carefully chosen ecstasy users, whose cognitive function was compared against 59 closely-matched non-users, with tests administered at several stages to make sure participants were telling the truth about their drug and alcohol use.

So does this mean that ecstasy really is the risk-free, hangover-free, miracle drug that lets young ravers and gamers party all weekend without having to pay the price?

Says Halpern, "No. Ecstasy consumption is dangerous: illegally-made pills can contain harmful contaminants, there are no warning labels, there is no medical supervision, and in rare cases people are physically harmed and even die from overdosing. It is important for drug-abuse information to be accurate, and we hope our report will help upgrade public health messages. But while we found no ominous, concerning risks to cognitive performance, that is quite different from concluding that ecstasy use is 'risk-free'."

https://www.sciencedaily.com/releases/2011/02/110215081736.htm

MDMA (ecstasy): Empathogen or love potion?

December 16, 2010

Science Daily/Elsevier

MDMA -- commonly known as ecstasy -- increases feelings of empathy and social connection. These 'empathogenic' effects suggest that MDMA might be useful to enhance the psychotherapy of people who struggle to feel connected to others, as may occur in association with autism, schizophrenia, or antisocial personality disorder.

However, these effects have been difficult to measure objectively, and there has been limited research in humans. Now, University of Chicago researchers, funded by the National Institute on Drug Abuse, are reporting their new findings in healthy volunteers in the current issue of Biological Psychiatry.

Dr. Gillinder Bedi, author, explained: "We found that MDMA produced friendliness, playfulness, and loving feelings, even when it was administered to people in a laboratory with little social contact. We also found that MDMA reduced volunteers' capacity to recognize facial expressions of fear in other people, an effect that may be involved in the increased sociability said to be produced by MDMA."

These data suggest that MDMA produces effects that make others seem more attractive and friendly, which may serve as a significant motivator in its use as a recreational drug. Importantly, it also makes others appear less threatening, which could increase users' social risk-taking.

"Within the context of treatment, these effects may promote intimacy among people who have difficulty feeling close to others," observed Dr. John Krystal, Editor of Biological Psychiatry. "However, MDMA distorts one's perception of others rather than producing true empathy. Thus, MDMA may cause problems if it leads people to misinterpret the emotional state and perhaps intentions of others."

Certainly, further research in controlled settings is necessary before MDMA could be considered for use as a psychotherapy treatment. But, these findings also underscore the need to understand more about the ways in which different drugs affect social experiences, given that abused drugs are so commonly used in social settings.

https://www.sciencedaily.com/releases/2010/12/101215082936.htm

MDMA (Ecstasy)-assisted psychotherapy relieves treatment-resistant PTSD

July 20, 2010

Science Daily/SAGE Publications UK

MDMA (±3,4-methylenedioxymethamphetamine, also known as Ecstasy), may one day offer hope for individuals with posttraumatic stress disorder (PTSD), even people for whom other treatments have failed. Clinical trial results out July 19 in the Journal of Psychopharmacology suggests that MDMA can be administered to subjects with PTSD without evidence of harm and could offer sufferers a vital window with reduced fear responses where psychotherapy can take effect.

Before MDMA became used recreationally under the street name Ecstasy, hundreds of psychiatrists and psychotherapists around the world administered MDMA as a catalyst to psychotherapy. MDMA was criminalized in the US in 1985 (it had been illegal in the UK since 1977). Several decades later, this study is the first completed randomised, double-blinded clinical trial to evaluate MDMA as a therapeutic adjunct in any patient population.

Belmont, MA-based Rick Doblin, Ph.D., President of the Multidisciplinary Association for Psychedelic Studies (a non-profit psychedelic and medical marijuana research and educational organization that sponsored the study), together with South Carolina-based psychiatrist Michael Mithoefer, MD and colleagues, conducted a pilot Phase II clinical trial with 20 patients with chronic PTSD persisting for an average of over 19 years. Prior to enrolling in the MDMA study, subjects were required to have received, and failed to obtain relief, from both psychotherapy and psychopharmacology.

Participants treated with a combination of MDMA and psychotherapy saw clinically and statistically significant improvements in their PTSD -- over 80% of the trial group no longer met the diagnostic criteria for PTSD, stipulated in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV-TR) following the trial, compared to only 25% of the placebo group. In addition, all three subjects who reported being unable to work due to PTSD were able to return to work following treatment with MDMA.

The trial centred on two eight-hour psychotherapy sessions scheduled about 3-5 weeks apart, where 12 subjects received MDMA, and eight took a placebo. Subjects were also given psychotherapy on a weekly basis before and after each experimental session. A blinded, independent rater tested each subject using a PTSD scale at baseline, and at intervals four days after each session and two months after the second session. The clinical response was significant -- 10 of the 12 in the treatment group responded to the treatment compared with just two of the eight in the placebo group. During the trial, the subjects did not experience any drug-related Serious Adverse Events (SAEs), nor any adverse neurocognitive effects or clinically significant blood pressure or temperature increases.

After the two-month follow-up, subjects in the placebo group were offered the option to participate in the treatment process again, to receive MDMA on an open-label basis, acting as their own controls. Seven of the eight placebo subjects elected to receive MDMA-assisted psychotherapy, with successful treatment outcomes similar to the subjects initially randomized to MDMA.

PTSD involves exaggerated and uncontrolled fear responses. To treat these, psychotherapists need to help sufferers revisit traumatic experiences. But patients often suffer intolerable feelings when they revisit the trauma, or numb themselves emotionally, resulting in the psychotherapy having little effect. The goal of using MDMA is to temporarily reduce fear and increase trust without inhibiting emotions, especially painful emotions, allowing these patients a window where psychotherapy for their PTSD is effective.

MDMA's pharmacological effects include serotonin release, 5HT2 receptor stimulation and increase in levels of the neurohormones oxytocin, prolactin and cortisol.

Importantly, this trial involved concentrated periods of patient-therapist contact (31 hours over two months) including two all-day therapy sessions and overnight stays in the clinic. "These are not usual features of psychotherapy practice in the outpatient setting," says Michael Mithoefer. MDMA-assisted psychotherapy would require special clinics equipped for longer treatment sessions and overnight stays if an MDMA-based treatment were approved. "This method also involves patient preparation and close follow-up to support further processing of emotions and integration of cognitive shifts that may occur," Mithoefer adds, stressing that these are vital for safety and therapeutic effect.

Measures like these may prove a price worth paying, however, to alleviate the debilitating effects of PTSD on sufferers in future.

The authors caution that the study does have limitations -- for example they did not look at gender and ethnic factors in their sample selection. Another important limitation was that most participants and trial investigators guessed accurately whether they were in the treatment or the placebo group. The placebo had no psychoactive effect and investigators could detect raised blood pressure and other symptoms in the MDMA group. A long-term follow-up to the study just published, evaluating subjects an average of about 40 months post-treatment, is underway.

The investigators have now received the go ahead from the US Food and Drug Administration (FDA) for a protocol for a three-arm, dose-response design that they expect will result in successful blinding. This new study is for US veterans with war-related PTSD, most from Iraq and Afghanistan and a few from Vietnam. MAPS is currently sponsoring MDMA/PTSD Phase 2 pilot studies in Switzerland and Israel, and is working to start additional pilot studies in Canada, Jordan and Spain.

https://www.sciencedaily.com/releases/2010/07/100719082927.htm

Ecstasy use may lead to sleep apnea: Illegal 'club drug' poisons neurons involved in control of breathing during sleep

December 3, 2009

Science Daily/Johns Hopkins Medical Institutions

Repeated use of the drug popularly known as "ecstasy" significantly raises the risk of developing sleep apnea in otherwise healthy young adults with no other known risk factors for the sleep disturbance, a new study by Johns Hopkins scientists suggests. The finding is the latest highlighting the potential dangers of the amphetamine-style chemical, currently used illegally by millions of people in the United States.

The Johns Hopkins scientists note that sleep apnea itself can lead to an assortment of health problems, including a decline in cognitive function, an increased risk of diabetes, and an increased risk of death from heart disease.

"We know that abusing drugs can have numerous harmful effects. Our findings show yet another reason not to use ecstasy," according to lead researcher Una D. McCann, M.D.

Users claim the drug enhances intimacy, diminishes anxiety, and facilitates some forms of psychotherapy.

The team led by McCann, professor in the Department of Psychiatry at the Johns Hopkins University School of Medicine, previously linked ecstasy, or methylenedioxymethamphetamine (MDMA), to a variety of neurological problems, including subtle cognitive deficits, impulsive behavior, and altered brain wave patterns during sleep. These problems are thought to arise from the drug's targeted toxic effects on neurons that produce the hormone serotonin. Studies in animals and people have shown that MDMA use shortens the filament-like ends of these nerve cells, preventing them from making normal connections with other neurons.

Because these cells regulate multiple aspects of sleep, McCann's team recruited 71 sleep study volunteers, all MDMA users, by advertising for "club drug users" in newspapers and fliers. All had typically used other recreational drugs as well. They also recruited 62 participants who had similar patterns of illegal drug use but had never taken MDMA. The MDMA users had taken the drug at least 25 times in the past, a number previously shown to have lasting effects on serotonin neurons. All of the volunteers were otherwise physically and mentally healthy and had abstained from drug use for at least two weeks prior to the study.

To evaluate the participants' breathing patterns during sleep, each volunteer spent a few nights at a sleep research center. From "lights out" at 11:00 p.m. to "lights on" at 7:00 a.m., study volunteers slept while hooked up to a variety of devices to measure breathing, including airflow monitors at their noses and mouths and bands around their chests and abdomens to measure expansion.

The researchers diagnosed sleep apnea by counting the rate of incidences of shallow or suppressed breathing, with mild apnea requiring five to 14 of these incidences, moderate apnea requiring 15 to 29, and severe apnea requiring 30 or more.

Results published in the Dec. 2, 2009, issue of Neurology, the medical journal of the American Academy of Neurology, showed that rates of mild apnea were similar between the two groups, with 15 MDMA users and 13 other volunteers affected. However, while 8 MDMA users had the moderate form of apnea and 1 had the severe form, none of the other volunteers had either of these more serious forms. Results showed that the more participants had used MDMA in the past, the more severe their apnea was likely to be.

Known risk factors for sleep apnea include older age, obesity, and other medical conditions. However, McCann says, of the 24 ecstasy users who had sleep apnea, 22 were age 31 or younger, and none had any known serious medical problems.

"Our subjects were otherwise healthy young adults, so this is a very surprising finding," she says.

Though the researchers suspect that the cause for the MDMA users' sleep apnea centers on affected serotonin neurons, the exact mechanism remains a mystery. McCann explains that these neurons appear to help sense blood oxygen levels, control airway opening and generate breathing rhythms. Any of these pathways could be separately influenced by ecstasy use, she says. The researchers are currently working to tease apart which pathway is at play in MDMA users.

https://www.sciencedaily.com/releases/2009/12/091202162332.htm

Ecstasy for Treatment of Traumatic Anxiety

January 10, 2009

Science Daily/The Norwegian University of Science and Technology

Treatment with a pharmacological version of the drug ecstasy makes PTSD patients more receptive to psychotherapy, and contributes to lasting improvement. Norwegian researchers explain why.

People who have survived severe trauma - such as war, torture, disasters, or sexual assault - will often experience after-effects, in a condition called posttraumatic stress disorder (PTSD). The symptoms can include anxiety, uncontrolled emotional reactions, nightmares, intrusive memories, sleep and concentration difficulties, evasion of situations that resemble the trauma, and feelings of shame or amnesia.

For many, the condition gradually goes away by itself. Other individuals experience PTSD as a chronic condition that needs treatment, which typically involves drugs that help with anxiety and depression, and/or psychotherapy.

More than just happy pills

Psychotherapy usually involves a combination of talk sessions and tasks. In exposure therapy, the focus is to help the patient digest the traumatic event in a safe context. So the patient realizes that the memories of the traumatic event and the situation surrounding it are not dangerous. The patient learns to deal with the traumatic incident as a painful memory, and not as if it will happen again.

“Studies show that exposure therapy can be a very effective treatment of post traumatic disorders. Yet far too many patients receive treatment only with drugs. But anxiety reducing drugs and anti-depressants may work against our efforts and reduce the patient’s emotional learning”, says Pål-Ørjan Johansen, a psychologist at the Norwegian University of Science and Technology.

Along with Teri Krebs, a neurobiologist at the university, he is now exploring what happens when chronic trauma patients are treated with a combination of psychotherapy and pharmacological versions of ecstasy, MDMA (3,4 methylenedioxy-N-methyl-amphetamine). A U.S. study,* recently conducted by psychiatrist Michael Mithoefer, has shown remarkable success with this combination.

More open with ecstasy

Mithoefer took 21 people with chronic PTSD, all of whom had been subjected to documented abuse. All had also been through six months of treatment with traditional therapy, in addition to a three-month treatment with drugs. None, however, had shown any improvement from the treatment.

Under Mithoefer’s treatment, the patients stopped their usual anxiety-reducing drugs, and began a new treatment with twelve sessions of psychotherapy. During two of these therapy sessions, some patients were given doses of MDMA, while the others were given a placebo (a fake pill).

Two months after the treatment, 92 percent of MDMA patients had clinically significant improvement in their conditions: They were more open to therapy and were able to process the trauma. They managed to escape from their shells and shame, and to see lifelong patterns of behaviour. They were less dispirited, evasive and afraid. In contrast, only 25 percent of the patients in the placebo group showed progress. Everyone in this group was subsequently offered treatment with MDMA, and the results have been good, with no serious or lasting side effects.

Neuropsychological tests suggested that patients had improved mental ability after treatment. None of MDMA patients continued to take the drug after treatment. But many of them had managed to transform a crippling trauma into "only" a memory -- a painful memory, but still more manageable than before.

Changes in brain activity

 “This was a small study, and it must be followed up by more. But the results are promising, both in terms of safety and the effects of treatment. It is also important to stress that this is not about daily medication, but short-term, controlled use," Johansen and Krebs say.

The Norwegian scientists have investigated both this and a number of other studies, and suggest the following explanation:

“For the first, MDMA contributes to increasing the level of oxytocin in the brain. This hormone stimulates emotions such as connection, proximity and trust. In a therapeutic context, it means that the patient may be better able to open up and have confidence in the therapist.

For the second, MDMA increases activity in the ventromedial prefrontal cortex. This is an area in the anterior part of the brain that processes fear, lowers stress, and enables us to see events in perspective. This is where decisions are taken and feelings are regulated. Activity here is closely linked to activity in the amygdala, the area of the brain that is the centre for feeling fear. You could say that fear is formed in the amygdala, but is processed in the ventromedial prefrontal cortex. While activity in the cortex is increased with MDMA, the drug simultaneously reduces activity in the amygdala. We believe this will help improve the regulation of emotions, allay fears and reduce evasive behaviours in a therapy situation.

For the third, MDMA triggers the ‘stress’ hormones noradrenalin and cortisol. These hormones are necessary to activate the emotional learning that leads to long-term reduction of fear.

In summary, we suggest that MDMA is an emotional enhancer that helps the patient feel safer and in control, better able to connect with memories, and more capable of the emotional processing that is needed for improvement.”

Teri Krebs’ and Pål-Ørjan Johansen’s explanatory model is being published in the Journal of Psychopharmacology.

*Mithoefer, M, Mithoefer, A, Wagner, M (2008) Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in subjects with chronic posttraumatic stress disorder: A Phase II clinical trial completed 19 September, 2008. Poster presented at the 24th Annual Meeting of the International Society of Traumatic Stress Studies, Chicago.

https://www.sciencedaily.com/releases/2009/01/090108121656.htm

Why Cannabis Stems Inflammation

July 22, 2008

Science Daily/ETH Zurich/Swiss Federal Institute of Technology

Cannabis has long been accredited with anti-inflammatory properties. Researchers, however, have now discovered that it is not only the familiar psychoactive substances that are responsible for this; a compound we take in every day in vegetable nutriment also plays a significant role.

People not only rate cannabis sativa L. highly because of its intoxicating effects; it has also long been used as a medicinal plant. Although the plant has been scrutinized for years, surprising new aspects keep cropping up. For example, researchers from ETH Zurich and Bonn University examined a component in the plant’s essential oil that until then had largely been ignored and found it to have remarkable phar- macological effects. The findings open up interesting perspectives, especially for the prevention and treatment of inflammations.

Completely different molecule structure

 The hemp plant contains over 450 different substances, only three of which are responsible for its intoxicating effect. They activate the two receptors in the body CB1 and CB2. Whilst the CB1 receptor in the central nervous system influences perception, the CB2 receptor in the tissue plays a crucial role in inhibiting inflammation. If the receptor is activated, the cell releases fewer pro-inflammatory signal substances, or cytokines. The scientists have now discovered that the substance beta-carophyllene, which composes between 12 and 35 percent of the cannabis plant’s essential oil, activates the CB2 receptor selectively.

Unlike the three psychoactive substances, however, beta-carophyllene does not latch onto the CB1 receptor and consequently does not trigger the intoxicating effect. “Due to the various effects of cannabis, we had suspected for quite some time that other substances could come into play besides the psychoactive ones”, explains Jürg Gertsch from the Institute of Pharmaceutical Sciences at ETH Zurich. “However, astonishingly we didn’t know what substances these were until now.”

Gertsch finds it remarkable that beta-carophyllene has a very different molecule structure to that of the classical cannabinoids. “This is presumably why no one realized that the substance can also activate the CB2 receptor.” The scientists were not only able to prove that beta-carophyllene binds with the CB2 receptor in vitro but also in animal tests, where they treated mice that were suffering from an inflammatory swelling on their paws with orally administered doses of the substance. The swelling declined in up to 70 percent of the animals, even for deep doses. For mice lacking the gene for the CB2 receptor, however, the substance did not make an impact.

Common substance

 The results are encouraging for the prevention or treatment of ailments in which the CB2 receptor plays a positive role. However, Gertsch explains that we are still very much in the early stages on that score. That said, the scientist can conceive that some day the compound will not only help heal certain forms of inflammation, but also be instrumental in treating chronic illnesses, such as liver cirrhosis, Morbus Crohn, osteoarthritis and arteriosclerosis. In all of these diseases, the CB2 receptor and the associated endocannabinoid system play a crucial role.

The beauty is that beta-carophyllene is not only found in cannabis but also often in plants as a whole and we consume the substance in our diet. The non-toxic compound, which incidentally has been used as a food additive for many years, can be found in spice plants like oregano, basil, cinnamon and black pepper. “Whether we have found a new link between the vegetable diet and the prevention of so-called lifestyle diseases in our study remains to be seen in future studies”, adds Gertsch.

https://www.sciencedaily.com/releases/2008/07/080720222549.htm

Mechanism of Hallucinogens' Effects Discovered

February 2, 2007

Science Daily/Cell Press

The brain mechanism underlying the mind-bending effects of hallucinogens such as LSD, mescaline, and psilocybin has been discovered by neuroscientists. They said their discoveries not only shed light on the longtime mystery of how hallucinogens work, but that the findings also offer a pathway to understanding the function of drugs used to treat neuropsychiatric disorders, which are now being used largely without an understanding of their fundamental mechanism.

Stuart Sealfon, Jay Gingrich, and colleagues published their findings in the February 1, 2007 issue of the journal Neuron, published by Cell Press.

Researchers have long known that hallucinogens activate specific receptors in the brain, called 5-HT2A receptors (2ARs), that are normally triggered by the neurotransmitter serotonin. Neurotransmitters are chemicals that one brain cell launches at receptors on another to trigger a nerve impulse in the receiving cell. However, a fundamental mystery has been why other compounds that activate the same receptors are not hallucinogenic.

In their studies, the researchers compared the differences between the effects of LSD and a nonhallucinogenic chemical that also activates 2AR receptors on the mouse neural machinery. Since the animals could not report the kinds of perception-altering effects that humans experience on hallucinogens, the researchers determined hallucinogenic properties by measuring a head twitch response the mice characteristically showed when under hallucinogens but not when under nonhallucinogens.

The scientists concentrated their studies on the cortex of the brain, which earlier studies had shown to be the center for action of the hallucinogens. Their analysis revealed that LSD produced genetic, electrophysiological, and internal cellular signaling responses that were distinctively different from those induced by a nonhallucinogenic compound.

They also explored whether 2ARs were central to the hallucinogenic effect of LSD by producing mice lacking the receptors, but in which receptor activity could be selectively restored in the cortex. The researchers found that mice without functioning receptors showed no hallucinogenic response to LSD, but restoring the receptors rendered LSD hallucinogenic in the animals.

The researchers wrote that "These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens."

They also concluded that "The strategy we developed to elucidate [hallucinogen] action should be applicable to [central nervous system]-active compounds, with therapeutic potential in other disorders. Thus, our findings may advance the understanding of neuropsychiatric disorders that have specific pharmacological treatments whose mechanisms of action are not fully understood."

https://www.sciencedaily.com/releases/2007/01/070131135536.htm

Ecstasy Can Harm the Brains of First-time Users

November 28, 2006

Science Daily/Radiological Society of North America

Researchers have discovered that even a small amount of MDMA, better known as ecstasy, can be harmful to the brain, according to the first study to look at the neurotoxic effects of low doses of the recreational drug in new ecstasy users. The findings were presented today at the annual meeting of the Radiological Society of North America (RSNA).

"We found a decrease in blood circulation in some areas of the brain in young adults who just started to use ecstasy," said Maartje de Win, M.D., radiology resident at the Academic Medical Center at the University of Amsterdam in the Netherlands. "In addition, we found a relative decrease in verbal memory performance in ecstasy users compared to non-users."

Ecstasy is an illegal drug that acts as a stimulant and psychedelic. A 2004 survey by the National Institute on Drug Abuse (NIDA) found that 450,000 people in the United States age 12 and over had used ecstasy in the past 30 days. In 2005, NIDA estimated that 5.4 percent of all American 12th graders had taken the drug at least once.

Ecstasy targets neurons in the brain that use the chemical serotonin to communicate. Serotonin plays an important role in regulating a number of mental processes including mood and memory.

Research has shown that long-term or heavy ecstasy use can damage these neurons and cause depression, anxiety, confusion, difficulty sleeping and decrease in memory. However, no previous studies have looked at the effects of low doses of the drug on first-time users.

Dr. de Win and colleagues examined 188 volunteers with no history of ecstasy use but at high-risk for first-time ecstasy use in the near future. The examinations included neuroimaging techniques to measure the integrity of cells and blood flow in different areas of the brain and various psychological tests. After 18 months, 59 first-time ecstasy users who had taken six tablets on average and 56 non-users were re-examined with the same techniques and tests.

The study found that low doses of ecstasy did not severely damage the serotonergic neurons or affect mood. However, there were indications of subtle changes in cell architecture and decreased blood flow in some brain regions, suggesting prolonged effects from the drug, including some cell damage. In addition, the results showed a decrease in verbal memory performance among low-dose ecstasy users compared to non-users.

"We do not know if these effects are transient or permanent," Dr. de Win said. "Therefore, we cannot conclude that ecstasy, even in small doses, is safe for the brain, and people should be informed of this risk."

This research is part of the Netherlands XTC Toxicity (NeXT) study, which also looks at high-dose ecstasy users and aims to provide information on long-term effects of ecstasy use in the general population.

Co-authors are Gerard J. Den Heeten, M.D., Ph.D., Gerry Jager, M.S., Liesbeth Reneman, M.D., T. Schilt, M.S., Jan Booij, M.D., Ph.D., C. Lavini, D.Phil., and Win van den Brink, M.D., Ph.D.

https://www.sciencedaily.com/releases/2006/11/061128084458.htm

LSD Finds New Respectability

September 1, 2005

Science Daily/McMaster University

It was the drug of choice on university campuses, the drug that spawned psychedelic culture as well as countless jail sentences and fines, but LSD actually has respectable roots—roots that a McMaster University researcher is uncovering.

"Far from being fringe medical research, trials of LSD were once a legitimate branch of psychiatric research," explains Erika Dyck, a doctoral researcher in the Department of History at McMaster. "LSD produced a "model psychosis," meaning people who took the drug exhibited symptoms of illnesses such as schizophrenia. Doctors used this as a new method for studying mental illness."

In a recent issue of the Canadian Journal of Psychiatry, Dyck traces the history of LSD—and its eventual withdrawal from medical research. LSD, ord-lysergic acid diethylamide, first appeared in scientific literature in 1943. For nearly a decade, it gave psychiatrists insight into experiences of schizophrenic patients and showed potential as a cure for alcoholism.

In the 1960s, as the media increasingly associated the drug with love-ins, anti-war demonstrations and the counterculture, governments intervened to criminalize LSD, restricting and then terminating medical research into its potential therapeutic effects.

Now, therapeutic uses of psychedelic drugs are resurfacing. Research groups in the United States are currently examining the usefulness of MDMA, or "ecstasy," in treating pain in medical conditions such as Parkinson's disease and cancer.

This makes Dyck optimistic that LSD may become a valid area of research again. "Many illegal drugs are used in medical settings. Scientists who studied LSD made important contributions to psychiatry, and found it helped many people cope with mental illness."

Dyck discovered another interesting fact while researching LSD: The term "psychedelic”, it turns out, was a Canadian invention – coined in Weyburn, Sask. in the 1950s.

The paper is available online at 

www.cpa-apc.org/Publications/Archives/CJP/2005/june/InRevDyck.asp.

McMaster University, named Canada's Research University of the Year by Research Info Source, has world-renowned faculty, and state-of-the-art research facilities. McMaster's culture of innovation fosters a commitment to discovery and learning in teaching, research and scholarship. Based in Hamilton, the University has a student population of more than 23,000, and an alumni population of more than 115,000 in 128 countries.

https://www.sciencedaily.com/releases/2005/09/050901073759.htm

Ecstasy Can Trigger Heart Attacks in Users

November 26, 2003

Science Daily/American College of Emergency Physicians

The illegal drug MDMA (Methylene 3, 4 dioxy-methamphetamine) more commonly known as "Ecstasy" or "XTC," can trigger heart attacks, according to a case report in the December issue of Annals of Emergency Medicine. The case report describes a 27-year-old male who sought treatment at an emergency department after experiencing symptoms of chest tightness and discomfort for three hours.

The man reported that prior to experiencing these symptoms he drank a bottle of whisky and taken half of a pill of MDMA. He was diagnosed and treated in the emergency department for acute myocardial infarction as a result of MDMA use. This is only the second case reported showing evidence that MDMA can cause heart attacks similar to those caused by amphetamines, according to the report's authors. (Methylene 3, 4 Dioxy-Methamphetamine-Induced Acute Myocardial Infarction, p. 759)

The role of MDMA on coronary vessels is not well documented. However, the case report's authors from the National Taiwan University Hospital in Taipei, Taiwan, speculate that MDMA-related heart attacks may be similar to those caused by cocaine or amphetamine use. Other studies have found cocaine and amphetamines promote coagulation of blood that can lead to blood clots in the arteries, which can cause heart attacks.

Physicians in the emergency department should become familiar with this drug because of its emerging trend toward its use, advise the case report's authors. Although it was once thought that the drug does not cause dependency and adverse side effects, this belief has been overturned by many reports of side effects in recent literature, the report further explains.

Annals of Emergency Medicine is the peer-reviewed journal of the American College of Emergency Physicians, a national medical specialty organization with nearly 23,000 members.

https://www.sciencedaily.com/releases/2003/11/031126064222.htm

Ecstasy Use Depletes Brain's Serotonin Levels

July 28, 2000

Science Daily/American Academy of Neurology

ST. PAUL, MN -- Use of the recreational drug Ecstasy causes a severe reduction in the amount of serotonin in the brain, according to a study in the July 25 issue of Neurology, the scientific journal of the American Academy of Neurology.

The study examined the brain of a 26-year-old man who had died of a drug overdose. He had been using Ecstasy for nine years, and in the last months of his life had also started using cocaine and heroin. His brain was compared to those from autopsies of 11 healthy people.

"The levels of serotonin and another chemical associated with serotonin were 50 to 80 percent lower in the brain of the Ecstasy user," said study author Stephen Kish, PhD, of the Centre for Addiction and Mental Health in Toronto, Canada. "This is the first study to show that this drug can deplete the level of serotonin in humans."

Ecstasy, which is known chemically as methylenedioxymethamphetamine, or MDMA, is structurally related to the hallucinogen mescaline and the stimulant amphetamine. MDMA causes neurons, or nerve cells, to release serotonin, a neurotransmitter that controls mood, pain perception, sleep, appetite and emotions. Ecstasy users report an increased awareness of emotion and a heightened sense of intimacy.

"Some of the behavioral effects of this drug are probably due to the massive release and depletion of serotonin," Kish said. "And the depression that people feel after going off the drug could also be explained by the depletion of serotonin in the brain."

The low levels of serotonin were found in the striatal area of the brain, which plays a key role in coordinating movement. In addition to serotonin, the level of 5-hydroxyindoleacetic acid, also known as 5-HIAA and a major breakdown product of serotonin, was also low in the brain of the Ecstasy user.

"Of course, these findings should be confirmed through additional studies," Kish said. "Conclusions based on a single case can only be tentative."

Researchers confirmed the man's drug use through analysis of his brain, blood and hair. The analysis also confirmed that he had been using cocaine and heroin in the last months of his life. Kish said other research has shown that those drugs do not affect serotonin levels.

The man started using Ecstasy once a month at age 17. His usage increased, and in the last three years of his life he used it four to five nights a week at "rave" clubs, usually including a three-day weekend binge during which he took six to eight tablets. On the day after these binges, his friends said he appeared depressed and had slow speech, movement and reaction time.

Kish said research should also be done to determine whether increasing serotonin levels in people who are going off the drug would help eliminate some of the behavioral problems that occur during withdrawal.

The American Academy of Neurology, an association of more than 16,500 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research.

A neurologist is a medical doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system.

For more information about the American Academy of Neurology, visit its Web site athttp://www.aan.com. For online neurological health and wellness information, visit NeuroVista at http://www.aan.com/neurovista.

https://www.sciencedaily.com/releases/2000/07/000727081324.htm