Sunday, October 23, 2011

Long-term Ecstasy use as Risk Factor for Alzheimer's

What is Ecstasy?

The drug known as Ecstasy, X, or Adam has become a relatively common drug among adolescents today. Ecstasy is known as 3, 4-methylenedioxymethamphetamine or MDMA for short. It is a synthetic drug that can act as both a stimulant and hallucinogenic drug that enhances sensory processing, increases sexual sensations, and creates euphoric mood elevations in the user. MDMA is known to cause major changes the level of neurotransmitters in the brain, such as serotonin and dopamine, which control our mood and behaviors.

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Serotonin (5-Hydroxytrptanamine, 5HT) and dopamine are chemical mediators that are released in synaptic gaps of neurons. These neurotransmitters excite the post-synaptic membranes of neurons allow for the millions of neurons in the central nervous system to communicate with one another. Serotonin is a central neurotransmitter that is released from the mid-brain region, where the cerebral hemispheres and thalamus-hypothalamus are bridged to the spinal cord. Serotonin receptors are present mostly in the smooth muscle and central nervous system. The role of serotonin in the body is to regulate mood, sleep, and stimulate or inhibit the release of particular hormones in the body. Amphetamines such as MDMA cause the release of serotonin in the body, creating a heightened sensory experience for the drug user.

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The drug came on my monitor last week, when I researched for the potential link between Ecstasy and Depression, taking in account that there are multiple ongoing researches, trying to design a new Ecstasy-based drug, which will be safe and efficient in treating PTSD (post-traumatic stress disorder). In this post, I would like to review the suggestion, expressed by some medical professionals, that the long-term Ecstasy use may cause the irreversible brain damage, which may potentially trigger Alzheimer’s Disease.

Brain Damage and Alzheimer’s Risk

A study from Vanderbilt University has found physical changes in the brains of Ecstasy users that suggest that their brains are not functioning as efficiently as they once did. These changes did not disappear after a year of abstinence from Ecstasy. Ecstasy use is associated with a loss of serotonin signaling, which leads to hyper-excitability in the brain.

Ecstasy or MDMA (3-4-methylenedioxymethamphetamine), is a man-made drug. It is used as a recreational drug and known as a club drug because of its amphetamine-like and hallucinogenic properties. It is classified as a stimulant. Ecstasy produces changes in brain chemistry. But these may not be the type of changes its users are after.

The Vanderbilt study found increased brain activation in three brain areas associated with visual processing in subjects with the highest lifetime Ecstasy use. The researchers interpret this as signs of hyper-excitability in these regions of the brain — the need for more brain to be used to perform a task, which means a loss of brain efficiency.

In discussing the Vanderbilt study, Dr. Ronald Cowan, who headed the Vanderbilt study, says that its results are what were expected, based on previous animal studies: Ecstasy use is associated with a loss of serotonin signaling, which leads to hyper-excitability in the brain.

The study was of 20 long-term Ecstasy users, all of whom were abstinent for at least two weeks before the study, and 20 non-users. All underwent fMRI (functional magnetic resonance imaging) scans during visual stimulation. The researchers looked at three brain areas: the visual system lateral geniculate nucleus and Brodmann Areas (BA) 17 and 18.

The scans showed a direct, linear relationship between lifetime Ecstasy use and activation in all three brain regions — the more Ecstasy a subject had taken during their life, the greater was the activation seen in all three brain regions. The heaviest Ecstasy users also showed a greater spatial extent of activation (more of the region was active) in BA 17 and BA 18.

Dr. Cowan interprets this increased activation as a sign of a less functional brain. Cowan points out that this pattern of hyper-excitability is similar to that seen in studies of individuals at risk for or with early Alzheimer's disease. He says this does not mean that Ecstasy users are at risk of dementia, but that there's a loss of brain efficiency in both Ecstasy users and early Alzheimer's patients.

"We think this shift in cortical excitability may be chronic, long-lasting, and even permanent, which is a real worry," Cowan said. The results of this study appeared in the May 2011 issue of Neuropsychopharmacology.

This comes on the heels of another study published in March 2011 that found a definite brain drain in ten long-time Ecstasy users: their hippocampus measured, on average, more than 10% smaller than that of non-users. That study was published in the Journal of Neurology, Neurosurgery and Psychiatry.

Several previous researches have suggested that people who use ecstasy can develop serious memory problems, so a team of Dutch researchers decided to investigate whether the drug caused structural changes in the brain. They used MRI scans to measure the volume of the hippocampus in 10 men in their mid-20s who were long-term ecstasy users and seven men in the same age group who had never used the drug.

The hippocampus is the area of the brain responsible for long-term memory. On average, the ecstasy users had not taken the drug for more than two months before undergoing the MRI scans, but had taken an average of 281 ecstasy tablets over the previous six and half years. The scans revealed that ecstasy users had an average of 10.5 percent less hippocampal volume than non-users. The users also had an average 4.6 percent lower overall proportion of grey matter in the brain, which suggests that the effects of ecstasy may not be limited to the hippocampus.

"Taken together, these data provide preliminary evidence suggesting that ecstasy users may be prone to incurring hippocampal damage, following chronic use of this drug," the researchers wrote in a journal news release. The researchers noted that atrophy of the hippocampus "is a hallmark for diseases of progressive cognitive impairment in older patients, such as Alzheimer's disease."

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No Brain Damage from Ecstasy

In his presentation, Dr. Cowan expressed his concerned over some recent media coverage of Ecstasy — pieces reporting on possible therapeutic uses of Ecstasy in PTSD sufferers that suggest that some of Ecstasy's negative effects have been overstated.

"There's tension in the fields of psychiatry and psychotherapy between those who think Ecstasy could be a valuable therapeutic that's not being tested because of overblown fears, and those who are concerned about the drug's potentially harmful effects," Cowan said in a university press release.

A new study led by Professor John Halpern of Harvard Medical School, one of the studies Dr. Cowan referred to, suggested that many previous researches made overarching conclusions from insufficient data and exaggerated the drugs dangers. Professor David Halpern was critical of previous investigations which had linked the use of ecstasy to brain damage and said, "Too many studies have been carried out on small populations, while overarching conclusions have been drawn from them".

He went on to say, "For a start, some previous research has studied users who were taken from a culture dominated by all-night dancing, which thus exposed these individuals to sleep and fluid deprivation – factors that are themselves known to produce long-lasting cognitive effects. Non-users were not selected from those from a similar background, which therefore skewed results".

Halpern added, "In addition, past studies have not taken sufficient account of the fact that ecstasy users take other drugs or alcohol that could affect cognition or that they may have suffered intellectual impairment before they started taking ecstasy".

Professor David Halpern explained the new study outcomes: "Essentially compared one group of people who danced and raved and took ecstasy with a similar group of individuals who danced and raved but who did not take ecstasy. When we did that, we found that there was no difference in their cognitive abilities".


While the results of the studies on the potential danger of Ecstasy use to the brain are quite controversial, I still would not advocate it for medical and recreational purposes and for its decriminalization. The main reason is that for some people, MDMA can be addictive. A survey of young adult and adolescent MDMA users found that 43 percent of those who reported ecstasy use met the accepted diagnostic criteria for dependence, as evidenced by continued use despite knowledge of physical or psychological harm, withdrawal effects, and tolerance (or diminished response). These results are consistent with other studies that suggest a high rate of MDMA dependence among users. MDMA abstinence-associated withdrawal symptoms include fatigue, loss of appetite, depressed feelings, and trouble concentrating.

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