'ECSTASY' MAY CAUSE LONG-TERM CHANGES IN BRAIN CHEMISTRY

Recreational use of the illegal drug known as ecstasy is associated
with long-term changes in brain chemistry, a small, new study reveals.

Based on research with women, it appears that the so-called "rave"
drug can induce a drop in serotonin levels that can last up to two
years. Serotonin, the research team noted, is critical to the
regulation of mood, appetite, sleep, learning and memory.

"We've always known that ecstasy produced transient effects, but with
the suggestion that there would be recovery over time," explained
study co-author Dr. Ronald Cowan, an associate professor of psychiatry
in the department of psychiatry with Vanderbilt University Medical
Center's School of Medicine in Nashville, Tenn. "But here we find that
these effects may be sustained over time with no evidence of
reversal," he added.

"Now this is an observational study, so we can't do really any more
than suggest causation," Cowan noted. "But I would say that this is
nevertheless the strongest evidence we have that there is chronic
change in serotonin levels for those who use the drug."

Cowan and his colleagues report their findings in the Dec. 5 online
issue of the Archives of General Psychiatry.

The authors noted that nearly 16 million Americans aged 12 and older
have reportedly used ecstasy at some point in their life.

As described by the U.S. National Institute on Drug Abuse, ecstasy
(otherwise known by its chemical name, MDMA) is a psychoactive
stimulant that is similar in structure to methamphetamine and mescaline.

The drug increases serotonin levels in the brain, and users feel a
sense of euphoria and emotional warmth. On the downside, the institute
notes that the drug prompts a potentially problematic increase in both
heart rate and blood pressure, and can lead to sleep disturbance and
lingering feelings of confusion, depression and anxiety.

On the other end of the spectrum, some researchers have pointed to the
therapeutic potential for the controlled, clinical use of MDMA to help
patients struggling with post-traumatic stress disorder (PTSD) and/or
dysfunctional social skills.

Cowan's team focused on 24 women, including 14 who were described as
MDMA users. The study was confined to women to avoid the complication
of gender-specific serotonin level differences between men and women.

The average age of the women was 22. Cowan noted that those who were
MDMA users had taken ecstasy for a period of between three to four
years, with the number of pills taken ranging from just five to
roughly 375 overall. At the start of the study, all had abstained from
ecstasy use for a minimum of 90 days, with the average length of
abstinence hovering at the two-year mark.

The team used positron emission tomography (PET) scans to assess
levels of serotonin receptors in the participants' brains, noting that
receptor levels are known to go up as serotonin levels go down. Those
women who had a history of taking ecstasy had higher receptor levels
than women who hadn't, suggesting a drop in serotonin levels among
MDMA users.

What's more, the team observed a dose-dependent impact: The more
ecstasy a woman had taken in her lifetime, the higher her receptor
levels.

"We don't actually know what the implications are," acknowledged
Cowan. "There is some evidence in prior research that a drop in
serotonin leads to sleep apnea, depression, anxiety and memory loss.
But in our work we didn't find evidence of mental health issues. No
increased anxiety, impulsivity or depression. And the IQs of the women
who took the drug were identical with those who had never taken it,"
he stated.

"We also have no proof that a drop in serotonin levels would be
forever," Cowan noted. "Animal studies have indicated that there could
be as much as a seven-year duration in such dips. But we don't know.
So, this work raises serious concerns and questions, but more research
is needed."

Michael Mithoefer, a clinical researcher in the field of MDMA-assisted
psychotherapy for PTSD, stressed "the importance of not jumping to
conclusions."

"You have to be careful with research like this," Mithoefer cautioned.
"There have been some other similar studies suggesting the possibility
of some long-term changes with ecstasy use. But the problem with
retrospective studies based on self-report is that there are other
factors at play that might not be accounted for. Did these people take
other drugs at the same time? Was it really MDMA that they took?
Exactly how much did they take? What really was the dose taken? That
kind of thing can become very unclear when you're asking people to
remember past behavior," he explained.

"It's also the case that in clinical research conducted with a few
different doses of pure MDMA we have no found evidence of these kinds
of problems," noted Mithoefer.

"I do, however, think it's important that people not think that MDMA
is without risk," he added. "Especially with recreational use in an
uncontrolled setting. Whether that will lead to mental health issues
or not is unclear. But it is certainly something that bears further
study."