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A NIDA-supported study has provided the first direct evidence that
chronic use of MDMA, popularly known as "ecstasy," causes brain damage in
people. Using advanced brain imaging techniques, the study found that MDMA
harms neurons that release serotonin, a brain chemical thought to play an
important role in regulating memory and other functions. In a related
study, researchers found that heavy MDMA users have memory problems that
persist for at least 2 weeks after they have stopped using the drug. Both
studies suggest that the extent of damage is directly correlated with the
amount of MDMA use.
"The message from these studies is that MDMA does change the brain and
it looks like there are functional consequences to these changes," says
Dr. Joseph Frascella of NIDA's Division of Treatment Research and
Development. That message is particularly significant for young people who
participate in large, all-night dance parties known as "raves," which are
popular in many cities around the Nation. NIDA's epidemiologic studies
indicate that MDMA (3,4-methylenedioxymethamphetamine) use has escalated
in recent years among college students and young adults who attend these
social gatherings. (See "Facts
About MDMA," p. 15.)
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These brain scans show the amount of
serotonin activity over a 40-minute period in a non-MDMA user (top)
and an MDMA user (bottom). Dark areas in the MDMA user's brain show
damage due to chronic MDMA use.
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In the brain imaging study, researchers used positron emission
tomography (PET) to take brain scans of 14 MDMA users who had not used any
psychoactive drug, including MDMA, for at least 3 weeks. Brain images also
were taken of 15 people who had never used MDMA. Both groups were similar
in age and level of education and had comparable numbers of men and
women.
In people who had used MDMA, the PET images showed significant
reductions in the number of serotonin transporters, the sites on neuron
surfaces that reabsorb serotonin from the space between cells after it has
completed its work. The lasting reduction of serotonin transporters
occurred throughout the brain, and people who had used MDMA more often
lost more serotonin transporters than those who had used the drug
less.
Previous PET studies with baboons also produced images indicating MDMA
had induced long-term reductions in the number of serotonin transporters.
Examinations of brain tissue from the animals provided further
confirmation that the decrease in serotonin transporters seen in the PET
images corresponded to actual loss of serotonin nerve endings containing
transporters in the baboons' brains. "Based on what we found with our
animal studies, we maintain that the changes revealed by PET imaging are
probably related to damage of serotonin nerve endings in humans who had
used MDMA," says Dr. George Ricaurte of The Johns Hopkins Medical
Institutions in Baltimore. Dr. Ricaurte is the principal investigator for
both studies, which are part of a clinical research project that is
assessing the long-term effects of MDMA.
"The real question in all imaging studies is what these changes mean
when it comes to functional consequences," says NIDA's Dr. Frascella. To
help answer that question, a team of researchers, which included
scientists from Johns Hopkins and the National Institute of Mental Health
who had worked on the imaging study, attempted to assess the effects of
chronic MDMA use on memory. In this study, researchers administered
several standardized memory tests to 24 MDMA users who had not used the
drug for at least 2 weeks and 24 people who had never used the drug. Both
groups were matched for age, gender, education, and vocabulary scores.
The study found that, compared to the nonusers, heavy MDMA users had
significant impairments in visual and verbal memory. As had been found in
the brain imaging study, MDMA's harmful effects were dose-relatedÑthe more
MDMA people used, the greater difficulty they had in recalling what they
had seen and heard during testing.
The memory impairments found in MDMA users are among the first
functional consequences of MDMA-induced damage of serotonin neurons to
emerge. Recent studies conducted in the United Kingdom also have reported
memory problems in MDMA users assessed within a few days of their last
drug use. "Our study extends the MDMA-induced memory impairment to at
least 2 weeks since last drug use and thus shows that MDMA's effects on
memory cannot be attributed to withdrawal or residual drug effects," says
Dr. Karen Bolla of Johns Hopkins, who helped conduct the study.
The Johns Hopkins/NIMH research-ers also were able to link poorer
memory performance by MDMA users to loss of brain serotonin function by
measuring the levels of a serotonin metabolite in study participants'
spinal fluid. These measurements showed that MDMA users had lower levels
of the metabolite than people who had not used the drug; that the more
MDMA they reported using, the lower the level of the metabolite; and that
the people with the lowest levels of the metabolite had the poorest memory
performance. Taken together, these findings support the conclusion that
MDMA-induced brain serotonin neurotoxicity may account for the persistent
memory impairment found in MDMA users, Dr. Bolla says.
Research on the functional consequences of MDMA-induced damage of
serotonin-producing neurons in humans is at an early stage, and the
scientists who conducted the studies cannot say definitively that the harm
to brain serotonin neurons shown in the imaging study accounts for the
memory impairments found among chronic users of the drug. However, "that's
the concern, and it's certainly the most obvious basis for the memory
problems that some MDMA users have developed," Dr. Ricaurte says.
Findings from another Johns Hopkins/NIMH study now suggest that MDMA
use may lead to impairments in other cognitive functions besides memory,
such as the ability to reason verbally or sustain attention. Researchers
are continuing to examine the effects of chronic MDMA use on memory and
other functions in which serotonin has been implicated, such as mood,
impulse control, and sleep cycles. How long MDMA-induced brain damage
persists and the long-term consequences of that damage are other questions
researchers are trying to answer. Animal studies, which first documented
the neurotoxic effects of the drug, suggest that the loss of serotonin
neurons in humans may last for many years and possibly be permanent. "We
now know that brain damage is still present in monkeys 7 years after
discontinuing the drug," Dr. Ricaurte says. "We don't know just yet if
we're dealing with such a long-lasting effect in people."
View our summary of
links about MDMA (Ecstasy).
Sources
Bolla, K.I.; McCann, U.D.; and Ricaurte, G.A. Memory impairment in
abstinent MDMA ("ecstasy") users. Neurology 51:1532-1537, 1998.
Hatzidimitriou, G.; McCann, U.D.; and Ricuarte, G.A. Altered serotonin
innervation patterns in the forebrain of monkeys treated with MDMA seven
years previously: Factors influencing abnormal recovery. Journal of
Neuroscience 191(12):5096-5107, 1999.
McCann, U.D.; Mertl, M.; Eligulashvili, V.; and Ricaurte, G.A.
Cognitive performance in (±) 3,4-methylenedioxymethamphetamine (MDMA,
"ecstasy") users: a controlled study. Psychopharmacology
143:417-425, 1999.
McCann, U.D.; Szabo, Z.; Scheffel, U.; Dannals, R.F.; and Ricaurte,
G.A. Positron emission tomographic evidence of toxic effect of MDMA
("ecstasy") on brain serotonin neurons in human beings.
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