"ECSTASY" DAMAGES THE BRAIN AND IMPAIRS MEMORY IN HUMANS

By Robert Mathias

NIDA NOTES Staff Writer

ANIDA-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

two 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.

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 three 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

two 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 related, the 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 two 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 researchers 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,

according to Dr Bolla.

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 seven 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."

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Memory impairment in abstinent MDMA ("ecstasy") users.

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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 W

3,4-methylenedioxymethainphetamine (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

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brain serotonin neurons in human beings. Lancet 352

(9138):1433-37,1998.