Study examines effects of drug use

Dr. Leslie Jacobsen is courting ecstasy and marijuana addicts — in order to study their brains.

Pressing buttons in response to visual cues and drawing simple figures are two of several tests administered as part of a project studying cognitive effects of ecstasy and marijuana withdrawal in adolescents. Jacobsen, a psychiatry and pediatrics professor at the Yale School of Medicine, is the study’s principal investigator and received a $1.7 million grant from the National Institutes of Health to conduct her work.

The study will follow 200 adolescent participants with and without a history of cannabis, ecstasy and tobacco use for two years. Jacobsen said the study will examine whether adolescents experience cognitive deficits as a result of drug use, and whether sustained abstinence from drug use leads to recovery of cognitive function.

Psychiatry professor Dr. John Krystal, who studies the psychopharmacology and neurobiology of various forms of substance abuse, said Jacobsen’s work is the first to unite different fields of research. Given evidence that abuse of particular drugs impairs cognitive function, he said she plans to use sophisticated psychological tests to articulate which circuits in the brain are vulnerable.

“We are very aware of the fact that when teens are using drugs there are many highly visibly associated problems, but oftentimes impairments in particular aspects of cognitive function affecting learning and memory may not be apparent immediately,” Krystal said. “In the mature brain for an adult, the effects of a drug abuse may affect performance, but not necessarily change trajectory of the development of the brain, but we are concerned of the long-term effects of brain in adolescent because the brain changes so much.”

Jacobsen said she will use non-invasive methods such as functional magnetic resonance imaging to measure brain function while subjects are performing a task that involves attention and memory. The subjects will undergo approximately three hours of cognitive testing annually.

Computer-based tests assess the subject’s selective attention by presenting a stimulus and distractor. The subject must process the stimulus and screen out the distractor. In pencil and paper tests, subjects will recite a list of words after memorizing them, or copy a figure after being shown it, as measure of spatial memory.

“There was a study with marijuana use in the adult population where they have them stop using, and a month later their memory was better, but certain aspects of verbal memory didn’t improve as much,” Jacobsen said. “This is particularly pronounced in early onset users, hence our reason for wanting to look at teenagers.”

Functional magnetic resonance imaging tracks brain function by producing images of activated brain regions through detection of indirect effects of neural activity on local blood volume, flow and oxygen saturation. By visualizing changes in chemical composition in certain areas of the brain, fMRI pinpoints what mechanisms of the brain are most vulnerable to cognitive impairments.

“Meditating level of analysis helps make sense of what we see in terms of behavior consequences of the drug,” said Kenneth Pugh, senior scientist at Haskins Laboratories in New Haven, who collaborated with Jacobsen on the micro neuro-imaging aspect of the study. “By scanning the brain and looking for effects on brain response, we get a sensitive biological measure to understand how the effects of drains on memory and attention are mediated.”

Krystal said a pilot study conducted 12 years ago indicated memory impairment in heavy ecstasy users but said it was uncontrolled and preliminary. Jacobsen’s work related these memory impairments to an abnormality in the hippocampus, a ridge in the brain with a central role in memory processes.

“In my work at the National Institutes of Health, this area of study has been targeted as a high priority, and I think [Jacobsen] is filling a very critical role in this field by moving these studies forward,” Pugh, an NIH panel member, said. “It’s a very high priority, and she’s doing a terrific job of beginning to attack these questions.”