UCLA Neuropsychiatric Institute researchers measuring brain activity with Positron Emission Tomography (PET) find that methamphetamine abusers suffer abnormal brain activity related to depression and anxiety during the first days after stopping drug use. If left unaddressed, mood disorders may undercut success in therapy and contribute to relapse.

Detailed in the peer-reviewed Archives of General Psychiatry for January 2004, the study is the first to map the underlying pathology in the brains of methamphetamine users in early abstinence, when most begin a course of treatment. The researchers used PET to examine glucose metabolism in seven brain areas known to regulate emotion, motivation and behavior. Each research participant also completed standard questionnaires designed to identify symptoms of depression and anxiety.

The study findings open an opportunity to improve addiction treatment results among methamphetamine abusers by also treating depression and anxiety symptoms that accompany drug cravings during the first week of therapy. Behavioral therapy is a primary component of standard treatment for methamphetamine abuse. No medication has proven helpful in assisting recovery from addiction to the drug.

"In order to develop more effective therapies for treating methamphetamine users, it's imperative to understand the underlying pathology in the brain," said the study's principal investigator, Dr. Edythe D. London, a senior research scientist at the UCLA Neuropsychiatric Institute and professor of psychiatry and pharmacology at the David Geffen School of Medicine at UCLA.

"Treatment of methamphetamine addicts typically focuses on drug craving," London said. "Our PET images for the first time pinpoint abnormal brain activity that has been closely linked to symptoms of depression and anxiety. Targeting these complicating conditions as part of a more comprehensive treatment program may improve success rates of methamphetamine addiction therapy."

The study involved 17 inpatient methamphetamine users and 18 control subjects. Participants in both groups were otherwise healthy and not undergoing treatment with psychoactive medications.

All study participants completed standard questionnaires used to identify symptoms of depression and anxiety. They also received PET scans used to measure cerebral glucose metabolism - an indicator of local function in the brain - while they performed an attention task.

The methamphetamine users received PET scans after four to seven days of abstinence on an inpatient research ward, where they received no medication but were given daily evaluations and the opportunity for occupational therapy. Activity was measured in the brain's orbitofrontal, cingulate, lateral prefrontal and insular cortices, and in the amygdala, striatum and cerebellum.

The scans of methamphetamine users identified abnormal activity in regions of the brain linked to mood by past studies. These abnormalities were not observed in the control group. The questionnaires also identified elevated symptoms of depression and anxiety among the methamphetamine users.

Funding for the study was provided by the National Institute on Drug Abuse (NIDA).

According to the 2000 National Household Survey on Drug Abuse, an estimated 8.8 million people in the United States (4 percent of the population) have tried methamphetamine at least once in their lives. The number of admissions for methamphetamine substance abuse rose from 14,554 in 1992 to 66,052 in 2000, according to the Treatment Episode Data Sheet.

Since 1998 the Office of Community Oriented Policing Services has invested $223.5 million nationwide to combat the spread of methamphetamine use. In fiscal year 2002, the office awarded $39.2 million to 93 law enforcement agencies to fight the escalating problem.

London's body of research, first at NIDA and now at the UCLA Neuropsychiatric Institute, has advanced the study of substance abuse and the development of new approaches and probes for studies of brain function. Her most recognized accomplishments involve PET scanning of human subjects who suffer from addictions.

Dr. London and her colleagues were the first to show a relationship between drug craving and activity of brain regions that link memory with emotion. She also showed that drug abusers have structural abnormalities in prefrontal cortex and deficits in decision-making tasks that depend on prefrontal cortex function.

For her latest study, London's research team conducted their study using the resources and expertise of Program of Neuroimaging Research on Addictive Disorders at the David Geffen School of Medicine at UCLA, and both the Integrated Substance Abuse Programs and the Ahmanson-Lovelace Brain Mapping Center at the UCLA Neuropsychiatric Institute.

In addition to colleagues at UCLA, researchers from NIDA and the University of California at Irvine participated in the study.

The UCLA Neuropsychiatric Institute is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders.