BNL Addiction Symposium

Abstract Details

February 16, 2007, San Francisco, CA  |  Symposium Home

Methamphetamine and the Brain: A Problem of Inhibitory Control

Authors: Edythe D. London, Ph.D.
Semel Institute of Neuroscience and Biobehavioral Science, UCLA

Methamphetamine (METH), commonly called “crystal”, “crystal meth”, “meth”, “speed” and “tina”, presents the fastest growing drug abuse problem in the world. Amphetamines are used by more people worldwide than any illicit drug besides cannabis. To some extent, the prevalence of METH abuse reflects high availability, low cost, and the fact that the “high” from METH can last six hours.

Aside from the immediate good feelings produced by METH, abuse of the drug also has been linked to aggression, crime, impaired cognition, and risky behaviors. Because of the dramatically negative impact of METH abuse on individuals, families, and society at large, it is imperative to develop treatments to help METH-dependent individuals stop their addiction. Effective treatments for this purpose are lacking, but brain imaging studies are providing the information needed to design treatments based on METH-related problems in brain function.

Brain structure, studied with MRI scanning, shows remarkable deficits in research subjects that received the diagnosis of METH dependence and then stopped using the drug for 1-4 weeks. In these subjects, gray matter volume (generally reflecting the number and size of nerve cells) is smaller, especially in the cerebral cortex on the medial surface of brain, in regions that are important for mood and control of certain cognitive processes (e.g., monitoring errors, focusing attention). In contrast to these observations, former users who have resisted METH for months exhibit larger gray matter volumes in several brain areas than healthy people. Further research is needed to determine whether these possible rebound effects reflect a rebound with improved brain function in prolonged abstinence.

PET scans that use a radioactive form of glucose have revealed deficits in brain function during early abstinence from METH (4 -11 days), yielding information on the state of the brain of a METH abuser at the beginning of a treatment episode. Activity is measured by how fast different brain regions use glucose as a source of energy; very active regions use glucose rapidly. Activity is abnormally low in medial portions of the cerebral cortex (including those with structural deficits noted above), and is related to symptoms of depression in METH abusers. This finding accompanies unusually high relative activity in other areas that mediate emotional responses to environmental triggers and that operate under control of the cerebral cortex. These scans suggest that METH can impair cortical control, resulting in unchecked, abnormally strong reactions to cues in the environment.

Another brain imaging technique, functional MRI (fMRI), is providing additional evidence that METH abusers suffer a loss of inhibitory control from the cortex. METH abusers in early abstinence view pictures of threatening or of emotionally evocative items, and are provided with training (reappraisal techniques) in how to suppress negative feelings. While they report weaker emotional responses to the pictures than healthy subjects, they show heightened activity of the amygdala, a brain region important in mediating emotion. In addition, while the healthy participants activate a portion of the prefrontal cortex during successful suppression of negative feeling, the METH abusers do not show this activation, again suggesting a loss of cortical control.

Related to these findings, a new direction targets impaired inhibitory control mechanisms in METH addicts. For example, under consideration is modafinil, a drug that shows evidence of improving inhibitory control in healthy subjects, and in others with attention deficit-hyperactivity disorder or schizophrenia. It is important to consider, however, that METH dependence is a complicated disorder, and bolstering inhibitory control function may help only some METH abusers who seek treatment. It may be necessary to characterize the range of factors that maintain dependence in individual clients with the understanding that one treatment may not be best for all. 

Last Modified: January 31, 2008

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