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Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, Lee JY, Toga AW, Ling W, London ED. 
“Structural abnormalities in the brains of human subjects who use methamphetamine”. 
J Neurosci. 2004 Jun 30;24(26):6028-36.
We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.
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Apr 17, 2011 1:59
Forest Fire Metaphor and Cognitive Testing Issues #

This paper also uses the same subject set as London 2004.

Note that both of these papers are detailing the acute withdrawal of long time methamphetamin users, 4-7 days after they went into rehab. Although frequently mis-represented to show long term damage, this paper does not, by design, show that. If they wanted to show lasting damage, they should do tests months and years after cessation of use.

This is a decent paper, but the news hype for it exaggerates the speed of the damage and doesn't mention a confounding issue with the memory and depression tests that were given.

The NY Times story quotes the lead researcher:
'a forest fire of brain damage,' said Dr. Paul Thompson, an expert on brain mapping at the University of California, Los Angeles. 'We expected some brain changes but didn't expect so much tissue to be destroyed.'
The two main problems with the reporting are:
  1. Forest Fire metaphor suggests damage happened quickly
  2. Cognitive Tests used cannot be considered reliable because of very short abstinence period
The MRI's showing actual tissue damage are quite concerning. Although tissue damage is expected from methamphetamine use, the extent of the damage is somewhat higher than expected. Although it is usually a mistake to jump on findings of a single study and assume they accurately reflect The Truth, the tissue damage mapping are assumed correct.

The 'Forest Fire' metaphor Dr. Thompson uses might more appropriately be an erosion problem, since the average use in the study was over 10 years with an average of 3.5 grams per week over the entire period! That's a whole lot of methamphetamine use. Smouldering pile, perhaps.

The problem with the research and not just the reporting, however, is that the neurocognitive tests that showed actual cognitive problems are not as strong as the physical data. The tests were administered to chronic methamphetamine users about 7 days after their last dose. The researchers report that the meth users had used meth 19 days of the last 30 days, with an average period of abstinence just prior to the testing of 6.5 days. Its possible I'm reading this wrong (and I'll write to the authors to see), but that means that of the last 30 days, the last week was in withdrawal and 19 of the 23 other days they were using the meth.

It seems little surprise that after 10 years of near-daily stimulant use, it would be hard to concentrate on boring, repetitive tasks as well as better educated, healthy, well-rested controls.

So, despite the problems with the design of the study, the results showing the damage are very likely correct. And users should be aware they face a 'beach erosion of brain damage' if they use methamphetamine at rates this high.
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