Thursday, December 01, 2011

Meth Really Isn't That Bad for You? (Part 2)

Methamphetamine Use and Risk for HIV/AIDS

... Methamphetamine is very addictive, it can be injected, and it can increase sexual arousal while reducing inhibitions. Because of these attributes, public health officials are concerned that users may be putting themselves at increased risk of acquiring or transmitting HIV infection―a valid concern, considering that methamphetamine use has been linked with increased numbers of HIV infections in some populations [1]. 1

Meth addiction can cause alterations in brain function and cognitive performance, according to hundreds of published studies (reviewed in Barr et al., 2006; Baicy & London, 2007). However, a new paper concludes that prior studies have exaggerated the harmful effects of methamphetamine on brain structure and function, cognition, mental health, and dental health (Hart et al., 2011).

So who's right? The previous post (Meth Really Isn't That Bad for You... Or is it?) covered the acute effects of meth on cognitive performance. This post will focus on the cognitive consequences of chronic meth abuse. The bulk of the literature suggests that long-term use "leads to neurocognitive deficits in a dose-dependent manner, with deficits relating to both the frequency and severity of METH dependence" (McCann et al., 2008). In that study, chronic meth users performed worse than controls on some tests of memory and attention, with intact performance on other tests. Another paper found similar differences between controls and former meth users (abstinent anywhere from 3 months to over 1o yrs) on some tests but not others (Johanson et al. , 2006). Those authors were cautious in interpreting their findings:
In the present study, MA users showed deficits in the DSST [Digit Symbol Substitution Test] of the WAIS-III relative to the controls. However, neither the mean standard score (9.63) nor individual scores were greater than one SD (3) below the age-controlled norm (10.0). This finding suggests that although MA may produce long-term, possibly irreversible deficits in speed and accuracy of information manipulation, these deficits are relatively small and for some may not reach clinical significance.
...and...
In the present investigation, MA users showed significantly poorer performance on several of the subtests of the CVLT [California Verbal Learning Test] including both cued and noncued short and long delayed recall. However, despite this statistically significant difference compared to controls, their performance was not outside the normal range for their age group. Thus, the functional significance of these differences in memory function is questionable. Nevertheless, it seems likely that these deficits are permanent because they were not correlated with duration of abstinence. It is obvious that the possibility remains that these deficits predated drug use but the present study cannot address this possibility.
These statements were much appreciated in the review article, which repeatedly downplayed observations of poorer performance as having any functional significance whatsoever. However, I will draw your attention to Johanson et al. 's inclusionary criteria and their table below:
To qualify for the study, MA participants had to report at least one 3-month period when they experienced MA-induced toxic symptoms (agitation, sleeplessness, paranoia, or tremors).

Table 5 (Johanson et al. , 2006). Other self-reported symptoms



Clearly, every symptom listed above is of functional significance. Meth use was detrimental to many areas of their lives when they were using. However, those participants were given the cognitive tests a mean of 3.4 yrs after they stopped using. We'll return to the issue of recovery a bit later.

Returning now to the comparison of acute low dose meth vs. chronic abuse, in the abstract Hart et al. (2011) stated:
In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures.
Let’s take a closer look. Of the 16 studies on the acute effects of meth shown in Table 1 of Hart et al., five of them (by the authors) tested inhibitory control. Meth had no effect on inhibition performance in any of those studies.

Am I just being persnickety? Well, if the authors are going to say that long-term meth abuse results in “poorer performance on a minority of cognitive tasks” [which appears to be true in many cases], they should be more precise when describing their own data. Perhaps something like this: "Acute meth sometimes improves the performance of infrequent users on a minority of cognitive tasks, but these results are inconsistent (see Table 1)."

Again, what about the specific cognitive impairments observed in chronic abusers? There was a didactic paragraph on the use on the word “impairment”:
The literature on methamphetamine use is focused on ‘impairment,’ and seems to conflate two different meanings of this term. One meaning is captured by the canonical situation in which one group of participants performs statistically significantly less well on a task than does a control group. Although there is a statistically significant difference, its clinical relevance, or everyday import, is rarely specified. A second meaning of ‘impairment’ is that of a substantial loss of function, a dysfunction, in which performance may even fall outside of normal range and bears clinical significance. (The two meanings probably represent end points on a continuum of meanings of ‘impairment’ that appears in the general literature on group differences.) The problem in the literature on methamphetamine use is that in many studies the results support only the first or difference interpretation, but the results are discussed in terms of the ‘dysfunctional’ interpretation. In essence, the English word ‘impairment’ (or ‘deficit’) is ambiguous, and researchers in this field often switch meanings in moving from actual findings to discussion of the implications of these findings.
One reason for avoiding use of the word “impairment” is to reduce the stigma attached to meth abuse, which is an important goal. To that end, it’s puzzling that the authors failed to cite some of the literature on recovery.

GREEN RED BLUE

One such paper (Salo et al., 2009) compared 38 recently-abstinent meth abusers (3 weeks to 6 months), 27 longer-abstinent meth abusers (at least 1 yr), and 33 controls on the Stroop Color-Word Interference Test. In this task, the participant is instructed to say the font color and ignore the word. It's much more automatic to read the word than to say the font color, so people are slower to respond when the two dimensions are in conflict ("Stroop effect"). Successful performance on this task requires cognitive control to overcome the routine behavior.

The results suggested that cognitive performance improved with persistent drug abstinence (Salo et al., 2009). The Stroop effect was significantly greater in the recent abstainers (186 msec) than in both the long-term abstainers (138 msec) and the controls (132 msec), who did not differ from each other. Furthermore, the increase in Stroop interference correlated with years of meth abuse, and any relative decrease correlated with the length of abstinence.

The long- and short-term abstainers were very well matched on years of use (13.9 vs. 13.4 yrs), age at first use, current age, and total years of education, yet they still differed from each other. One criticism of Hart et al. is that control groups are often not well-matched to the MA abusers for age and especially for education. The meth abusers typically have less education than controls (perhaps because they started using in their late teens), and this could present a problem in some tasks. In the current study, the same results persisted in an additional analysis that controlled for differences in education and an estimate of pre-meth-use IQ.

In my opinion, the review raises legitimate issues about how certain findings are interpreted, but then waves away all control data as invalid, therefore the addicted folks aren't impaired (in either sense of the term). A paper by Kim et al (2009) merited two paragraphs of critique because there are no published Korean norms for the Wisconsin Card Sorting Task (WCST). This was despite the fact that meth users performed significantly worse than controls (p<.01) on the three WCST measures listed. Then the lower education level of the meth abusers (10.5 yrs vs. 12.4 yrs in controls) was brought up as a confound, because it is "known" that education affects WCST performance. However, one of the cited papers did not demonstrate that at all, because the effects of education were no longer significant when the data were corrected for multiple comparisons.

At any rate, doesn't the fact that the meth abusers were high school dropouts tell you anything?? One suggestion for researchers in the field would be to relate their cognitive and brain findings to functional outcomes in daily life. The literature is rather extensive (and mostly unfamiliar to me), so there might be a raft of papers that have already done this, but went uncited in the review article.

Ending on a positive note, studies finding improvements in cognitive performance and normalization of brain function after quitting the drug offer hope for the future, as noted by Salo et al. (2009):
The understanding of how the human brain may recover or partially recover as a function of extended drug abstinence has important implications both for the neurobiology of addiction as well as substance abuse treatment. If cognitive improvements occur across extended periods of abstinence; this finding would be clinically salient. These cognitive improvements can then be applied in substance abuse treatment programs and utilized as predictors of treatment outcome in vulnerable difficult to treat populations (Streeter et al., 2008).


Footnote

1 Also see The New Yorker, “HIGHER RISK: Crystal meth, the Internet, and dangerous choices about AIDS” {PDF}.


References

Baicy K, London ED. (2007). Corticolimbic dysregulation and chronic methamphetamine abuse. Addiction 102 Suppl 1:5-15.

Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, Lecomte T. (2006). The need for speed: an update on methamphetamine addiction. J Psychiatry Neurosci. 31:301-13.

Hart, C., Marvin, C., Silver, R., & Smith, E. (2011). Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review. Neuropsychopharmacology DOI: 10.1038/npp.2011.276

Johanson CE, Frey KA, Lundahl LH, Keenan P, Lockhart N, Roll J, Galloway GP, Koeppe RA, Kilbourn MR, Robbins T, Schuster CR. (2006). Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers. Psychopharmacology 185: 327–338.

McCann UD, Kuwabara H, Kumar A, Palermo M, Abbey R, Brasic J, Ye W, Alexander M, Dannals RF, Wong DF, Ricaurte GA (2008). Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users. Synapse 62: 91–100.

Salo, R., Nordahl, T., Galloway, G., Moore, C., Waters, C., & Leamon, M. (2009). Drug abstinence and cognitive control in methamphetamine-dependent individuals. Journal of Substance Abuse Treatment, 37 (3), 292-297 DOI: 10.1016/j.jsat.2009.03.004




...I am a glass human. I am a glass human disappearing in rain. I am standing among all of you waving my invisible arms and hands. I am shouting my invisible words. I am getting so weary. I am growing tired. I am waving to you from here. I am crawling around looking for the aperture of complete and final emptiness. I am vibrating in isolation among you. I am screaming but it comes out like pieces of clear ice. I am signalling that the volume of all this is too high. I am waving. I am waving my hands. I am disappearing. I am disappearing but not fast enough*

-David Wojnarowicz,
Memories That Smell Like Gasoline (spiral)

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