TL neuro

March 27, 2012

Cognitive impairment in Khat users

Filed under: Cathinones, Cognition — mtaffe @ 1:52 pm

ResearchBlogging.orgA recently published study examines the cognitive effects of khat (Catha edulis) chewing. Colzato and colleagues (2011) recruited 20 khat users with 10.5 (6.5 SD) years of use, averaging 3.1 (1.8 SD) times per week. The average time spent chewing khat in each session was 5.8 hrs (1.7 SD) and all khat users met at least four criteria which define addiction under DSM-IV or ICD-10 criteria. Marijuana consumption in these individuals and the khat-free controls was about 2 joints per week, they consumed 6-8 drinks per week and had zero lifetime exposure to cocaine, amphetamines or ketamine. Subjects were also matched on IQ (using the Ravens Standard Matrices), age (~31 years), ethnicity/origin (all African) and sex (2 female in each group), although two male subjects from the khat-user group had to be excluded for excessive error rates in the switching task.

The primary behavioral measures were an N-back task (Wikipedia) and a task-switching (Wikipedia) task. The N-back is a test of working memory in which single letters are presented sequentially on a computer screen. The subject is to respond when the current letter matches the one immediately previously presented (1-back trials) or the one presented two trials before (2-back trials). The task switching task first involved blocks of trials of the discrimination of large stimulus shapes (square, rectangle) made up of lines outlined by smaller shapes with subjects to respond initially to only the “global” or “local” shape element. (Examples of similar global/local stimuli can be found here and here.) The critical test trial consisted of trials in which the response to “global” or “local” was cued across 4 trial mini-blocks with the primary outcome measures being the response time in the “switch” versus “repetition” trial types.

The study found significant reductions in accuracy within the khat user group on the 1-back (70 vs 91% correct) and 2-back (62 vs 81% correct) trials in the working memory task. Significant increases in switching cost (difference between trials where the global/local cue was the same versus when they had to switch from global to local or vice versa) were found in the khat user group compared with controls (87 vs 37 ms) in the Task Switching test as well. Together these data suggest (within the usual limits of the non-random group assignment) that chronic exposure to khat produces cognitive deficits.

The authors point to other findings of impaired inhibitory control and/or working memory in amphetamine users as evidence of a parallel effect of the active psychoactive constituents of khat which include cathinone, phenylpropanolamine and cathine (norpseudoephedrine). If so, this suggests that imaging and post-mortem investigations should be directed at dopaminergic systems of khat users.

One final caveat to the investigation is that the subjects were requested to remain drug free (including alcohol) for 24 hrs prior to the study. Given that the khat users met 4 criteria traditionally associated with addiction and dependence, it may be the case that these findings reflect acute withdrawal and cannot necessarily be inferred to represent permanent, lasting effects of chronic khat chewing.

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Colzato LS, Ruiz MJ, van den Wildenberg WP, & Hommel B (2011). Khat use is associated with impaired working memory and cognitive flexibility. PloS one, 6 (6) PMID: 21698275

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February 29, 2012

Δ9-Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory

Filed under: Cannabis, CANTAB, Cognition, MDMA, SOSS, vsPAL — mtaffe @ 6:59 am

This paper has been accepted for publication:

Taffe, M.A. Δ9-Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques, J Psychopharmacol, October 2012 26: 1299-1306, first published on April 22, 2012 doi:10.1177/0269881112443743 [PubMed] [DOI]

In this paper we show that acute treatment with Δ9-THC interferes with the performance of two memory tasks in a manner that depends on both trial difficulty within the task and the dose administered. These results contrast with much prior literature using recognition memory or related tasks in which the effect of THC did not appear to be task specific, i.e., degrading performance in a difficulty-dependent manner. Our results are consistent with a prior observations using spatial delayed response tasks, further emphasizing a role for intact endocannabinoid function in spatial and/or working memory and learning.

Figure 3. The mean (N=4; ±SEM) percentage of trials correctly performed in the vsPAL task on the first attempt, and after a maximum of 6 attempts, are presented for baseline, vehicle and THC treatment conditions. The open symbols indicate significantly improved trial completion after repetition when compared with the initial attempt for a given treatment condition and trial type. Within a given trial-difficulty level, a significant difference from the vehicle and baseline conditions is indicated by #, from the vehicle condition (only) by &, and a difference from the 0.1 mg/kg condition by *.

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