Cognitive Impairment in Methamphetamine Buprenorphin and Tramadol Users

European Journal of Scientific Research ISSN 1450-216X Vol.68 No.3 (2012), pp. 321-327 EuroJournals Publishing, Inc. 2012 http://www.europeanjournalofscientificresearch.com Cognitive Impairment in Methamphetamine Buprenorphin and Tramadol Users Zakaryaee, H. Corresponding Author, MA, Dept of Clinical Psychology Islamic Azad University, Arsanjan Branch, Iran E-mail: zakarya832@gmail.com Mollazadeh, J. PhD, Dept of Clinical Psychology, Shiraz University, Iran E-mail: molazade.javad@gmail.com Aflakseir, A. PhD, Dept of Clinical Psychology, Shiraz University, Iran E-mail: aaflakseir@shirazu.ac.ir Khormaei, F. PhD, Dept of Clinical Psychology, Shiraz University, Iran E-mail: khormaee_78@yahoo.com Soofi, A. Medical School, Shiraz University of Medical Sciences, Iran E-mail: shokrpourn@gmail.com Abstract Drug use, a common problem in many countries, has led to cognitive impairment, having neuropsychological effects. The present study was to address this issue by comparing the performance of users and non-users of drugs. In this study, 104 participants were enrolled in four groups (26 methamphetamine, 26 buprenorphine and 26 tramadol abstinence group with 26 non-users in the control group) matched for education and mail gender. The three neuropsychological tests used were Word-color stroop test, Wisconsin classified papers test, and Wechesler Memory Scale (WMS). To analyze the data, multivariate analysis of variance (Manova) and for moderating variables (dose and during of drug use) covariance method were used. The analysis of data showed that there were significant differences between the drug users and the control group [F(15/265)=33/97, P<./000, Partial λ=./627]. The results indicated that the use of methamphetamine, buprenorphine and tramadol negatively affects the individuals' neuropsychological performance. Keywords: Cognitive impairment, Addiction, Methamphetamine, Buprenorphine, Tramadol

Cognitive Impairment in Methamphetamine Buprenorphin and Tramadol Users 322 1. Introduction Addiction to any drug or substance is common throughout the world, being considered as a serious problem. 1 Despite our increasing knowledge about its harmful effects, drug use is growing around the world. 2 For example, marijuana, which leads to sustained major problems in short term memory and learning new information, is used in most countries. 1 Today, among other drugs Methamphetamine can be noted as a public concern in various countries. 3 Brain image studies and neuropsychological tests have shown that all drugs make changes in the brain, reducing its function. 4 In addition, drug users show reduced memory and verbal learning, psychomotor speed, transmission and response inhibition. 3 Reduced psychomotor speed and eye-hand coordination, problems in executive functions, 2 problems in cognitive flexibility, control of inappropriate responses and repetitive errors in cognitive skills, 5 concentration, attention, reminder, visual spatial and psychomotor speed skills in any type of acute or chronic use are common. 2 Working memory, fluid intelligence, and executive function have shown significant differences in the first period of abstinence; some studies have indicated that reduced executive function can also be seen in the next abstinence. 6 This finding is consistent with the rate of zero correlation found between days of abstinence and visual performance reduction. A non-significant negative correlation between visual function and duration of drug use has been reported 7,8 while previous studies have reported a negative correlation between the dosage of use and visual performance. 9 Memory, verbal skills and visual spatial function were more affected in heroin and methadone users than the control group. 10 In methadone users and drug dependent patients, significant deficiencies have been reported in the verbal intelligence, visual perception, visual memory and divided attention with response inhibition-stroop test. 10 The results showed that heroin dependency had a negative effect on impulse control 6 and cocaine had a negative impact on visual memory; in some patients defects in verbal skills were mentioned. 11 Chronic methamphetamine abusers have shown significant impairments in external dimentional changes (one of the main components of Wisconsin card sorting), while heroin users were affected in learning internal dimensional changes.12 In both groups, some aspects of spatial memory showed defects and recognition memory pattern, being sensitive to temporal lobe damage, was reduced, producing less fluid words in the verbal test. Reduction in memory and psychomotor speed with one year or more abstinance in methamphetamine users 13 and similarities with frontal lobe damage patients have been reported. 3 Research on young (mean age of 19 years) methamphetamine users reported that the dopaminergic system was affected even for months to years of follow-up after abstinence 14,15,3,16 and the subcortical, frontal, and temporal lobes have shown disfunction. 3 The frontal lobe has been introduced to be a mediator in cognitive responses to therapeutic intervention. 17 Other studies have shown that reduction in dopamine neurotransmitter in methamphetamine users is associated with a decline in motor function and memory; however, the level of decrease is less than that in Parkinson s patients 13 and white matter damage patients. 18 In another study by Volkow et al. 13 it was reported that methamphetamine users showed neurological disfunction even after a year or more of abstainance, and heroin users showed reduced attention, working memory, verbal fluency and periodical memory. 8 But conflicting research 19 on patients with a history of six month of abstinence did not find specific cognitive defects. Brain biochemical studies have shown that serotonin poisoning occurs in ecstasy users 20 ; verbal and working memory is decreased in buprenorphin and methadone/naloxone users. 21 Some evidence indicates that buprenorphin's destructive effects on attention are less than methadone. 22 However, both methadone and buprenorphine users reduced visual memory more than the control group, even after 12 months of abstinence. 23 In contrast, in another research 24, 23 mg of buprenorphine did not create cognitive destructive performance in drug users. It seems that the type of drug, dosage, and individual vulnerability are variables that affect cognitive impairment. In other words, these factors may increase or modulate cognitive impairment. These effects can also appear in cognitive functioning in a wide range of attention, concentration, visual and verbal recall in any form of acute and chronic use. 20 Generally

323 Zakaryaee, H., Mollazadeh, J., Aflakseir, A., Khormaei, F. and Soofi, A. decreased cerebral blood flow -associated with dependency- is one of the main factors leading to inadequate brain energy and the changes release several neurotransmitters such as acetylcholine and cathecholamines. 25,26 It should be reminded that cathecholamine is important to formation of working memory and acetylcholine is considered as an essential factor for learning and memory consolidation. 27 Methamphetamine could potentially damage terminal axons in dopaminergic and srotonergic system. 5 The review literature in this field shows that there is a focus on three clear interaction areas: 1) Cognitive Impairment: including abstract thinking, cognitive transition, attention, memory, verbal fluency, etc. 2) Neurological Dysfunction: including the frontal and prefrontal cortex, hippocampus. 3) Neurotransmitters: including dopamine, serotonin, acetylcholine. 2. Methods 2.1. Participants As tramadol is not commonly used among women in Iran, participation of the women in the study was not possible. Therefore, in the large group of men who visited the outpatient addiction treatment centers of Shiraz University of Medical Sciences, three groups of metamphetamaine, Buprenorphine and tramadol users were selected (26 for each group, N=104). Based on the initial interview, the following criteria were considered as exclusion criteria: 1) History of poly-substance use 2) History of head trauma, brain damage and mental retardation 3) History of less than one year of drug use 4) Educational level lower than grade 8 5) Major psychotic disorders and hospitalization 6) Age under 18 years 7) Positive result of morphine in the urine The instruments used were Word-color stroop test,wisconsin card sorting test, and Wechesler Memory Scale. 2.2. Material Incomplete data were not included in the analysis. Demographic data and the participants' medical records and the history of disorders were recorded based on their self report. All the users were aged 18-25 years. The users had a past history of occasional use of other drugs but did not meet the polysubstance user criteria 2.3. Procedure The participants were interviewed at first by a trained clinical psychologist and did not meet any meaningful criteria in AXIS I except drug dependence. Duration of the participants' abstinence when taking part in the study was between 1 to 3 months (30-90 days). The distance between interview and the test was one day. Morphine urine test was used before the test and the participants who were positive were excluded from the study. A matched control group was selected from the local people. During the test, the participants in both groups did not use alchol and other drugs except cigarette. Past history of occational alchol use was found in the control group, the last use being three months ago. 3. Results Table 1 displays descriptive results of the drug use.

Cognitive Impairment in Methamphetamine Buprenorphin and Tramadol Users 324 Table 1: Does and duration of drug use Drug Does (per day) Drug use Duration(months) Range Methamphetamine. / 2 g 15./1g -./3g Buprenorphin 20 mg 15.6 18mg 22mg Tramadol 900 mg 14.6 400 mg-1300 mg First, the data were analyzed using one-way analysis of variance (ANOVA). There was a significant difference between the users and control group. The result for five dependent variables are as follows: Error number in stroop test [F(3,100 = 60.13), P<.000 ], Elapsed time in stroop test [F(3,103 = 14), P<.000 ], Error number (perseveration) in Wisconsin test [F(3,100 = 82.55), P<.000 ], Category number in Wisconsin test [F(3,100 = 64), P<.000 ], and Wechesler memory scale (WMS) [F(3,100 = 39.38), P<.000] (see Table 2). Table 2: Comparison of the drug users and control group Stroop error Stroop time Wi. Perseveration Wi. category WMS Sum of Df Squares Square F Sig. Between Groups 734.308 3 244.769 60.128.000 Within Groups 407.077 100 4.071 Total 1141.385 103 Between Groups 6577.567 3 2192.522 14.003.000 Within Groups 15657.808 100 156.578 Total 22235.375 103 Between Groups 41018.644 3 13672.881 82.545.000 Within Groups 16564.192 100 165.642 Total 57582.837 103 Between Groups 168.183 3 56.061 64.013.000 Within Groups 87.577 100.876 Total 255.760 103 Between Groups 2532.385 3 844.128 39.317.000 Within Groups 2147.000 100 21.470 Total 4679.385 103 Multivariate analysis of variance (Manova) was used for analysis. Based on the results, there were a significant difference between the users and control group in all dependent variables combined: [F(15/265)=33/97, P<./000, Partial λ=./627] (see Table 3). Table 3: Comparison of the drug users and the control group in Effect Value F Hypothesis df Error df Sig. Partial Eta Squared Pillai's Trace 1.209 13.232 15.000 294.000.000.403 Wilks' Lambda.052 33.970 15.000 265.415.000.627 Hotelling's Trace 13.486 85.113 15.000 284.000.000.818 Roy's Largest Root 13.144 2.576E2 b 5.000 98.000.000.929 For moderating variables [dose (per day) and the duration of drug use (per month) ], covariance method was used and the following results were obtained (Table 4).

325 Zakaryaee, H., Mollazadeh, J., Aflakseir, A., Khormaei, F. and Soofi, A. Table 4: Source Gruope Error Covariance table for Dose (use per day) and drug use duration (months) Dependent Type III Sum Partial Eta df F Sig. Variable of Squares Square Squared Stroop error 70.078 3 23.359 6.270.001.161 Stroop time 2572.071 3 857.357 5.801.001.151 WI.perseveration 295.352 3 98.451.682.05.020 WI.category 3.915 3 1.305 1.527.04.045 WMS 318.788 3 106.263 8.988.000.216 Stroop error 365.126 98 3.726 Stroop time 14482.833 98 147.784 WI.perseveration 14137.897 98 144.264 WI.category 83.764 98.855 WMS 1158.575 98 11.822 4. Discussion According to the results, chronic use of methamphetamine, buprenorphine and tramadol has a negative effect on neuropsychological performance. This study showed that the users have lower performance in attention/response inhibition and cognitive shift compared with the control group; smilar results have been obtained in the users of other drug in the previous research. 28,29,20,2 In other words, methamphetamine, buprenorphine and tramadol use has a negative effect on the frontal lobe and executive functions such as attention and response inhibition. Therefore, this finding can indicate defects in the frontal cortex. 6,3 In the researchers' opinion, declined cognitive function in the users on Stroop test can explain a part of the inability of the users in abstinence - as the users in the Stroop test were unable to separate two factors (color and word) and provide adaptive responses. They were also unable to separate adaptive and non-adaptive responses and did not provide adaptive inhibition responses in social situations associated with drug, i.e. continuous use and failure in abstinence. Performance of the user group in the Wisconsin card sorting test showed a significant difference. Pervious studies have reported similar results. 12,6,2,27,28 Recent studies report the frontal cortex as being responsible in Wisconsin test performance. 30 As the adaptive response in this test requires high cognitive flexibility and ability to understand and build abstract concepts, the users inability in sorting cards in Wisconsin test is probably the consequence of disruption in cognitive flexibility, understanding of abstract conceptualization and frontal lobe dysfunction. The user group showed a significant difference in comparison with the control group in the Wechsler memory test. Memory deficiency in users is in the same line with the findings of the previous studies. 12,14,3,8,27,30 Defects in learning, semantic memory, visual memory and working memory can indicate dysfunction in the hippocampus and reduced levels of acetylcholine and katecholamine neurotransmitters. 27,21 Also, memory defects have a relationship with seretonergic and dopaminergic system 5 and decreased cerebral blood flow as well. 25 But it is noteworthy to mention that personal information memory and orientation were not defective. This finding is consistent with previous research, showing that merely drug dependency has no significant effect on the personal information and orientation. It can be concluded that drug has a negative impact on at least one stage of memory formation or consolidation. In our opinion, drugs can interfere with memory in necessary chemical changes in synapses during storage, consolidation, remember or recall phase, probably damaging responsible areas for memory in the hippocampus. With regard to the results of previous research as well as those of this study, it can be suggested that drug use has negative effects on the field of cognitive skills like memory, abstract thinking, concentration, and other aspects such as prefrontal, frontal cortex and hippocampus, and brain biochemical filed such as dopamine, serotonin and acetylcholine. It seems essentially noteworthy that follow up and long-term research can provide further knowledge. Conflicting studies on the history of users with six months of abstinence have reported no specific cognitive defects. 19,13 This finding could indicate that cognitive defects probably recover after abstinence or other variables affect

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