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CORK Bibliography: Drug Use and Memory

46 citations. January 2009 to present

Prepared: June 2011

Bartholomew J; Holroyd S; Heffernan TM. Does cannabis use affect prospective memory in young adults? Journal of Psychopharmacology 24(2): 241-246, 2010. (39 refs.)

The aim of the present study was to examine prospective memory impairments associated with cannabis use in young adults. An independent measures design utilising pre-existing groups of users and non-users was employed in which an opportunity sample of 90 undergraduates studying at universities in the north east of England participated. The number of prospective memory failures reported on the Prospective Memory Questionnaire and the number of location-action combinations correctly recalled during a video-based prospective memory task were measured. The number of strategies used to assist memory, level of anxiety and depression, and use of alcohol, nicotine and any other recreational drugs in addition to cannabis were also measured and controlled during the analysis. Analysis revealed no significant differences in the number of self-reported prospective memory failures; however, cannabis users recalled significantly fewer location-action combinations than non-users in the video-based prospective memory task. The findings from the present study suggest that cannabis use has a detrimental effect on prospective memory ability in young adults but users may not be aware of these deficits.

Battisti RA; Roodenrys S; Johnstone SJ; Respondek C; Hermens DF; Solowij N. Chronic use of cannabis and poor neural efficiency in verbal memory ability. Psychopharmacology 209(4): 319-330, 2010. (50 refs.)

The endogenous cannabinoid system is sensitive to the introduction of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, which are known to impact upon memory functioning. We sought to examine the impact of chronic cannabis use upon memory-related brain function via examination of the subsequent memory effect (SME) of the event-related potential (ERP). The SME is predictive of recall outcome and originates in structures that are dense with cannabinoid receptors (hippocampus and parahippocampus). The SME and performance on a verbal memory task were compared between 24 cannabis users (mean 17 years of near daily use) in the unintoxicated state and 24 non-using controls. The task involved the presentation of word lists, each with a short delay before recall. ERPs were recorded during encoding and later averaged by outcome (correctly recalled/not recalled). Cannabis users showed poorer recall and altered patterns of SME activation: specifically, attenuation of the negative N4 and an increase in the late positive component. Duration of cannabis use and age of initial use correlated significantly with SME amplitudes. A longer history of use also correlated with greater recall that was related to N4 expression. The results indicate that relative to non-using controls, chronic users of cannabis have altered memory-related brain activation in the form of dysfunctional SME production and/or poorer neural efficiency, which is associated with deficits in memory recall. Greater alteration was associated with a longer history of cannabis use and an earlier onset of use. Neuroadaptation to the effects of chronic exposure may additionally play a role.

Becker B; Wagner D; Gouzoulis-Mayfrank E; Spuentrup E; Daumann J. Altered parahippocampal functioning in cannabis users is related to the frequency of use. Psychopharmacology 209(4): 361-374, 2010. (63 refs.)

Converging lines of evidence suggest an association between cannabis use and impaired episodic memory as well as related associative learning. These deficits have been associated with the duration, frequency, and age of onset of cannabis use. However, it remains unclear whether these parameters of use differently impact memory-related hippocampal functioning. Forty-two cannabis users were examined by means of functional magnetic resonance imaging while they encoded and retrieved face-profession associations. Region of interest analysis was subsequently used to compare (para-)hippocampal functioning in users with (1) a longer and shorter duration of use, (2) a higher and lower frequency of use, and (3) an earlier and later onset. To further separate the effects of these parameters of use on performance and (para-)hippocampal activity, linear regression analysis was applied. Compared to low-frequency users, high-frequency users displayed stronger blood oxygenation level-dependent response during encoding in the left parahippocampal gyrus. No differences were obvious for the groups separated according to duration of use or an earlier and later onset of use. Linear regression analysis confirmed the association between a higher frequency of use and increased activity in the left parahippocampal gyrus. Our findings suggest that the frequency of use might have a particular critical impact on intact parahippocampal functioning in cannabis users. Increased activity within the encoding-related network might reflect functional compensation to maintain cognitive functioning.

Becker B; Wagner D; Gouzoulis-Mayfrank E; Spuentrup E; Daumann J. The impact of early-onset cannabis use on functional brain correlates of working memory. (review). Progress In Neuro-Psychopharmacology & Biological Psychiatry 34(6): 837-845, 2010. (69 refs.)

Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n = 26) and (2) late-onset cannabis users (age at onset at least sixteen; n = 17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations.

Brigham J; Lessov-Schlaggar CN; Javitz HS; Krasnow RE; Tildesley E; Andrews J et al. Validity of recall of tobacco use in two prospective cohorts. American Journal of Epidemiology 172(7): 828-835, 2010. (32 refs.)

This project studied the convergent validity of current recall of tobacco-related health behaviors, compared with prospective self-report collected earlier at two sites. Cohorts were from the Oregon Research Institute at Eugene (N = 346, collected 19.5 years earlier) and the University of Pittsburgh, Pennsylvaniasylvania (N = 294, collected 3.9 years earlier). Current recall was examined through computer-assisted interviews with the Lifetime Tobacco Use Questionnaire from 2005 through 2008. Convergent validity estimates demonstrated variability. Validity estimates of some tobacco use measures were significant for Oregon subjects (age at first cigarette, number of cigarettes/day, quit attempts yes/no and number of attempts, and abstinence symptoms at quitting; all P < 0.03). Validity estimates of Pittsburgh subjects' self-reports of tobacco use and abstinence symptoms were significant (P < 0.001) for all tobacco use and abstinence symptoms and for responses to initial use of tobacco. These findings support the utility of collecting recalled self-report information for reconstructing salient lifetime health behaviors and underscore the need for careful interpretation.

Brown J; McKone E; Ward J. Deficits of long-term memory in ecstasy users are related to cognitive complexity of the task. Psychopharmacology 209(1): 51-67, 2010. (84 refs.)

Despite animal evidence that methylenedioxymethamphetamine (ecstasy) causes lasting damage in brain regions related to long-term memory, results regarding human memory performance have been variable. This variability may reflect the cognitive complexity of the memory tasks. However, previous studies have tested only a limited range of cognitive complexity. Furthermore, comparisons across different studies are made difficult by regional variations in ecstasy composition and patterns of use. The objective of this study is to evaluate ecstasy-related deficits in human verbal memory over a wide range of cognitive complexity using subjects drawn from a single geographical population. Ecstasy users were compared to non-drug using controls on verbal tasks with low cognitive complexity (stem completion), moderate cognitive complexity (stem-cued recall and word list learning) and high cognitive complexity (California Verbal Learning Test, Verbal Paired Associates and a novel Verbal Triplet Associates test). Where significant differences were found, both groups were also compared to cannabis users. More cognitively complex memory tasks were associated with clearer ecstasy-related deficits than low complexity tasks. In the most cognitively demanding task, ecstasy-related deficits remained even after multiple learning opportunities, whereas the performance of cannabis users approached that of non-drug using controls. Ecstasy users also had weaker deliberate strategy use than both non-drug and cannabis controls. Results: were consistent with the proposal that ecstasy-related memory deficits are more reliable on tasks with greater cognitive complexity. This could arise either because such tasks require a greater contribution from the frontal lobe or because they require greater interaction between multiple brain regions.

Capek S; Guenther RK. Caffeine's effects on true and false memory. Psychological Reports 104(3): 787-795, 2009. (31 refs.)

Caffeine's effects on recall of word lists were investigated using the Deese-Roediger-McDermott (DRM) paradigm. College students were administered either 200 mg of caffeine or a 250-mg lactose placebo; after 30 min., they were tested on recall using six word lists. Words of each list were semantically related to a single word (a "critical lure") that was not presented in the list. Participants administered caffeine recalled more list words and more critical lures than participants administered lactose. Recall of list words was negatively correlated with recall of critical lures. Caffeine appears to intensify the strength of connections among list words and critical lures, thereby enhancing both true and false memory.

Caspers K; Arndt S; Yucuis R; McKirgan L; Spinks R. Effects of alcohol- and cigarette-use disorders on global and specific measures of cognition in middle-age adults. Journal of Studies on Alcohol and Drugs 71(2): 192-200, 2010. (42 refs.)

Objective: This study examined the effects of alcohol- and tobacco-use disorders on global and specific cognitive abilities in middle age. Method: The sample consisted of 118 men and 169 women ranging in age from 31 to 60 years (M [SD] = 43.59 [6.58]). Lifetime diagnoses were determined from a semistructured interview. Information about current levels of alcohol and cigarette use was also collected. A comprehensive neurocognitive assessment measuring global cognition, memory, and executive-functioning abilities was administered. Baseline cognition was estimated from average composite scores of the Iowa Test of Basic Skills school-achievement tests administered from third through eighth grade. Repeated-measures analysis of variance was used. Covariates comprised baseline cognition, current depression symptoms, and medication use. Results: Lifetime alcohol- and tobacco-use disorders were not associated with cognition among men. Women having a diagnosis of tobacco dependence (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) performed less well on measures of global cognition and executive functioning. A lifetime diagnosis of DSM-IV alcohol abuse or dependence was associated with higher working memory among women only. Conclusions: These results demonstrate few negative effects of alcohol-use disorders on midlife cognition, especially if current consumption is light. Differential susceptibility to the effects of cigarette use on cognition was found with women showing greater deficits in visuospatial abilities, processing speed, and executive-functioning abilities.

Dayan PBoning J. Addiction memory as a specific, individually learned memory imprint. Pharmacopsychiatry 42(Supplement 1): S66-S68, 2009. (20 refs.)

The construct of "addiction memory" (AM) and its importance for relapse occurrence has been the subject of discussion for the past 30 years. Neurobiological findings from "social neuroscience" and biopsychological learning theory, in conjunction with construct-valid behavioral pharmacological animal models, can now also provide general confirmation of addiction memory as a pathomorphological correlate of addiction disorders. Under multifactorial influences, experience-driven neuronal learning and memory processes of emotional and cognitive processing patterns in the specific individual "set" and "setting" play an especially pivotal role in this connection. From a neuropsychological perspective, the episodic (biographical) memory, located at the highest hierarchical level, is of central importance for the formation of the AM in certain structural and functional areas of the brain and neuronal networks. Within this context, neuronal learning and conditioning processes take place more or less unconsciously and automatically in the preceding long-term-memory systems (in particular priming and perceptual memory). They then regulate the individually programmed addiction behavior implicitly and thus subsequently stand for facilitated recollection of corresponding, previously stored cues or context situations. This explains why it is so difficult to treat an addiction memory, which is embedded above all in the episodic memory, from the molecular carrier level via the neuronal pattern level through to the psychological meaning level, and has thus meanwhile become a component of personality.

De Oliveira LG; Barroso LP; Silveira CM; Sanchez ZV; Ponce JD; Vaz LJ; Nappo SA. Neuropsychological assessment of current and past crack cocaine users. Substance Use & Misuse 44(13): 1941-1957, 2009. (50 refs.)

Background: Cognitive changes due to crack cocaine consumption remain unclear. Methods: For clarification, 55 subjects were assigned to three groups: control group, crack cocaine current users, and ex-users. Participants were submitted to Mini-Mental State Examination (MMSE) and tasks evaluating executive functioning and verbal memory Mood state was also measured. Intergroup comparisons were carried out. Results: Control group performance on the MMSE was better than that of users and ex-users. Verbal memory performance for logical memory of users was impaired. Ex-users scored lower on DSST and Trail Making Test (Part B). Conclusion: Chronic crack cocaine use seems to disrupt general cognitive functioning (MMSE), verbal memory, and attentional resources, but findings suggest that some of these effects could be reversed by abstinence.

Dingwall KM; Lewis MS; Maruff P; Cairney S. Assessing cognition following petrol sniffing for indigenous Australians. Australian and New Zealand Journal of Psychiatry 44(7): 631-639, 2010. (33 refs.)

Background: Chronic petrol inhalation can be associated with significant cognitive impairment. While rehabilitation programs can rely on such skills to educate clients and achieve treatment outcomes, cognitive function is rarely assessed on admission. This is particularly true for Indigenous populations where standard assessments are not appropriate. This paper describes a process for assessing cognition in Indigenous Australians. Two studies investigate firstly the demographic factors impacting on cognition for healthy Indigenous Australians and secondly the utility of the assessment process for detecting petrol sniffing related cognitive impairments. Methods: Study One assessed a naturalistic sample of healthy Indigenous Australians from the Northern Territory (N = 206; mean age = 28.03) on computerised tests of psychomotor speed, visual attention, memory, learning, spatial awareness and executive functions. Multiple regression analyses determined the unique contributions of six factors (age, education, gender, familiarity with computers, regular long term cannabis use and locality) to the variance in performance for this group. Study Two examined group differences in cognitive performance on the same tests between healthy Indigenous Australians (N = 96) and Indigenous petrol sniffers (N = 50; both age restricted to < 26 years) while controlling those factors found to impact on performance from Study One. Results: Age, computer familiarity, and education significantly contributed to the variance in performance measures. While controlling these factors, petrol abuse was associated with poorer performance on complex tasks of psychomotor, visual attention, memory, learning, spatial awareness and executive function. Conclusions: This assessment process is useful for detecting substance abuse related impairments in Indigenous Australians and when using this assessment process, age and computer familiarity in particular should be controlled for.

Fernandez-Serrano MJ; Perez-Garcia M; Rio-Valle JS; Verdejo-Garcia A. Neuropsychological consequences of alcohol and drug abuse on different components of executive functions. Journal of Psychopharmacology 24(9): 1317-1332, 2010. (122 refs.)

Several studies have shown alterations in different components of executive functioning in users of different drugs, including cannabis, cocaine and heroin. However, it is difficult to establish a specific association between the use of each of these drugs and executive alterations, since most drug abusers are polysubstance abusers, and alcohol is a ubiquitous confounding factor. Moreover, in order to study the association between consumption of different drugs and executive functioning, the patterns of quantity and duration of drugs used must be considered, given the association between these parameters and the executive functioning alteration degree. Based on the multicomponent approach to executive functions, the aims of the present study were: (i) to analyse the differential contribution of alcohol versus cocaine, heroin and cannabis use on executive functions performance; and (ii) to analyse the contribution made by the severity of the different drugs used (quantity and duration patterns) on these functions in a sample of polysubstance abusers that requested treatment for cannabis-, cocaine-or heroin-related problems. We administered measures of fluency, working memory, analogical reasoning, interference, cognitive flexibility, decision-making and self-regulation to two groups: 60 substance-dependent individuals (SDIs) and 30 healthy control individuals (HCIs). SDIs had significantly poorer performance than HCIs across all of the executive domains assessed. Results from hierarchical regression models showed the existence of common correlates of the use of alcohol, cannabis and cocaine on verbal fluency and decision-making; common correlates of quantity of cannabis and cocaine use on verbal working memory and analogical reasoning; common correlates of duration of cocaine and heroin use on shifting; and specific effects of duration of cocaine use on inhibition measures. These findings indicate that alcohol abuse is negatively associated with fluency and decision-making deficits, whereas the different drugs motivating treatment have both generalized and specific deleterious effects on different executive components.

Froeliger B; Gilbert DG; McClernon FJ. Effects of nicotine on novelty detection and memory recognition performance: Double-blind, placebo-controlled studies of smokers and nonsmokers. Psychopharmacology 205(4): 625-633, 2009. (57 refs.)

Dependent smokers exhibit deficits in attentional and memory processes when smoking abstinent as compared to when satiated. While nicotine replacement therapy improves attention during abstinence, it is unclear whether this is due to the alleviation of withdrawal-related deficits or inherent beneficial effects of nicotine. The primary aim of these studies was to test whether nicotine exerts a beneficial effect on novelty detection and whether such effects occur in nonsmokers as well as habitual smokers. In two parallel, double-blind, placebo-controlled studies, 24 smokers (study 1) and 24 nonsmokers (study 2) were tested in two counterbalanced sessions: once while wearing a nicotine patch (smokers = 14 mg; nonsmokers = 7 mg) and once while wearing a placebo patch. On each day, participants performed three content-specific oddball tasks (perceptual, semantic, and emotional) that required them to press a button whenever they saw a novel target (20% of stimuli) embedded in a stream of common nontarget stimuli (80% of stimuli). Recognition memory for targets was subsequently tested. Reports of mood, smoking withdrawal, patch side effects, and blind success were collected in each session. Among smokers, compared to placebo, nicotine decreased target reaction time during all oddball tasks. Among nonsmokers, nicotine increased target detection accuracy and subsequent memory recognition. Nicotine's enhancement on each respective measure was not task-content specific in either sample. These data suggest that acute nicotine administration may exert direct beneficial effects on novelty detection and subsequent memory recognition in both smokers and nonsmokers. Moreover, these effects are not content-specific.

Garia AM; Ramon-Bou N; Porta M. Isolated and joint effects of tobacco and alcohol consumption on risk of Alzheimer's disease. Journal of Alzheimer's Disease 20(2): 577-586, 2010. (32 refs.)

The roles of smoking and alcohol on the development of Alzheimer's disease (AD) remain unclear. We performed a case-control study on the effects of both exposures before the age of onset of the disease in the cases (and same reference age for their age-matched controls) on disease risk. Interviews were conducted with population controls (n = 246) and relatives of cases (n = 176) identified through local Alzheimer's Disease Associations. Logistic regression models were built adjusting by gender, age, residence, education, economic situation, employment, and history of dementia in close relatives. Risk of AD was unaffected by any measure of tobacco consumption. Alcohol consumers showed a lower risk of AD than never consumers (adjusted odds ratio, aOR = 0.53, 95% CI 0.32, 0.88), with differences by gender (women aOR = 0.48, 95% CI 0.27, 0.84; men aOR = 0.80, 95% CI 0.23, 2.80). Mean daily total consumption of alcohol and time consuming alcohol showed increasingly protective dose-response relationships in women. Lower AD risk was observed in alcohol drinkers of both genders who never smoked (aOR = 0.37, 95% CI 0.21, 0.65). All these associations were independent of the presence of apolipoprotein E4 allele(s) in the cases. Although the sample was small for some analyses addressing these interactions, our results suggest a protective effect of alcohol consumption, mostly in non-smokers, and the need to consider interactions between tobacco and alcohol consumption, as well as interactions with gender, when assessing the effects of smoking and/or drinking on the risk of AD.

Greenstein JE; Kassel JD. The effects of smoking and smoking abstinence on verbal and visuospatial working memory capacity. Experimental and Clinical Psychopharmacology 17(2): 78-90, 2009. (81 refs.)

Several studies have examined the effects of smoking and abstaining from smoking on working memory (WM) but have yielded inconclusive findings. Thus, the authors used a repeated measures design to assess the effects of smoking and abstaining from smoking on both visuospatial and verbal WM capacity (WMC) using highly reliable, well-validated, and theoretically driven WM span tasks. Verbal n-back was also administered to examine its relationship to these complex WM span tasks and to compare this study's results with previous findings. Smokers (n = 23) and nonsmokers (n = 21) participated in 2 sessions separated by I week. During I session, smokers completed the WM tasks after abstaining from smoking for at least 12 hr, whereas in the other session smokers did not abstain from smoking and were tested immediately after smoking (all WM tasks were completed 45 min or less since last cigarette). Results indicated that smokers' verbal WM span was lower than nonsmokers' and was lower during the nonabstinent session compared with the abstinent session. Smokers' verbal n-back performance was also lower than nonsmokers', although there was no difference in verbal n-back performance between the smoking sessions. In contrast, there was no difference in visuospatial WM span between the smoking sessions or between smokers and nonsmokers. Taken together, these findings demonstrate that (a) smokers' verbal WM is lower than nonsmokers, (b) smokers' verbal WMC is lower during nonabstinence compared with abstinence, and (c) smoking exhibits differential effects on the different WM domains.

Greenstein JE; Kassel JD; Wardle MC; Veilleux JC; Evatt DP; Heinz AJ et al. The separate and combined effects of nicotine and alcohol on working memory capacity in nonabstinent smokers. Experimental and Clinical Psychopharmacology 18(2): 120-128, 2010. (63 refs.)

Research indicates that nicotine and alcohol are often used on the same occasion. However, the reasons for their concurrent use are not well understood. We hypothesized that one reason smokers use tobacco when they drink alcohol is to compensate for alcohol's negative effects on processing capacity with nicotine's enhancement of processing capacity. As such, the present study tested this theory by using an independent groups design to examine the separate and combined acute effects of alcohol and nicotine on working memory (WM) capacity. Nonabstinent daily smokers (n = 127) performed the counting span task (CSPAN) after consuming either an alcohol (men: 0.8 g/kg; women: 0.7 g/kg) or placebo beverage and smoking either nicotinized (1.14 mg nicotine, 15.9 mg tar) or denicotinized (.06 mg nicotine, 17.9 mg tar) cigarettes. Analyses revealed that smokers who smoked the nicotinized cigarettes performed significantly worse on the CSPAN task than smokers who smoked the denicotinized cigarettes. Although there was no main effect of alcohol on WM performance, women exhibited better WM performance than men after consuming alcohol whereas men performed better than women on the WM task after consuming the placebo beverage. Findings also revealed no interaction between the two substances on WM performance. Taken together, results suggest that nicotine impairs nonabstinent smokers' verbal WM capacity and that gender moderates the effects of alcohol on WM. Furthermore, the present findings failed to support the notion that nicotine compensates for alcohol-related decrements in working memory capacity.

Heffernan T; O'Neill T; Moss M. Smoking and everyday prospective memory: A comparison of self-report and objective methodologies. Drug and Alcohol Dependence 112(3): 234-238, 2010. (30 refs.)

Aims: To examine whether persistent smoking leads to impairments in self-reported and objective measures of prospective memory (PM the cognitive ability to remember to carry out activities at some future point in time). Methods: An opportunity sample of 18 existing smokers and 22 who had never smoked were compared An existing-groups design was utilised comparing a smoking group with a never-smoked control group as the independent factor Scores on the sub-scales of the Prospective and Retrospective Memory Questionnaire (PRMQ) and scores on the Cambridge Prospective Memory Test (CAMPROMPT) constituted the dependent factors. Age, mood, other drug use strategy scores and IQ were also measured. Each participant was tested in a laboratory setting. Self-reported PM lapses were measured using the PRMQ. The CAMPROMPT was used as an objective measure of PM. Alcohol and other drug use were assessed by a Recreational Drug Use Questionnaire, The Hospital Anxiety and Depression Scale gauged levels of anxiety and depression. A strategy scale measured the number of strategies used to aid memory. The National Adult Reading Test measured IQ. Results: After observing no between-group differences on age mood alcohol use strategy use and IQ, smokers and the never-smoked did not differ on the self-reported lapses measured on the PRMQ. However smokers recalled significantly fewer items on the CAMPROMPT than the never-smoked group. Conclusion The results of the present study suggest that persistent smoking leads to impairments in everyday PM.

Huestegge L; Radach R; Kunert HJ. Long-term effects of cannabis on oculomotor function in humans. Journal of Psychopharmacology 23(6): 714-722, 2009. (37 refs.)

Cannabis is known to affect human cognitive and visuomotor skills directly after consumption. Some studies even point to rather long-lasting effects, especially after chronic tetrahydrocannabinol (THC) abuse. However, it is still unknown whether long-term effects on basic visual and oculomotor processing may exist. In the present study, the performance of 20 healthy long-term cannabis users without acute THC intoxication and 20 control subjects were examined in four basic visuomotor paradigms to search for specific long-term impairments. Subjects were asked to perform: 1) reflexive saccades to visual targets (prosaccades), including gap and overlap conditions, 2) voluntary antisaccades, 3) memory-guided saccades and 4) double-step saccades. Spatial and temporal parameters of the saccades were subsequently analysed. THC subjects exhibited a significant increase of latency in the prosaccade and antisaccade tasks, as well as prolonged saccade amplitudes in the antisaccade and memory-guided task, compared with the control subjects. The results point to substantial and specific long-term deficits in basic temporal processing of saccades and impaired visuo-spatial working memory. We suggest that these impairments are a major contributor to degraded performance of chronic users in a vital everyday task like visual search, and they might potentially also affect spatial navigation and reading.

Indlekofer F; Piechatzek M; Daamen M; Glasmacher C; Lieb R; Pfister H et al. Reduced memory and attention performance in a population-based sample of young adults with a moderate lifetime use of cannabis, ecstasy and alcohol. Journal of Psychopharmacology 23(5): 495-509, 2009. (78 refs.)

Regular use of illegal drugs is suspected to cause cognitive impairments. Two substances have received heightened attention: 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') and delta-9-tetrahydrocannabinol (THC or 'cannabis'). Preclinical evidence, as well as human studies examining regular ecstasy consumers, indicated that ecstasy use may have negative effects on learning, verbal memory and complex attentional functions. Cannabis has also been linked to symptoms of inattention and deficits in learning and memory. Most of the published studies in this field of research recruited participants by means of newspaper advertisements or by using word-of-mouth strategies. Because participants were usually aware that their drug use was critical to the research design, this awareness may have caused selection bias or created expectation effects. Focussing on attention and memory, this study aimed to assess cognitive functioning in a community-based representative sample that was derived from a large-scale epidemiological study. Available data concerning drug use history allowed sampling of subjects with varying degrees of lifetime drug experiences. Cognitive functioning was examined in 284 young participants, between 22 and 34 years. In general, their lifetime drug experience was moderate. Participants completed a neuropsychological test battery, including measures for verbal learning, memory and various attentional functions. Linear regression analysis was performed to investigate the relationship between cognitive functioning and lifetime experience of drug use. Ecstasy and cannabis use were significantly related to poorer episodic memory function in a dose-related manner. For attentional measures, decrements of small effect sizes were found. Error measures in tonic and phasic alertness tasks, selective attention task and vigilance showed small but significant effects, suggesting a stronger tendency to experience lapses of attention. No indication for differences in reaction time was found. The results are consistent with decrements of memory and attentional performance described in previous studies. These effects are relatively small; however, it must be kept in mind that this study focussed on assessing young adults with moderate drug use from a population-based study.

Kalechstein AD; De La Garza R; Newton TF. Modafinil administration improves working memory in methamphetamine-dependent individuals who demonstrate baseline impairment. American Journal on Addictions 19(4): 340-344, 2010. (26 refs.)

Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects. This double-blind, placebo-controlled study evaluated whether a daily dose of 400 mg of modafinil, administered over three consecutive days, would enhance performance on a measure of working memory relative to test performance at baseline and following 3 days of placebo administration in 11 methamphetamine addicted, nontreatment-seeking volunteers. The results revealed that participants demonstrating relatively poor performance on the third day of a 3-day washout period (ie, at baseline), showed significant improvement on measures of working memory, but not on measures of episodic memory or information processing speed. In contrast, for participants demonstrating relatively high performance at baseline, modafinil administration did not affect test scores. The findings provide an initial indication that modafinil can reverse methamphetamine-associated impairments in working memory.

Kiluk BD; Nich C; Carroll KM. Neurocognitive indicators predict results of an informed-consent quiz among substance-dependent treatment seekers entering a randomized clinical trial. Journal of Studies on Alcohol and Drugs 71(5): 704-712, 2010. (63 refs.)

Objective: This study sought to determine the extent to which key aspects of a clinical trial's protocol were recalled by participants entering a clinical trial for alcohol and illicit substance-use treatment after standard informed-consent procedures, as well as to explore the possible relationships between recall, neuropsychological functioning, and substance-use outcomes. Method: Before entering a randomized clinical trial testing the effectiveness of a computer-based training version of cognitive-behavioral therapy, 76 participants (55% male) meeting criteria for current substance dependence (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) completed a 14-item true/false quiz that assessed their comprehension of basic information provided in the consent form. Results: Only 15% of participants correctly answered all 14 consent quiz items. The percentage of correct recall was associated with measures of intelligence (r = .29, p = .01) and attention (r = -.26, p = .04). Quiz scores were also moderately associated with the amount of substance use during the treatment period (r = -.26, p = .03). Conclusions: These findings highlight the importance of formally evaluating research participants' understanding of the informed-consent process, and they call to attention the potential utility of a brief neuropsychological screening to identify individuals in need of enhanced consent procedures, particularly within vulnerable populations, such as substance users.

Krank MD; Schoenfeld T; Frigon AP. Self-coded indirect memory associations and alcohol and marijuana use in college students. Behavior Research Methods 42(3): 733-738, 2010. (32 refs.)

Indirect memory associations for substance use predict both the concurrent and prospective levels of substance use. These methods assess spontaneous, possibly implicit, and easily accessible associations that predict substance use over direct (explicit) methods of assessment (e. g., outcome expectancies). The present study tested and expanded the application of a coding method for alcohol and marijuana associations on the basis of self-coding of indirect responses (Frigon & Krank, 2009). College students generated free associates to (1) ambiguous words (e. g., draft or weed), (2) situations (e. g., at a party, hanging out with friends), and (3) emotions (having fun, feeling dreamy). Later, participants were shown their responses and were asked to code their responses according to both nonrisk and risk activities, such as alcohol and marijuana use. Self-coded scores were higher than researcher-coded scores, captured the same variance, and improved the prediction of substance use. Self-coding of indirect memory associations provides accurate and efficient prediction of the level of alcohol and marijuana. Self-coding is efficient and may be useful for reducing ambiguities in coding of many different kinds of open-ended responses.

Latvala A; Castaneda AE; Perala J; Saarni SI; Aalto-Setala T; Lonnqvist J et al. Cognitive functioning in substance abuse and dependence: A population-based study of young adults. Addiction 104(9): 1558-1568, 2009. (41 refs.)

Aims: To investigate whether substance use disorders (SUDs) are associated with verbal intellectual ability, psychomotor processing speed, verbal and visual working memory, executive function and verbal learning in young adults, and to study the associations of SUD characteristics with cognitive performance. Participants: A population-based sample (n = 466) of young Finnish adults aged 21-35 years. Measurements: Diagnostic assessment was based on all available information from a structured psychiatric interview (SCID-I) and in- and out-patient medical records. Established neuropsychological tests were used in the cognitive assessment. Confounding factors included in the analyses were comorbid psychiatric disorders and risk factors for SUDs, representing behavioural and affective factors, parental factors, early initiation of substance use and education-related factors. Findings: Adjusted for age and gender, life-time DSM-IV SUD was associated with poorer verbal intellectual ability, as measured with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) vocabulary subtest, and slower psychomotor processing, as measured with the WAIS-R digit symbol subtest. Poorer verbal intellectual ability was accounted for by parental and own low basic education, whereas the association with slower psychomotor processing remained after adjustment for SUD risk factors. Poorer verbal intellectual ability was related to substance abuse rather than dependence. Other SUD characteristics were not associated with cognition. Conclusions: Poorer verbal intellectual ability and less efficient psychomotor processing are associated with life-time alcohol and other substance use disorders in young adulthood. Poorer verbal intellectual ability seems to be related to parental and own low basic education, whereas slower psychomotor processing is associated with SUD independently of risk factors.

Mahmood OM; Jacobus J; Bava S; Scarlett A; Tapert SF. Learning and memory performances in adolescent users of alcohol and marijuana: Interactive effects. Journal of Studies on Alcohol and Drugs 71(6): 885-894, 2010. (61 refs.)

Objective: Lifetime alcohol hangover and withdrawal symptoms in youth have been shown to predict poorer recall of verbal and nonverbal information, as well as reduced visuospatial skills. Some evidence has suggested that negative effects of alcohol on the brain may be buffered in part by potential neuroprotective properties of cannabinoids. We hypothesized that a history of more alcohol hangover symptoms would predict worse performances on measures of verbal and visual memory, and that this relationship would be moderated by marijuana involvement. Method: Participants were 130 adolescents (65 with histories of heavy marijuana use, and 65 non-marijuana-using controls), ranging in age from 15.7 to 19.1 years. Neuropsychological tests for visual and verbal memory and interviews assessing lifetime and recent substance use, hangover/withdrawal symptoms, and abuse and dependence criteria were administered. Results: Regression models revealed that greater alcohol hangover symptoms predicted worse verbal learning (p < .05) and memory (p < .05) (California Verbal Learning Test, Second Edition) scores for non-marijuana users, but alcohol hangover symptoms were not linked to performance among marijuana users. Alcohol hangover symptoms did not predict visual memory in either group. Conclusions: Results confirm previous studies linking adolescent heavy drinking to reduced verbal learning and memory performance. However, this relationship is not seen in adolescents with similar levels of alcohol involvement who also are heavy users of marijuana.

McCann UD; Wilson MJ; Sgambati FP; Ricaurte GA. Sleep deprivation differentially impairs cognitive performance in abstinent methylenedioxymethamphetamine ("ecstasy") users. Journal of Neuroscience 56(29): 44, 2009

Methylenedioxymethamphetamine (MDMA; "Ecstasy") is a popular recreational drug and brain serotonin (5-HT) neurotoxin. Neuroimaging data indicate that some human MDMA users develop persistent deficits in brain 5-HT neuronal markers. Although the consequences of MDMA-induced 5-HT neurotoxicity are not fully understood, abstinent MDMA users have been found to have subtle cognitive deficits and altered sleep architecture. The present study sought to test the hypothesis that sleep disturbance plays a role in cognitive deficits in MDMA users. Nineteen abstinent MDMA users and 21 control subjects participated in a 5d inpatient study in a clinical research unit. Baseline sleep quality was measured using the Pittsburgh Sleep Quality Inventory. Cognitive performance was tested three times daily using a computerized cognitive battery. On the third day of admission, subjects began a 40 h sleep deprivation period and continued cognitive testing using the same daily schedule. At baseline, MDMA users performed less accurately than controls on a task of working memory and more impulsively on four of the seven computerized tests. During sleep deprivation, MDMA users, but not controls, became increasingly impulsive, performing more rapidly at the expense of accuracy on tasks of working and short-term memory. Tests of mediation implicated baseline sleep disturbance in the cognitive decline seen during sleep deprivation. These findings are the first to demonstrate that memory problems in MDMA users may be related, at least in part, to sleep disturbance and suggest that cognitive deficits in MDMA users may become more prominent in situations associated with sleep deprivation.

McGuinness TM. Update on marijuana. Journal of Psychosocial Nursing and Mental Health Services 47(10): 19-22, 2009. (17 refs.)

Marijuana, the illicit drug most widely used by adolescents, is not a benign substance. Inhalation of marijuana smoke is more harmful than tobacco smoke; cannabis smoke delivers 50% to 70% more carcinogens. Other physiological effects include decreased immune function, higher rates of cardiac arrhythmias, and documented cases of cerebellar infarction. Mood and cognitive effects of marijuana include exacerbation of depression and anxiety (including panic attacks), as well as memory problems that may persist for a month after last use. Cannabis abuse is a risk factor for psychosis in genetically predisposed people and may lead to a worse outcome of schizophrenia. The cumulative respiratory, cardiovascular, metabolic, and mental health risks of marijuana are significant and should be emphasized by nurses who work with adolescents.

Merritt PS; Cobb AR; Moissinac L; Hirshman E. Evidence that episodic memory impairment during tobacco abstinence is independent of attentional mechanisms. Journal of General Psychology 137(4): 331-342, 2010. (24 refs.)

Previous studies have demonstrated reductions in episodic memory during nicotine withdrawal. However, these studies have been unable to dissociate memory reductions from losses in attention associated with tobacco abstinence. In the present study, the authors sought to determine whether episodic memory reduction is a primary effect of nicotine withdrawal during tobacco abstinence. Heavy smokers were tested when smoking normally and following 24 hrs of abstinence. Participants were tested with a recognition memory task in which items were studied under full and divided attention conditions. Forward digit span and backward digit span were also included as control measures. Withdrawal was associated with a reduction in memory performance that was independent of attention at encoding. The authors conclude that impairment of episodic memory is a primary effect of nicotine withdrawal during tobacco abstinence. Further research is required to determine if this is associated with continued use of tobacco and cessation failures.

Moeller FG; Steinberg JL; Schmitz JM; Ma LS; Liu SJ; Kjome KL et al. Working memory fMRI activation in cocaine-dependent subjects: Association with treatment response. Psychiatry Research-Neuroimaging 181(3): 174-182, 2010. (48 refs.)

Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared with non-drug-using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alterations of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections.

Morgan CJA; Muetzelfeldt L; Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: A 1-year longitudinal study. Addiction 105(1): 121-133, 2010. (39 refs.)

Background: 'Recreational' use of ketamine is spreading rapidly among young people. In healthy individuals an acute dose of the N-methyl D-aspartate (NMDA) receptor antagonist ketamine induces marked psychosis-like effects and cognitive impairments, but little is known about the long-term effects of the drug. Aims: To evaluate the long-term neuropsychiatric or cognitive consequences. Methods: A total of 150 individuals were assessed, 30 in each of five groups: frequent ketamine users, infrequent ketamine users, abstinent users, polydrug controls and non-users of illicit drugs. Twelve months later, 80% of these individuals were re-tested. Results: Cognitive deficits were mainly observed only in frequent users. In this group, increasing ketamine use over the year was correlated with decreasing performance on spatial working memory and pattern recognition memory tasks. Assessments of psychological wellbeing showed greater dissociative symptoms in frequent users and a dose-response effect on delusional symptoms, with frequent users scoring higher than infrequent, abstinent users and non-users, respectively. Both frequent and abstinent using groups showed increased depression scores over the 12 months. Conclusions: These findings imply that heavy use of ketamine is harmful to aspects of both cognitive function and psychological wellbeing. Health education campaigns need to raise awareness among young people and clinicians about these negative consequences of ketamine use.

Morgan CJA; Rothwell E; Atkinson H; Mason O; Curran HV. Hyper-priming in cannabis users: A naturalistic study of the effects of cannabis on semantic memory function. Psychiatry Research 176(2-3): 213-218, 2010. (42 refs.)

Psychotic symptoms have theoretically been linked to semantic memory impairments in patients with schizophrenia. Little is known of the effects of cannabis, the world's most popular illicit drug, on semantic memory and whether they are linked to the psychotomimetic states elicited by the drug. Thirty-six cannabis users were tested whilst under the influence of cannabis. They were then tested again when not intoxicated and compared with 38 non-drug using controls. Semantic memory was assessed using a semantic priming task with a long and short stimulus onset asynchrony (SOA) to differentiate automatic and controlled processing. Under the influence of cannabis, users showed increases in both automatic semantic priming and schizotypal symptoms compared with controls. When abstinent, cannabis users exhibited hyper-priming at long SOAs. Cannabis users did not differ from controls in either trait schizotypy or state schizotypy when not intoxicated. Acute cannabis use increases schizotypyal symptoms and may increase automatic semantic priming in recreational users of this drug. When drug-free, cannabis users did not differ from controls in schizotypy but did show hyper-priming at the long SOA. The acute increase in automatic semantic priming may be one factor contributing to the psychotomimetic effects of cannabis.

Patterson F; Jepson C; Loughead J; Perkins K; Strasser AA; Siegel S et al. Working memory deficits predict short-term smoking resumption following brief abstinence. Drug and Alcohol Dependence 106(1): 61-64, 2010. (17 refs.)

As many as one-half of smokers relapse in the first week following a quit attempt, and subjective reports of cognitive deficits in early abstinence are associated with increased relapse risk. This study examined whether objective cognitive performance after 3 days of abstinence predicts smoking resumption in a 7-day simulated quit attempt. Sixty-seven treatment-seeking smokers received either varenicline or placebo (randomized double-blind) for 21 days. Following medication run-up (days 1-10), there was a 3-day mandatory (biochemically confirmed) abstinence period (days 11-13) during which working memory (Letter-N-Back Task) and sustained attention (Continuous Performance Task) were assessed (day 13). Participants were then exposed to a scheduled smoking lapse and instructed to try to remain abstinent for the next 7 days (days 15-21). Poorer cognitive performance (slower correct reaction time on Letter-N-Back task) during abstinence predicted more rapid smoking resumption among those receiving placebo (p = 0.038) but not among those receiving varenicline. These data lend further support for the growing recognition that cognitive deficits involving working memory are a core symptom of nicotine withdrawal and a potential target for the development of pharmacological and behavioral treatments.

Pickett KE; Kasza K; Biesecker G; Wright RJ; Wakschlag LS. Women who remember, women who do not: A methodological study of maternal recall of smoking in pregnancy. Nicotine & Tobacco Research 11(10): 1166-1174, 2009. (44 refs.)

Retrospective recall of smoking during pregnancy is assumed to be substantially biased, but this has rarely been tested empirically. We examined the validity of an interview-based retrospective recall more than a decade after pregnancy, in a cohort with repeated, multimethod characterization of pregnancy smoking (N = 245). Retrospective smoking patterns were examined in relation to prospective reported and biological estimates of overall and trimester-specific smoking status and intensity. We also compared characteristics of women whose smoking status was misclassified by either prospective or retrospective measures with women whose status was congruent for nonsmoking across timepoints. In general, sensitivity and specificity of recalled smoking were excellent relative to both prospective self-reported and cotinine-validated smoking status and trimester-specific intensity. However, measures were less congruent for amount smoked for women who recalled being heavy smokers. Further, retrospective measures captured some smokers not identified prospectively due to smoking that occurred prior to assessments. Women who would have been misclassified as nonsmokers based on either prospective or retrospective assessment differed significantly from congruently classified nonsmokers in a number of maternal, family, and neighborhood, but not child behavior, characteristics. When epidemiological studies of the impact of smoking in pregnancy use retrospective methods, misclassification may not be a significant problem if prenatal smoking is assessed in terms of the pattern across pregnancy. This type of interview-based recall of pregnancy smoking may be relatively accurate, although optimal measurement should combine retrospective and prospective self-report and biological assays, as each provide unique information and sources of error.

Rapeli P; Fabritius C; Kalska H; Alho H. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: Longitudinal change in comparison to healthy individuals. Substance Abuse Treatment, Prevention and Policy 4: e-article 6, 2009. (65 refs.)

Background: Opioid-substitution treatment (OST) for opioid dependence (OD) has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO) has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD) dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST. Methods: Within the first two months (T1) and between 6-9 months (T2) after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone-and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions. Results: Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine- only patients leaving 12 patients to buprenorphine/naloxone group. Conclusion: Working memory may be persistently affected in OST patients with BZD use. A high number of memory complaints among OST patients with BZD use may indicate memory consolidation impairment. These findings show that recovery of memory function in OD patients treated along with BZDs takes time, and their memory complaints may have practical relevance.

Reske M; Eidt CA; Delis DC; Paulus MP. Nondependent stimulant users of cocaine and prescription amphetamines show verbal learning and memory deficits. Biological Psychiatry 68(8): 762-769, 2010. (30 refs.)

Background: Stimulants are used increasingly to enhance social (cocaine) or cognitive performance (stimulants normally prescribed, prescription stimulants [e.g., methylphenidate, amphetamines]). Chronic use, by contrast, has been associated with significant verbal memory and learning deficits. This study sought to determine whether subtle learning and memory problems characterize individuals who exhibit occasional but not chronic use of stimulants. Methods: One hundred fifty-four young (age 18-25), occasional, nondependent stimulant users and 48 stimulant-naive comparison subjects performed the California Verbal Learning Test II. Lifetime uses of stimulants and co-use of marijuana were considered in correlation and median split analyses. Results: Compared with stimulant-naive subjects, occasional stimulant users showed significant performance deficits, most pronounced in the verbal recall and recognition domains. Lifetime uses of stimulants and marijuana did not affect California Verbal Learning Test II performance. The type of stimulant used, however, was of major relevance: users of cocaine only were less impaired, whereas cumulative use of prescription stimulants was associated with impaired verbal learning and memory capacities. Conclusions: These results support the hypothesis of subtle and possibly pre-existing neurocognitive deficiencies in occasional users of stimulants, which might be related to the motivation for using these drugs. More importantly, despite beneficial short-term effects, cumulative use, particularly of prescription amphetamines and methylphenidate, intensifies these deficits.

Roberts GMP; Nestor L; Garavan H. Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task. Brain Research 1292: 71-81, 2009. (67 refs.)

It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.

Schilt T; Koeter MWJ; de Win MML; Zinkstok JR; van Amelsvoort TA; Schmand B et al. The effect of ecstasy on memory is moderated by a functional polymorphism in the cathechol-O-methyltransferase (COMT) gene. European Neuropsychopharmacology 19(2): 116-124, 2009. (57 refs.)

There is ample evidence for decreased verbal memory in heavy Ecstasy users. However, findings on the presence of a dose-response relation are inconsistent, possibly due to individual differences in genetic vulnerability. Catechol-O-methyltransferase (COMT) is involved in the catabolism of Ecstasy. Therefore, COMT gene polymorphisms may moderate this vulnerability. We prospectively assessed verbal memory in subjects with a high risk for future Ecstasy use, and compared 59 subjects after first Ecstasy use with 60 subjects that remained Ecstasy-naive. In addition, we tested the interaction effect of Ecstasy and the functional Val (158)met polymorphism on verbal memory. Met-allele carriers were somewhat more sensitive to the effects of Ecstasy on verbal learning than homozygous vol-subjects. After correction for the use of other substances this effect was no longer statistically significant. The findings suggest that the COMT gene moderates the negative effect of Ecstasy on memory, but also other drug use seems to play a role.

Schweinsburg AD; Schweinsburg BC; Medina KL; McQueeny T; Brown SA; Tapert SF. The influence of recency of use on FMRI response during spatial working memory in adolescent marijuana users. Journal of Psychoactive Drugs 42(3): 401-412, 2010. (76 refs.)

Some neurocognitive recovery occurs within a month of abstinence from heavy marijuana use, yet functional magnetic resonance imaging (fMRI) has revealed altered activation among recent and abstinent adult users. We compared fMRI response during a spatial working memory (SWM) task between adolescent marijuana users with brief and sustained durations of abstinence. Participants were 13 recent users (two to seven days abstinent), 13 abstinent users (27 to 60 days abstinent), and 18 nonusing controls, all ages 15 to 18. Groups were similar on demographics, had no psychiatric or medical disorders, and user groups were similar on substance histories. Teens performed a two-back SWM task during fMRI. Recent users showed greater fMRI response in medial and left superior prefrontal cortices, as well as bilateral insula. Abstinent users had increased response in the right precentral gyms (clusters >= 1328 mu l, p < .05). Results suggest that adolescents who recently used marijuana show increased brain activity in regions associated with working memory updating and inhibition. This study preliminarily suggests that (1) recent marijuana use may disrupt neural connections associated with SWM and result in compensatory brain response, and (2) sustained abstinence from marijuana may be associated with improvements in SWM response among adolescents.

Shacham E; Cottler LB. Sexual behaviors among club drug users: Prevalence and reliability. Archives of Sexual Behavior 39(6): 1331-1341, 2010. (31 refs.)

HIV prevention efforts require a focus on reducing high risk sexual behavior. Because these are self-reported, assessments that reduce memory bias and improve elicitation of data are needed. As part of a multi-site psychometric study of club drug use, abuse, and dependence, data were collected with a test-retest design that measured the reliability of the Washington University Risk Behavior Assessment for Club Drugs (WU-RBA-CD). Reliability was assessed separately by sex via kappa coefficients and intraclass correlation coefficients (ICC); z tests compared coefficients by sex. A total of 603 participants were interviewed by independent assessors with 5 days in between interviews. Reliability for all 51 items of the sexual activity section of the WU-RBA-CD ranged from .23 to 1.00; 71% (n = 36) of items resulted in moderate to high reliability (.55-1.00). Number of lifetime sex partners was consistently reported for same-sex partners for both men and women and opposite-sex partners. Items with high reliability included reporting ever being under the influence of ecstasy (.87) or GHB (.87) while having sex. Items with lower reliability included those that queried the determinants of condom use (.45-.82) and about behaviors and attitudes experienced while using drugs (.23-.87). Very few sex differences were revealed in the reliability of reported sexual activities. Overall, the WU-RBA-CD performed with fairly high reliability rates. Assessing situations of when, how, and why individuals use condoms may offer the clearest evaluation of determinants of sexual behaviors, yet those items are not as reliable.

Sweet LH; Mulligan RC; Finnerty CE; Jerskey BA; David SP; Cohen RA et al. Effects of nicotine withdrawal on verbal working memory and associated brain response. Psychiatry Research: Neuroimaging 183(1): 69-74, 2010. (45 refs.)

Previous literature has reported effects of nicotine withdrawal on brain function during cognitive tasks such as verbal working memory (VWM). Mechanisms of these withdrawal effects have not been clearly identified. Functional neuroimaging offers an objective method to examine brain mechanisms associated with observable behavior and subjective reports. To investigate these mechanisms, 12 smokers were administered a 2-Back VWM challenge during two functional magnetic resonance imaging sessions. Participants abstained from smoking prior to both sessions: however, they applied a nicotine patch before one session and a placebo patch prior to the other. Among regions that exhibited a significant response to the 2-Back during either session, withdrawal was associated with significantly greater deactivation in left and right temporal poles and left medial frontal gyrus. The magnitude of task-related activation showed a significant inverse relationship to craving in the majority of regions during placebo administration. Also, individual brain responses varied more during placebo, suggesting inefficient neural processing. Results suggest that differences in brain response to a VWM challenge during abstinence may be attributed to increased craving. Further deactivation of regions associated with the default network (medial frontal and anterior temporal clusters) during the placebo condition suggests further suspension of default activity, possibly to compensate for inefficient neural processing.

Takagi M; Yucel M; Cotton SM; Baliz Y; Tucker A; Elkins K et al. Verbal memory, learning, and executive functioning among adolescent inhalant and cannabis users. Journal of Studies on Alcohol and Drugs 72(1): 96-105, 2011. (32 refs.)

Objective: Inhalant use is a common form of drug misuse among young adolescents. However, very little is known about how chronic inhalant misuse affects cognition. Several studies have examined cognitive deficits among inhalant users, but no study has thoroughly addressed the confounding issues frequently associated with inhalant users (e.g., polysubstance use). The aim of the current study was to examine possible deficits in memory, learning, and executive components of memory (interference susceptibility) among young, regular inhalant users relative to a statistically equivalent drug-using control group (primarily cannabis users) and a community control group. Method: Three groups of 21 young people (aged 13-24 years) were recruited: an inhalant-using group, a drug-using control group, and a community control group. The inhalant and drug-using controls were matched at the group level on demographic, clinical, and substance use measures. All three groups were statistically equivalent on age, sex, and education. The Rey Auditory Verbal Learning Test was used to assess memory, learning, and interference susceptibility. Results: Community controls performed significantly better than both drug-using groups, while inhalant users were more susceptible to proactive interference relative to drug-using controls. Conclusions: Difficulty in successful proactive interference resolution demonstrated by the inhalant group may relate to inhalant-specific deficits in executive functioning. These findings raise important questions regarding the hypothesized toxicity of inhalants and of substance-specific cognitive deficits among regular adolescent substance users. Future studies should consider using more specific, experimental probes of cognitive functioning to identify potentially subtle changes among substance-using adolescents.

Theberge FRM; Milton AL; Belin D; Lee JLC; Everitt BJ. The basolateral amygdala and nucleus accumbens core mediate dissociable aspects of drug memory reconsolidation. Learning & Memory 17(9): 444-453, 2010. (52 refs.)

A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim of this study was to investigate the involvement of the nucleus accumbens core and the basolateral amygdala in the reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intranucleus accumbens core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation impaired the reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the nucleus accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intrabasolateral amygdala zif268 ASO infusions. These results suggest that both the basolateral amygdala and nucleus accumbens core are key structures within limbic cortical-striatal circuitry where reconsolidation of a cue-drug memory occurs. However reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.

von der Goltz C; Kiefer F. Learning and memory in the aetiopathogenesis of addiction: Future implications for therapy? European Archives of Psychiatry and Clinical Neuroscience 259(Supplement 2): 183-187, 2009. (45 refs.)

Addiction is a chronic relapsing disorder. Even after long periods of abstinence from drugs, the risk of relapse, often precipitated by drug-associated cues, remains high. Especially learning processes have been shown to play a major role in the maintenance of addictive behaviour. Humans and animals rapidly learn cues and contexts that predict the availability of addictive drugs. Once learned, these cues and contexts initiate drug seeking, craving and relapse in both animal models and clinical studies. These observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. In this context, a substantial body of evidence suggests that several types of neuroadaptation occur, including synapse-specific adaptations of the type thought to underlie specific long-term associative memory. Consequently, understanding learning and memory processes in the brain in addiction is an important key for understanding the persistence of addiction, and it is reasonable to hypothesize that the disruption of drug-related memories may help to prevent relapses.

Zeeuws I; Deroost N; Soetens E. Effect of an acute d-amphetamine administration on context information memory in healthy volunteers: Evidence from a source memory task. Human Psychopharmacology: Clinical and Experimental 25(4): 326-334, 2010. (47 refs.)

Rationale: Previous research demonstrated a positive effect of d-amphetamine on long-term verbal memory. An improvement in memory for contextual information is proposed as a possible mechanism underlying the d-amphetamine facilitation effect. Objectives: A double blind, placebo controlled experiment was used to examine the processes involved in episodic memory affected by an acute administration of d-amphetamine. We investigated whether positive effects of d-amphetamine on item memory could be extended to context information by using a source memory paradigm. Methods In a within-subjects design with two sessions, two study lists were presented in each session and participants were required to make an old/new recognition decision (item memory) and a list discrimination judgment (source memory) after delays of 1 h, 1 day and 1 week. Results: Enhancement of item memory after d-amphetamine intake was observed on delayed tests only, confirming that amphetamine does not affect short-term memory or memory acquisition, but rather a process operating after initial encoding. Importantly, we found an enhancement in remembering the source of recognized items after d-amphetamine administration. Conclusion: The present study suggests that an acute administration of d-amphetamine helps to bind different features of an item in memory, in turn leading to an increased ability to recollect both the item and its context.

Zeeuws I; Deroost N; Soetens E. Verbal memory improved by D-amphetamine: influence of the testing effect. Human Psychopharmacology: Clinical and Experimental 25(5): 377-387, 2010. (33 refs.)

Objective: The improvement of long-term retention of verbal memory after an acute administration of D-amphetamine in recall and recognition tasks has been ascribed to an influence of the drug on memory consolidation. Because recent research has demonstrated that intermediate testing is of overriding importance for retention, we investigated whether D-amphetamine modulates the repeated testing effect in verbal long-term recognition. Method: Forty men participated in two double blind placebo controlled studies. In Experiment 1, we manipulated the number of recognition tests and in Experiment 2, we compared repeated with nonrepeated testing of the same items. Results Drug effects were observed on delayed tests only, leaving immediate recognition unaffected. Number of intermediate recognition tests and repeated testing of the same items were not affected by D-amphetamine. Conclusions: We conclude that the D-amphetamine memory enhancement is not related to the testing effect. This result supports that D-amphetamine modulates other aspects of the consolidation process, probably related to context effects.

Zhao LY; Shi J; Zhang XL; Lu L. Psychosocial stress enhances non-drug-related positive memory retrieval in male abstinent heroin addicts. Neuroscience Letters 485(1): 16-20, 2010. (28 refs.)

Stress exposure in addicted individuals is known to provoke drug craving, presumably through a memory-like process, but less is known about the effects of stress on non-drug-related affective memory retrieval per se in such individuals, which is likely to provide important insights into therapy for relapse. In present study, we explored the effect of stress on retrieval of neutral and emotionally valenced (positive and negative) words in abstinent heroin addicts. In present study, 28 male inpatient abstinent heroin addicts and 20 sex-, age-, education- and economic status-matched healthy control participants were assessed for 24 h delayed recall of valenced and neutral word lists on two occasions 4 weeks apart once in a nonstress control condition, once after exposure to the Trier Social Stress Test in a counterbalanced design. In addition, attention, working memory, blood pressure, heart rate and salivary cortisol were assessed. We found acute stress at the time of word list recall enhanced retrieval of positively valenced words, but no effect on negative and neutral word retrieval in abstinent heroin addicts was observed. No changes were detected for attention and working memory. The stressor induced a significant increase in salivary free cortisol, blood pressure and heart rate. Stress can enhance non-drug-related positive memory in abstinent heroin addicts. Our findings will provide richer information in understanding dysregulation of their emotional memory processing under stress and hopefully provide insight into designing improved treatments for drug addiction.

Zhao LY; Shi J; Zhang XL; Epstein DH; Zhang XY; Liu Y et al. Stress enhances retrieval of drug-related memories in abstinent heroin addicts. Neuropsychopharmacology 35(3): 720-726, 2010. (49 refs.)

Stress is associated with relapse to drugs after abstinence, but the mechanisms for this association are unclear. One mechanism may be that stress enhances abstinent addicts' recall of memories of drugs as stress relievers. This study assessed the effects of stress on free recall and cued recall of 10 heroin-related and 10 neutral words learned 24 h earlier by 102 abstinent heroin addicts. These participants were randomly assigned to three experiments that also assessed attention and working memory. Experiment 1 used a psychosocial stressor (Trier social stress test (TSST)) before testing for recall of heroin-related words. Experiment 2 added administration of the beta-adrenoceptor antagonist propranolol 1 h before the psychosocial stressor. Experiment 3 added administration of either cortisol with propranolol, cortisol alone, or propranolol alone 1 h before word recall to determine whether stress enhancement of heroin-related word recall required noradrenergic-glucocorticoid interactions. We found that free recall of heroin-related words in abstinent addicts was enhanced after stress or cortisol administration when compared with a non-stress condition or placebo, respectively, whereas these interventions had no effect on neutral word recall. beta-adrenergic blockade blocked the enhancing effect of stress or cortisol on free recall of heroin-related words. Neither stress nor cortisol affected cued recall, attention, or working memory. The potential of b-adrenergic blockade to reduce or block stress-induced enhancement of drug-related memory retrieval may be relevant to preventing stress-induced relapse in abstinent heroin addicts.