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CORK Bibliography: Memory and Drug Abuse

77 citations. 2003 to present

Prepared: June 2006

Abi-Saab D; Beauvais J; Mehm J; Brody M; Gottschalk C; Kosten TR. The effect of alcohol on the neuropsychological functioning of recently abstinent cocaine-dependent subjects. American Journal on Addictions 14(2): 166-178, 2005. (42 refs.)

Neuropsychological deficits in the areas of learning, memory, attention, and abstraction abilities have been associated with cocaine dependence, especially during the period of early abstinence. Although cocaine users tend to be multidrug users, few studies have focused on the combined effect of alcohol and cocaine on neuropsychological functioning. Consistent with prior research, results from the current study indicated that cocaine-dependent subjects showed a significantly greater degree of neuropsychological impairment as compared to controls. In addition, cocaine-dependent subjects with a history of alcohol disorder showed less memory impairment but similar impairments in attention and overall neuropsychological functioning as cocaine subjects with no such history. The vasodilatation produced by alcohol may attenuate some of the vasoconstriction and neurotoxic effects of cocaine, accounting for the fewer deficits in this group

Addington J; Addington D. Patterns of premorbid functioning in first episode psychosis: Relationship to 2-year outcome. Acta Psychiatrica Scandinavica 112(1): 40-46, 2005. (47 refs.)

OBJECTIVE: To determine how different patterns of premorbid functioning relate to outcome longitudinally. METHOD: Premorbid adjustment was assessed in 194 first-episode of psychosis subjects. Positive and negative symptoms, depression, substance misuse and social and cognitive functioning were assessed over 2 years. RESULTS: Four patterns of premorbid adjustment: stable-good, stable-intermediate, poor-deteriorating and deteriorating were identified. Relative to the stable-good group, the deteriorating and poor-deteriorating groups had significantly more positive symptoms at 1-year follow-up but not at 2-year follow-up and significantly more negative symptoms and significantly poorer social functioning at both 1 and 2-years. Only verbal fluency and memory differentiated between the groups with the stable-good group having a superior performance. CONCLUSION: Those who demonstrated poor or deteriorating functioning prior to the onset of acute psychosis have a poorer outcome up to at least 2 years in terms of negative symptoms and social functioning.

Barker MJ; Greenwood KM; Jackson M; Crowe SF. An evaluation of persisting cognitive effects after withdrawal from long-term benzodiazepine use. Journal of the International Journal of the International Neuropsychological Society 11(3): 281-289, 2005. (47 refs.)

Twenty participants with self-reported long-term benzodiazepine use (mean 108 months) who had previously withdrawn from medication (mean 42 months) were administered a battery of neuropsychological tests. Each long-term user was case matched for age, sex, and education to two control participants who reported never taking benzodiazepines (those with and those without anxiety), The results indicated that long-term benzodiazepine use may lead to impairments in the areas of verbal memory, motor control/performance, and nonverbal memory but not visuospatial skills and attention/concentration. The length of abstinence (> 6 months) indicates that these impairments persist well beyond cessation of benzodiazepine use. However, observed impairments in the area of nonverbal memory were not solely attributable to benzodiazepine use and may be influenced by the elevated anxiety levels present it both the case and the anxious control group.

Barrett SP; Gross SR; Garand I; Pihl RO. Patterns of simultaneous polysubstance use in Canadian rave attendees. Substance Use & Misuse 40(9-10): 1525-1537, 2005. (22 refs.)

The aim of this study was to examine rave-related polydrug drug use and to determine if patterns of substance use were associated with previous rave attendance. One hundred and eighty-six rave attendees (50% female) representing a wide range of ages (16 to 47 years; mean = 23.5, sd = 5.15) and levels of rave attendance experience (I to 400 events) completed structured interviews in Montreal, Canada between November 2002 and September 2003 about their rave attendance patterns and their use of various licit and illicit substances at the most recently attended event. On average, participants reported using 2.5 different psychoactive substances (excluding tobacco) at the most recent event attended. Cannabis, alcohol, MDMA (ecstasy), amphetamine, cocaine, ketamine, and GHB were the most frequently reported substances, and details about their orders of administration, dosages, and patterns of co-administration are presented and discussed. The total lifetime number of raves attended by participants varied considerably (mean = 48.6; sd = 69.7; median = 25), and there was a positive correlation between the number events attended and number of substances used at the most recent event attended (p < 0.001). Analyses revealed that individuals reporting the use of ketamine, GHB, and/or cocaine at the most recent event had attended significantly more events than nonusers even when controlling for various demographic variables. A subset of respondents (n = 27) completed a second interview to determine the reliability of their responses. Results indicated that respondents could reliably recall details about which drugs were used, the total doses administered, as well as order of drug administration.

Bechara A; Martin EM. Impaired decision making related to working memory deficits in individuals with substance addictions. Neuropsychology 18(1): 152-162, 2004. (68 refs.)

This study examined whether individuals with substance dependence (ISDs) show impairments in working memory and whether there is a relationship between their impairments in decision making as measured by the gambling task (GT) paradigm and working memory as measured by a delayed nonmatching to sample (DNMS) task. Using the GT, 11% of healthy control participants and 61% of ISDs opted for choices with high immediate gains in spite of higher future losses. For the ISDs and controls with equal GT impairments, the ISDs performed significantly lower than controls on the DNMS task, The nonimpaired ISDs on the GT also performed significantly worse than matched controls on the DNMS task. The DNMS task deficit in ISDs was across all delay times, suggesting the deficit may lie in the "executive" process of working memory, which supports earlier findings (E. M. Martin et al., 2003). The authors suggest that the prefrontal cortex hosts multiple distinct mechanisms of decision making and inhibitory control and that ISDs may be affected in any one or combination of them.

Budney AJ; Moore BA; Vandrey R. Health consequences of marijuana use. IN: Brick J, ed. Handbook of the Medical Consequences of Alcohol and Drug Abuse. Binghamton, NY: Haworth Press, 2004. pp. 171-218. (272 refs.)

There is rather limited research on the chronic effects of marijuana use in terms of health. This chapter provides a review of the existing literature, with particular attention to the respiratory system, immune system, cardiovascular system, endocrine, as well as its impact on reproductive function. There is also attention to the psychological and psychiatric effects of marijuana on psychomotor function, attention, memory, academic performance, driving ability, and motivation. It also touches upon the current discussion of medical use of marijuana.

Chang L; Smith LM; LoPresti C; Yonekura ML; Kuo J; Walot I. Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure. Psychiatry Research: Neuroimaging 132(2): 95-106, 2004. (45 refs.)

The purpose of this pilot study was to examine possible neurotoxic effects of prenatal methamphetamine (Meth) exposure on the developing brain and on cognition. Meth-exposed children (n=13) and unexposed control subjects (n=15) were evaluated with MRI. Global brain volumes and regional brain structures were quantified. Ten Meth-exposed and nine unexposed children also completed neurocognitive assessments. Meth-exposed children scored lower on measures of visual motor integration attention, verbal memory and long-term spatial memory. There were no differences among the groups in motor skills, short delay spatial memory or measures of non-verbal intelligence. Despite comparable Nidiole brain volumes in each group, the Meth-exposed children had smaller putamen bilaterally (-17.7%). smaller globus pallidus (left: -27%. right: 30%). smaller hippocampus volumes (left: -19%, right: -20%) and a trend for a smaller caudate bilaterally (-13%). The reduction in these brain structures correlated with poorer performance on sustained attention and delayed verbal memory No group differences in volumes were noted in the thalamus, midbrain or the cerebellum. In summary, compared with the control group, children exposed to Meth prenatally exhibit smaller subcortical volumes and, associated neurocognitive deficits. These preliminary findings suggest prenatal Meth exposure may be neurotoxic to the developing brain.

Daumann J; Fischermann T; Heekeren K; Thron A; Gouzoulis-Mayfrank E. Neural mechanisms of working memory in ecstasy (MDMA) users who continue or discontinue ecstasy and amphetamine use: Evidence from an 18-month longitudinal functional magnetic resonance Imaging study. Biological Psychiatry 56(5): 349-355, 2004. (33 refs.)

Background: Working memory processing in ecstasy (3,4-methlenedioxymethamphetamine) users is associated with neural alterations as measured by functional magnetic resonance imaging, Here, we examined whether cortical activation Patterns change after prolonged periods of continued use or abstinence from ecstasy and amphetamine. Methods: We used an n-back task and functional magnetic resonance imaging in 17 ecstasy users at baseline (t(1)) and after 18 months (t(2)). Based on the reported drug use at t(2) we separated subjects with continued ecstasy and amphetamine use from subjects reporting abstinence during the follow-up period (n = 9 and n = 8, respectively. Results: At baseline both groups bad similar task performance and similar conical activation patterns, Task performance remained unchanged in both groups. Furthermore, there were no detectable functional magnetic resonance imaging signal changes from t(1) to t(2) in the follow-up abstinent group. However. the continuing users showed a dose-dependent increased parietal activation for the 2-back task after the follow-up period. Conclusions: Our data suggest that ecstasy use, particularly in high doses. is associated with greater parietal activation during working memory performance. An altered activation pattern might appear before changes in cognitive performance become apparent and, hence, may reflect an early stage of neuronal injury from the neurotoxic drug ecstasy.

de Ceballos ML; Guzman M. The role of cannabinoids in preventing the neurodegenerative process occurring in Alzheimer's disease. (review). Drugs of the Future 30(8): 807-814, 2005. (66 refs.)

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and accounts for at least 50% of dementia cases. During the last decades, great strides have been made in our understanding of the molecular and cellular events leading to the pathology of AD, and results of some preclinical studies have been promising. However, only a few therapies have been introduced into the clinic. The characterization of the cannabinoid system within the last years has led to the development of cannabinoid-based therapies for the treatment of various diseases. In particular, the neuroprotective effects of this class of drugs against acute brain damage and their antiinflammatory properties prompted us to study cannabinoid receptors in AD brains and their possible neuroprotective effects in both in vivo and in vitro models. We found that the functioning of cannabinoid receptors is dramatically reduced in AD brain tissue and that cannabinoids prevent beta-amyloid peptide-induced neurotoxicity and cognitive decline in rats, effects which may be due to their ability to inhibit microglial activation both in vivo and in vitro. These findings may be the basis for the use of cannabinoids as a therapeutic approach for AD.

Di Chiara G; Bassareo V; Fenu S; De Luca MA; Spina L; Cadoni C et al. Dopamine and drug addiction: The nucleus accumbens shell connection. (review). Neuropharmacology 47(Supplement S): 227-241, 2004. (102 refs.)

Microdialysis studies in animals have shown that addictive drugs preferentially increase extracellular dopamine (DA) in the n. accumbens (NAc). Brain imaging studies, while extending these finding to humans, have shown a correlation between psychostimulant-induced increase of extracellular DA in the striatum and self-reported measures of liking and 'high' (euphoria). Although a correlate of drug reward independent from associative learning and performance is difficult to obtain in animals, conditioned taste avoidance (CTA) might meet these requirements. Addictive drugs induce CTA to saccharin most likely as a result of anticipatory contrast of saccharin over drug reward. Consistently with a role of DA in drug reward, D2 or combined D1/D2 receptor blockade abolishes cocaine, amphetamine and nicotine CTA. Intracranial self-administration studies with mixtures of D1 and D2 receptor agonists point to the NAc shell as the critical site of DA reward. NAc shell DA acting on D1 receptors is also involved in Pavlovian learning through pre-trial and post-trial consolidation mechanisms and in the utilization of spatial short-term memory for goal-directed behavior. Stimulation of NAc shell DA transmission by addictive drugs is shared by a natural reward like food but lacks its adaptive properties (habituation and inhibition by predictive stimuli). These peculiarities of drug-induced stimulation of DA transmission in the NAc shell result in striking differences in the impact of drug-conditioned stimuli on DA transmission. It is speculated that drug addiction results from the impact exerted on behavior by the abnormal DA stimulant properties acquired by drug-conditioned stimuli as a result of their association with addictive drugs.

Drake CL; Roehrs T; Turner L; Scofield HM; Roth T. Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance. Neuropsychology 28(2): 371-378, 2003. (67 refs.)

Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21-35 years old) underwent four conditions presented in a Latin Square Design: placebo-placebo, ethanol (0.5 g/kg)-placebo, ethanol (0.5 g/kg)-caffeine 150 mg, and ethanol (0.5 g/kg)-caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043 +/- 0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.

Fals-Stewart W; Bates ME. The neuropsychological test performance of drug-abusing patients: An examination of latent cognitive abilities and associated risk factors. Experimental and Clinical Psychopharmacology 11(1): 34-45, 2003. (75 refs.)

The purpose of this study was to examine the latent structure of neuropsychological abilities of drug-abusing patients. Four factors were identified in an exploratory factor analysis (N = 329) and a subsequent confirmatory factor analysis (N = 258): Executive Functioning, Verbal Ability, Memory, and Speed. Education, years of regular alcohol use, number of substance use dependence disorders, percentage of days of heavy drinking in the previous year, depression, familial alcoholism, premorbid level of cognitive functioning, liver functioning, and previous head injuries were identified as risk factors to these latent abilities.

Fisk JE; Montgomery C; Wareing M; Murphy PN. Reasoning deficits in ecstasy (MDMA) polydrug users. Psychopharmacology 181(3): 550-559, 2005. (43 refs.)

Rationale/objectives: Previous research has shown that ecstasy users are impaired in thinking and reasoning. The present study sought to explore the possibility that syllogistic reasoning errors in ecstasy users were due to an inability to construct a model of the premises due to working memory limitations. Methods: Twenty-nine ecstasy users and 25 nonecstasy user controls completed abstract syllogistic reasoning problems varying in difficulty. Pairs of premises were provided, and participants were required to generate conclusions that followed necessarily from them. Results: On the easier problems, both groups performed at well above chance although nonusers achieved significantly more correct responses. Consistent with existing research, on the more difficult problems, errors by nonusers were characterised by incorrect conclusions suggesting that while nonusers have the working memory capacity to construct a single model of the premises, this is not an exhaustive representation and usually results in an erroneous conclusion. On the other hand, for all problem types, ecstasy users, rather than produce incorrect responses, were more likely to fail to generate a conclusion. Conclusions: The present results are consistent with the possibility that ecstasy users with their reduced working memory capacity may experience difficulty in constructing even a single model of the premises. While this might be attributable to the effects of 3,4-methlylenedioxymethamphetamine neurotoxicity, many of the ecstasy users in the present study were polydrug users. Thus, the possibility that other drugs including cannabis and cocaine might contribute to the present results cannot be excluded.

Garcia AV; Torrecillas FL; de; Arcos FA; Garcia MP. Effects of executive impairments on maladaptive explanatory styles in substance abusers: Clinical implications. Archives OF Clinical Neuropsychology 20(1): 67-80, 2005. (54 refs.)

Our study examined the relation between neuropsychological impairment of executive functions and explanatory styles, according to the Abramson model of learned helplessness in humans, in a sample of substance abusers. Thirty-eight polysubstance abusers were assessed during an abstinence period using a selective neuropsychological battery for the evaluation of the executive functions, as well as the Attributional Style Questionnaire (ASQ) for the assessment of the three dimensions of explanatory style: Internality-Externality, Stability-Instability and Globality-Specificity. Multiple regression analyses showed significant relationships among performance on different neuropsychological tasks sensitive to executive functions and characteristic cognitive styles. The results showed the performance on cognitive flexibility and response inhibition tasks is directly related to making more Internal attributions for positive situations, and inversely related to the appearance of more stable attributions for negative events. Likewise, adequate performance on working memory tasks was related to development of more global attributions for failures. These results are partially congruent with the learned helplessness model and particularly relevant for the clinical management of substance abusers and the success on the treatment and rehabilitation of these subjects.

Gaulier JM; Fonteau F; Jouanel E; Lachatre G. Rape drugs: Pharmacological and analytical aspects. (review). Annales de Biologie Clinique 62(5): 529 -538, 2004. (44 refs.)

Rape drugs or compounds used for chemical submission are current hot topics of numerous media based on a few well-documented identified cases. In the aim of considering the compounds potentially involved and subsequently the samples to collect and the toxicological analyses to perform, and according to the aggressor's viewpoint (victim submission and impunity of himself or herself), the characteristics of such compounds were drawn following the drug pharmacological properties. The compounds or therapeutic classes potentially used are numerous and diverse because the expected effects can be obtained by many neuropharmacological mechanisms or combinations of mechanisms. However, a few drugs (i.e. several benzodiazepines, and gamma-hydroxybutyrate) seem to be the ideal candidates owing to advantageous pharmacological properties (low blood concentrations, short elimination half-life) and practical ones (availability, galenic forms). It appears that the quality and precocity of biological specimen collection, the use of specific and sensitive analytical techniques, and the collaboration between the clinician and the toxicologist, are the essential keys for successful toxicological investigations when a case of chemical submission is suspected.

Glass JM; Adams KM; Nigg JT; Wong MM; Puttler LI; Buu A et al. Smoking is associated with neurocognitive deficits in alcoholism. Drug and Alcohol Dependence 82(2): 119-126, 2006. (57 refs.)

Background: Impaired problem solving, visual-spatial processing, memory, and cognitive proficiency are consequences of severe alcoholism. Smoking is much more prevalent among alcoholics than the general population, yet the possible neurocognitive effects of cigarette smoking in alcoholism have not been studied, despite evidence that long-term smoking is associated with neurocognitive deficits. Objective: Determine whether smoking contributes to neurocognitive deficits associated with alcoholism. Design: Neurocognitive function was examined in a community-recruited (n = 172) sample of men. Alcohol problems/alcoholism were measured by the lifetime alcohol problems score (LAPS), DSM-IV diagnosis, and monthly drinking rate. Smoking was measured in pack-years. Neurocognitive function was measured with IQ (short version of WAIS-R), and cognitive proficiency (fast, accurate performance). Results: Both alcoholism and smoking were negatively correlated with neurocognitive function. When alcoholism and smoking were included in regression models, smoking remained a significant predictor for both measures, but alcoholism remained significant only for IQ. Conclusions: Both smoking and alcoholism were related to neurocognitive function. Smoking may explain some of the relationship between alcoholism and neurocognitive function, perhaps especially for measures that focus on proficiency. Future studies are necessary to more fully understand the effects of smoking on neurocognitive function in alcoholism.

Goulle JP; Anger JP. Drug-facilitated robbery or sexual assault: Problems associated with amnesia. Therapeutic Drug Monitoring 26(2): 206-210, 2004. (28 refs.)

Amnesia following sedative-hypnotic drug exposure is discussed. Anterograde amnesia clearly occurs with many benzodiazepines. Several drugs are assessed: benzodiazepines and two hypnotics in particular that are structurally unrelated to the benzodiazepines but share some of their properties: zolpidem and zopiclone. The amnesic effects of these drugs are described, memory process, biology of memory, and memory process impairment documented. With these drugs anterograde amnesia has been demonstrated to be dose dependent. This effect is associated with hypnotic drugs, however, the receptors are different. As regards forensic medicine, a significant and specific type of amnesia should be considered: amnesia automatism or amnesic complex automatism. Also, several cases observed in our laboratory are presented to demonstrate the impact of amnesia.

Gouzoulis-Mayfrank E; Fischermann T; Rezk M; Thimm B; Hensen G; Daumann J. Memory performance in polyvalent MDMA (ecstasy) users who continue or discontinue MDMA use. Drug and Alcohol Dependence 78(3): 317-323, 2005. (40 refs.)

Background: The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine = MDMA) is a serotonergic neurotoxin in animal studies. Several cross-sectional investigations reported low memory and learning performance in ecstasy users, particularly in those reporting heavy patterns of drug use. Since, serotonin has a recognized role in memory processes, these findings were mostly interpreted as evidence for ecstasy-related neurotoxicity in humans. However, studies with user populations and controls suffer from many inherent methodological problems. Moreover, longitudinal data on memory performance after continued or discontinued ecstasy use are scarce. Methods: In the present longitudinal study, we examined memory performance in 38 MDMA users over the course of 18 months. Results: Subjects who stopped MDMA use after the baseline examination (n = 17) did not improve, and subjects who continued MDMA use (n = 21) did not deteriorate in terms of test performance. Conclusions: Our data do not support, but they also do not rule out memory decline following use of the serotonergic neurotoxin MDMA. In light of the popularity of ecstasy among young people, further investigations are needed. In our view, research strategies should now move to prospective designs in order to shed more light on the course of possible adverse cognitive effects of ecstasy use.

Hartzler B; Fromme K. Fragmentary and en bloc blackouts: Similarity and distinction among episodes of alcohol-induced memory loss. Journal of Studies on Alcohol 64(4): 547-550, 2003. (20 refs.)

En bloc and fragmentary blackouts are distinguishable forms of alcohol-induced amnesia. The former are instances of full and permanent memory loss for intoxicated events, whereas the latter are episodes for which retrieval of experiences is facilitated by provision of cues. The current study assessed their characteristics as reported by a group of heavy drinking young adults. A sample of 136 young adult volunteers (54% male, mean age=22.71) were administered a Time-Line Follow-Back assessment, expanded to gather descriptive information about the occurrence and characteristics of en bloc and fragmentary blackouts. Although overall reporting of blackouts by the sample mirrored rates reported in prior research, prevalence and incidence of fragmentary blackouts were more than threefold those of en bloc blackouts. A surprising finding was that the two blackout types exhibited a similar range and distribution of corresponding blood alcohol concentrations. Most en bloc blackouts involved concurrent use of illicit substances; polysubstance use was reported for few fragmentary blackouts. In addition, subjective evaluations of en bloc blackouts were quite negative, whereas fragmentary blackouts were evaluated as only mildly negative. It is concluded that beyond nosological distinctions, en bloc and fragmentary blackouts differ on several descriptive dimensions. The collective findings expand understanding of diversity in experiences that accompany memory loss after drinking.

Heffernan TM; Ling J; Parrott AC; Buchanan T; Scholey AB; Rodgers J. Self-rated everyday and prospective memory abilities of cigarette smokers and non-smokers: A web-based study. Drug and Alcohol Dependence 78(3): 235-241, 2005. (41 refs.)

The present study examined self-ratings of two aspects of everyday memory performance: long-term prospective memory -- measured by the prospective memory questionnaire (PMQ), and everyday memory -- measured by the everyday memory questionnaire (EMQ). Use of other substances was also measured and used as covariates in the study. To ensure confidentiality and to expand the numbers used in previous studies, an Internet study was carried out and data from 763 participants was gathered. After controlling for other drug use and strategy use, the data from the PMQ revealed that smokers reported a greater number of long-term prospective memory errors than non-smokers. There were also differences between light and heavier smokers in long-term prospective memory, suggesting that nicotine may have a dose-dependent impact upon long-term prospective memory performance. There was also a significant ANOVA group effect on the EMQ, although the trend for more memory errors amongst the heavier smokers was statistically only borderline (p = .057). These findings suggest there are selective memory deficits associated with smoking and that long-term prospective memory deficits should be added to the growing list of problems associated with cigarette use.

Hernandez PJ; Kelley AE. Cracking addiction the second time around: Reconsolidation of drug-related memories. (editorial). Neuron 47(6): 772-775, 2005. (17 refs.)

One of the greatest challenges in the understanding and treatment of addiction is cue-elicited relapse to drug use. The present findings of Miller and Marshall and Lee et al. reported in this issue of Neuron demonstrate that retrieved drug-related memories undergo reconsolidation and thus suggest that these maladaptive associations may be more labile than previously thought.

Hyman SE. Addiction: A disease of learning and memory. (review). American Journal of Psychiatry 162(8): 1414-1422, 2005. (100 refs.)

If neurobiology is ultimately to contribute to the development of successful treatments for drug addiction, researchers must discover the molecular mechanisms by which drug-seeking behaviors are consolidated into compulsive use, the mechanisms that underlie the long persistence of relapse risk, and the mechanisms by which drug-associated cues come to control behavior. Evidence at the molecular, cellular, systems, behavioral, and computational levels of analysis is converging to suggest the view that addiction represents a pathological usurpation of the neural mechanisms of learning and memory that under normal circumstances serve to shape survival behaviors related to the pursuit of rewards and the cues that predict them. The author summarizes the converging evidence in this area and highlights key questions that remain.

Ilan AB; Smith ME; Gevins A. Effects of marijuana on neurophysiological signals of working and episodic memory. Psychopharmacology 176(2): 214-222, 2004. (75 refs.)

Rationale: The primary psychoactive constituent of marijuana, Delta(9)-THC, activates cannabinoid receptors, which are especially abundant in the frontal cortex and hippocampus. Acute marijuana smoking can disrupt working memory (WM) and episodic memory (EM) functions that are known to rely on these regions. However, the effects of marijuana on the brain activity accompanying such cognitive processes remain largely unexplored. Objectives: To examine such effects on performance and neurophysiological signals of these functions, EEG recordings were obtained from ten subjects (5M, 5F) performing cognitive tasks before and after smoking marijuana (3.45% Delta(9)-THC) or a placebo. WM was assessed with a spatial N-back task, and EM was evaluated with a test requiring recognition of words after a 5-10 min delay between study and test. Results: Marijuana increased heart rate and decreased global theta band EEG power, consistent with increased autonomic arousal. Responses in the WM task were slower and less accurate after smoking marijuana, accompanied by reduced alpha band EEG reactivity in response to increased task difficulty. In the EM task, marijuana was associated with an increased tendency to erroneously identify distracter words as having been previously studied. In both tasks, marijuana attenuated stimulus-locked event-related potentials (ERPs). Conclusions: The results suggest that marijuana disrupted both sustained and transient attention processes resulting in impaired memory task performance. In subjects most affected by marijuana a pronounced ERP difference between previously studied words and new distracter words was also reduced, suggesting disruption of neural mechanisms underlying memory for recent study episodes.

Izaute M; Paire-Ficout L; Bacon E. Benzodiazepines and semantic memory: Effects of lorazepam on the Moses illusion. Psychopharmacology 172(3): 309-315, 2004. (37 refs.)

Rationale. When asked "How many animals of each kind did Moses take on the ark?", people fail to notice the distortion introduced by the impostor "Moses" and respond "two". It has been argued that the effect must be due to the existence of a partial-match process. In most situations, the form of a question is not likely to closely match the memory representation it queries. Thus, for the partial match hypothesis people ignore some semantic distortions. In the same vein, it has been shown that the benzodiazepine lorazepam drug induces some impairments of semantic memory as participants under lorazepam provide more incorrect recalls than placebo do with general information questions. Objectives. The aim of this study was to investigate the effects of the benzodiazepine lorazepam on the Moses illusion paradigm. Method. The effects of lorazepam (0.038 mg/kg) and of a placebo were investigated in 28 healthy volunteers. Twenty-two illusory questions were presented along with 72 normal general information questions. Results. Lorazepam impaired the ability to detect the Moses illusion. Moreover, lorazepam participants appeared less biased to consider a question distorted than placebo participants. Conclusions. The temporary and reversible semantic memory impairments experienced by participants when falling into the Moses illusion are more frequent under lorazepam. The amnesic drug lorazepam may impair semantic processing as well as the strategic control of memory.

Jacobsen LK; Krystal JH; Mencl WE; Westerveld M; Frost SJ; Pugh KR. Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biological Psychiatry 57(1): 56-66, 2005. (85 refs.)

Background: In adult animals and humans, nicotine can produce short-term cognitive enhancement and, in some cases, neuroprotection. Recent work in animals, however, suggests that exposure to nicotine during adolescence might be neurotoxic. We tested for evidence of acute and chronic effects of tobacco smoking on cognition in adolescents who smoked tobacco daily and were tested for evidence of acute and chronic effects compared with adolescent nonsmokers. Methods: Verbal working memory, verbal learning and memory, selective, divided, sustained attention, mood, symptoms of nicotine withdrawal, and tobacco craving were examined in 41 adolescent daily smokers and 32 nonsmokers who were similar in age, gender, and education. Analyses were controlled for general intelligence, reading achievement, parental educational attainment, baseline affective symptoms, and lifetime exposure to alcohol and cannabis. Results: In adolescent smokers, cessation of tobacco use increased tobacco craving, symptoms of nicotine withdrawal, and depressed mood. Adolescent smokers were found to have impairments in accuracy of working memory performance irrespective of recency of smoking. Performance decrements were more severe with earlier age of onset of smoking. Adolescent smokers experienced further disruption of working memory and verbal memory during smoking cessation. As a group, male smokers initiated smoking at an earlier age than female smokers and were significantly more impaired during tests of selective and divided attention than female smokers and nonsmokers. Conclusions: Adolescent daily tobacco smokers experience acute impairments of verbal memory and working memory after smoking cessation, along with chronic decrements in cognitive performance that are consistent with preclinical evidence that neurotoxic effects of nicotine are more severe when exposure to nicotine occurs at earlier periods in development.

Johnson T; Fendrich M. Modeling sources of self, report bias in a survey of drug use epidemiology. Annals of Epidemiology 15(5): 381-389, 2005. (46] refs.)

PURPOSE: Well-documented errors in the reporting of drug-related behaviors have been attributed to several sources. These include: 1) respondent difficulties in understanding survey questions, 2) problems in recalling the information necessary to accurately answer these questions, and 3) social pressures that discourage accurate reporting. We report covariance structure models designed to simultaneously evaluate each of these potential sources of error. METHODS: Data examined are from a community survey of 627 Chicago adults which collected drug use self reports (via ACASI technology), multiple biological samples (including hair, urine, and saliva) that permit self-report validation, and a series of probes designed to collect systematic information regarding respondent comprehension and memory difficulties and social desirability concerns. These three sets of information were employed to construct latent variable covariance structure models that enabled an evaluation of the effects of each potential source of reporting error on the quality of drug use reporting. RESULTS: Social desirability concerns were predictive of discordant drug use reporting and drug use under-reporting. Memory difficulties were predictive of drug use over-reporting. Differences in the predictive power of these variables were found across race/ethnic groups. CONCLUSIONS: Both memory difficulties and social desirability concerns are independent sources of measurement error in surveys of drug use epidemiology.

Juan D; Zhou DHD; Li J; Wang JYJ; Gao C; Chen M. A 2-year follow-up study of cigarette smoking and risk of dementia. European Journal of Neurology 11(4): 277-282, 2004. (38 refs.)

The report focused on investigating the relationship between cigarette smoking and dementia in elderly people through prospective studies. We did a 2-year follow-up study of elderly people. A total of 2820 participants aged 60 years old and over from six communities of Chongqing agreed to take part. Dementia was diagnosed with MMSE (Mini-Mental State Examination) and DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders). Participants were classified as never smokers, past smokers, and current smokers. During follow-up, we recorded incident cases of dementia. The association of smoking and dementia was investigated using proportional hazards regression analysis. A total of 121 incident cases of dementia were detected, of which 84 (69%) were Alzheimer's disease, 17 (14%) were vascular dementia, and 21(17%) were other dementia. Compared with never smokers, current smokers had an increased risk of Alzheimer's disease (RR = 2.72 95% CI = 1.63-5.42) and vascular dementia (RR = 1.98; 95% CI = 1.53-3.12) adjusting for age, sex, education, blood pressure, and alcohol intake. Compared with light smokers, the adjusted risk of Alzheimer's disease was significantly increased among smokers with a medium level of exposure (RR = 2.56; 95% CI = 1.65-5.52), with an even higher risk of Alzheimer's disease in the heavy smoking group (RR = 3.03; 95% CI = 1.25-4.02). Smoking was associated with the risk of dementia. This study suggests that both smoking status and amount is associated with dementia.

Justice AC; McGinnis KA; Atkinson JH; Heaton RK; Young C; Sadek J et al. Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort Five-Site Study. AIDS 18(Supplement 1): S49-S59, 2004. (35 refs.)

Background: The risk for psychiatric and neurocognitive disorders among middle-aged and older individuals with HIV infection has not been well characterized. Methods: The Veterans Aging Cohort 5-Site Study enrolled 1803 patients (1047 HIV-positive) from VA infectious disease and general medicine clinics from September 2001 to June 2002. A convenience subset of 10 patients from each site (n=50) was consented for formal neurocognitive and psychiatric (NCP) testing. Data from this subset were linked to the larger sample. Results: Kappa scores for agreement beyond chance were fair for available measures when compared with formal NAP testing. Using available measures, depressive symptoms (PHQ-9 and provider reported), alcohol abuse or dependence (ICD-9 codes), and drug abuse or dependence (DAST-10) decreased with age in HIV-negative subjects (P trend <0.05) but did not among HIV-positive subjects (P>0.05). HIV-positive subjects demonstrated higher prevalence of these conditions with increasing age when compared to HIV-negative subjects. Patient report of memory problems increased with age among both groups after excluding those reporting symptoms of depression (PHQ-9egreater than or equal to10). Conclusion: Available measures were no substitute for formal NCP testing. Older HIV-positive veterans demonstrate greater prevalence of depressive symptoms, alcohol abuse or dependence, and drug abuse or dependence than age-matched, HIV-negative veterans. Both groups reported increased memory problems with advancing age. This preliminary work suggests a substantial prevalence of psychiatric and neurocognitive problems among middle-aged and older HIV-infected individuals.

Kelleher LM; Stough C; Sergejew AA; Rolfe T. The effects of cannabis on information-processing speed. Addictive Behaviors 29(6): 1213-1219, 2004. (17 refs.)

Despite extensive research on the effects of cannabis on cognitive and motor performance, studies administering computerised cognitive batteries and pencil-and-paper tests have not provided consistent results. Contributing factors are the broad range of tests used, together with a lack of sensitivity for assessing specific cognitive processes. This study for the first time assesses a very early cognitive process, information processing, that is sufficiently fundamental as to be immune from higher cognitive, motivational, and social processes. Information processes are thought to represent the basic building blocks of higher order cognitive processes. The inspection time (IT) task was used to investigate the effects of acute and subacute cannabis use on information processing in 22 heavy users, compared to 22 noncannabis-using controls. Findings indicate that users in the subacute state display significantly slowed information-processing speeds (longer ITs) compared to controls. Paradoxically, this deficit appears to be normalised whilst users are in the acute state. These results may be explained as a withdrawal effect, but may also be due to tolerance development as a result of long-term cannabis use. Furthermore, these results may assist in providing an explanation for the development of dependence with chronic cannabis users.

Kelley AE. Memory and addiction: Shared neural circuitry and molecular mechanisms. (review). Neuron 44(1): 161 -179, 2004. (197 refs.)

An important conceptual advance in the past decade has been the understanding that the process of drug addiction shares striking commonalities with neural plasticity associated with natural reward learning and memory. Basic mechanisms involving dopamine, glutamate, and their intracellular and genomic targets have been the focus of attention in this research area. These two neurotransmitter systems, widely distributed in many regions of cortex, limbic system, and basal ganglia, appear to play a key integrative role in motivation, learning, and memory, thus modulating adaptive behavior. However, many drugs of abuse exert their primary effects precisely on these pathways and are able to induce enduring cellular alterations in motivational networks, thus leading to maladaptive behaviors. Current theories and research on this topic are reviewed from an integrative systems perspective, with special emphasis on cellular, molecular, and behavioral aspects of dopamine D-1 and glutamate NMDA signaling, instrumental learning, and drug cue conditioning.

Kumari V; Gray JA; Ffytche DH; Mitterschiffthaler MT; Das M; Zachariah E et al. Cognitive effects of nicotine in humans: An fMRI study. Neuroimage 19(3): 1002-1013, 2003. (62 refs.)

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric "n-back" task in healthy nonsmoking males after the administration of nicotine (12 mug/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy (P = 0.008) in all active conditions (2%-11%), and had a load-specific effect on latency (P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task (P < 0.05, corrected at the voxel level), nicotine produced an increased response (P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest (P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.

Kuypers KPC; Ramaekers JG. Transient memory impairment after acute dose of 75 mg 3.4-Methylenedioxymethamphetamine. Journal of Psychopharmacology 19(6): 633-639, 2005. (21 refs.)

A range of studies has indicated that users of 3.4-Methylene-dioxymethamphetamine (MDMA, 'Ecstasy') display cognitive deficits, particularly memory impairment, as compared to non-drug using controls. Yet it is difficult to determine whether these deficits are caused by MDMA or some other confounding factor, such as polydrug use. The present study was designed to establish the direct relation between MDMA and memory impairment under placebo-controlled conditions. Eighteen recreational MDMA users participated in a double blind, placebo controlled, 3-way crossover design. They were treated with placebo, MDMA 75 mg and methylphemidate 20 mg. Memory tests were conducted between 1.5-2 h (intoxication phase) and between 25.5-26 h (withdrawal phase) post dosing. Results showed that a single dose of MDMA caused impairment of immediate and delayed recall on a verbal learning task during the intoxication phase. However, there was no residual memory impairment during the withdrawal phase. Subjects reported more fatigue and less vigour, but no symptoms of depression during the withdrawal phase of MDMA treatment. Methylphenidate did not affect memory or mood at any time of testing. A single dose of MDMA produces transient memory impairment.

Lamers CTJ; Ramaekers JG; Muntjewerff ND; Sikkema KL; Samyn N; Read NL et al. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance. Journal of Psychopharmacology 17(4): 379-387, 2003. (42 refs.)

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.

Lane SD; Cherek DR; Lieving LM; Tcheremissine OV. Marijuana effects on human forgetting functions. Journal of the Experimental Analysis of Behavior 83(1): 67-83, 2005. (39 refs.)

It has long been known that acute marijuana administration impairs working memory (e.g., the discrimination of stimuli separated by a delay). The determination of which of the individual components of memory are altered by marijuana is an unresolved problem. Previous human studies did not use test protocols that allowed for the determination of delay-independent (initial discrimination) from delay-dependent (forgetting or retrieval) components of memory. Using methods developed in the experimental analysis of behavior and signal detection theory, we tested the acute effects of smoked marijuana on forgetting functions in 5 humans. Immediately after smoking placebo, a low close, or a high close of marijuana (varying in Delta(9)-THC content), subjects completed delayed match-to-sample testing that included a range of retention intervals within each test session (0.5, 4, 12, and 24 s). Performances (discriminability) at each dose were plotted as forgetting functions, as described and developed by White and colleagues (White, 1985; White & Ruske, 2002). For all 5 subjects, both Delta(9)-THC closes impaired delay-dependent discrimination but not delay-independent discrimination. The outcome is consistent with current, nonhuman studies examining the role of the cannabinoid system on delayed matching procedures, and the data help illuminate one behavioral mechanism through which marijuana alters memory performance.

Lee JLC; Di Ciano P; Thomas KL; Everitt BJ. Disrupting reconsolidation of drug memories reduces cocaine-seeking behavior. Neuron 47(6): 795-801, 2005. (45 refs.)

Maladaptive memories that associate environmental stimuli with the effects of drugs of abuse are known to be a major cause of relapse to, and persistence of, a drug addictive habit. However, memories may be disrupted after their acquisition and consolidation by impairing their reconsolidation. Here, we show that infusion of Zif268 antisense oligodeoxynucleotides into the basolateral amygdala, prior to the reactivation of a well-learned memory for a conditioned stimulus (CS)-cocaine association, abolishes the acquired conditioned reinforcing properties of the drug-associated stimulus and thus its impact on the learning of a new cocaine-seeking response. Furthermore, we show that reconsoliclation of CS-fear memories also requires Zif268 in the amygdala. These results demonstrate that appetitive CS-drug memories undergo reconsoliclation in a manner similar to aversive memories and that this amygdala-dependent reconsolidation can be disrupted to reduce the impact of drug cues on drug seeking.

Lundqvist T. Cognitive consequences of cannabis use: Comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacology, Biochemistry and Behavior 81(2): 319-330, 2005. (91 refs.)

This review aims to compare cognitive consequence between cannabis, and stimulants and heroin with regards to attention, memory and executive functions. The available studies using brain imaging techniques and neuropsychological tests show that acutely, all drugs create a disharmony in the neuropsychological network, causing a decrease of activity in areas responsible for short-term memory and attention, with the possible exception of heroin. Cannabis induces loss of internal control and cognitive impairment, especially of attention and memory, for the duration of intoxication. Heavy cannabis use is associated with reduced function of the attentional/executive system, as exhibited by decreased mental flexibility, increased perserveration, and reduced learning, to shift and/or sustain attention. Recent investigations on amphetamine/methamphetamine have documented deficits in learning, delayed recall, processing speed, and working memory. MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks. The degree of executive impairment increases with the severity of use, and the impairments are relatively lasting over time. Chronic cocaine users display impaired attention, learning, memory, reaction time and cognitive flexibility. Heroin addiction may have a negative effect on impulse control, and selective processing.

Medina KL; Shear PK; Corcoran K. Ecstasy (MDMA) exposure and neuropsychological functioning: A polydrug perspective. Journal of the International Neuropsychological Society 11(6): 753-765, 2005. (58 refs.)

Ecstasy (MDMA) is a popular drug that can act as a selective serotonin neurotoxin in several species. The goal of the present study was to examine the relationship between ecstasy exposure and cognitive functioning after controlling for other drug use and demographic variables. Furthermore, we assessed whether gender was a moderator of the relationship between cognitive functioning and ecstasy use. Data were collected from 31 men and 34 women with a wide range of ecstasy use (17 marijuana users with no ecstasy use and 48 ecstasy users ranging from low to heavy use). Participants were interviewed and administered a battery of neuropsychological tests. The primary finding was that ecstasy exposure was significantly related to poorer verbal learning and memory ability in a dose-dependent manner, while no such relationship was observed between ecstasy exposure and executive functioning or attentional ability. Gender was found to significantly moderate the relationship between ecstasy consumption and design fluency. These results suggest primary memory dysfunction among abstinent recreational ecstasy users. This finding is consistent with reports of hippocampal vulnerability, particularly among heavy users.

Mintzer MZ; Griffiths RR. Drugs, memory and metamemory: A dose-effect study with lorazepam and scopolamine. Experimental and Clinical Psychopharmacology 13(4): 336-347, 2005. (49 refs.)

This experiment was designed to use the graded dose-related amnesia produced by the benzodiazepine lorazepam (1.0, 2.0 mg/70 kg, oral) and the anticholinergic scopolamine (0.3, 0.6 mg/70 kg, subcutaneous) as a tool to explore the cognitive and neurochemical mechanisms underlying metamemory in the judgment of learning paradigm, with a placebo-controlled independent groups design in healthy volunteers (n=12/group). Results provide evidence for a pharmacological dissociation between effects on memory versus metamemory (relative accuracy of item-by-item monitoring) across a range of levels of memory performance and suggest that the drugs selectively impair those aspects of metamnemonic monitoring that require participants' awareness of their overall current state of functioning (absolute accuracy of prospective item-by-item monitoring, prospective global monitoring) but not those that rely solely on assessment of individual item characteristics (relative accuracy of item-by-item monitoring).

Mintzer MZ; Griffiths RR. Triazolam-amphetamine interaction: Dissociation of effects on memory versus arousal. Journal of Psychopharmacology 17(1): 17-29, 2003. (58 refs.)

It is well-documented that benzodiazepine sedative/hypnotics produce robust dose-dependent memory-impairing effects. However, benzodiazepines also induce marked sedation, as reflected in changes in observer and subjective ratings of arousal and impaired psychomotor performance. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects, and do not reflect a specific, primary, benzodiazepine effect on memory mechanisms. This study was designed to use the non-specific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam. Across four sessions, 20 healthy adult volunteers received via oral capsule administration placebo, 0.25 mg/70 kg triazolam alone, 20 mg/70 kg d-amphetamine sulfate alone, and triazolam (0.25 mg/70 kg) and d-amphetamine (20 mg/70 kg) conjointly, in a double-blind, staggered dosing, cross-over design. d-Amphetamine significantly reversed the effects of triazolam on all participant rating and psychomotor performance-based measures of sedative effects, and selectively reversed the memory-impairing effects of triazolam on some measures (e.g. working memory assessed by a 2-back task, episodic memory assessed by free recall, metamemory), but not others (e.g. working memory assessed by a digit recall task, episodic memory assessed by recognition memory). Results suggest that benzodiazepines do have specific effects on memory that are not merely a by-product of the drugs' sedative effects, and that the degree to which sedative effects contribute to the amnestic effects may vary as a function of the particular memory process being assessed. In addition to enhancing the understanding of the mechanisms underlying benzodiazepine-induced amnesia, these results may also contribute to a better understanding of the complex relationship between specific memory processes and level of arousal.

Montgomery C; Fisk JE; Newcombe R; Wareing M; Murphy PN. Syllogistic reasoning performance in MDMA (Ecstasy) users. Experimental and Clinical Psychopharmacology 13(2): 137-145, 2005. (47 refs.)

Previous research has demonstrated working memory and executive deficits in recreational users of MDMA (3,4-methylenedioxymethamphetamine; Ecstasy). In turn, both of these constructs have been implicated in syllogistic reasoning performance. Twenty-two MDMA users (mean age = 21.36) and 26 MDMA nonuser controls (mean age = 21.31) were tested on syllogisms of varying difficulty and on measures of working memory and executive functioning. MDMA users were significantly impaired in aspects of syllogistic reasoning, and the effect remained significant after the authors controlled for the use of other drugs. However, the MDMA-related variance was reduced to below statistical significance following control for group differences in working memory span. The results are consistent with the possibility that MDMA-related deficits in aspects of executive functioning result in impaired reasoning performance among MDMA users.

Morgan CJA; Mofeez A; Brandner B; Bromley L; Curran HV. Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study. Psychopharmacology 172(3): 298-308, 2004. (54 refs.)

Rationale. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has medical indications but is also used as a recreational drug. Previous research has found persisting cognitive and psychotogenic effects of ketamine in chronic abusers of this drug 3 days after an acute dose. Objective. The present study aimed to investigate the effects of ketamine on two processes related to drug abuse, response inhibition and reinforcement, and to examine whether an acute dose of ketamine produced residual cognitive effects in healthy volunteers. Methods. Fifty-four healthy volunteers were given an 80-min infusion of one of two doses (0.4, 0.8 mg kg(-1)) of ketamine or placebo. Subjects completed a battery of tests at three time points: pre-infusion, during the infusion and 3 days later at follow-up. The battery consisted of tests of episodic and semantic memory, schizophrenic-like and dissociative symptoms, response inhibition and measures of subjective effects, including mood, bodily symptoms and enjoyment of and desire for the drug. Results. Ketamine acutely impaired response inhibition and had related biphasic effects on the subjective reinforcing effects of the drug. Ketamine also acutely impaired episodic but not semantic memory and increased schizophrenic-like and dissociative symptoms. No residual cognitive effects were observed 3 days following an acute dose. Conclusions. The lack of residual effects in healthy volunteers on day 3 indicates that impairments found on day 3 in ketamine abusers are chronic effects. The abuse of ketamine may be related to its capacity both to reinforce and to decrease response inhibition.

Morgan CJA; Monaghan L; Curran HV. Beyond the K-hole: A 3-year longitudinal investigation of the cognitive and subjective effects of ketamine in recreational users who have substantially reduced their use of the drug. Addiction 99(11): 1450-1461, 2004. (47 refs.)

Rationale: Ketamine is a dissociative anaesthetic that is also a drug of abuse. Previous studies have demonstrated persisting episodic and semantic memory impairments in recreational ketamine users 3 days after taking ketamine. However, the degree to which these deficits might be reversible upon reduction or cessation of ketamine use was not known. Objective: To follow-up a population of ketamine users tested 3 years previously and examine whether impairments observed 3 days after drug use are enduring or reversible. Methods: Eighteen ketamine users and 10 polydrug controls from studies conducted between 3 and 4 years earlier were re-tested on the same battery of cognitive tasks and subjective measures. These tapped episodic, semantic and working memory and executive and attentional functioning. Subjective schizotypal, dissociative, mood and bodily symptoms were also examined and a drug use history recorded. Results: The ketamine users had reduced their frequency of use of ketamine by an average of 88.3%. Performance of ketamine users on tasks tapping semantic memory had improved and this improvement was correlated with their reduction in ketamine use. On tasks tapping episodic memory and attentional functioning, ketamine users still showed deficits compared to polydrug controls. Higher levels of schizotypal symptoms and perceptual distortions were exhibited by the ketamine group, although dissociative symptoms were similar to controls. Conclusions: These findings indicate that semantic memory impairments associated with recreational ketamine are reversible upon marked reduction of use; however, impairments to episodic memory and possibly attentional functioning appear long-lasting. In addition, schizotypal symptoms and perceptual distortions may persist after cessation of ketamine use. Ketamine users, or potential users, should be aware of the enduring effects of this drug on aspects of memory and subjective experience.

Morgan CJA; Riccelli M; Maitland CH; Curran HV. Long-term effects of ketamine: Evidence for a persisting impairment of source memory in recreational users. Drug and Alcohol Dependence 75(3): 301-308, 2004. (43 refs.)

Rationale: Ketamine is an N-methyl--aspartate (NMDA)-receptor antagonist that is increasingly being used as a recreational drug. Previous research has shown gross generalised verbal memory impairments persisting 3 days after ketamine use in chronic users, however episodic memory has not specifically investigated in this population. Objective: To determine whether ketamine, on the night of drug use (day 0) and 3 days later, is associated with impaired episodic memory as assessed by a source memory task. Methods: Twenty ketamine users and 20 poly-drug controls were compared on a source memory task both on day 0 and 3. Participants also completed questionnaires on both days indexing schizophrenic-like and dissociative symptoms. Results: On day 0, ketamine abusers were impaired on both source memory and item recognition and scored more highly on schizophrenic and dissociative symptom scales compared to poly-drug controls. On day 3 ketamine abusers only displayed source memory impairments and these positively correlated with the level of schizophrenic-like symptoms on day 0. No differences on day 3 in schizophrenic-like or dissociative symptoms were observed. Conclusions: Ketamine abusers exhibit a persisting deficit in source memory on day 3 but not in item recognition. These findings suggest that repeated use of ketamine produces chronic impairments to episodic memory.

Myers CS; Robles O; Kakoyannis AN; Sherr JD; Avila MT; Blaxton TA; Thaker GK. Nicotine improves delayed recognition in schizophrenic patients. Psychopharmacology 174(3): 334-340, 2004. (49 refs.)

Rationale. Nicotine has been shown to enhance some aspects of memory, attention and cognition in normal subjects and in some patient populations such as Alzheimer's and Parkinson's disease groups. Objectives. Memory disorders are consistently observed in schizophrenic patients, so it is of interest to determine whether nicotine might improve memory performance in these patients. Methods. Delayed recognition was assessed using yes/no recognition of visuospatial designs. Working memory was assessed in a delayed match-to-sample paradigm using unfamiliar faces. Nicotine (1.0 mg delivered via nasal spray) was administered to schizophrenic patients and normal volunteers prior to testing in the nicotine condition. Results were compared to a baseline condition in which no nicotine was given. Results. On both tasks, normal volunteers performed better overall than schizophrenic patients. Significant improvement following nicotine administration was obtained only on the delayed recognition task and only for the subset of schizophrenic patients who were smokers. This improvement reflected a reduction in false alarm rates in the nicotine condition; hit rates were unaffected by nicotine. Conclusions. These results suggest that nicotine enhances delayed recognition memory in schizophrenic patients who smoke, but that similar performance enhancement is not observed for working memory.

Nicholson AN; Turner C; Stone BM; Robson PJ. Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. Journal of Clinical Psychopharmacology 24(3): 305-313, 2004. (32 refs.)

The effects of cannabis extracts on nocturnal sleep, early-morning performance, memory, and sleepiness were studied in 8 healthy volunteers (4 males, 4 females; 21 to 34 years). The study was double-blind and placebo-controlled with a 4-way crossover design. The 4 treatments were placebo, 15 mg Delta-9-tetrahydrocannabinol (THC), 5 mg THC combined with 5 mg cannabidiol (CBD), and 15 mg THC combined with 15 mg CBD. These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 PM. The electroencephalogram was recorded during the sleep period (11 PM to 7 AM). Performance, sleep latency, and subjective assessments of sleepiness and mood were measured from 8:30 AM (10 hours after drug administration). There were no effects of 15 mg THC on nocturnal sleep. With the concomitant administration of the drugs (5 mg THC and 5 mg CBD to 15 mg THC and 15 mg CBD), there was a decrease in stage 3 sleep, and with the higher dose combination, wakefulness was increased. The next day, with 15 mg THC, memory was impaired, sleep latency was reduced, and the subjects reported increased sleepiness and changes in mood. With the lower dose combination, reaction time was faster on the digit recall task, and with the higher dose combination, subjects reported increased sleepiness and changes in mood. Fifteen milligrams THC would appear to be sedative, while 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC.

Nowakowska E; Kus K; Florek E; Czubak A; Jodynis-Liebert J. The influence of tobacco smoke and nicotine on antidepressant and memory-improving effects of venlafaxine. Human and Experimental Toxicology 25(4): 199-209, 2006. (51 refs.)

In experimental and clinical studies, central nicotinic systems have been shown to play an important role in cognitive function. Nicotinic acetylcholine receptors also mediate the reinforcing properties of nicotine (NIC) in tobacco products. A variety of studies have shown that acute treatment with NIC or nicotinic agonists can improve working memory function. Moreover, it is known that the monoaminergic system plays an important role in memory function. And there is evidence suggesting that prolonged use of NIC may exert antidepressant action via nicotinic receptors. The purpose of this study was to investigate the interactions between a novel antidepressant, venlafaxine (VEN), a blocker of noradrenaline and 5-hydroxytryptamine reuptake sites, and pure NIC in the context of antidepressant and memory function in tobacco smoke exposed and non-exposed rats. The animals were subjected to Porsolt's test for testing antidepressant activity and their memory function ( spatial memory) was evaluated in the Morris Water Maze Test. In tobacco smoke non-exposed and exposed rats both single and chronic administration of VEN (20 mg/kg po) shortened immobility time. NIC (0.2 mg/kg sc) significantly reduced immobility time on the 1st, 7th and 14th test days in both non-exposed and exposed rats. Combined VEN + NIC treatment in tobacco smoke non-exposed rats reduced immobility too. This effect of the combination of drugs was significantly stronger as compared to the effects obtained after individual administration of VEN or NIC. In the group exposed to tobacco smoke, joint administration of VEN + NIC induced a significant reduction of immobility as compared to the control and NIC groups. In the Morris Water Maze Test single and chronic administration of VEN, lower values of escape latencies and lower numbers of crossed quadrants were noted in both exposed and non-exposed rats, which indicates improved performance. After administering NIC we could observe improvement of spatial memory in both the exposed and non-exposed group. A similar effect of improvement of spatial memory was observed after joint administration of VEN and NIC. The study results support the involvement of nicotinic systems in memory processes in rats. Memory improvement and antidepressant effects following joint administration of VEN and NIC may depend on nicotinic interactions with monoaminergic systems and VEN may represent a new therapeutic approach to smoking cessation.

Papageorgiou C; Rabavilas A; Liappasa L; Stefanis C. Do obsessive-compulsive patients and abstinent heroin addicts share a common psychophysiological mechanism? Neuropsychobiology 47(1): 1-11, 2003. (88 refs.)

Background/Aim: Working memory (WM) and attentional deficits have been implicated in the pathophysiology of both obsessive-compulsive disorder (OCD) and opioid addiction. The P300 component of event-related potentials (ERPs) is considered as an index of on-line updating of Wm and/or attentional operations involved in this function. The present study aimed at comparing the P300 elicited during a WM test in patients with prolonged heroin abstinence, those with OCD and healthy controls, in order to demonstrate possibly common underlying psychophysiological mechanisms. Methods: The P300 component was evaluated during the anticipatory period of a WM test in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 OCD patients, and 20 healthy subjects matched for age, sex and educational level. Results: The two patient groups showed a considerable reduction of the P300 amplitudes, located at the right frontal area as compared with healthy controls. The abstinent heroin addicts exhibited a significantly lower P300 amplitude at central frontal areas and a significantly higher P300 amplitude at the left occipital region relative to the other two groups. Furthermore, the abstinent group showed a notable delay of P300 latency relative to controls and OCD patients at the right occipital region. Moreover, the OCD patients manifested a significant prolongation of P300 located at the central prefrontal area, relative to addicts and healthy controls. Conclusions: These findings point to considerable WM and/or attentional deficits in the long-term abstinent syndrome of heroin misuse and OCD associated with distributed and prefrontal cortical circuits, respectively. Furthermore, the present findings suggest that both OCD and long-term abstinent heroin addicts may share a common impairment of WM and/or attention involving or affecting the right prefrontal areas.

Parrott AC; Milani RM. Cannabis, ecstasy/MDMA and memory: A commentary on Simon & Mattick's recent study. (letter). Addiction 98(7): 1003-1004, 2003. (9 refs.)

Pasquini M; Garavini A; Biondi M. Nicotine augmentation for refractory obsessive-compulsive disorder. A case report. (review). Progress in Neuro-Psychopharmacology & Biological Psychiatry 29(1): 157-159, 2005. (17 refs.)

The authors present a case of obsessive-compulsive disorder (OCD) resistant to conventional treatments. which improved following nicotine augmentation administered as 4 mg chewing gum. The role of acetylcholine in the pathophysiology of OCD is not clear. The authors discuss the effect of nicotine on memory for actions.

Poltavski DV; Petros T. Effects of transdermal nicotine on prose memory and attention in smokers and nonsmokers. Physiology & Behavior 83(5): 833-843, 2005. (39 refs.)

Previous research investigating cognitive effects of nicotine has produced mixed findings partly due to the use of abstaining smokers and cigarettes as a delivery system. The present study examined effects of nicotine delivered via a transdermal patch on prose memory and sustained attention in male smokers (n=25) and nonsmokers (n=22), who were randomly assigned to either a placebo or a nicotine condition. All groups were matched on their verbal ability and gross personality characteristics (state/trait anxiety levels, extroversion-introversion, and impulsivity level). In the nicotine condition, smokers were treated with a 21-mg transdermal patch, while nonsmokers received a 7-mg nicotine patch. Six hours following patch application, their performance was assessed on a computerized prose memory task and the Rapid Visual Information Processing task (RVIP) in a counterbalanced order and double-blind fashion. The results demonstrated that smokers in the placebo group recalled a significantly greater number of propositions than their counterparts in the nicotine group. Nonsmokers in the nicotine condition also remembered significantly more of the prose material than smokers in the same condition and showed a trend towards better recall of propositions of medium importance in the nicotine condition in comparison to the nonsmokers in the placebo group. No beween-group differences were found on the RVIP task. A significant effect of time was found for systolic blood pressure and heart rate. The results cannot be interpreted using the arousal theory of nicotine effects on attention and are explained on the basis of a dose-dependent nicotinic action possibly recruiting cholinergic cortical projections.

Pomara N; Facelle TM; Roth AE; Willoughby LM; Greenblatt DJ; Sidtis JJ. Dose-dependent retrograde facilitation of verbal memory in healthy elderly after acute oral lorazepam administration. Psychopharmacology 185(4): 487-494, 2006. (48 refs.)

Rationale: Retrograde facilitation (RF) refers to a paradoxical phenomenon in which recall of information presented before acute administration of agents generally associated with anterograde amnestic and sedative effects, such as benzodiazepines, is enhanced relative to a placebo condition. However, it is unclear whether this effect occurs in elderly individuals and if it is influenced by plasma drug levels, baseline cognitive function, or genetic factors such as the APOE e-4 allele, that may modulate drug-induced cognitive toxicity. Objectives: To determine if acute oral doses of lorazepam (0.5 mg, 1 mg) produced RF in elderly individuals exposed to interference tasks, and the variables associated with RF. Materials and methods: Sixty-four cognitively intact and highly educated (> 12 years) older adults (mean age, 66.09 years) participated in a placebo-controlled double-blind crossover study. The Buschke Selective Reminding Test was used to assess RF and amnestic effects for verbal memory. Self-ratings of mood states were also obtained. Results: Lorazepam administration resulted in significant dose-dependent RF, i.e., better recall of pre-drug word lists compared to placebo [F(1,63)= 15.358; p < 0.001 and F(1,63)= 46.163; p < 0.001 for 0.5 and 1 mg lorazepam, respectively]. Also, more of the pre-drug words were recalled in the 1.0-mg-lorazepam condition relative to the 0.5-mg-lorazepam condition [F(1,63)=29.498; p < 0.001]. In both the 0.5 and 1 mg lorazepam conditions, participants who exhibited high RF experienced significantly greater lorazepam-induced memory impairments over time [F(3,61)=2.901; p < 0.05; F(3,61)=2.698; p < 0.05; 0.5 and 1 mg lorazepam, respectively]. Also, in the 1-mg-lorazepam condition, participants who exhibited high RF reported significantly greater drowsiness relative to participants who showed less RF [t(62)=-2.521; p < 0.05]. RF was not significantly associated with age, the APOE epsilon 4 allele, years of education, global cognitive status, vocabulary scores, or a memory index score. Conclusion: In healthy elderly, acute oral lorazepam administration resulted in dose-dependent RF, which was associated with greater anterograde amnestic and sedative effects.

Qiu J. Addiction: Brainwashing. (editorial). Nature Reviews Neuroscience 6(11): 824-824, 2005. (3 refs.)

For recovering addicts, the sight of drug-taking paraphernalia and other reminders of drug use can trigger intense cravings and relapses. Two studies published in this issue report that it is possible to impair rats' memories associated with taking cocaine and that such treatments significantly reduce their drug-seeking behaviours. Both studies are based on the belief that retrieval of some forms of memory are followed by an active 'refiling' process, known as memory reconsolidation. If this process is disrupted, memories might be weakened or even lost. As only drug-related memories were being recalled when the inhibitors were given, the resulting amnesia might be specific to those memories rather than having a general effect on all memories. These findings hint at an exciting new approach that might help addicts kick the habit.

Rapeli P; Kivisaari R; Kahkonen S; Puuskari V; Autti T; Kalska H. Do individuals with former amphetamine dependence have cognitive deficits? Nordic Journal of Psychiatry 59(4): 293-297, 2005. (26 refs.)

The association between former amphetamine dependence and cognitive performance was studied in a sample of 12 individuals with former amphetamine dependence who had been abstinent for at least 1 year and in 12 age-, gender- and verbal IQ- matched controls. The groups were compared by cognitive tests on attention, memory, executive function and fluid intelligence. Individuals with former amphetamine dependence performed significantly poorer than controls in memory domain. Follow-up analysis of variance showed minor deficits in tests of delayed verbal memory. The results remained essentially the same when participants with current DSM-IV axis I diagnosis were excluded from the analysis. It is concluded that individuals with former amphetamine dependence have normal cognitive function with the possible exception of verbal memory. Thus, if widespread cognitive deficits are found in individuals with former amphetamine dependence, etiologies other than amphetamine abuse as such should be carefully investigated.

Richardson M; Powell JH; Curran HV. Effects of cigarette smoking on reward responsivity and cognitive function in brain injured individuals. Neuropsychological Rehabilitation 13(3): 365-378, 2003. (32 refs.)

Abstinence from smoking has been associated with acute impairments of performance in a number of tasks associated with incentive motivation and executive functioning in non-injured participants. The current study aimed to investigate the effects of smoking on various cognitive and motivational measures in 18 brain injured smokers, thus generalising previous findings from non-injured participants. A within-subjects cross-over design was utilised, to compare performance after an acute period of abstinence from smoking with performance after smoking. The test battery included measures of reward responsivity (a card-sorting task providing a behavioural index of incentive motivation), verbal fluency, and working memory. Reward responsivity was enhanced after a cigarette had been smoked compared to when abstinent. Performance on the card sorting task was particularly enhanced when the task was novel. There was no significant enhancement on any other measure. It was concluded that smoking has a direct effect on responsiveness to incentive, which we have found elsewhere to be closely related to motivation in therapy. Implications for clinical neuropsychological assessment and treatment are discussed.

Ridenour TA. Inhalants: Not to be taken lightly anymore. Current Opinion in Psychiatry 18(3): 243-247, 2005. (40 refs.)

Purpose of review: Until recently, inhalant abuse and dependence have been overlooked as serious problems, perhaps because of their relatively low prevalence. The purpose of this review is to summarize recent advances in our understanding of the consequences, pharmacology, and etiology of inhalant use, and how we might develop preventive and management strategies to combat abuse and dependence on these drugs. Recent findings: Animal models have cast light on how reinforcement of inhalant use occurs, and on mechanisms of development of tolerance and dependence. The reinforcing effects occur principally through GABA and dopamine-mediated mechanisms (rather than NMDA-mediated mechanisms). Assays for inhalants provide greater opportunities for accurate diagnosis. In addition to known medical consequences of inhalant use (including death), other risks associated with inhalant use and addiction include addiction to other substances, major depression, suicide, and impaired learning and memory. Summary: The extensive medical, psychiatric, and psychological damage that can be caused by inhalant use argues for much greater attention to be paid to developing prevention and treatment programmes for inhalant abuse and dependence. These are currently nonexistent, but are badly needed.

Robinson TE; Kolb B. Structural plasticity associated with exposure to drugs of abuse. (review). Neuropharmacology 47(Supplement S): 33-46, 2004. (119 refs.)

Persistent changes in behavior and psychological function that occur as a function of experience, such those associated with learning and memory, are thought to be due to the reorganization of synaptic connections (structural plasticity) in relevant brain circuits. Some of the most compelling examples of experience-dependent changes in behavior and psychological function, changes that can last a lifetime, are those that accrue with the development of addictions. However, until recently, there has been almost no research on whether potentially addictive drugs produce forms of structural plasticity similar to those associated with other forms of experience-dependent plasticity. In this paper we summarize evidence that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produces persistent changes in the structure of dendrites and dendritic spines on cells in brain regions involved in incentive motivation and reward (such as the nucleus accumbens), and judgment and the inhibitory control of behavior (such as the prefrontal cortex). It is suggested that structural plasticity associated with exposure to drugs of abuse reflects a reorganization of patterns of synaptic connectivity in these neural systems, a reorganization that alters their operation, thus contributing to some of the persistent sequela associated with drug use-including addiction.

Rodgers J; Buchanan T; Scholey AB; Heffernan TM; Ling J; Parrott AC. Patterns of drug use and the influence of gender on self-reports of memory ability in ecstasy users: a web-based study. Journal of Psychopharmacology 17(4): 389-396, 2003. (29 refs.)

Research indicates that the use of recreational drugs, including MDMA ('ecstasy') can result in impairments in cognitive functioning. Recent evidence, based on accounts of 'on drug' effects and cortical binding ratios suggests that women may be more susceptible to the effects of MDMA; however, no research has explored whether there are differences in the long-term behavioural sequelae of the drug between men and women. In addition, little is known about the profile of functioning of the 'typical' user. The present investigation accessed a large sample of recreational drug users, using the Internet, to obtain self-reports of memory functioning with a view to exploring any differences in self-reported ability amongst male and female users, and the level of difficulty reported by the 'typical' ecstasy user. A web site (www.drugresearch.org.uk) was developed and used for data collection. Prospective memory ability was assessed using the Prospective Memory Questionnaire. Self-report of day-to-day memory performance was investigated using the Everyday Memory Questionnaire. The UEL Drug Questionnaire assessed the use of other substances. The number of mistakes made while completing the questionnaires was also taken as an objective measure of performance errors. Findings, based on datasets submitted from 763 respondents, indicate no differences in self-reports of functioning between male and female participants. An overall dissociation between the effects of cannabis and ecstasy on self-reported memory functioning and on the likelihood of making an error during the completion of the questionnaire was found. Typical ecstasy users were found to report significantly more difficulties in long-term prospective memory and to make more completion errors than users of other substances and drug naive controls. Whilst taking into account the fact that participants were recruited via the World Wide Web and that a number of stringent exclusion criteria were applied to the data, a number of conclusions can be drawn. Recreational drug users perceive their memory ability to be impaired compared to non-users. The type of memory difficulties reported varies depending upon the drug of choice. These difficulties are exacerbated in ecstasy users. Individuals reporting average levels of use of ecstasy are more likely to report memory problems than non-ecstasy drug users or drug free individuals. The deleterious effects of ecstasy are therefore not restricted to heavy or chronic users. No gender differences were detected, suggesting that there may be a dissociation between cognitive impairment and cortical binding worthy of further exploration.

Rycroft N; Rusted JM; Hutton SB. Acute effects of nicotine on visual search tasks in young adult smokers. Psychopharmacology 181(1): 160-169, 2005. (42 refs.)

Rationale: Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives: We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods: In experiment I smokers and nonsmokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results: In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions: Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory.

Schinka JA; Belanger H; Mortimer JA; Graves AB. Effects of the use of alcohol and cigarettes on cognition in elderly African American adults. Journal of the International Neuropsychological Society 9(5): 690-697, 2003. (37 refs.)

In this study we examined the independent and interactive effects of lifetime patterns of drinking and smoking on cognitive performance in elderly African Americans. A sample of 230 individuals with varying histories of alcohol and cigarette use was drawn from the Hillsborough Elder African American Life Study, a community-based, cross-sectional study of older adults aged 60 to 84. Dependent variables were the results of a neuropsychological battery that provided measures of general cognitive ability, executive function, and memory. Specifically, our study addressed (1) whether individuals with a lifetime history of sustained smoking and/or drinking show lower levels of cognitive performance in comparison to lifetime abstainers, (2) whether cumulative lifetime doses of alcohol or cigarettes, or of the two substances in interaction, have an effect on cognition, and (3) whether individuals who have histories of periodic, intense use of either alcohol or cigarettes show lower levels of cognitive performance in comparison to lifetime abstainers. When significant results were obtained, effect sizes were small, not exceeding 5% of the variance. A single exception occurred for the intensity analyses, in which drinking explained approximately 16% of the variance in global cognitive ability after adjusting for the contributions of control variables. In these analyses, drinking was found to have a U-shaped effect on global cognitive ability and total acquisition in the memory trials. Specifically, moderate users performed at a lower level than abstainers or heavy users, who did not differ from each other.

Schroeder JP; Packard MG. Facilitation of memory for extinction of drug-induced conditioned reward: Role of amygdala and acetylcholine. Learning & Memory 11(5): 641 -647, 2004. (84 refs.)

These experiments examined the effects of posttrial peripheral and intra-amygdala injections of the cholinergic muscarinic receptor agonist oxotremorine on memory consolidation underlying extinction of amphetamine conditioned place preference (CPP) behavior. Male Long-Evans rats were initially trained and tested for an amphetamine (2 mg/kg) CPP. Rats were subsequently given limited extinction training, followed by immediate posttrial peripheral or intrabasolateral amygdala injections of oxotremorine. A second CPP test was then administered, and the amount of time spent in the previously amphetamine-paired and saline-paired apparatus compartments was recorded. Peripheral (0.07 or 0.01 mg/kg) or intra-amygdala (10 etag/0.5muL) postextinction trial injections of oxotremorine facilitated CPP extinction. Oxotremorine injections that were delayed 2 h posttrial training did not enhance CPP extinction, indicating a time-dependent effect of the drug on memory consolidation processes. The findings indicate that memory consolidation for extinction of approach behavior to environmental stimuli previously paired with drug reward can be facilitated by posttrial peripheral or intrabasolateral amygdala administration of a cholinergic agonist.

Seifert J; Seeland I; Borsutzky M; Passie T; Rollnik JD; Wiese B et al. Effects of acute alcohol withdrawal on memory performance in alcohol-dependent patients: A pilot study. Addiction Biology 8(1): 75-80, 2003. (18 refs.)

Studies on the neuropsychological performance in detoxified alcoholic patients often begin by acknowledging that there is a cognitive impairment to be found. Only little attention has been paid to date to the question as to how acute alcohol withdrawal might affect cognitive functions. Twenty-nine alcohol-dependent inpatients, nine in moderate alcohol withdrawal, treated with carbamazepine (group 1), 10 in mild alcohol withdrawal without pharmacological treatment (group 2), 10 in mild alcohol withdrawal with carbamazepine treatment (group 3) and 31 healthy subjects as controls (group 4) underwent repeated investigations using memory tests. The tests were performed on the first, third, seventh and fourteenth days of withdrawal. Immediate free recall of a word-list was impaired in the three patient groups in comparison with the control group on the 1st day. Thereafter no significant differences could be revealed between patients and controls. In a word-list recognition test the memory functions were not impaired in group 1 and group 2 in comparison with the control subjects. However, patients in group 3 showed impairment in this recognition test in comparison with the healthy subjects on the first and third days. The present study suggests that acute alcohol withdrawal impairs memory functions, especially free recall. This should be considered in treatment interventions in the early days of withdrawal.

Shukla PC; Moore UB. Marijuana-induced transient global amnesia. Southern Medical Journal 97(8): 782-784, 2004. (9 refs.)

A 6-year-old boy accidentally became intoxicated with marijuana secondary to ingesting cookies laced with marijuana. He presented with retentive memory deficit of sudden onset that was later diagnosed as transient global amnesia. Transient global amnesia as a result of marijuana intoxication is an extremely rare event.

Simon SL; Dacey J; Glynn S; Rawson R; Ling W. The effect of relapse on cognition in abstinent methamphetamine abusers. Journal of Substance Abuse Treatment 27(1): 59-66, 2004. (45 refs.)

Data from 75 participants in a longitudinal study of methamphetamine (MA) abuse were used to differentiate the cognitive performance of those who remained abstinent, relapsed, or continued to use during treatment. Participants were divided into three groups: continuous abstinence, initial abstinence but relapse, and continuous use. Groups did not differ on age, education, gender or ethnicity. Participants in the longitudinal study completed a battery of cognitive tests within 7 days of their last use of MA, then were re-tested monthly for up to 6 months (average time for this analysis was 92 days). For episodic memory, the relapse groups performance was worse than the abstinent and significantly worse than that of the continued use group who had the best performance on all measures. Relapse to methamphetamine use may affect episodic memory differently than it affects the other cognitive functions measured.

Soo-ampon S; Wongwitdecha N; Plasen S; Hindmarch I; Boyle J. Effects of word frequency on recall memory following lorazepam, alcohol, and lorazepam alcohol interaction in healthy volunteers. Psychopharmacology 176(3-4): 420-425, 2004. (47 refs.)

Free recall of words has been extensively used in psychopharmacology to assess the effects of CNS-active drugs on memory functions. However, there is a relative lack of information on the impact of word frequency on the subsequent recall of words following the administration of psychoactive drugs. The present double-blind, placebo-controlled, repeated-measures experiment used lorazepam and alcohol to test the effects of word frequency on immediate and delayed word recall in 24 healthy volunteers. One half of the words contained in the lists had a high frequency (HF) of occurrence and the remainder were of low frequency (LF). The results showed that LF words were more sensitive to memory impairment than HF words. However, the more accurate recall of HF words (with respect to LF words) was eliminated when a combination of lorazepam with alcohol was administered. These findings indicate that word frequency has a significant impact on memory and, as such, is a factor to be taken into account when using memory recall tasks to assess the effects of psychoactive drugs on memory.

Toomey R; Lyons MJ; Eisen SA; Xian H; Chantarujikapong S; Seidman LJ et al. A twin study of the neuropsychological consequences of stimulant abuse. Archives of General Psychiatry 60(3): 303-310, 2003. (54 refs.)

Background: Previous studies document neuropsychological deficits associated with stimulant abuse, but findings are inconsistent. Methods: We identified 50 twin pairs in which only I member had heavy stimulant abuse (cocaine and/or amphetamines) ending at least I year before the evaluation. The co-twin control research design controls for familial vulnerability and makes it easier to identify neuropsychological deficits that are consequences of stimulant abuse. Subjects were administered an extensive neuropsychological test battery organized into the following 5 functions: attention, executive functioning, motor skills, intelligence, and memory. Results: Multivariate tests showed that abusers performed significantly worse than nonabusers on functions of attention and motor skills. Within each of these functions, univariate tests showed that abusers performed significantly worse on certain tests of motor skills and attention. In contrast, abusers performed significantly better on one test of attention measuring visual vigilance. Within the abuser group, higher levels of stimulant use were largely uncorrelated with neuropsychological test scores, although a few significant correlations indicated better functioning with more stimulant use. Conclusions: With ideal controls, this study demonstrates that deficits in attention and motor skills persist after I year of abstinence from stimulant use and raises hypotheses regarding relative strengths on a vigilance task among abusers.

Verbaten MN. Specific memory deficits in ecstasy users? The results of a meta-analysis. Human Psychopharmacology: Clinical and Experimental 18(4): 281-290, 2003. (35 refs.)

A meta-analysis was carried out on the possible functional neurotoxic effects of ecstasy use in humans on verbal short-term memory (STM), verbal long-term memory (LTM), processing speed (RT) and % errors (attention). To that end studies were found on the effect of ecstasy that fulfilled the criteria for a meta-analysis (number of subjects, means and standard deviations of the dependent variables). Ten studies were included on STM, ten on LTM, eight on RT and eight on % errors (attention). In addition meta-regression analyses were carried out on the effect sizes with total lifetime ecstasy consumption (TLEC) as predictor. It was found that in all four meta-analyses the mean effect size (ES) was significant: ecstasy users had lower verbal STM and LTM scores, reacted slower and made more errors. The meta-regression coefficients were not significant, indicating no support for a linear relationship between the mean ES values and TLEC, leaving open the possibility for a stepwise relationship. Additional meta-analyses on ecstasy groups that did not differ in lifetime cannabis consumption showed that only the ES for LTM became insignificant. This suggests that ecstasy use does not decrease LTM, but the number of studies on which this conclusion is based was very low.

Verdejo A; Orozco-Gimenez C; Sanchez-Jofre MM; de Arcos FA; Perez-Garcia M. The impact exerted by the severity of recreational drug abuse on the different components of the executive function. Revista de Neurologia 38(12): 1109-1116, 2004. (49 refs.)

Introduction. A number of neuropsychological studies have shown the relationship between severity of drug abuse and the executive functioning of substance abusers, along with its negative impact on treatment results. Aim. The aim of this study is to examine the relationship between severity of consumption of alcohol, cannabis, cocaine, heroin, amphetamines and ecstasy on the executive processes of fluency, working memory, response inhibition, concept formation and decision-making. Patients and methods. Forty poly-substance abusers participated in this study. In a series of setwise regression analyses we introduced the standardized scores of a severity index as predictor variables, and the raw scores of five indexes sensitive to executive functioning as dependent variables: the Ruff Figural Fluency Test (RFFT), the Letter Number Sequencing subtest (LyN), the 5 Digit Test (5DT), the Category Test (TC) and the Gambling Task (GT). Best subsets of predictors for each dependent variable were included in multiple regression models. Results and conclusions. We obtained significant relationships between severity of heroin and ecstasy abuse and RFFT perfonnance; between severity of alcohol, cocaine, heroin and amphetamines and LyN performance; between severity of alcohol, cannabis, cocaine, heroin and ecstasy and 5DT performance; and between severity of heroin and amphetamines and TC performance. These results show the significant influence of severity of drug abuse on executive impairment, which may have a negative impact on treatment results.

Verdejo A; Toribio I; Orozco C; Puente KL; P�rez-Garc�a M. Neuropsychological functioning in methadone maintenance patients versus abstinent heroin abusers. Drug and Alcohol Dependence 78(3): 283-288, 2005. (20 refs.)

Several studies have reported on neuropsychological status as an important contributing variable in drug abuse rehabilitation outcomes. However, few studies have dealt with cognitive impairment in methadone maintenance patients (MMP), despite the fact that methadone is the most frequently used opioid substitution treatment in European countries. The objective of the present study is to contrast the neuropsychological performance of MMP with that of abstinent heroin abusers (AHA). Participants were matched with respect to age, education, pre-morbid IQ, employment status and lifetime drug abuse, and they underwent a set of tests aimed at assessing visuo-spatial attention, processing speed and executive functions. Although processing speed and attention deficits have previously been the focus of studies with MMP, executive functions have not received a similar degree of attention. The purpose of comparing matched MMP and AHA is two-fold: firstly, to test the differential effects of current opioid consumption and past opioid abuse on cognitive-executive performance and secondly, to assess the potential consequences of opioid-related neuropsychological deficits. Results showed a significantly slower performance by MMP on processing speed, visuo-spatial attention, and cognitive flexibility tests (Five Digit Test (FDT) parts 1 and 3; Oral Trails (OT) parts 1, 2; Interference 2-1), and less accuracy in working memory and analogical reasoning tests extracted from the Wechsler Adult Intelligence Scale (WAIS III). Effect sizes for significant comparisons ranged from 0.67 to 1. These results seem to suggest that methadone consumption by itself induces significant cognitive impairments that could compromise drug-treatment outcomes in MMP.

Vermeeren A. Residual effects of short half-life non-benzodiazepine hypnotics. Glasgow: ICADTS, 2004. (17 refs.)

This paper considers non-benzodiazepine hypnotics, namely cyckopyrolone (e.g., Zopiclone, Imovane); Imidazopyridine (Ambien, Zolpidem), Pyrazolopyrimidine (Zaleplon, Sonata), which are used for the treatment of insomnia. Pharmacological properties, such as half-life, receptor binding, and recommended dose is provided. The aim of the study reported was to evaluate Zopiclone's effects on driving and memory, and impact on a highway driving test. The conclusion was that zopiclone had significant residual effects on driving, with the effects comparable to an alcohol BAC between 0.5 and 1.0 mg/ml. Of note too is that a short half0-life can not be presumed to mean it is free of residual effects. There is an accompanying PowerPoint presentation with 21 slides.

Verwey B; Muntendam A; Ensing K; Essink G; Pasker-De; Jong PCM; Willekens FLA et al. Clinically relevant anterograde amnesia and its relationship with blood levels of benzodiazepines in suicide attempters who took an overdose. (review). Progress in Neuro-Psychopharmacology & Biological Psychiatry 29(1): 47-53, 2005. (16 refs.)

The relationship between anterograde amnesia, sedation and plasma levels of benzodiazepines was studied prospectively in a group of 24, patients who took an overdose of benzodiazepines. Patients were tested on two sequential days after having taken an overdose. Anterograde amnesia was tested by using a verbal recall test and a photo recognition test. Sedation was scored on a visual analogue scale (VAS) by the patient and the interviewer. The concentration of benzodiazepines in plasma was measured by using a radioreceptor assay that adds benzodiazepines and their active metabolites. The cumulative amount of benzodiazepines was expressed as diazepam equivalents (DZE). Diazepam equivalents determined by this radioreceptor assay were significantly higher on the first day than on the second day. Ratings on the verbal recall test were significantly lower on the first day than on the second day. There,vas a significant relation between decrease of diazepam equivalents and increase of verbal recall: more than 30% of increase of verbal recall was explained by decrease of diazepam equivalents. There was not a strong relation between decrease of diazepam equivalents and reduction of level of sedation as scored by the patients. There was almost no relation between decrease of diazepam equivalents and reduction of level of sedation as scored by the interviewer. No relation was found between verbal recall, sedation and diazepam equivalents. There was no relation between diazepam equivalents and photo recognition. It was concluded that anterograde amnesia was strongly associated with benzodiazepines in patients who take benzodiazepines in an overdose. Sedation does not predict the degree of anterograde amnesia.

Wareing M; Fisk JE; Murphy P; Montgomery C. Verbal working memory deficits in current and previous users of MDMA. Human Psychopharmacology: Clinical and Experimental 19(4): 225-234, 2004. (42 refs.)

Previous research suggests that MDMA users are impaired in various aspects of cognitive functioning, however, it remains unclear whether they might experience deficits in established measures of verbal working memory functioning. In the present study current and previous MDMA users were compared with non-users on verbal working memory measures including reading and computation span. Both user groups were found to be impaired on the computation span measure while current users also exhibited impairment in reading span. The MDMA-related deficit on the computation span measure remained significant following the introduction of statistical controls for the potentially confounding effects of cannabis and other drugs. The results are discussed in the context of recent research on executive processes. It is suggested that MDMA may produce differential effects on specific components within a fractionated executive system.

Wareing M; Murphy PN; Fisk JE. Visuospatial memory impairments in users of MDMA ('ecstasy'). Psychopharmacology 173174(3-4): 391-397, 2004. (24 refs.)

Rationale. Previous studies have presented conflicting findings regarding visuospatial span deficits in MDMA ('ecstasy') users, possibly attributable to a lack of distinction between simple visuospatial span and visuospatial working memory span. Both draw upon central executive processing, while the latter also involves concurrent goal-orientated visuospatial processing. Objectives. This study compared visuospatial working memory span for MDMA users and controls. An additional concurrent task also loading on the central executive tested for inter-group differences related to central executive workload. Method. MDMA user group (25 current users, 10 previous users and 18 non-users) was between-participants, and dual task condition (concurrent alphabetic generation, random letter generation, and no dual task) was within-participants. The visuospatial working memory task required participants to serially recall a spatial sequence while simultaneously completing a visual judgement task, and was completed on its own and under dual task conditions. Results. Overall, non-users performed significantly better than both MDMA user groups. However, contrary to expectation, the performance decrement among users was no worse with concurrent random generation than under control conditions. Analyses controlling for background variables and the use of other drugs in the previous 3 months showed that the main effect of MDMA remained significant following control for intelligence, alcohol, amphetamines and cocaine, among other potential confounds. Unclear results were found following control for cannabis use. Conclusions. The MDMA users experienced deficits in visuospatial working memory span. The lack of interaction between dual task condition and user group may be due to inter-group differences in central executive utilisation under different task conditions.

Westra HA; Stewart SH; Teehan M; Johl K; Dozois DJA; Hill T. Benzodiazepine use associated with decreased memory for psychoeducation material in cognitive behavioral therapy for panic disorder. Cognitive Therapy and Research 28(2): 193-208, 2004. (59 refs.)

In laboratory studies with nonanxious participants, benzodiazepines (BZ) reliably induce anterograde amnesia. It remains unclear whether memory impairments exist for information presented in therapy among anxiety patients who are concomitantly taking BZs. This naturalistic study compared 16 panic disorder patients who were daily BZ users with 16 age- and education-matched, nonmedicated panic disorder patients. An incidental memory task assessed memory for psychoeducation material on the origins and management of somatic anxiety symptoms presented during group cognitive behavioral therapy (CBT). BZ users showed significantly poorer memory performance than controls although there were no group differences in anxiety symptoms, rates of psychiatric comorbidity, or sedation. Among BZ users, a higher number of minutes away from post peak drug-blood concentration when encoding began, was also associated with better incidental memory performance. Although causation cannot be inferred from this naturalistic study, the memory impairments observed among BZ users may contribute to the poorer efficacy of CBT previously documented in panic disorder patients receiving adjunctive BZs.

White HK; Levin ED. Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment. Psychopharmacology 171(4): 465-471, 2004. (42 refs.)

Objectives. Chronic transdermal nicotine has been found to improve attentional performance in patients with Alzheimer's disease (AD), but little is known about chronic nicotine effects in age-associated memory impairment (AAMI), a milder form of cognitive dysfunction. The current study was performed to determine the clinical and neuropsychological effects of chronic transdermal nicotine in AAMI subjects over a 4-week period. Design. The double-blind, placebo-controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Setting. An outpatient setting was used. Participants. The subjects (n=11) met criteria for AAMI. Interventions. The subjects were given nicotine patches (Nicotrol) to wear for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during week 2 and week 3 and 5 mg/day during week 4. Measurements. The effects of nicotine treatment were determined with the clinical global impressions questionnaire, Conners' Continuous Performance test, and the automated neuropsychologic assessment metrics (ANAM) computerized neuropsychology battery. Results. Nicotine significantly improved the clinical global impression score as assessed by participants, as well as objective tests of attentional function on the Connors' Continuous Performance Test and decision reaction time on the neuropsychology test battery. Nicotine did not improve performance on other tests measuring motor and memory function. Conclusion. Chronic transdermal nicotine treatment in AAMI subjects caused a sustained improvement in clinical symptoms and objective computerized tests of attention. These results support the further investigation of nicotinic treatment as a promising therapy for AAMI.

Wixted JT. A theory about why we forget what we once knew. Current Directions in Psychological Science 14(1): 6-9, 2005. (15 refs.)

Traditional theories of forgetting assume that everyday forgetting is a cue-overload phenomenon, and the primary laboratory method used for investigating that phenomenon has long been the A-B, A-C paired-associates procedure. A great deal of research in psychology, psychopharmacology, and neuroscience suggests that this approach to the study of forgetting may not be very relevant to the kind of interference that induces most forgetting in everyday life. An alternative interference theory holds that recently formed memories that have not yet had a chance to consolidate are vulnerable to the interfering force of mental activity and memory formation, even if the interfering activity does not involve material similar to what was previously learned. This account helps to explain why sleep, alcohol, and benzodiazepines all forestall forgetting of a recently learned list, and it is consistent with recent work on the variables that affect the induction and maintenance of long-term potentiation in the hippocampus.

Woods SP; Rippeth JD; Conover E; Gongvatana A; Gonzalez R; Carey CL; HIV Neurobehavioural Research Center Group. Deficient strategic control of verbal encoding and retrieval in individuals with methamphetamine dependence. Neuropsychology 19(1): 35-43, 2005. (62 refs.)

Methamphetamine (MA) dependence is associated with deficits in episodic verbal memory. but the cognitive mechanisms underlying such impairments are not known. The authors evaluated a component process model of episodic Verbal memory in 87 persons with MA dependence (MA) and 71 demographically similar non-MA-using controls (MA-). Compared with MA- controls, Ma + participants demonstrated deficient overall learning, free recall, and utilization of semantic clustering, as well as higher rates of repetitions and intrusions. No between-groups differences were evident on measures of serial clustering, retention, or recognition discrimination. Taken together. these findings indicate that MA dependence is associated with deficient strategic (i.e., executive) control of verbal encoding and retrieval. which is consistent with the sequelae of MA-related prefronto-striatal circuit neurotoxicity.

Xu JS; Mendrek A; Cohen MS; Monterosso J; Rodriguez P; Simon SL et al. Brain activity in cigarette smokers performing a working memory task: Effect of smoking abstinence. Biological Psychiatry 58(2): 143-150, 2005. (65 refs.)

Background: When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. Methods: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (<= 1.5 hours abstinence) and abstinence (>= 14 hours abstinence) conditions. Results: Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (Satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. Conclusions: We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.