Biomedical subjects

H V Curran

Publications and source records attributed to H V Curran.

At least 19 recordsLinked to original sources

PubMed2000

Effects of a low dose of alcohol on recollective experience of illusory memory.

RATIONALE: Memory illusions are currently a focus of memory research. Studies using the Deese/Roediger and McDermott paradigm have shown a differential pattern of illusory memories is associated with amnesia and ageing. The effects of pharmacological agents in this paradigm are not yet known. OBJECTIVE: Using this paradigm, the present study investigated the effects of a low dose of alcohol upon recollective experience of illusory memories. METHODS: A double-blind cross-over design was used to compare the effects of alcohol (0.26-0.28 g.kg-1) with a matched placebo drink. RESULTS: High levels of false recognition were obtained across both treatments, replicating previous results. Although the small dose of alcohol employed did not produce gross changes in measures of false memory, it did modify the pattern of recollective experience in terms of remember and know responses. Specifically, it increased the level of remember responses for falsely recognised items (critical lures). CONCLUSION: These results are discussed in terms of ethanol's effects on false recognition of information which was not presented during the study episode. The effects of low dose alcohol on illusory memory are similar to the pattern found in ageing rather than that found in organic amnesia.

Adult↗

PubMed2000

Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later.

AIMS: Recreational use of the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, is increasing. The present study aimed to examine both the acute and residual effects of this drug on cognitive function, dissociation and schizotypal symptomatology in recreational users. DESIGN AND PARTICIPANTS: A parallel group design was used to compare 20 volunteers who reported having taken ketamine with 19 volunteers who reported no consumption of ketamine on the relevant night (day 0). All 39 participants were tested on day 0 and again 3 days later. On each test occasion a battery of tests was administered which tapped a wide range of memory functions, attention, dissociation, schizotypal symptomatology and mood. FINDINGS: Groups were broadly matched for polydrug use apart from ketamine. Acute effects on day 0 replicated previous laboratory studies showing a broad spectrum of cognitive impairments following ketamine administration as well as marked dissociative effects and schizotypal symptomatology. Three days later, ketamine users had significantly higher scores than controls on both dissociation and schizotypal symptomatology. On some cognitive measures there were no group differences on day 3; however, on tests tapping semantic memory, the ketamine users showed persisting impairments compared with controls. CONCLUSIONS: Ketamine appears to induce acute and severe impairments of working, episodic and semantic memory as well as psychotogenic and dissociative effects. Three days after drug ingestion, recreational users display semantic memory impairment and dissociative and schizotypal symptomatology which could reflect chronic or residual effects of taking the drug or pre-existing differences in ketamine users.

Adolescent↗

PubMed2000

Is MDMA ('Ecstasy') neurotoxic in humans? An overview of evidence and of methodological problems in research.

Evidence from research with a range of animal species, from rodents to non-human primates, has shown that MDMA (+/-3, 4-methylenedioxymethamphetamine) is neurotoxic. This article explores the evidence that MDMA may be neurotoxic in humans by briefly overviewing three types of research: (1) neurobiological, (2) psychological/somatic and (3) psychiatric. The first type of evidence derives from neuropharmacological and neuroendocrine studies, the second type focuses on psychological function and somatic symptoms in MDMA users, and the third involves studies of psychiatric cases in people who have taken MDMA. Evidence from these types of studies is indirect and differs in the degree to which any causative links are implied between observed effects, MDMA use and human neurotoxicity. These issues are critically discussed within the context of the wide-ranging methodological problems in human research with MDMA.

Hallucinogens↗

PubMed1999

Dissociative effects of alcohol on recollective experience.

This article reports a study comparing the effects of a single dose of alcohol with a matched placebo drink on recognition memory with and without conscious recollection. A double-blind, cross-over design was used with healthy volunteers who were all social drinkers. Processing depth at study was manipulated using generate versus read instructions. Conscious recollection at test was assessed using the remember-know-guess paradigm (Gardiner, 1988; Tulving, 1985). Alcohol significantly reduced conscious recollection (remember responses) but had no effect on recognition in the absence of conscious recollection (know responses). False alarms rates were low and unaffected by alcohol. Previous findings that generation effects are found only for remember responses were closely replicated. A further dissociation of the generation effect occurred between treatments in that deeper processing at study facilitated recognition on placebo but not on alcohol. That both alcohol and depth of processing produce dissociative effects on recollective experience provides further evidence that remembering and knowing reflect distinct memory systems.

Adult↗

PubMed1999

Selective impairment in the recognition of anger induced by diazepam.

RATIONALE: Facial expressions appear to be processed by at least partially separable neuro-cognitive systems. Given this functional specialization of expression processing, it is plausible that these neurocognitive systems may also be dissociable pharmacologically. OBJECTIVE: The present study therefore compared the effects of diazepam (15 mg) with placebo upon the ability to recognize emotional expressions. METHODS: A double blind, independent group design was used to compare the effects of diazepam and matched placebo in 32 healthy volunteers. Participants were presented morphed facial expression stimuli following a paradigm developed for use with patients with brain damage and asked to name one of the six basic emotions (sadness, happiness, anger, disgust, fear and surprise). RESULTS: Diazepam selectively impaired subjects' ability to recognize angry expressions but did not affect recognition of any other emotional expression. CONCLUSIONS: The findings are interpreted as providing further support for the suggestion that there are dissociable systems responsible for processing emotional expressions. It is suggested that these findings may have implications for understanding paradoxical aggression sometimes elicited by benzodiazepines.

Adult↗

PubMed1999

Long-term effects of alprazolam on memory: a 3.5 year follow-up of agoraphobia/panic patients.

BACKGROUND: Benzodiazepines (BZs) can impair explicit memory after a single dose and also when taken repeatedly for treatment of anxiety disorders. A previous study with agoraphobia/panic patients found that the BZ alprazolam impaired memory during an 8-week treatment and residual impairments were still manifest several weeks after drug withdrawal (Curran et al. 1994). The present study followed up the same group of patients 3.5 years after treatment to determine whether those memory impairments persisted. METHOD: Thirty-one patients, 15 who had originally been treated with alprazolam and 16 with placebo, were assessed on a battery of psychometric tests and self-rating scales. RESULTS: Ex-alprazolam patients performed at the same levels as ex-placebo patients on the memory task and on other objective tests. Performance levels of both groups were similar to pre-treatment baselines, however there were differences in subjective ratings whereby ex-alprazolam patients rated themselves as less attentive and clear headed and more incompetent and clumsy than ex-placebo patients. CONCLUSIONS: Explicit memory impairments found while patients were taking alprazolam and weeks after drug withdrawal did not persist 3.5 years later. We suggest that the memory impairments observed in our previous study weeks after withdrawal of alprazolam were not residual effects of alprazolam but rather were due to the drug's interference with practice effects on the tests and habituation of anxiety over repeated exposure to the test situation.

Adult↗

PubMed1999

Additional methadone increases craving for heroin: a double-blind, placebo-controlled study of chronic opiate users receiving methadone substitution treatment.

AIMS: To assess the acute-on-chronic effects of methadone on drug craving, mood and cognitive and psychomotor functioning in patients on long-term methadone substitution treatment. DESIGN AND PARTICIPANTS: A double-blind, cross-over design was used to compare the effects of a 33% increase in patient's daily dosage of methadone with a matched placebo linctus. Eighteen patients completed the study; all were assessed pre- and post-drug on two separate testing days. FINDINGS: Methadone significantly increased both positive craving (expected positive effects) and negative craving (expected relief of withdrawal discomfort) for heroin. Patients were unable to distinguish between methadone and placebo treatments. No differences between treatments emerged in cognitive or psychomotor effects. In terms of mood, patients were more alert and more contented following placebo than following methadone. CONCLUSIONS: Additional methadone may "prime" cravings for heroin in methadone substitution patients.

Adult↗

PubMed1999

Brain uptake of iomazenil in cirrhotic patients: a single photon emission tomography study.

Brain uptake of 123I-iomazenil was studied in seven cirrhotic patients and eight normal controls using single photon emission computerized tomography. The highest concentration of the ligand was found in the occipital cortex, which corresponds to the brain region with the highest concentration of benzodiazepine receptors. The peak uptake was delayed in patients across all brain regions. The uptake in occipital cortex was higher in low albumin cirrhotics. Patients with low albumin also presented a more delayed peak uptake in occipital cortex and a higher volume of distribution of iomazenil in plasma, compared to patients with normal albumin levels and controls. The changes in brain uptake (delayed peak uptake and increased maximal uptake in occipital cortex) appears to reflect changes in the pharmacokinetics of the ligand, particularly in cirrhotics with low levels of plasma albumin. The curve of brain uptake of the tracer was modelled into a two compartments equation, which seems to provide a practical and reliable method to calculate the slopes of acquisition and decay, time to peak and maximal acquisition.

Adult↗

PubMed1998

Differentiating the effects of centrally acting drugs on arousal and memory: an event-related potential study of scopolamine, lorazepam and diphenhydramine.

The degree to which apparent amnesic effects of various centrally acting drugs are secondary to their effects on arousal remains a contentious issue. The present study uses two methods to dissociate memory and arousal effects of the cholinergic antagonist, scopolamine (SP), and the GABA-A/benzodiazepine receptor agonist, lorazepam (LZ). First, it compared their effects to those of an antihistamine, diphenhydramine (DPh), to provide an active control for arousal reduction. Second, it used the same measure--event-related potentials (ERPs)--as as a parallel index of both the arousal and cognitive effects of the drugs. Fifty participants were allocated to one of five parallel treatment groups (0.6 mg SP; 2 mg LZ; 25, 50 mg DPh; placebo). ERPs were recorded during a continuous word recognition task as well as during an "oddball" task. SP, LZ and 50 mg DPh produced a similar profile of effects on certain indices of arousal and on early components of ERPs. However, SP and LZ (but not DPh) produced marked impairments of episodic memory, and this pattern was similar to that on later components of ERPs. Memory impairments by SP and LZ were highly significant on retention in the continuous recognition task and further, no drug effects were found on response bias. Subsequent free recall was similarly very impaired by SP and LOR but not by the antihistamine. We conclude that benzodiazepines and anticholinergic drugs both reduce arousal and induce amnesia, but these effects are not interdependent. Our findings provide strong evidence for a dissociation between the effects on episodic memory and on arousal of these centrally acting compounds.

Adult↗

PubMed1998

Proactive interference and temporal context encoding after diazepam intake.

Two experiments were designed to test whether the memory impairment induced by benzodiazepines (BZDs) is due to impaired memory for temporal context. In both experiments, subjects were administered either diazepam (15 mg oral) or placebo, and a standard BZD impairment on prose recall as well as a decreased subjective arousal was found. Key tasks to explore temporal context memory were an A-B A-C proactive interference paradigm and a list discrimination task. Initial learning of both groups on these tasks was broadly matched. In experiment 1, diazepam did not increase susceptibility to proactive interference using semantically related words. However, in experiment 2, using unrelated word pairs, diazepam markedly increased the number of prior list intrusions. Furthermore, after diazepam intake, subjects were clearly impaired in learning unrelated word pairs. Subjects after diazepam intake were not impaired in the list discrimination task. We conclude that (1) diazepam impairs the forming of new associations, whether this is the formation of links between two or more targets or between targets and context, (2) a temporal context encoding deficit cannot account for a broader diazepam-induced memory impairment.

Adult↗

PubMed1998

An investigation of the effects of benzodiazepine receptor ligands and of scopolamine on conceptual priming.

Scopolamine and lorazepam both produce anterograde impairments of explicit memory but only lorazepam impairs implicit memory as assessed by perceptual priming tasks. The main aim of the two experiments reported in this article was to determine the effects of these drugs on conceptual priming. Experiment 1 compared the effects of lorazepam (1,2 mg PO) with scopolamine (0.3,0.6 mg SC) and placebo in a study with 60 healthy volunteers. Experiment 2 compared the separate and combined effects of lorazepam (2 mg PO) and flumazenil (2 mg IV) with placebo in a study with 48 healthy volunteers. We found that conceptual priming in category generation tasks was intact following lorazepam in both studies. This preservation of conceptual priming contrasted with lorazepam-induced impairments on explicit memory tasks. In conjunction with previous findings, these results are interpreted as providing further support for the notion that conceptual and perceptual priming are subserved by distinct memory systems, one based on the operations of semantic memory, the other possibly based on a perceptual representation system. That lorazepam impairs perceptual but not conceptual priming suggests that the neurochemical substrates of the two kinds of priming are distinct.

Adolescent↗

PubMed1998

The influence of alcoholism and cirrhosis on benzodiazepine receptor function.

In a previous study we reported that the affinity of the platelet benzodiazepine receptor was greater in alcoholic cirrhotic patients compared with normal controls and that there were detectable ligands for the neuronal benzodiazepine receptor in plasma from both alcoholic and nonalcoholic cirrhotic patients. The aim of the present study was to assess the separate contributions of alcoholism and cirrhosis to the presence of ligands in plasma for the neuronal and peripheral benzodiazepine receptors and to changes in peripheral benzodiazepine receptor binding in platelets. These parameters were measured in 10 alcoholic cirrhotics, 9 nonalcoholic cirrhotics, 7 alcoholics with a normal liver function, and 15 nonalcoholic subjects and normal liver function. Both groups of alcoholics had been abstinent for several months and the nonalcoholic groups had abstained for 24 h before the study. The concentration of ligands for the peripheral benzodiazepine receptor were significantly higher in both cirrhotic groups compared with the other two groups, suggesting that cirrhosis was responsible for this accumulation. Furthermore, the cirrhotic patients with detectable concentrations of these ligands had significantly poorer episodic memory than those without ligands. However, the presence of ligands for the peripheral benzodiazepine receptor did not correlate with the change in receptor affinity, which was increased in the alcoholic cirrhotic group compared with all other groups. Neither cirrhosis nor alcoholism altered the peripheral benzodiazepine receptor number. The cirrhotic patients with detectable ligands for the neuronal benzodiazepine receptor showed psychomotor slowing and executive dysfunction. The results suggest that the ligands for the peripheral benzodiazepine receptor may contribute to some of the cognitive deficits seen in hepatic encephalopathy, but are not responsible for the receptor affinity change seen in the alcoholic cirrhotics. This affinity change is not solely due to the effects of alcohol and could possibly serve as a marker for those at risk for developing alcoholic cirrhosis.

Adult↗

PubMed1997

Mood and cognitive effects of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'): week-end 'high' followed by mid-week low.

AIMS: Recreational use of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is widespread. The present study aimed to examine both the acute and residual effects of this drug on users' mood and cognitive function. DESIGN AND PARTICIPANTS: A parallel group design was used to compare 12 participants who reported having taken MDMA with 12 participants who reported having consumed only alcohol, on the relevant night (day 1). These same participants were then re-assessed the following day (day 2) and again mid-week (day 5). FINDINGS: Acute effects of MDMA broadly replicated previous findings. MDMA users rated elevated mood on day 1 but significantly low mood on day 5, at which point some participants scored within the range for clinical depression. In contrast, the alcohol group showed less pronounced changes, which followed a U-shaped curve over days with the lowest point being day 2. The MDMA group also showed significant impairments on an attentional/working memory task, compared with alcohol users. CONCLUSIONS: Weekend use of MDMA may lead to depressed mood mid-week. Possible mechanisms underlying the findings are discussed in terms of temporary depletion of serotonin, serotonergic neurotoxity and psychological aspects of mood change.

Adult↗

PubMed1996

Benzodiazepine effects on memory tests: dependence on retrieval cues?

Acute effects of oral flunitrazepam (0.5 and 1 mg), nitrazepam (5 and 10 mg) and placebo were assessed on direct (free recall of words and prose, stem-cued recall) and indirect (stem and fragment completion) memory tasks. Fifty health volunteers took part in this double-blind, independent group study. The relative effects of the two benzodiazepines (BZs) on memory revealed a different pattern from their effects on alertness, indicating that their amnesic effects are not totally secondary to their sedative effects. The higher dose of flunitrazepam impaired free recall of words and prose but not cued recall, while neither drug affected the two indirect tasks. Differences in drug effects on the direct and indirect memory tasks were discussed in terms of resource demands of the various tests. We conclude that whether BZs impair performance on memory tasks depends more on the cues given at retrieval than the retrieval instructions (direct/indirect). The implications for this in terms of BZ amnestic effects are drawn out for contextual encoding deficits induced by BZs.

Administration, Oral↗

PubMed1996

Cognitive impairments of alcoholic cirrhotic patients: correlation with endogenous benzodiazepine receptor ligands and increased affinity of platelet receptors.

OBJECTIVES: To determine whether differences in cognitive function between alcoholic and non-alcoholic cirrhotic patients relate to differences in endogenous ligands for the benzodiazepine receptor and/or benzodiazepine binding. METHODS: Seventeen grade-I hepatic encephalopathic patients (nine alcoholic, eight non-alcoholic) were compared with 10 matched controls on plasma concentrations of endogenous ligands for the neuronal benzodiazepine receptor, benzodiazepine binding in platelets, and performance on tests of cognitive function. RESULTS: Both groups of patients were impaired on verbal recall and on reaction time tasks compared with controls; alcoholic patients were also impaired on Reitan's trails test and digit cancellation. Four of the 17 patients had detectable concentrations of endogenous benzodiazepine ligands and they were more impaired than other patients on trails and cancellation tests. The groups did not differ in the density of benzodiazepine platelet receptors, but receptor affinity was higher in alcoholic patients than in controls; furthermore, receptor affinity correlated with the time to complete the cancellation task and with reaction time. CONCLUSION: Alcoholic cirrhotic patients may have enhanced concentrations of ligands for neuronal and peripheral benzodiazepine receptors and these may contribute to cognitive impairments in these patients.

Adult↗

PubMed1995

Behavioural aggression in panic disorder after 8 weeks' treatment with alprazolam.

23 patients with a diagnosis of panic disorder with agoraphobia were randomly assigned to 8 weeks' treatment with alprazolam or placebo. They filled in self-ratings before and after treatment and competed on a competitive reaction time task, designed to measure behavioural aggression, after 8 weeks' treatment. Patients taking both alprazolam and placebo rated decreased anxiety after 8 weeks' treatment but those on alprazolam also tended to report less hostility. On the behavioural task, patients on alprazolam behaved more aggressively in response to provocation. This is the first study to confirm clinical reports of benzodiazepine-induced dyscontrol on an objective laboratory measure. It is important that it is followed up in a larger group of patients.

Adult↗

PubMed1995

Psychopharmacological analysis of implicit and explicit memory: a study with lorazepam and the benzodiazepine antagonist flumazenil.

Recent studies have suggested that the benzodiazepine (BZ) lorazepam (LZ) differs from other BZs in its impairing effects on implicit memory tasks. The present study was designed to assess whether this atypical effect withstood the experimental rigour of Schacter's retrieval intentionality criterion and further, whether it could be reversed by the BZ antagonist, flumazenil (FL). The separate and combined effects of LZ, FL and placebo (PL) were assessed on indices of memory, sedation, and attention in 48 healthy volunteers. LZ disrupted performance on both explicit and implicit memory tasks, induced motor sedation and impaired focussed attention. Fl attenuated LZ-induced attentional deficits but did not affect motor sedation. FL also attenuated LZ-induced impairment on the implicit retrieval task. On the explicit retrieval task FL attenuated LZ-induced impairment for words which had been deeply processed at study but not words which had been shallowly processed. A subsequent recognition test showed LZ impaired recognition memory only when accompanied by recollective experience and flumazenil again attenuated this effect. FL itself lowered performance on several measures, reflecting intrinsic activity of this "antagonist". Assessment of the relationship between the mnestic and other effects of the drugs suggested that attentional effects contribute to, but do not explain, effects on implicit memory tasks. These results imply that the apparent atypical effects of LZ on implicit memory tasks are mediated by the same BZ receptor complex as mediates LZ's other effects.

Adolescent↗

PubMed1995

Encoding, remembering and awareness in lorazepam-induced amnesia.

The effects of lorazepam (1,2 mg) and placebo on encoding, remembering and awareness were assessed in a study with 54 healthy volunteers. All subjects studied stimulus materials in a levels of processing (L-o-p) task. Half the subjects were assessed on an explicit memory task of word recognition and the other half were given an implicit memory task of word-stem completion. Following the implicit task, awareness of retrieval was further investigated by questions and by subjects' recollective experience in recognising the actual words they had completed from stems. L-o-p effects and marked lorazepam-induced impairments were found in the implicit task of word-stem completion although the interaction between L-o-p and drug effects emerged only as a trend in the data. Lorazepam-induced impairments on stem-completion may then be explained at least in part as being due to contamination by explicit retrieval processes, but we cannot rule out the possible role of drug effects on perceptual processes at encoding. Results from responses to "awareness" questions and from analysis of subsequent recollective experience indicated that subjects were not aware of using explicit retrieval during the implicit task. Results also replicated previous findings showing that both lorazepam and L-o-p independently affect performance in an explicit memory task of word recognition. Thus drug-induced deficits at encoding persist regardless of the level at which information is initially processed.

Adult↗