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Biomedical subjects

J G Ramaekers

Publications and source records attributed to J G Ramaekers.

At least 19 recordsLinked to original sources
PubMed2007

Acute effects of nocturnal doses of MDMA on measures of impulsivity and psychomotor performance throughout the night.

INTRODUCTION: Previous studies on the acute effects of MDMA on psychomotor performance and impulsivity showed that MDMA acts as a stimulant. These studies assessed performance during daytime, whereas in real life, dance-attendees leaving a party use the drug during the night. OBJECTIVES: The present study aimed to assess the effects of nocturnal doses of MDMA on psychomotor performance and impulsivity during the night and after a night of sleep deprivation. MATERIALS AND METHODS: Fourteen healthy subjects participated in a double-blind, placebo-controlled, two-way within-subject study. The treatment was MDMA (75 and 50 mg) divided over the evening or double placebo. Psychomotor and impulsivity tasks were conducted four times throughout the evening and night. A vigilance test was conducted once, at 5 A.M.,: and a sleepiness scale was presented to the subjects ten times throughout the evening and night. RESULTS: MDMA impaired tracking performance in a simple tracking task. Divided attention task performance was also impaired as indicated by a decrease in secondary task performance under the influence of MDMA compared with placebo. MDMA did not affect impulsivity measures. Vigilance performance decreased as a function of time on task, but this decrement was less during MDMA treatment compared to placebo. After the administration of MDMA, the sleepiness scale scores were lower during the night when compared with placebo. This difference between MDMA and placebo disappeared in the morning. CONCLUSION: It is concluded that nocturnal doses of MDMA may produce impairments of tracking performance and divided attention throughout the night that are additive to performance impairment produced by sleep loss.

Adult↗
PubMed2006

Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI.

Serotonergic neurotransmission has been implicated in memory impairment. It is unclear however if memory performance is mediated through general 5-HT availability, through specific 5-HT receptors or both. The aim of the present study was to assess the contribution of 5-HT reuptake inhibition and specific blockade of 5-HT(1A) and 5-HT(2A) receptors to memory impairment. The study was conducted according to a randomized, double-blind, placebo-controlled, four-way cross-over design including 16 healthy volunteers. The treatment consisted of oral administration of escitalopram 20 mg + placebo, escitalopram 20 mg + ketanserin 50 mg, escitalopram 20 mg + pindolol 10 mg and placebo on 4 separate days with a washout period of minimum 7 days. Different memory tasks were performed including verbal memory, spatial working memory and reversal learning. Escitalopram showed an impairing effect on immediate verbal recall which nearly reached statistical significance. No effects of escitalopram were found on other types of memory. In combination with pindolol, immediate verbal recall was significantly impaired. Escitalopram in combination with ketanserin impaired spatial working memory significantly. No effects were found on reversal learning. Selective impairment of immediate verbal recall after a 5-HT(1A) partial agonist and selective impairment of spatial working memory performance after 5-HT(2A) receptor antagonist, both in combination with a selective serotonergic reuptake inhibitor (escitalopram), suggests that 5-HT(1A) and 5-HT(2A) receptors are distinctly involved in verbal and spatial memory.

Administration, Oral↗
PubMed2006

MDMA and alcohol effects, combined and alone, on objective and subjective measures of actual driving performance and psychomotor function.

RATIONALE: The party drug ecstasy is frequently used in combination with other drugs like marihuana and alcohol. In addition, a substantial proportion of the MDMA users has claimed to drive a car when under the influence of MDMA and/or other drugs. OBJECTIVE: To assess the effects of MDMA and alcohol, combined and alone, on actual driving performance and laboratory tasks related to driving. METHODS: Eighteen healthy subjects participated in a double-blind, placebo-controlled, six-way cross-over study. Treatments consisted of MDMA 0, 75, and 100 mg with and without alcohol, aiming at 0.06 mg/ml BAC. Laboratory tests (critical tracking task, object movement estimation task) were conducted between 1.5 and 2 h postdrug (0.5 and 1 h postalcohol). Actual driving tests (road tracking test, car-following test) were conducted between 3 and 5 h postdrug (2 and 4 h postalcohol). Subjects completed the addiction research center inventory (ARCI) and rated their driving quality and mental effort during driving. RESULTS: Alcohol alone impaired critical tracking performance, as well as a number of actual driving performance parameters [i.e., standard deviation of lateral position (SDLP), brake reaction time, and coherence]. MDMA alone reduced SDLP and standard deviation of speed. MDMA significantly moderated alcohol induced impairment of road tracking performance but did not affect alcohol impairments of car-following and laboratory task performance. Subjective data seemed to support objective data. CONCLUSION: MDMA moderated the impairing effects of a low dose of alcohol on road tracking performance but it could not overcome alcohol-induced impairment on other aspects of driving behavior or driving related performance.

Adult↗
PubMed2006

Demands on scientific studies in different fields of forensic medicine and forensic sciences. Traffic medicine--impaired driver: alcohol, drugs, diseases.

Since human performance is a key factor in crash causation detailed knowledge of the involvement of alcohol, drugs and diseases is of fundamental interest for road safety. To better understand the effect of these influencing factors it is important to use a combination of witness observations and a range of experimental and epidemiological studies. Epidemiological approaches to research such as road-side-surveys, case-control-studies, culpability analysis, pharmaco-epidemiological studies are usually seen as being able to provide the best answers. This article discusses the relative merits of experimental and epidemiological approaches.

Accidents, Traffic↗
PubMed2006

Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment.

Cannabis use has been associated with increased risk of becoming involved in traffic accidents; however, the relation between THC concentration and driver impairment is relatively obscure. The present study was designed to define performance impairment as a function of THC in serum and oral fluid in order to provide a scientific framework to the development of per se limits for driving under the influence of cannabis. Twenty recreational users of cannabis participated in a double-blind, placebo-controlled, three-way cross-over study. Subjects were administered single doses of 0, 250 and 500 microg/kg THC by smoking. Performance tests measuring skills related to driving were conducted at regular intervals between 15 min and 6h post smoking and included measures of perceptual-motor control (Critical tracking task), motor impulsivity (Stop signal task) and cognitive function (Tower of London). Blood and oral fluid were collected throughout testing. Results showed a strong and linear relation between THC in serum and oral fluid. Linear relations between magnitude of performance impairment and THC in oral fluid and serum, however, were low. A more promising way to define threshold levels of impairment was found by comparing the proportion of observations showing impairment or no impairment as a function of THC concentration. The proportion of observations showing impairment progressively increased as a function of serum THC in every task. Binomial tests showed an initial and significant shift toward impairment in the Critical tracking task for serum THC concentrations between 2 and 5 ng/ml. At concentrations between 5 and 10 ng/ml approximately 75-90% of the observations were indicative of significant impairment in every performance test. At THC concentrations >30 ng/ml the proportion of observations indicative of significant impairment increased to a full 100% in every performance tests. It is concluded that serum THC concentrations between 2 and 5 ng/ml establish the lower and upper range of a THC limit for impairment.

Adult↗
PubMed2006

Verbal memory performance during subchronic challenge with a selective serotonergic and a mixed action antidepressant.

OBJECTIVES: Effects of escitalopram 10-20 mg/day and mirtazapine 30-45 mg/day on verbal memory of 18 healthy participants were assessed in a randomized, double-blind, placebo-controlled, three-way crossover trial. METHOD: Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Participants received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16 a visual verbal memory task was performed measuring drug effects during the acute phase, after dose increase and at steady state. RESULTS: Escitalopram did not affect immediate or delayed verbal memory score throughout treatment. During mirtazapine treatment, participants performed less well in the overall immediate recall score compared to placebo. This impairment was most pronounced in the final trial of the visual verbal learning task. CONCLUSION: Verbal memory was not affected by acute and subchronic escitalopram treatment in healthy participants. Overall immediate verbal memory was slightly but significantly impaired throughout mirtazapine treatment, probably due to a general reduction in overall arousal caused by H1 blockade.

Adult↗
PubMed2006

Stimulant effects of 3,4-methylenedioxymethamphetamine (MDMA) 75 mg and methylphenidate 20 mg on actual driving during intoxication and withdrawal.

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA) is currently one of the most popular drugs of abuse in Europe. Its increasing use over the last decade has led to concern regarding possible adverse effects on driving. The aims of the present study were to investigate the acute effects of MDMA on actual driving performance during the intoxication and withdrawal phase. METHODS: Eighteen recreational MDMA-users (nine males, nine females) aged 21-39 years participated in a double-blind, placebo-controlled, three-way cross-over study. MDMA 75 mg, methylphenidate 20 mg and placebo were administered on day 1 of treatment (intoxication phase). Driving tests were conducted between 3 and 5 hours post-drug. Subjects returned the following day for a repetition of the driving tests between 27 and 29 hours post-drug (withdrawal phase). On-the-road driving tests consisted of a road-tracking test and a car-following test. Its main parameters were standard deviation of lateral position (SDLP), time to speed adaptation (TSA), brake reaction time (BRT) and gain. FINDINGS: MDMA and methylphenidate significantly decreased SDLP in the road-tracking tests by about 2 cm relative to placebo on day 1 (intoxication phase). In addition, MDMA intoxication decreased performance in the car-following test as indicated by a significant rise in the 'overshoot' of the subjects' response to speed decelerations of the leading vehicle. Driving performance was not affected by treatments during withdrawal on day 2. CONCLUSION: Collectively, these data indicate that MDMA is a stimulant drug that may improve certain aspects of the driving task, such as road-tracking performance, but may reduce performance in other aspects of the driving task, such as accuracy of speed adaptation during car-following performance.

Adult↗
PubMed2006

Cognitive function and mood in MDMA/THC users, THC users and non-drug using controls.

Repeated ecstasy (MDMA) use is reported to impair cognition and cause increased feelings of depression and anxiety. Yet, many relevant studies have failed to control for use of drugs other than MDMA, especially marijuana (THC). To address these confounding effects we compared behavioural performance of 11 MDMA/THC users, 15 THC users and 15 non-drug users matched for age and intellect. We tested the hypothesis that reported feelings of depression and anxiety and cognitive impairment (memory, executive function and decision making) are more severe in MDMA/THC users than in THC users. MDMA/THC users reported more intense feelings of depression and anxiety than THC users and non-drug users. Memory function was impaired in both groups of drug users. MDMA/THC users showed slower psychomotor speed and less mental flexibility than non-drug users. THC users exhibited less mental flexibility and performed worse on the decision making task compared to non-drug users but these functions were similar to those in MDMA/THC users. It was concluded that MDMA use is associated with increased feelings of depression and anxiety compared to THC users and non-drug users. THC users were impaired in some cognitive abilities to the same degree as MDMA/THC users, suggesting that some cognitive impairment attributed to MDMA is more likely due to concurrent THC use.

Adult↗
PubMed2006

Serotonin and human cognitive performance.

In the past decade, experimental studies involving healthy human volunteers have revealed that manipulations of the central serotonin (5-HT) system can produce quite specific changes in cognitive functioning, independent of overt mood changes. Reduced 5-HT turnover is consistently associated with impaired long-term memory functioning. Low 5-HT function may also impair cognitive flexibility and improve focused attention. On the other hand, stimulation of central 5-HT has repeatedly been found to impair performance in a true vigilance task. Currently, there is little evidence for mirrored cognitive changes due to opposite 5-HT manipulations in healthy volunteers. Given the mounting evidence for a role of 5-HT in human cognition, reduced 5-HT function could be directly linked to cognitive disturbances in certain conditions, such as in depression and Alzheimer's Disease (AD). There is evidence that stimulating (i.e. normalizing) 5-HT activity in depression may have specific beneficial effects on cognition, independent of a general relief of depressive symptoms, but this premise needs to be confirmed by larger-scale clinical studies. Recently, a potential role of 5-HT in the cognitive symptoms in AD has been identified, but there is insufficient data to evaluate the effects of 5-HT stimulation on cognitive symptoms in AD. It is concluded that serotonin is a potential target for pharmacological cognition enhancement, particularly for restoration of impaired cognitive performance due to 5-HT dysfunction. Further differentiation of the role of 5-HT in normal and disturbed cognition and evaluation of the effects of 5-HT manipulations in various populations is required to establish the full potential of 5-HT drugs as cognition enhancers.

Arousal↗
PubMed2005

Impaired perception of self-motion (heading) in abstinent ecstasy and marijuana users.

RATIONALE: Illicit drug use can increase driver crash risk due to loss of control over vehicle trajectory. This study asks, does recreational use of +/-3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) and tetrahydrocannabinol (THC; marijuana) impair cognitive processes that help direct our safe movement through the world? OBJECTIVE: This study assesses the residual effects of combined MDMA/THC use, and of THC use alone, upon perceived trajectory of travel. METHODS: Perception of self-motion, or heading, from optical flow patterns was assessed using stimuli comprising random dot ground planes presented at three different densities and eight heading angles (1, 2, 4 and 8 degrees to the left or right). On each trial, subjects reported if direction of travel was to the left or the right. RESULTS: Results showed impairments in both drug groups, with the MDMA/THC group performing the worst. CONCLUSIONS: The finding that these psychoactive agents adversely affect heading perception, even in recently abstinent users, raises potential concerns about MDMA use and driving ability.

Adult↗
PubMed2004

Effects of desloratadine, diphenhydramine, and placebo on driving performance and psychomotor performance measurements.

INTRODUCTION: First-generation antihistamines taken for relief of allergic rhinitis are sedating and pose potential risks for those driving a car or operating machinery. Desloratadine is a potent, selective, histamine H(1)-receptor antagonist that does not easily cross the blood-brain barrier. It is nonsedating at therapeutic doses and should not affect driving or psychomotor performance. OBJECTIVE: This study compared the acute effects of desloratadine with diphenhydramine (active control) and placebo on the performance of healthy subjects evaluated with standard over-the-road driving tests (primary objective). The subjects' performances were also evaluated (secondary objective) with the use of conventional performance tests. METHODS: Eighteen men and women received a single dose of desloratadine 5 mg, diphenhydramine 50 mg, or placebo during each period of this randomized, double-blind, three-way, crossover study. Two hours post-dosing, subjects operated a specially instrumented vehicle in a 90-min test designed to measure their ability (1) to maintain constant speed and lateral position while following another vehicle at a constant distance and (2) to respond to brake signals. Additionally, a full battery of performance tests was administered. RESULTS: No significant differences were noted between desloratadine and placebo in standard deviation of lateral position (SDLP), whereas diphenhydramine treatment significantly increased SDLP ( P< 0.001 for both comparisons). Brake reaction time was significantly faster following treatment with desloratadine than diphenhydramine (473.72 ms vs 541.22 ms; P< 0.001) or placebo (512.06 ms; P=0.033). No differences were seen among treatments in deviation of speed or distance to the lead car. The majority of performance tests showed no significant differences among groups. CONCLUSION: Desloratadine at a therapeutic dose does not impair driving performance.

Adult↗
PubMed2004

Dose related risk of motor vehicle crashes after cannabis use.

The role of Delta(9)-tetrahydrocannabinol (THC) in driver impairment and motor vehicle crashes has traditionally been established in experimental and epidemiological studies. Experimental studies have repeatedly shown that THC impairs cognition, psychomotor function and actual driving performance in a dose related manner. The degree of performance impairment observed in experimental studies after doses up to 300 microg/kg THC were equivalent to the impairing effect of an alcohol dose producing a blood alcohol concentration (BAC) >/=0.05 g/dl, the legal limit for driving under the influence in most European countries. Higher doses of THC, i.e. >300 microg/kg THC have not been systematically studied but can be predicted to produce even larger impairment. Detrimental effects of THC were more prominent in certain driving tasks than others. Highly automated behaviors, such as road tracking control, were more affected by THC as compared to more complex driving tasks requiring conscious control. Epidemiological findings on the role of THC in vehicle crashes have sometimes contrasted findings from experimental research. Case-control studies generally confirmed experimental data, but culpability surveys showed little evidence that crashed drivers who only used cannabis are more likely to cause accidents than drug free drivers. However, most culpability surveys have established cannabis use among crashed drivers by determining the presence of an inactive metabolite of THC in blood or urine that can be detected for days after smoking and can only be taken as evidence for past use of cannabis. Surveys that established recent use of cannabis by directly measuring THC in blood showed that THC positives, particularly at higher doses, are about three to seven times more likely to be responsible for their crash as compared to drivers that had not used drugs or alcohol. Together these epidemiological data suggests that recent use of cannabis may increase crash risk, whereas past use of cannabis does not. Experimental and epidemiological research provided similar findings concerning the combined use of THC and alcohol in traffic. Combined use of THC and alcohol produced severe impairment of cognitive, psychomotor, and actual driving performance in experimental studies and sharply increased the crash risk in epidemiological analyses.

Accidents, Traffic↗
PubMed2004

A dose-ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo.

BACKGROUND: Mequitazine is a so-called 'non-sedative' second-generation antihistamine even though it has never been firmly established that this drug's sedative potential actually differs from that of the 'sedative' first-generation antihistamines. OBJECTIVE: The present study compares the sedative effects of three doses of mequitazine on actual driving, psychomotor performance and memory with those of a first- and a second-generation antihistamine. METHODS: Eighteen healthy volunteers received on separate days a single dose of 5, 10 and 15 mg mequitazine, 10 mg cetirizine, 6 mg dexchlorpheniramine and placebo. Drug effects were assessed using two actual driving tests (highway-driving test and car-following test), cognitive and psychometric tests (tracking, divided attention, memory, reasoning and critical flicker fusion), pupil size and questionnaires. RESULTS: Highway-driving data revealed an overall effect of Treatment on the standard deviation of lateral position (SDLP). Dexchlorpheniramine impaired driving performance as indicated by a significant rise in SDLP. Mequitazine significantly increased SDLP in a dose-related manner, but the separate dose effects failed to reach statistical significance. Divided attention performance was also affected by Treatment. Reaction time (RT) during mequitazine treatments increased in a dose-related manner and significantly differed from placebo at the highest dose. Subjects reported to be less alert after treatment with dexchlorpheniramine. Cetirizine did not affect performance in any of the tasks. CONCLUSION: It was concluded that mequitazine is mildly sedating. The effects of mequitazine are comparable to those of other second-generation antihistamines, in that it causes mild driving impairment, particularly at higher doses.

Adult↗
PubMed2003

Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance.

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.

Adult↗
PubMed1999

Psychomotor, Cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic.

The primary objective of this study was to compare the objective and subjective effects of amisulpride with those of a classic antipsychotic, haloperidol, when both were given to healthy volunteers in representative therapeutic doses over 5 days. The secondary objective was to compare the effects of relatively low and high doses of amisulpride to confirm the suspected duality of its pharmacologic activity. Twenty-one subjects participated in the four-way, randomized, double-blind, crossover study with repeated daily doses of amisulpride 50 mg, amisulpride 400 mg, haloperidol 4 mg, and placebo. Subjects were institutionalized during treatment periods and were under 24-hour medical supervision. They underwent a series of psychomotor and cognitive tests 1 hour before and 3 and 6 hours after dosing on days 1 and 5. Their extrapyramidal disturbances and drug-related feelings were assessed at the end of each replication. Psychiatric interviews and ratings of depression, subjective well-being, and negative symptoms occurred on day 4. Amisulpride 50 mg had no significant effect on any parameter. Amisulpride 400 mg had several adverse effects on psychomotor and, although less severe, on cognitive performance on the fifth day only. Amisulpride 400 mg produced no significant extrapyramidal disturbances in the group as a whole, although it may have in some individual subjects. Also, it produced no signs of mental disturbances on clinical rating scales or during a structured psychiatric interview. Haloperidol ubiquitously impaired psychomotor and cognitive performance in a similar fashion after the first and the final doses. It produced extrapyramidal disturbances in nearly every subject, the most common being akathisia and the most severe, in the case of one individual, being acute dystonia. Unlike amisulpride, haloperidol produced a number of mental disturbances, the most noteworthy being negative symptoms. Amisulpride seems to be a well-tolerated drug. Its side effects should be much less troublesome to patients using the drug on a long-term basis than those of classic antipsychotics, like haloperidol.

Adult↗
PubMed1998

Behavioural toxicity of medicinal drugs. Practical consequences, incidence, management and avoidance.

Behavioural toxicity is relatively common among medicinal drug users and evidence shows that drugs frequently produce adverse effects that prevent their users from performing everyday operations in a normal manner. Epidemiological research generally indicates that the use of sedative drugs is associated with an increased risk of becoming involved in injurious accidents. Empirical studies have also demonstrated adverse effects of sedative drugs on the performance of healthy volunteers and patients in laboratory tests designed to measure psychomotor and cognitive function, and in real life-tests measuring on-the-road driving performance. Empirical studies also indicate that behavioural toxicity can vary widely between individual drugs depending on differences in dose, dosing regimen, duration of treatment, pharmacokinetics or mechanisms of actions. Besides sedation, other CNS adverse effects such as aggression, paranoia, social withdrawal or lack of motivation may disrupt or prevent the initiation of normal performance, thus imposing a burden on the ability of the patients to function in a normal manner. Emotional disturbances are rare as indicated by the small number of case reports that mention their existence. Yet theses disturbances sometimes involve severe reactions that are more debilitating than sedation. Behavioural toxicity can be minimised by avoidance of pharmacodynamic and pharmacokinetic drug interactions, adjustment of dosage regimens to a patient's individual response to a drug, nocturnal administration of drugs that are expected to produce sedation and patient education on the potential risks of the drugs they receive. Much of this information can be gained from experimental literature comparing the effect of individual drugs on performance. Unfortunately this is presently incomplete, since most research on behavioural toxicity has been confined to psychiatric drugs. Yet, in the interest of the patient, it should be the responsibility of drug manufacturers and regulators to always identify problematic drugs.

Accidental Falls↗
PubMed1997

Considering the P450 cytochrome system as determining combined effects of antidepressants and benzodiazepines on actual driving performance of depressed outpatients.

Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking them as comedication. Therapeutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test that measures standard deviation of lateral position (SDLP). Similar remissions in depressive symptoms and side effects occurred in both groups. Patients drove with normal and reliable (r = 0.87) SDLPs before treatments. Most continued to do so but a few drove with progressively rising SDLPs and the overall trends were significant in both groups (p < 0.03). A post-hoc multiple regression analysis was applied for identifying factors that correlated with SDLP in separate tests after the beginning of therapy. At 3 and 6 weeks there were significant (p < 0.03) relationships involving the same factor; patients who drove with progressively higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particular antidepressant.

Adolescent↗