Effects of marihuana on reaction time and short-term memory in human volunteers

Twenty-seven adult male marihuana smokers volunteered to participate in a hospital research ward study for a 31-day period. Following five days of baseline acclimatization, subjects could purchase and smoke marihuana cigarettes on a free choice basis for a period of 21 consecutive days. The marihuana smoking period was followed by a concluding five-day baseline. Measurements of simple reaction time, choice reaction time and short-term memory were carried out during the entire study. Analysis of variance revealed no statistically significant differences between control and marihuana performance; however, a correlational analysis showed that individual subject performances on all three tasks were significantly correlated from test session to test session during control conditions but not during marihuana smoking conditions. Findings are discussed in relation to attentional and motivational factors associated with performance on the three tasks.     

Circadian and genetic influences on tissue sensitivity and sleep time to ethanol in LS and SS mice

Circadian variations in response to ethanol were studied in long-sleep (LS) and short-sleep (SS) mice. Each LS animal received a 2.5 g/kg intraperitoneal ethanol injection, while the SS animals were injected with 4.1 or 5.0 g/kg. Different groups of mice were assessed for sleep time, waking blood alcohol concentration (BAC), and waking brain ethanol concentration (BREC) at 03.00, 09.00, 15.00, or 21.00 hr. Sleep times, waking BACs, and waking BRECs showed circadian variations in the LS mice. SS animals given the 4.1 g/kg dose showed circadian variations for waking BAC and waking BREC, but not for sleep time. The observed variations in the physiological parameters for these animals may have been confounded by a short sleep time so that they reflected circadian variations in drug absorption and/or distribution rather than in CNS sensitivity. SS mice given the 5.0 g/kg dose slept longer than those given the 4.1 g/kg dose and did not show circadian variations for sleep time, waking BAC, or waking BREC. These results suggest both circadian and genetic influences on tissue sensitivity to ethanol.     

Effects of smoking on simple and choice reaction time

Twenty-nine subjects performed a reaction time task with four levels of choice-task complexity under non-smoking, sham smoking, and low, medium and high nicotine cigarette conditions. Nicotine reduced decision time, while sham smoking increased decision time. This effect was independent of subjects' habitual levels of cigarette consumption. No effect of smoking was found on movement time.     

Alcohol consumption in free-feeding rats: procedural,genetic and pharmacokinetic factors

Voluntary consumption of alcohol by rats (i.e. in the absence of food or water deprivation, sweetening of the alcohol solution, etc.) that results in the attainment of behaviorally significant or pharmacologically detectable blood alcohol levels (BALs) has been difficult to demonstrate. In this study, we showed that free-feeding Wistar rats given access to increasingly concentrated solutions of alcohol in separate drinking cages on a 1-h per day basis drank on average close to 1 g/kg, resulting in average BALs close to 50 mg%. This drinking was comparable to that obtained by rats trained according to a procedure used widely by others in which animals are maintained at reduced body weights. Weight restriction alone, however, did not enhance amount of alcohol consumption over that of free-feeding animals in the 1-h session. There was also a strain difference in that Wistar rats drank significantly more than did Sprague-Dawley rats. Post hoc absorption curves showed that the initial absorption of alcohol from both the stomach and the peritoneum was slower in Wistar than in Sprague-Dawley rats, suggesting rate of absorption may be inversely related to amount of alcohol consumed; metabolic rates and volumes of distribution appeared unrelated to consumption. This periodic availability paradigm might be useful to investigate the effect of biological variables on individual bouts of alcohol consumption.     

Tolerance to the effects of ethanol on the speed and success of reaction time responding in the rat: effects of age and intoxicated practice

An animal model of human reaction time (RT) was used to investigate the effects of age and intoxicated practice on the development of tolerance to the motor impairing effects of ethanol (EtOH). Young (8–9 month) and old (24–26 month) Fischer 344 rats were trained to release a lever in response to an auditory and visual stimulus in order to avoid mild footshock. The animals were divided into groups to receive either intoxicated (EtOH-before) or unintoxicated (EtOH-after) RT testing. Successful avoidance and response latencies were impaired in young and old rats after the initial exposure to EtOH (EtOH-before group). Tolerance developed to EtOH's effects on successful avoidance and on response latencies whether or not the rats received intoxicated RT practice; however, intoxicated practice facilitated tolerance development to EtOH's effects on successful avoidance but not on response latencies. While the initial sensitivity and the level of tolerance that developed to EtOH's effects were similar in young and old rats, the old rats were generally more sensitive to EtOH and developed tolerance at a slower rate. These results suggest that tolerance develops to the effects of EtOH on RT and that intoxicated practice can have different effects on the parameters of the behavioral response.     

Smoking,processing speed and attention in a choice reaction time task

Nineteen subjects performed a choice reaction time task in which two levels of choice (two and four stimuli), and two levels of spatial attention (narrow and wide) were manipulated under each of two smoking conditions: sham smoking (denicotinised cigarette) or regular smoking (0.8 mg nicotine cigarette). All three factors significantly affected reaction time, with the smallest reaction times being recorded to the two-choice narrow grouped stimuli recorded under the high nicotine condition. Nicotine appears to speed decision time for both complex and hard-to-attend tasks, which is compatible with a role for nicotinic receptors in systems jointly mediating attention, memory and processing speed.     

Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics.

In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.     

Acute dose of alcohol affects cognitive components of reaction time to an omitted stimulus: differences among sensory systems

Rationale The possibility that moderate blood alcohol concentrations (BACs) may impair cognitive processes before disturbing motor functions has raised concern about the safety of BACs ≤80 mg/100 ml. Reaction time (RT) to the presentation of a stimulus or to the omission of a regularly occurring stimulus has been fractionated into independent premotor (cognitive) and motor (movement) components. It has been suggested that cognitive processes may be impaired at lower BACs than are motor processes, but the effects of moderate rising and declining BACs on these component RT measures have not been investigated. Objectives An omitted stimulus RT task was used to test the hypothesis that moderate rising BACs impair (slow) premotor RT (PMRT) when motor RT (MRT) remains unaffected. The task included visual, auditory, and tactile stimuli to explore differences in sensory sensitivity to alcohol. Methods Thirty male social drinkers were randomly assigned to three groups (n=10) that received 0.62 g/kg alcohol, 0.8 g/kg alcohol, or a placebo (0 g/kg). All participants performed the task three times: baseline and during rising and declining BACs. Results Comparisons of the alcohol and placebo groups showed rising BACs slowed PMRT and had no detectable effect on MRT. Impairment in visual PMRT occurred under both alcohol doses. Auditory PMRT was impaired only under the 0.8 g/kg dose, and tactile PMRT was unaffected. Conclusions Cognitive functions are impaired by moderate increasing BACs that do not affect motor movement, and the tactile sensory system may be relatively insensitive to this impairment.     

Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol

Rationale Sleep deprivation has a negative effect on cognitive and psychomotor performance and mood state, partially due to decreases in creatine levels in the brain. Therefore, creatine supplementation should lessen the negative effects of sleep deprivation. Objectives The objective of this study was to examine the effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Method Subjects were divided into a creatine group (n=10) and a placebo group (n=9). They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a time a day for 7 days, immediately prior to the experiment. The study was double blind. Subjects undertook tests of random movement generation (RMG), verbal and spatial recall, choice reaction time, static balance and mood state pre-test (0 h), after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. They were tested for plasma concentrations of catecholamines and cortisol at 0 and 24 h. Results At 24 h, the creatine group demonstrated significantly less change in performance from 0 h (Δ) in RMG, choice reaction time, balance and mood state. There were no significant differences between groups in plasma concentrations of catecholamines and cortisol. Norepinephrine and dopamine concentrations were significantly higher at 24 h than 0 h, but cortisol were lower. Conclusions Following 24-h sleep deprivation, creatine supplementation had a positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex.     

Effects of route of administration of ethanol on high-speed reaction time in young and old rats

The blood ethanol concentrations (BECs) and reactive capacity of young (8 months) and old (24 months) male Fischer 344 rats were compared at 5, 10, 20, 45, 65, and 90 min following the administration of ethanol (EtOH). The time-dependent effects of intragastric intubation (IG; 3 g/kg) and intraperitoneal injection (IP; 1.5 g/kg) of EtOH (20% w/v) were determined. Subsequent to IG delivery, BECs rose most rapidly within the first 20 min, but did not reach peak levels until 90 min for both young (240 mg/dl) and old rats (250 mg/dl). Following IP injections, BECs escalated within 5 min to 250 mg/dl in the young, to 175 mg/dl in the old, and declined gradually to a stabilized value of 150 mg/dl (young) and 130 mg/dl (old). The old rats never achieved the high BECs seen in the young. Reactive capacity, a measure of auditory/visual reaction time, was inversely related to BECs. As BECs (IP) declined, performance improved at a similar rate in both age groups, although the old rats' performance was more impaired than that of the young. However, BEC per se was not an adequate predictor of reactive capacity. When EtOH was delivered by IG so that BECs remained high for long periods of time, reactive capacity was far less impaired compared with IP delivery in which comparable BECs were present for only a few minutes. The possibility was noted that behavioral tolerance may have developed during the 90-min post-EtOH period, and that the IP delivery method may disrupt behavior in ways independent of brain ethanol levels.     

Gender related effects of heroin abuse on the simple reaction time task

Accumulated studies have demonstrated that there are serious negative consequences of drug abuse, especially the impairment of central nervous system (CNS) function. The simple reaction time (SRT) is the simplest model of measuring the function of the CNS. The purpose of the present study is to examine whether the SRT is affected by heroin abuse and whether such drug effect, if exists, is gender related. We found significant slowing of the SRT in both male and female heroin dependent patients at 1-3 months from withdrawal. However, the SRT slowing remitted after 3 months of abstinence in heroin dependent males but not in females. Our results suggested that the SRT is slowed by heroin abuse and such slowing is gender related.     

Alcohol pharmacodynamics in young-elderly adults contrasted with young and middle-aged subjects

Effects of aging on ethyl alcohol (EtOH) pharmacodynamics were examined over progressive dosing schedules (0.4, 0.6, 0.8, 1.0 g/kg) in groups of young (25.0±2.9 years), middle-aged (41.1±6.6 years), and young-elderly adults (60.9±2.6 years) using three computerized cognitive-neuromotor tasks: digitsymbol substitution (DSS), keypad reaction time (KRT), and subcritical tracking (SCT). Hysteresis curves of performance impairment (adjusted for pre-drug baseline) as a function of blood alcohol concentration (BAC) were examined for time-course effects, and regression analyses were performed to assess the contribution of age beyond that accounted for by BAC. Results reflected differences in the patterning but not magnitude of impairment for elderly subjects, with earlier decrements and more rapid acute tolerance observed for DSS, in conjunction with less pharmacodynamic sensitivity for SCT. Regression analyses furthermore indicated that age and impairment were negatively related, arguing against synergistic intoxication effects as a function of aging. Analyses specifically comparing performance at baseline versus legally intoxicating BACs (>1.0 mg/ml) likewise reflected a lack of interactive effects involving the elderly. Elderly subjects nevertheless exhibited significantly lower baseline performance for DSS and KRT than young subjects and achieved higher BACs with equivalent doses. These latter findings support the exercise of caution by elderly individuals consuming EtOH prior to engaging in neuromotor pursuits such as driving.Supported by NIDA Grant 5 R01 DA01883     

Modulation of lead-induced performance deficit in children by varying signal rate in a serial choice reaction task

Evidence is presented showing that serial choice reaction performance is disrupted at low blood lead levels (PbB), and that parametric variation of task characteristics modulates the degree of disruption. This evidence is based on two independent studies in 6- to 9-year-old children living in two lead smelter areas in the cities of Nordenham (N = 114) and Stolberg (N = 109) in West Germany. Average PbB was 8.2 μg/100 ml (4.4–23.8 μg/100 ml) in the Nordenham sample and 7.4 μg/100 ml (4.2–18.0 μg/100 ml) in the Stolberg sample. Serial choice reaction performance was assessed by means of the Vienna reaction device in which a random sequence of light and tone signals has to be answered by pressing appropriate response buttons. Correct (hits) and false responses (errors) were evaluated as performance measures, and signal rate was varied in order to achieve easy and difficult task conditions. Exposure-related performance deficit was more pronounced for errors than for hits, more clearcut for high than for low signal rates, and proved significant in both studies after correction for confounding using confounder models of different complexities. Some features of the observed deficit resemble clinical observations in children presenting with attention deficit disorder.     

Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task demands

RATIONALE: Beneficial effects of nicotine on cognitive processes including attention have potential therapeutic uses and have been proposed as incentives for tobacco smoking. OBJECTIVES: To establish task conditions under which the effects of nicotine on attention are obtained reliably and to characterise such effects further. METHODS: Rats were trained in a modified version of the five-choice serial reaction time task (5-CSRTT) to detect 1-s light stimuli with greater than 70% accuracy and fewer than 20% omission errors. Nicotine was tested under different task requirements by varying signal event rate, stimulus duration and stimulus predictability, and by introducing white-noise distractors. RESULTS: Nicotine (0.05-0.2 mg/kg, s.c.) repeatedly improved accuracy and reduced omission errors and reaction times, leading to increases in numbers of reinforcers earned. Anticipatory responding was increased. Parametric modifications intended to increase demands on sustained attention did not affect performance in a manner suggesting that this subtype of attention was being taxed, and the effects of nicotine were not more marked under such conditions. Shorter stimulus durations impaired performance, but this manipulation weakened the effect of nicotine on accuracy. In contrast, the presence of noise distractors facilitated the effects of nicotine to the extent that distractor-induced impairments were abolished by the drug. CONCLUSIONS: The 5-CSRTT can provide a sensitive rodent model for the attention-enhancing effects of nicotine. Changes made to the procedure may have increased its sensitivity to nicotine, particularly with respect to accuracy. There were indications that the effects of nicotine were largest on processes of selective attention or on disengaging attention from irrelevant events and shifting it to behaviourally significant stimuli.     

Contextual Determinants of Alcohol Consumption Changes and Preventive Alcohol Policies: A 12-Country European Study in Progress

Beginning with France in the 1950s, alcohol consumption has decreased in Southern European countries with few or no preventive alcohol policy measures being implemented, while alcohol consumption has been increasing in Northern European countries where historically more restrictive alcohol control policies were in place, even though more recently they were loosened. At the same time, Central and Eastern Europe have shown an intermediate behavior. We propose that country-specific changes in alcohol consumption between 1960 and are explained by a combination of a number of factors: (1) preventive alcohol policies and (2) social, cultural, economic, and demographic determinants. This article describes the methodology of a research study designed to understand the complex interactions that have occurred throughout Europe over the past five decades. These include changes in alcohol consumption, drinking patterns and alcohol-related harm, and the actual determinants of such changes.     

Intra-striatal haloperidol and scopolamine injections: effects on choice reaction time performance in rats

In this study the behavioral consequences of intra-striatal haloperidol and scopolamine injections were examined using a reaction time task. Haloperidol was found to increase the response time of the rats and had a modest effect on the motor components of the task. The manner in which haloperidol affected the response time distribution suggested that this drug affected attentional functions. Scopolamine did not affect the reaction time or motor performance in the reaction time task. However, a clear decrease in the number of completed trials and an increase in anticipatory responses was observed. At present no ready explanation could be given for the behavioral effects of scopolamine. The present data suggest that although dopamine and acetylcholine are intimately related in the striatal network and have been supposed to have antagonistic functions, the behavioral consequences of blockade of dopamine and acetylcholine receptors are dissimilar.     

Predictors of partying prior to bar attendance and subsequent BrAC

Pre-drinking (e.g., pre-gaming, pre-loading) occurs frequently among young adult and college-aged drinkers and is associated with increased intoxication as well as alcohol-related problems. The purpose of the following study was to examine pre-drinking behaviors in situ, and to test whether drinking intentions mediate the relationship between heavy episodic drinking history and pre-drinking behaviors. We randomly selected a sample of 1040 young adults bar patrons at 32 bars in a major metropolitan city in Southern California and asked participants to complete an interview concerning drinking behavior as well as provide a breath sample used to measure breath alcohol concentration. We used multilevel path analysis to test two meditational models. Results showed drinking intentions mediated the relationship between heavy episodic drinking history and pre-drinking behavior as well as the relationship between heavy episodic drinking history and level of pre-drinking intoxication. Gender did not moderate these meditational relationships suggesting similar pre-drinking behaviors for both men and women. Potential methods to prevent pre-drinking behaviors in this population of young people are discussed.     

Enhancement of continuous performance task reaction time by smoking in non-deprived smokers

In a test of thewithdrawal-deficit hypothesis of the cognitive effects of cigarette smoking, non-deprived smokers participated in two sessions held on consecutive days. In both sessions, subjects performed two 20-min continuous performance tasks (CPTs). The CPT was a relatively easy version designed to require minimal practice (digit 0 target response; digits 1–9 nontarget response; 19% of stimuli targets). In one session, subjects smoked a cigarette prior to each CPT; in the other session they did not smoke (session order counterbalanced). Reaction time (RT) was significantly faster in the smoking session than in the non-smoking session with no difference in number of incorrect responses, a finding incompatible with the withdrawal-deficit hypothesis. Further, light inhalers (as assessed by pre-smoking to post-task increase in expired air carbon monoxide) appeared to process nontarget stimuli faster than deep inhalers, especially in the no smoking session. The results also indicated that, at least during the first CPT of each session, the performance of females in the no smoking session was poorer than in the smoking session and poorer than males regardless of session. In the latter part of the first CPT, the performance of males in the smoking session was better than their performance in the no smoking session. No clear pattern emerged for the second CPT.     

Alcohol and suicide at the population level--the Canadian experience

Studies suggest that the population level link between alcohol and suicide differs across countries and between men and women. The aim of this paper was to estimate the relationship between alcohol consumption and suicide in Canada and to put the results in a comparative perspective. The relationship was elucidated for whole Canada, different provinces and also separately for men and women. The total suicide rate in Canada increased significantly by around 4% as alcohol consumption increased by one litre per capita, suggesting that approximately 25 - 30% of Canadian suicides were related to alcohol. The relationship was stronger for women than for men. A significant effect was found in all provinces except from Quebec, but the overall regional variation was not statistically significant. In an international perspective, the relationship for women was somewhat weaker than in Sweden and Norway, but larger than in Finland, the United States and Southern European countries. For men, the association was similar to what is found in the United States and Finland, weaker than in Sweden, Norway and Russia but stronger than in Southern European countries. The results only partly support the idea that intoxication frequency explains national differences in this relationship. Possible explanations for the stronger association among women are also discussed.