Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans

RATIONALE: One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information. OBJECTIVE: The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways. METHODS: Fifteen occasional cannabis users participated in a double-blind, placebo-controlled, six-way cross-over study. On separate test days, subjects received combinations of pretreatment (placebo, vardenafil 20 mg or rivastigmine 3 mg) and treatment (placebo or 1,376 mg cannabis/kg body weight). Cognitive tests were administered immediately after inhalation of treatment was finished and included measures of memory (visual verbal learning task, prospective memory test, Sternberg memory test), perceptual-motor control (critical tracking task), attention (divided attention task) and motor impulsivity (stop signal task). RESULTS: The results of this study demonstrate that subjects under the influence of cannabis were impaired in all memory tasks, in critical tracking, divided attention and the stop signal task. Pretreatment with rivastigmine attenuated the effect of cannabis on delayed recall and showed a trend towards significance on immediate recall. When cannabis was given in combination with vardenafil, there were no significant interaction effects in any of the tasks. CONCLUSIONS: The present data therefore suggest that acetylcholine plays an important role in cannabis-induced memory impairment, whereas similar results for glutamate have not been demonstrated in this study

Transient memory impairment after acute dose of 75mg 34-Methylene-dioxymethamphetamine.

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

Acute Effects of 3 4-Methylenedioxymethamphetamine (MDMA) on Behavioral Measures of Impulsivity: Alone and in Combination with Alcohol.

The use of 3,4-methylenedioxymethamphetamine (MDMA) has frequently been associated with increased levels of impulsivity during abstinence. The effects of MDMA on measures of impulsivity, however, have not yet been studied during intoxication. The present study was designed to assess the acute effects of MDMA and alcohol, alone and in combination, on behavioral measures of impulsivity and risk-taking behavior. A total of 18 recreational users of MDMA entered a double-blind placebo-controlled six-way crossover study. The treatments consisted of MDMA 0, 75, and 100 mg with and without alcohol. Alcohol dosing was designed to achieve a peak blood alcohol concentration (BAC) of about 0.06 g/dl during laboratory testing. Laboratory tests of impulsivity were conducted between 1.5 and 2 h post-MDMA and included a stop-signal task, a go/no-go task, and the Iowa gambling task. MDMA decreased stop reaction time in the stop-signal task indicating increased impulse control. Alcohol increased the proportion of commission errors in the stop-signal task and the go/no-go task. Signal detection analyses of alcohol-induced commission errors indicated that this effect may reflect impairment of perceptual or attentive processing rather than an increase of motor impulsivity per se. Performance in the Iowa gambling task was not affected by MDMA and alcohol, but there was a nonsignificant tendency towards improvement following alcohol intake. None of the behavioral measures of impulsivity showed a MDMA x alcohol interaction effect. The lack of interaction indicated that the CNS stimulant effects of MDMA were never sufficient to overcome alcohol-induced impairment of impulse control or risk-taking behavior

Memory and mood during the night and in the morning after repeated evening doses of MDMA

Previously it has been shown that MDMA causes memory impairment during daytime testing. However, MDMA is usually taken in the evening or during the night. In addition, it is known that sleep deprivation also causes memory impairment. The present study aimed to assess whether evening doses of MDMA added to, or interacted with the memory impairment due to sleep deprivation. Fourteen healthy subjects participated in a double-blind, placebo-controlled, two-way cross-over study. Treatments consisted of MDMA 75 and 50 mg divided over the evening or double placebo. Memory tests and subjective measures of mood were conducted at baseline and three times post dosing that is at 6.30 pm, 9.30 pm, 1.30 am and 7 am, respectively -1.5, 1.5, 5.5 and 11 h relative to drug intake (first dose). Memory performance detoriated progessively over time as a function of sleep loss, independent of treatment. MDMA added to this impairment as indicated by a significant main effect of MDMA on verbal and spatial memory performance. Mood ratings and response speed revealed an MDMA by Time interaction. After administration of MDMA response speed improved and feelings of vigor, friendliness, elation, anxiety, confusion, arousal and positive mood increased in magnitude during the night, while all these parameters returned to placebo-like levels on the final morning session. It is concluded that evening doses of MDMA selectively impair memory performance, and that this impairment is additional to the effect of sleep deprivation on memory performance

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. Conclusions 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

The role of 5-HT(1a) and 5-HT (2a) receptors in attention and motor control: a mechanistic study in healthy volunteers

Rationale: Various studies have demonstrated a modulating role for serotonin in attention. Selective serotonin inhibitors have repeatedly been shown to impair performance in sustained attention tasks. Objectives: To assess the contribution of serotonin reuptake inhibition and specific blockade of the pre-synaptic 5-HT1a receptor and the 5-HT2a receptor to deficits in attention. Materials and methods: The study was conducted according to a randomized, double-blind, placebo controlled, four-way crossover design including 16 healthy volunteers. Treatments consisted of oral administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram 20 mg + placebo; escitalopram 20 mg + ketanserin (5-HT2a antagonist), 50 mg; escitalopram 20 mg + pindolol (5-HT1a antagonist) 10 mg; and placebo + placebo on four separate days. A range of performance tasks were conducted to assess the subjects' attention and motor functions. Results: Escitalopram administered alone impaired tracking performance in a divided attention task. The combination of escitalopram and pindolol and escitalopram and ketanserin impaired divided attention as compared to placebo. In addition, escitalopram and ketanserin impaired sustained attention. Divided attention impairment observed after combined treatments did not significantly differ from impairments after escitalopram alone. Sustained attention impairment observed after combined escitalopram and ketanserin significantly differed from escitalopram alone. Conclusions: 5HT(1a) blockade hardly affected SSRI effects on attention. Additional 5HT(2a) blockade, however, produced impairments of sustained attention and motor impulse control