Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers.

RATIONALE: In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. OBJECTIVE: The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. MATERIALS AND METHODS: We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. RESULTS: Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. CONCLUSIONS: Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function.

The role of sedation tests in identifying sedative drug effects in healthy volunteers and their power to dissociate sedative-related impairments from memory dysfunctions.

The study investigated whether four specified drugs would show similar patterns on tests considered to measure sedation. In addition, their drug-effect patterns on sedation and memory performance were compared to determine whether the sedative effects could be differentiated from the memory effects. Two double-blind, placebo-controlled, crossover studies, each with 16 healthy volunteers, were performed, one testing lorazepam (2.5 mg) and mirtazapine (15 mg) and the other olanzapine (10 mg) and haloperidol (2.5 mg). Subjective sedation was assessed by means of visual analogue scales (VAS) and objective sedation using a simple-reaction-time (SRT) task and a choice-reaction-time (CRT) task, code substitution (symbol digit substitution test (SDST)) and the peak velocity of saccadic eye movements (SEM). A verbal memory test (VMT) was administered to evaluate memory capacity. Apart from haloperidol, all drugs proved to impair performance on all five sedation indices. Contrary to the VAS, the objective measures yielded different response profiles. Two types of drug-effect patterns emerged: one for greater impairments in response speed (SRT, SEM) and one for greater impairments in information processing (CRT, SDST). Lorazepam and olanzapine impeded memory performance, whereas mirtazapine did not. With the use of standardized scores it proved possible to differentiate between the size of the effects of the drugs on the sedation and memory tests. To accurately assess the level and nature of sedation and to differentiate sedation from memory impairments different types of sedation measures are required. Besides studying the subjective effects, it is recommended to also test psychomotor responses and information processing speed.

Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects.

RATIONALE: The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function. OBJECTIVE: In the current study, we tried to replicate those findings. In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions, a selective anticholinergic drug, biperiden, was compared to a selective acetylcholinesterase-inhibiting drug, rivastigmine, in healthy elderly subjects. METHODS: A double-blind, placebo-controlled, randomised, cross-over study was performed in 16 healthy, elderly volunteers (eight men, eight women; mean age 66.1, SD 4.46 years). All subjects received biperiden (2 mg), rivastigmine (3 mg) and placebo with an interval of 7 days between them. Testing took place 1 h after drug intake (which was around Tmax for both drugs). Subjects were presented with tests for episodic memory (wordlist and picture memory), working memory tasks (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Visuospatial abilities were assessed by tests with high visual scanning components (tangled lines and Symbol Digit Substitution Test). RESULTS: Episodic memory was impaired by biperiden. Rivastigmine impaired recognition parts of the episodic memory performance. Working memory was non-significantly impaired by biperiden and not affected by rivastigmine. Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine. CONCLUSIONS: These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities.