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

Kuypers, Kim P. C.; Samyn, Nele; Ramaekers, Johannes G.

doi:10.1007/s00213-006-0434-z

Cited by 90 publications

(103 citation statements)

References 24 publications

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“…Cassel et al also implies that our results differ from previous human studies by Hernandez-Lopez et al (2002) and Kuypers et al (2006), showing a dissociation between subjective and objective measures of sedation and psychomotor function. However, we also report this dissociation.…”

contrasting

confidence: 87%

Response to the comments by Cassel et al.

et al. 2008

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In response to Cassel et al., we clearly agree that our findings relate only to our employed blood alcohol concentration (BAC) of 0.56 mg/ml. Different ethanol concentrations may indeed induce different effects, and research in animals such as that reported by Cassel et al. (2005) suggest that higher doses may induce more dramatic interactions. At the same time, it is unfeasible to examine every possible combination of ethanol levels and 3,4-methylenedioxymethamphetamine (MDMA) doses. Although our design is inevitably a model, we believe that it is appropriate for the estimation of the effects of recreational drug use by humans for the following reasons.We employed an ethanol clamp that provides a continuous steady-state BAC of approximately 0.6 mg/ml, which is a radically different approach from the single oral administration of alcohol as employed in the previous studies mentioned by Cassel et al. Although our target BAC reflects the peak achieved after 2-3 alcoholic drinks, due to the continuous infusion of alcohol over 3 h to maintain this BAC, the total amount of alcohol administered represents a much larger intake of alcoholic drinks corresponding to almost one bottle of wine, a relevant dose of ethanol which is comparable to the amounts as cited by Cassel et al. in relation to recreational drug use. As recreational alcohol users are expected to spread their alcohol use over the night, our design, thus, represents continuous moderate use of alcohol. A single high dose of oral alcohol (based on total drinks consumed during or around MDMA exposure), on the other hand, will show a rapid increase and a steady decline in BAC, resembling binge drinking. This will induce larger peak effects compared to the effects of our more steady infusion of alcohol. It is unknown whether binge drinking or moderate continuous drinking is more prevalent in MDMA users, and our study represents only the latter pattern of alcohol use. Cassel et al. rightly point to the lack of evidence regarding the real world drinking behavior and achieved BAC by recreational drug users combining MDMA and ethanol, and we welcome further research regarding these uncertainties.Next, Cassel et al. cites the study by Hernandez Lopez et al. (2002) who achieved a higher BAC (employing a single oral alcohol dose) and reported an increase in MDMA concentration after ethanol coadministration (compared to the MDMA only condition), an effect which we did not find. This report indeed shows a significant increase in MDMA peak levels (Cmax) but not for total MDMA concentrations (AUC0-6 h). This is in line with our expectations and suggestions regarding the difference in ethanol administration route and resulting kinetics. Hernandez-Lopez et al. (2002) also reported a decrease in BAC after ethanol administration, which we did not address in our report. A subsequent evaluation of our data indicated that after MDMA coadministration, significantly more ethanol was needed to maintain the same stable levels of BAC compared to the ethanol only condition (effect of dr...

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contrasting

confidence: 87%

Response to the comments by Cassel et al.

et al. 2008

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“…However, while blood alcohol levels up to 0.05 per cent may not significantly impair psychomotor performance, they invoke a level of drowsiness sufficient to impair performance and increase motor vehicle crash risk (Banks et al 2004;Barrett et al 2004;Barrett et al 2005). This is compounded if alcohol is combined with other drugs such as cannabis (Lamers & Ramaekers 2001;Kuypers et al 2006).…”

Section: Acute Effects Of Alcoholmentioning

confidence: 99%

Survey of alcohol-related presentations to Australasian emergency departments

et al. 2014

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Objective: To determine the proportion of alcohol‐related presentations to emergency departments (EDs) in Australia and New Zealand, at a single time point on a weekend night shift. Design, setting and participants: A point prevalence survey of ED patients either waiting to be seen or currently being seen conducted at 02:00 local time on 14 December 2013 in 106 EDs in Australia and New Zealand. Main outcome measures: The number of ED presentations that were alcohol‐related, defined using World Health Organization ICD‐10 codes. Results: At the 106 hospitals (92 Australia, 14 New Zealand) that provided data, 395 (14.3%; 95% CI, 13.0%–15.6%) of 2766 patients in EDs at the study time were presenting for alcohol‐related reasons; 13.8% (95% CI, 12.5%–15.2%) in Australia and 17.9% (95% CI, 13.9%–22.8%) in New Zealand. The distribution was skewed left, with proportions ranging from 0 to 50% and a median of 12.5%. Nine Australian hospitals and one New Zealand hospital reported that more than a third of their ED patients had alcohol‐related presentations; the Northern Territory (38.1%) and Western Australia (21.1%) reported the highest proportions of alcohol‐related presentations. Conclusions: One in seven ED presentations in Australian and New Zealand at this 02:00 snapshot were alcohol‐related, with some EDs seeing more than one in three alcohol‐related presentations. This confirms that alcohol‐related presentations to EDs are currently underreported and makes a strong case for public health initiatives.

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“…Conditions were separated by minimum washout period of 7 days to avoid cross-condition contamination. The 75 mg dose of MDMA was selected because it falls within the normal range of and has been consistently shown to impair memory performance and produce robust subjective mood changes in a number of previous studies from our lab Ramaekers, 2005, 2007;Kuypers et al, 2006;Ramaekers et al, 2009). Doses of pindolol 20 mg and ketanserin 50 mg represent regular therapeutic doses that block B40% of 5HT 1A receptors and 91% of 5HT 2 receptors, respectively (Brogden and Sorkin, 1990;Rabiner et al, 2000;Sharpley et al, 1994).…”

Section: Treatments and Proceduresmentioning

confidence: 99%

Blockade of 5-HT2 Receptor Selectively Prevents MDMA-Induced Verbal Memory Impairment

Wel

Kuypers

Theunissen

et al. 2011

Neuropsychopharmacol

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3,4-Methylenedioxymethamphetamine (MDMA) or 'ecstasy' has been associated with memory deficits during abstinence and intoxication. The human neuropharmacology of MDMA-induced memory impairment is unknown. This study investigated the role of 5-HT 2A and 5-HT 1A receptors in MDMA-induced memory impairment. Ketanserin is a 5-HT 2A receptor blocker and pindolol a 5-HT 1A receptor blocker. It was hypothesized that pretreatment with ketanserin and pindolol would protect against MDMA-induced memory impairment. Subjects (N ¼ 17) participated in a double-blind, placebo-controlled, within-subject design involving six experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 min. T1-T2 combinations were: placebo-placebo, pindolol 20 mg-placebo, ketanserin 50 mg-placebo, placebo-MDMA 75 mg, pindolol 20 mg-MDMA 75 mg, and ketanserin 50 mg-MDMA 75 mg. Memory function was assessed at Tmax of MDMA by means of a word-learning task (WLT), a spatial memory task and a prospective memory task. MDMA significantly impaired performance in all memory tasks. Pretreatment with a 5-HT 2A receptor blocker selectively interacted with subsequent MDMA treatment and prevented MDMA-induced impairment in the WLT, but not in the spatial and prospective memory task. Pretreatment with a 5-HT 1A blocker did not affect MDMA-induced memory impairment in any of the tasks. Together, the results demonstrate that MDMA-induced impairment of verbal memory as measured in the WLT is mediated by 5-HT 2A receptor stimulation.

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

Abstract: 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.

Cited by 90 publications

References 24 publications

Response to the comments by Cassel et al.

Response to the comments by Cassel et al.

Survey of alcohol-related presentations to Australasian emergency departments

Blockade of 5-HT2 Receptor Selectively Prevents MDMA-Induced Verbal Memory Impairment

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