Ecstasy and Driving Ability

2.2 Vollenweider et al studying the effects of a dose of 1.7mg/kg in 13x healthy ecstasy-na"ve volunteers, found "MDMA produced an effective state of enhanced mood, well-being, and increased emotional sensitiveness, little anxiety, but no hallucinations or panic reactions. Mild depersonalization and derealization phenomena occurred together with moderate thought disorder, first signs of loss of body control, and alterations in the meaning of percepts. Subjects also displayed changes in the sense of space and time, heightened sensory awareness, and increased psychomotor drive. MDMA did not impair selective attention as measured by the Stroop test. MDMA increased blood pressure moderately, with the exception of one subject who showed a transient hypertensive reaction. "

2.3 Hermle et al found ecstasy "produced a partially controllable state of enhanced insight, empathy, and peaceful feelings. All subjects displayed a general stimulation with increased psychomotor drive, logorrhea, and facilitation of communication. " Mas et al noted significant increases in resting heart rate (+30bpm) and blood pressure (+40mmHg) following administration of single doses of 75-125mg MDMA in healthy volunteers.

2.4 Verkes et al assessed reaction time, direct recall, and recognition in two groups, all from the same subculture, of 21 males with moderate and heavy recreational MDMA use, and a control group of 20 males without use of MDMA, finding "Ecstasy users showed a broad pattern of statistically significant, but clinically small, impairment of memory and prolonged reaction times. Heavy users were affected stronger than moderate users."

2.5 Studying rhesus monkeys, Frederic et al found tolerance developed to the behavioural and psychomotor effects of repeated doses of ecstasy, although baseline values remained unaltered on the "operant test battery (OTB) designed to model aspects of time estimation, short-term memory, motivation, learning, and color and position discrimination." Taffe et al found "Behavioral performance was disrupted during acute MDMA treatment but returned to baseline within one week following treatment."

3.1 Morgan found chronic ecstasy users to show significant memory deficits, and commented "...deficits in memory performance in recreational ecstasy users are primarily associated with past exposure to ecstasy, rather than with the other legal and illicit drugs consumed by these individuals, and are consistent with reduced serotonergic modulation of mnemonic function as a result of long-term neurotoxic effects of MDMA in humans." Bolla et al found "Abstinent MDMA users have impairment in verbal and visual memory. The extent of memory impairment correlates with the degree of MDMA exposure"

3.2 Parrott & Lasky compared the performances of regular and novice ecstasy users in a club environment, together with other drug, but not ecstasy, using controls, concluding "Cognitive performance on both tasks (verbal recall, visual scanning) was significantly reduced on-MDMA. Memory recall was also significantly impaired in drug-free MDMA users, with regular ecstasy users displaying the worst memory scores at every test session. This agrees with previous findings of memory impairments in drug-free ecstasy users."

3.3 Gerra et al, studying human volunteers, reported "Dysphoria and mood changes were exhibited in seven individuals, tiredness in five and sensation-seeking behaviour in twelve at the clinical evaluation. Significantly higher scores were found in MDMA individuals than in control individuals for MMPI subscale for Depression, for Buss Durkee Hostility Inventory direct and guilt subscales, for Hamilton Depression Rating Scale and for novelty-seeking Tridimensional Personality Questionnaire subscale. "

3.4 Rodgers studied cognitive function in 15 regular users of ecstasy; 15 regular users of cannabis who had never taken ecstasy and 15 control subjects who had never taken any illicit substances, and found "Performance was similar across all three groups for measures of visual reaction time, auditory reaction time, complex reaction time, visual memory and attention and concentration. Significant impairment was found on measures of verbal memory in both cannabis users and ecstasy users. A significant impairment in performance was found on measures of delayed memory for the ecstasy users compared to both the cannabis group and the control group. Despite these findings, no differences in subjective ratings of cognitive failures were found between the groups."

3.5 Curran et al noted the tendency of ecstasy users to suffer mood swings, with elation at weekends and depression during the week, and also reported "The MDMA group showed significant impairments on an attentional/working memory task" Krystal et al noted in a study of 9 chronic ecstasy users "a pattern of mild-to-moderate impairment was observed on both the Initial and Delayed Paragraph Tests of the Wechsler Memory Scale; eight of the subjects had at least mild impairment on at least one test in the neuropsychological battery."

3.6 Gouzoulis-Mayfrank et al studied abstinent former recreational users of ecstasy, compared to cannabis users and non-drug using controls, and reported "Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not differ significantly in their performance from the non-users."

3.7 Parrott et al studied two abstinent groups of "novice" and "experienced" ecstasy users, compared with non-using controls on a computerised battery of tests, and found "Performance on the response speed and vigilance measures (simple reaction time, choice reaction time, number vigilance), was similar across the three subgroups. However on immediate word recall and delayed word recall, both groups of MDMA users recalled significantly less words than controls."

3.8 Studying rats, Marston et al reported "MDMA exposure elicits a classical 5-HT syndrome. In the long-term, exposure results in 5-HT neurotoxicity and a lasting cognitive impairment. These results have significant implications for the prediction that use of MDMA in humans could have deleterious long-term neuropsychological/psychiatric consequences." Also with rats, Robinson et al reported "Partial depletion of neocortical serotonin (72.6%) did not produce deficits on a variety of behavioral tests, including a place navigation learning-set task, skilled forelimb use, or the ability to make complex judgements regarding the stimulus properties of food in a foraging situation, and neither did additional cholinergic blockade. MDMA-pretreated rats had a mild impairment in rapidly developing an efficient search strategy in the place navigation task, but once the goal was located, MDMA pretreated rats performed at control levels and showed no deficits in memory for spatial location." In pigeons, LeSage et al found MDMA impaired accuracy in a delayed-matching task, but that tolerance developed with repeated administration.

4.2 In a learned review, Morland reported ecstasy to cause effects including "euphoria, central nervous stimulation, and feeling of closeness to mild hallucinations, impairment of cognition and co-ordination and further to serious reactions like agitation, disturbed and bizarre behaviour, and possibly psychosis." and noted: "It has been assumed that the risk of being involved in fatalities and accidents during the state of MDMA influence is increased, but this possible risk increase has so far not been determined. Observations of the prevalence of MDMA involvement in cases of reckless driving and the MDMA blood concentrations measured indicate a risk increase comparable to that observed after use of amphetamines." Moeller et al reported ecstasy levels in impaired drivers, and Crifasi et al reported a case history of a fatal road accident attributed to MDMA use by a na"ve user, although I am currently unaware of any evidence as to causation or circumstances of that accident.

4.3 Giroud et al reported "MDMA and related compounds display unique psychoactive properties, acting as a stimulant and inducing feelings of empathy.... Forensic investigations performed at our institute showed significant blood levels of MDMA, MDEA and MDA in samples drawn from people suspected of driving under the influence of psychoactive drugs.... Our study shows that because of the variable composition of ecstasy tablets, unpredictable types and amounts of drugs may be taken by MDMA misusers. Moreover, there is considerable concern that traffic accidents may be caused by MDMA-abusers."

6 Ecstasy Pharmacokinetics & Drug-Testing

6.2 Detection times for MDMA depend on the bodily fluid and analytical method used, Gombos quotes 1-3 days using radioimmunoassay screening and GCMS confirmation, with a GCMS cutoff level of 200ng/ml. Studying human volunteers, Mas et al reported "Elimination half-life was 8.6 h and 7.7 h for high (125mg) and low (75mg) MDMA doses, respectively."

6.3 Crifasi et al reported MDMA levels in a na"ve user following a fatal accident "The concentrations of MDMA in clotted blood, sodium fluoride-potassium oxalate anticoagulated blood, vitreous humor, and urine were 2.32 mg/L, 2.14 mg/L, 1.11 mg/L, and 118.8 mg/L, respectively. The concentrations of the metabolite MDA were less than 0.25 mg/L in blood and vitreous, and 3.86 mg/L in the urine."

6.4 Fallon et al noted the differential plasma half-lives of stereoscopic enantiomers R-MDMA (5.8 +/- 2.2 h) and S-MDMA (3.6 +/- 0.9 h), when a racemic mixture was administered, and noted "Mathematical modeling of plasma enantiomeric composition vs sampling time demonstrated the applicability of using stereochemical data for the prediction of time elapsed after drug administration." In humans, Moore et al reported "These data indicate that S(+)-MDMA is metabolized and eliminated faster than R(-)-MDMA.". In rats given subcutaneous or intravenous injections of 20-40mg/kg, Fitzgerald et al reported "The average half-life (+/- SD) for all dosing groups was 2.5 +/- 0.8 h for (-)-(R)-MDMA and 2.2 +/- 0.8 h for (+)-(S)-MDMA." The same team had earlier noted "This may be significant since it has been shown that the S(+) isomer of MDMA is the more neurotoxic isomer of the racemic drug of abuse MDMA. "

6.5 A hair testing study by Nakahara et al indicated MDMA to be rapidly incorporated into dark hair, and remain for a prolonged period, but hardly any incorporation into white hair. Nonetheless, Kikura et al considered "a hair sample is a good specimen for the confirmation of retrospective use of methylenedioxyamphetamines. "