Saturday, 18th November 2017

Ecstasy

Ecstasy and Driving Ability

 

Overview - Effects of ecstasy

Ecstasy and related drugs (phenethylamines) are stimulant drugs chemically related to amphetamine, but with other psychoactive (entheogenic) properties affecting mood. The main physiological action is to increase the release of serotonin (5-hydroxy tryptamine) and dopamine in the brain, changing the mood of the user by altering the processing of information. The half-life of ecstasy (MDMA) in blood is around 6 hours. In general the effects are similar to, but more pronouced than, those of Prozac or similar antidepressants which block reuptake of serotonin thus raising the levels. It could be said that they achieve the same effects by ecstasy "turning on the taps", and Prozac "putting in the plug".

Physiological effects are similar to other stimulants - increased alertness and physical energy, raised body temperature (in many cases dangerously so), and dehydration. Liver and kidney damage has been reported. Most deaths have occurred due to overheating (heat stroke).

The main short-term psychological effects are reported by Leister & Grob as "altered time perception (90%), increased ability to interact with or be open with others (85%), decreased defensiveness (80%), decreased fear (65%), decreased sense of separation or alienation (60%), changes in visual perception (55%), increased awareness of emotions (50%), decreased aggression (50%), speech changes (45%), awareness of unconscious memories (40%), decreased obsessiveness (40% and cognitive changes (40%)." Medium-term changes (up to a week) included "decreased sleep (40%), decreased appetite (30%), increased sensitivity to emotions (25%), decreased ability or desire to perform mental or physical tasks (20%), increased ability to interact with or be open with others (20%), and decreased defensiveness (20%)." Longer-term effects (more than one week) included "improved social-interpersonal functioning (50%), changes in religious orientation or practice (46%), changed values or life priorities (45%), improved occupational functioning (40%), increased ability to interact with or be open with others (35%), decreased defensiveness (30%), changes in ego boundaries (30%), decreased desire to use alcohol (25% )and decreased fear (20%)" Other researchers have identified problems with memory and judgement, or increased sensitivity to touch and sound.

Short-term side effects include dry mouth, clenching or grinding of teeth, reduced appetite, weight loss, nystagmus, twitches, nausea and cramp. Adverse effects on mood are attributed by Saunders to the increased vulnerability of users when under the influence, due to increased openness and reduced defensiveness, such that insights may bring unbearable truths, and candid disclosures may be regretted. Adverse psychological effects include sleep disturbance, depression and paranoia, and exhaustion after use. Tolerance to the effects of ecstasy develops rapidly, such that the extreme euphoric effects tend to be limited to the first few occasions of use, and users may take increasing quantities in attempting to achieve a desired level of intoxication. Regular users can experience medium term depression when not under the influence, which tends to reinforce ecstasy-seeking behaviour.

Evidence of damage to serotonergic neurons, and lower serotonin levels among users and laboratory animals, provides a physiological model predicting long-term depressive illness in many chronic users. The neuronal damage also explains why toleranceoccurs, as no matter how much stimulation they receive, the fewer remaining neurons can only secrete a limited amount of serotonin.

The effects of ecstasy typically last for 4-6 hours, although where high or multiple doses are taken the effects can be prolonged and sustained in a pattern of "chronic binge use".

Laboratory Studies of Psychomotor performance

Laboratory tests are frequently used to assess the effects of drugs on performance of psychomotor tests (dexterity, reaction time, tracking etc) and cognitive function (mental ability and judgement). The effects frequently differ between naive users of a drug and experienced users who have developed tolerance.

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. "

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.

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."

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."

Ecstasy and Cognitive Function

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"

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."

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. "

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."

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."

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."

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."

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.

Driving Performance

There have been very few studies specifically investigating the effect of ecstasy on driving ability, although there is a wealth of evidence as to the psychomotor effects of stimulant drugs in general (e.g. amphetamine and cocaine), which suggests low doses may enhance performance (more alert, vigilant, quicker reaction times) whereas high doses may impair judgement (overconfidence, more aggressive driving, paranoia). However ecstasy are considered to be qualitatively different from those of either amphetamine or hallucinations such as LSD, and the class of drugs has been designated "entactogens"

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.

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."

IDMU"s 1998 and 1999 drug user surveys found the overall accident rate for the survey respondents as a whole to be 0.608 per 100,000km (898 accidents in 147.8 million km), close to the national average. Frequency of ecstasy use was assessed as experimental (less than 10 times), occasional, regular, and daily. The accident rate for all ecstasy users was slightly (9%) higher than the group as a whole at 0.664, although regular users of Ecstasy showed a significantly increased risk of accidents (+50% in mean accidents) and a significantly increased accident rate (0.849) compared to non-users (+58%) or all users of other drugs (+40%). However the extent to which this increase reflects the effects of the drug itself, rather than the ecstasy using lifestyle (more likely to be driving in the small hours of the morning) is unclear.

Ecstasy & Accidents (IDMU 1998-1999 data)

Freq

No Drivers

Mean accidents*

Total Number

Mean km/ 5yrs

Total km/5yrs

Total accids

Accident Rate

% users drive

Never

1020

0.39

1395

53200.93

74215297

398

0.536

73.1

Exp

288

0.43

367

50140.52

18401571

124

0.673

78.5

Occ

278

0.36

358

56314.91

20160738

100

0.496

77.7

Reg

350

0.59

477

50973.81

24314507

207

0.849*

73.4

Daily

5

0.60

8

50600

404800

3

0.741

62.5

Ex-users

122

0.36

161

55294.18

8902363

44

0.493

75.8

Total

1121

0.46

1492

52054.68

77665583

516

0.664

75.1

The study also asked respondents whether they had had accidents under the influence of particular drugs. Of 245 such accidents reported, 29 (12%) involved ecstasy (7 alone and 22 in combination with other drugs). Taking into account the probability that drivers would be under the influence of the drug at any particular time (a function of the incidence of use and frequency of use), this rate was 80% higher than should have been expected.

In the 1994 IDMU study, heavy polydrug use was associated with a significantly higher level of accidents.

Culpability analysis studies

Crouch et al considered that in 50 out of 56 cases where drugs or alcohol were found, these contributed to the accident, however it is unclear to what extent drugs other than alcohol were increased culpability.

An Australian study of Drummer, investigated over 1000 accidents, using risk analysis to compare the relative accident risks of alcohol, cannabis and other drugs, finding alcohol (p<0.0001) and multiple drug use (p<.05) to significantly increase the accident risk, whereas cannabinoids reduced the risk ratio to a degree which approached statistical significance (p=.065). Stimulants (amphetamine, cocaine and ecstasy) were present in 3.3% of cases, with a slightly increased level of culpability - an odds ratio of 2.0 (range 0.7-5.6). Although this result did not approach statistical significance, such an increase cannot be ruled out due to the low incidence of stimulant positives.

Ecstasy Pharmacokinetics & Drug-Testing

Pharmacokinetics is the study of the time course of how drugs are distributed in the body, how long the effects last and how such effects relate to drug tests.

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."

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."

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. "

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. "

Passive Exposure & False Positives

Passive inhalation of smoked cocaine, heroin or cannabis can result in a false-positive test result. However as Ecstasy is taken orally, the only circumstances where passive exposure is likely to become an issue is where a drink has been spiked or a person otherwise administered the drug without knowledge or consent.

I am not aware of any studies as to substances which could produce false positive test results for MDMA, although it is theoretically possible that some herbal or medicinal preparations containing precursor chemicals could be converted within the body to active substances.

Summary - Drug Testing for Ecstasy

Blood or urine tests can remain positive for 1-3 days following an individual dose of ecstasy, and up to 4-5 days following cessation among chronic heavy users, or where high doses are used.

If a test to determine ecstasy intoxication is required (as in driving cases), rather than just to determine whether an individual has used at some time in the near to medium-term past (e.g. for employment and rehabilitation purposes), an assay of MDMA, and other markers (e.g. stereoisomers and MDA) is required from blood or saliva samples.

Presence of MDMA in urine may indicate use of ecstasy in the previous 1-7 days, however presence of drugs in urine provides only evidence of past exposure, and cannot provide evidence of a person being under the influence of a drug at the time the sample was taken, or at any particular point in the past.

Summary - Ecstasy and Driving

As a stimulant, the effects of ecstasy on psychomotor performance are relatively limited, with few differences in test scores (e.g. reaction time, vigilance) between users and non-users. However cognitive function, particularly memory can be severely impaired not only in intoxicated users, but also in regular users currently abstinent from the drug, most notably memory where long-term deficits have been recorded.

Our own studies suggest regular Ecstasy use to be associated with higher risk of accidents among drug-using drivers, however this may result from the greater likelihood of ecstasy users to driving in the small hours of the morning when they would otherwise be fatigued in any event.

The culpability analysis studies from Australia neither confirm nor rule out a role for stimulant in accident causation, as the number of stimulant positive accident victims from which conclusions are drawn fails to achieve statistical significance, despite large initial sample populations. By contrast, alcohol and benzodiazepines were associated with significantly increased rates of culpability.

However, our own studies provide evidence to support the proposition that ecstasy use may be a significant causal factor in road traffic accidents, as regular ecstasy users have reported significantly higher accident rates than non-users or users of other drugs. Users with heavy poly-drug habits, or involvement in the wholesale drugs trade, may be more likely to be involved in road accidents than other drug users. This may result from a greater propensity to risk-taking behaviour in such individuals.

Further research is required into the effects of ecstasy on driving simulator performance and in actual driving situations, as no controlled published studies appear available.

The presence of levels of ecstasy within urine or blood can not be presumed to indicate that a person is under the influence of the drug at the time of the test, or at any specific time beforehand, or to establish recent use, intoxication, or impairment. McBay concluded thus:

"The relationship of specific blood drug levels to driving impairment has not been established for drugs other than alcohol, except in cases of extreme doses that may be expected to produce gross impairment. Thus even though a blood-drug level may be determined it is often not clear what it means in impairment".