Andrew C. Parrott

Ecstasy (MDMA) effects upon mood and cognition: Before, during and after a Saturday night dance

Abstract Three groups of young people (aged 19–30 years) were compared: 15 regular ecstasy users who had taken MDMA (3,4-methylenedioxymethamphetamine) on ten or more occasions; 15 novice ecstasy users who had taken MDMA on fewer than ten previous occasions; and 15 controls who had never taken MDMA. Each subject completed a cognitive test and mood scale battery four times: an initial drug-free baseline, at a Saturday night dance/club (on-drug), then 2 days later, and 7 days later. On the Saturday night, regular ecstasy users took an average of 1.80 MDMA tablets, novice users took 1.45 MDMA tablets, while controls mostly drank alcohol. The consumption of cannabis and cocaine at the club was similar across groups. All three groups reported positive moods at the dance club (on-drug), although there were borderline trends (P < 0.10) for less sadness/depression in the MDMA subgroups. However 2 days afterwards, the ecstasy users felt significantly more depressed, abnormal, unsociable, unpleasant, and less good tempered, than the controls. 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. Animal data have shown that MDMA can generate long-term serotonergic neurodegereration in various brain areas, including the hippocampus. The cognitive deficits in drug-free recreational ecstasy users, suggest that MDMA may also be neurotoxic in humans.

Psychobiological problems in heavy ‘ecstasy’ (MDMA) polydrug users

Twelve heavy recreational ecstasy drug users (30-1000 occasions), 16 light ecstasy users (1-20 occasions) and 22 non ecstasy user controls, with group mean ages around 21 years, were compared. Three self-rating questionnaires were completed when drug-free: the SCL-90 (an outpatient psychiatric symptom checklist), the impulsiveness venturesomeness and empathy (IVE) scale; and the uplifts, hassles, stresses and cognitive failures questionnaire. Heavy Ecstasy users reported significantly higher scores than controls on the following SCL-90 factors: paranoid ideation, psychoticism, somatisation, obsessionality, anxiety, hostility, phobic anxiety, altered appetite and restless sleep, together with greater IVE impulsiveness. Light ecstasy users generally produced intermediate scores, with significantly higher scores than controls on two factors and significantly lower scores than heavy ecstasy users on another two. Previous reports have described various psychiatric and psychobiological disorders in recreational ecstasy users, but it is not known how typical they are, being mainly based on individual case studies. This is the first study to describe psychological problems in a non clinical sample of young recreational ecstasy users. However, our ecstasy users were polydrug users, with both groups showing significantly greater usage of amphetamine, LSD and cocaine, than the controls. These other illicit drugs probably contributed to their adverse psychobiological profiles, while there is also the possibility of pre-existing differences between ecstasy users and non users. However, since repeated MDMA can cause serotonergic neurotoxicity in laboratory animals and man, these problems may reflect reduced serotonin activity induced by regular ecstasy use.

Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity.

AimsNot every tablet sold as “ecstasy” contains MDMA (3,4-methylenedioxymethamphetamine). The historical origins and evolution of this mismatch will be reviewed, in order to estimate the proportions of ecstasy tablets containing MDMA at different periods over the past 30 years.MethodsSurveys into the pharmacological constituents of ecstasy tablets, dosage levels, and empirical reports of their perceived purity, provide the main data for this review.ResultsDuring the 1980s and early 1990s there were few problems with the purity of ecstasy tablets, and the biochemical evidence shows that they nearly always contained MDMA. During the mid-1990s, the majority of ecstasy tablets continued to contain MDMA, while many others comprised MDA (3,4-methylenedioxyamphetamine), MDEA (3,4-methylenedioxyethylamphetamine), or amphetamine drug mixtures. However, a small proportion (4–20% according to survey, time and place), comprised non-amphetamine drugs such as caffeine, ephedrine, ketamine, paracetamol, or placebo. During the late 1990s, the proportion of ecstasy tablets containing MDMA increased to around 80–90%. The latest reports suggest that non-MDMA tablets are now very infrequent, with purity levels between 90% and 100%. Dosage levels of tablets are also highly variable, with low dose tablet often encountered during the mid-1990s, and high dose tablets now seen more frequently. The theoretical and practical implications of these findings will be debated.ConclusionsThe ecstasy purity problem was predominantly a phenomenon of the mid to late 1990s, when many tablets contained substances other than MDMA. Before and since then, the proportion of ecstasy tablets containing MDMA has been very high.

Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy

This review of chronic tolerance to MDMA (3,4-methylenedioxymetamphetamine) covers the empirical data on dosage escalation, reduced subjective efficacy and bingeing in recreational Ecstasy users. Novice users generally take a single Ecstasy tablet, regular users typically take 2-3 tablets, whereas the most experienced users may take 10-25 tablets in a single session. Reduced subjective efficacy following repeated usage is typically described, with many users subjectively reporting the development of tolerance. Intensive self-administration or bingeing is often noted by experienced users. This can comprise ‘stacking’ on several tablets together, and ‘boosting’ on successive doses over an extended period. Some experienced users snort Ecstasy powder nasally, whereas a small minority inject MDMA. Chronic tolerance and bingeing are statistically linked to higher rates of drug-related psychobiological problems. In terms of underlying mechanisms, neuroadaptive processes are certainly involved, but there is a paucity of evidence on hepatic and behavioural mechanisms. Further studies specifically designed to investigate chronic tolerance, involving low intermittent dose regimens, are required. Most animal research has involved intensive MDMA dosing regimens designed to engender serotonergic neurotoxicity, and this may comprise another underlying mechanism. If distal serotonin axon terminal loss was also developing in recreational users, it may help to explain why reducing subjective efficacy, dosage escalation and increasing psychobiological problems often develop in parallel. In conclusion, there is extensive evidence for chronic pharmacodynamic tolerance to recreational Ecstasy/MDMA, but the underlying mechanisms are currently unclear. Several traditional processes are probably involved, but one of the possible causes is a novel mechanism largely unique to the ring substituted amphetamine derivatives, namely serotonergic neurotoxicity.

Human Research on MDMA (3,4-Methylene- dioxymethamphetamine) Neurotoxicity: Cognitive and Behavioural Indices of Change

Laboratory animals can develop serotonergic neurotoxicity after repeated doses of 3,4-methylenedioxymethamphetamine (MDMA) or ‘Ecstasy’. If similar neural damage occurs in humans, this may be evident in cognitive or behavioural impairments. In a review of the behavioural skills shown by drug-free recreational Ecstasy users, three aspects of cognitive performance are often affected: reduced memory for new information (Rivermead Behavioral Memory, supraspan word recall), impaired higher executive processing (Wisconsin Card Sort, Tower of London), and heightened impulsivity (Impulsiveness, Venturesomeness and Empathy Questionnaire, Matching Familiar Figures test). Performance on other more basic cognitive functions is generally unimpaired (simple reaction time, choice reaction time, number vigilance, Stroop, trail making). Some Ecstasy users also complain of poor memories and/or concentration difficulties, which they attribute to MDMA use. There are many methodological problems and uncertainties with research in this field: non-random allocation of subjects to drug conditions, the deleterious effects of other psychoactive drugs, and the possibility that these adverse profiles reflect pre-existing personality characteristics in Ecstasy users. However, this particular pattern of cognitive decrements in humans, is consistent with the animal data on those brain areas showing serotonergic damage following MDMA: the frontal cortex (impulsivity and higher cognitive impairments), and hippocampus (memory deficits). Finally, this profile of cognitive deficits is also consistent with a hypothetical integrative construct: namely reduced cortical inhibition.

MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress

Many recreational ecstasy/MDMA users display neuropsychobiological de.cits, whereas others remain problem free. This review will investigate some of the drug and non-drug factors which in.uence the occurrence of these de.cits. Acute and chronic MDMA usage are both important. Intensive use within a session is often associated with more problems. In term of lifetime usage, novice users generally remain unimpaired, whereas most heavy users report memory or other psychobiological problems which they attribute to ecstasy. These complaints are con.rmed by objective de.cits in working memory, attention, frontal-executive, and episodic memory tasks. Psychobiological de.cits include disturbed sleep, sexual dysfunction, reduced immuno-competence, and increased oxidative stress. Further MDMA-related factors which may contribute to these changes, include acute and chronic tolerance, and drug dependence. Around 90ñ95% of ecstasy/MDMA users also take cannabis, and this can independently contribute to the adverse neuropsychobiological pro.les; although in some situations the acute co-use of these two drugs may be interactive rather than additive, since cannabis has relaxant and hypothermic properties. Alcohol, nicotine, amphetamine, and other drugs, can also affect the psychobiological pro.les of ecstasy polydrug users in complex ways. Pure MDMA users are rare but they have been shown to display signi.cant neurocognitive de.cits. Psychiatric aspects are debated in the context of the diathesisstress model. Here the stressor of ecstasy polydrug drug use, interacts with various predisposition factors (genetic, neurochemical, personality), to determine the psychiatric outcome. Recreational MDMA is typically taken in hot and crowded dances/raves. Prolonged dancing, feeling hot, and raised body temperature, can also be associated with more psychobiological problems. This is consistent with the animal literature, where high ambient temperature and other metabolic stimulants boost the acute effects of MDMA, and cause greater serotonergic neurotoxicity. In conclusion, the neuropsychobiological effects of MDMA are modulated by a wide range of drug and non-drug factors. These multiple in.uences are integrated within a bioenergetic stress model, where factors which heighten acute metabolic distress lead to more neuropsychobiological problems.

Ecstasy (MDMA) in Recreational Users: Self-Reported Psychological and Physiological Effects

Twenty recreational drug users were asked to describe the psychological and physiological effects they experienced under MDMA (3,4‐methylenedioxymethamphetamine). The subjects comprised 11 males and nine females, in the age range 18–31 years. Five subjects had taken MDMA once, nine had taken it 2–9 times, while six subjects had taken it +10 times. Each subject completed a modified Profile of Mood States Questionnaire (POMS), an Ecstasy Effect Questionnaire, and a structured interview, covering past experience with MDMA. Increased feelings of elation, agreeableness, energy, and mental confusion were reported on‐drug (p < 0·001), together with faster heart rate, feeling hot, increased sweating and dehydration, dilated pupils, and tight jaw (trismus). Coming off‐Ecstasy led to feelings of lethargy, moodiness, insomnia, depression, irritability, and paranoia. Bad MDMA trips were reported by 25 per cent of the sample, following a variety of unpleasant experiences. Chronic pharmacodynamic tolerance was not apparent, since although regular users all described their first MDMA experience as ‘the most intense’, later trips were affected by knowledge and expectancy, rather than any diminution in drug response. Acute pharmacodynamic tolerance was, however, evident, with a period between drugs being described as necessary in order to maintain drug effectiveness. This may help explain the low addiction potential of MDMA.

MDMA (3,4-Methylenedioxymethamphetamine) or Ecstasy: The Neuropsychobiological Implications of Taking It at Dances and Raves

MDMA (3,4-methylenedioxymethamphetamine) or ‘ecstasy’ is a ring-substituted amphetamine derivative, which is widely used as a recreational drug, most particularly at dances and raves. Around 80–95% of dancers/ravers report using ecstasy/MDMA, compared to 5–15% of young people in general. This paper will consider the possible contribution of stimulatory environmental conditions to the neuropsychobiological effects of MDMA. Animal research shows that heat and crowding potentiate the acute effects of MDMA. Social interaction and intravenous drug self-administration in laboratory rats are significantly enhanced when MDMA is given under hot ambient temperatures. Loud noise and physical activity can also contribute to the general overarousal. Furthermore, MDMA impairs homeostatic thermal control in rats, leading them to overheat in hot environments. The human implications of these findings are that the hot, noisy and overcrowded conditions at raves may be providing the ideal environment to heighten the acute drug response. In recreational users, the acute medical dangers of MDMA comprise a constellation of hyperthermia-related abreactions, which generally only occur when it has been taken in hot and crowded environments. MDMA is well established as a serotonergic neurotoxin in laboratory animals, but heat and overcrowding increase the degree of distal axon terminal loss. If this also occurs in humans, then the stimulatory environments of clubs and raves may heighten the likelihood of adverse neuropsychological sequelae in recreational ecstasy users. Consistent with this prediction, the extent of self-reported dancing/exercise when on MDMA has recently been shown to be associated with significantly more psychobiological problems afterwards.

Cigarette Smoking and Abstinence: Comparative Effects Upon Cognitive Task Performance and Mood State over 24 Hours

Twenty regular smokers were assessed over 24‐h of normal cigarette smoking, and an equivalent period of abstinence. In both conditions, a non‐deprived baseline was followed by performance tests 2, 6 and 24 h later, while subjective feelings were assessed every 2 h. Compared to normal smoking, abstinence led to reduced heart rate, worse task performance, feelings of depression, stress, irritability, restlessness, poor concentration, and urges to smoke. Letter cancellation and number vigilance task performance were significantly poorer after 2 and 6 h of abstinence. Subjective feeling states were significantly worse after 4 h of abstinence, and became increasingly impaired over the rest of the day. However many abstinence symptoms (except heart rate), were reduced in severity at the 24‐h session, held on the morning of the following day. This suggests that many of the psychological effects of smoking abstinence, may build‐up afresh each day.

Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research

This paper aimed to review how scientific knowledge about the human psychobiology of MDMA has developed over time.