Increased cortisol levels in hair of recent Ecstasy/MDMA users.

Previous research has revealed an acute 8-fold increase in salivary cortisol following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not known to what extent repeated usage impacts upon activity of the hypothalamic-pituitary-adrenal axis over a more prolonged period of time. This study investigated the integrated cortisol levels in 3-month hair samples from recent Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants (53 males, 48 females; mean age 21.75 years) completed the University of East London recreational drug use questionnaire, modified to cover the past 3-months of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3 months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair cortisol levels were observed to be significantly higher in recent heavy MDMA users (mean = 55.0 ± 80.1 pg/mg), compared to recent light MDMA users (19.4 ± 16.0 pg/mg; p=0.015), and to non-users (13.8 ± 6.1 pg/mg; p<0.001). Hence the regular use of Ecstasy/MDMA was associated with almost 4-fold raised hair cortisol levels, in comparison with non-user controls. The present results are consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts that repeated stimulant drug use may increase cortisol production acutely, and result in greater deposits of the hormone in hair. These data may also help explain the neurocognitive, psychiatric, and other psychobiological problems of some abstinent users. Future study design and directions for research concerning the psychoneuroendocrinological impact of MDMA are also discussed.

MDMA and temperature: a review of the thermal effects of 'Ecstasy' in humans.

AIMS: To review the thermal effects of MDMA in humans, and discuss the practical implications. METHODS: The literature on Ecstasy/MDMA, body temperature, and subjective thermal self-ratings was reviewed, and explanatory models for the changes in thermal homeostasis were examined and debated. RESULTS: In human placebo-controlled laboratory studies, the effects of MDMA were dose related. Low doses had little effect, moderate doses increased body temperature by around +0.4°C, and higher doses caused a mean increase of +0.7°C. With Ecstasy/MDMA using dance clubbers, the findings showed greater variation, due possibly to uncontrolled factors such as physical activity, ambient temperature, and overcrowding. Some real world studies found average body temperature increases of over +1.0°C. Thermal homeostasis involves a balance between heat production and heat dissipation, and MDMA affects both aspects of this homeostatic equation. Cellular metabolic heat output is increased, and heat dissipation mechanisms are stressed, with the onset of sweating delayed. Subjective responses of 'feeling hot' or 'hot-cold flushes' are frequent, but can show individual variation. Some recreational users report that heat increases or reinstates the positive mood effects of Ecstasy/MDMA. The dangers of acute hyperthermia can include rare fatalities. It is unclear why moderate hyperthermia can occasionally progress to severe hyperpyrexia, although it may reflect a combination or cascade of events. In chronic terms, the bioenergetic stress model notes that the adverse psychobiological effects of MDMA are heightened by various co-stimulatory factors, including heat stress. CONCLUSIONS: MDMA increases core body temperature and thermal stress in humans.

Hair MDMA samples are consistent with reported ecstasy use: findings from a study investigating effects of ecstasy on mood and memory.

AIMS: Our group has conducted several Internet investigations into the biobehavioural effects of self-reported recreational use of MDMA (3,4-methylenedioxymethamphetamine or Ecstasy) and other psychosocial drugs. Here we report a new study examining the relationship between self-reported Ecstasy use and traces of MDMA found in hair samples. METHODS: In a laboratory setting, 49 undergraduate volunteers performed an Internet-based assessment which included mood scales and the University of East London Drug Use Questionnaire, which asks for history and current drug use. They also provided a hair sample for determination of exposure to MDMA over the previous month. RESULTS: Self-report of Ecstasy use and presence in hair samples were consistent (p < 0.00001). Both subjective and objective measures predicted lower self-reported ratings of happiness and higher self-reported stress. Self-reported Ecstasy use, but not presence in hair, was also associated with decreased tension. CONCLUSION: Different psychoactive drugs can influence long-term mood and cognition in complex and dynamically interactive ways. Here we have shown a good correspondence between self-report and objective assessment of exposure to MDMA. These data suggest that the Internet has potentially high utility as a useful medium to complement traditional laboratory studies into the sequelae of recreational drug use.

Cortisol and 3,4-methylenedioxymethamphetamine: neurohormonal aspects of bioenergetic stress in ecstasy users.

AIMS: 3,4-Methylenedioxymethamphetamine (MDMA) can affect both neurotransmitter and neurohormonal activity. This review will debate the role of the metabolic activation hormone cortisol for the psychobiological effects of ecstasy/MDMA. METHODS: The empirical literature on cortisol release following acute MDMA administration and cortisol functioning in drug-free recreational ecstasy/MDMA users will be reviewed. This will be followed by an overview of cortisol as a bioenergetic stress neurohormone, and a debate on how it could be modulating the acute and chronic psychobiological effects of MDMA. RESULTS: Cortisol release is increased by stimulatory factors, including physical activity, thermal stress and stimulant drugs. In laboratory studies MDMA leads to an acute cortisol increase of around 150% in sedentary humans. In MDMA-using dance clubbers, the cortisol levels are increased by around 800%, possibly due to the combined factors of stimulant drug, physical exertion and psychosocial stimulation. Regular ecstasy/MDMA users also demonstrate changes in baseline cortisol levels and cortisol reactivity, with compromised hypothalamic-pituitary-adrenal activity. Nonpharmacological research has shown how cortisol is important for psychological aspects such as memory, cognition, sleep, impulsivity, depression and neuronal damage. These same functions are often impaired in recreational ecstasy/MDMA users, and cortisol may be an important modulatory co-factor. CONCLUSIONS: The energizing hormone cortisol is involved in the psychobiology of MDMA, probably via its effects on energy metabolism. Acute cortisol release may potentiate the stimulating effects of MDMA in dance clubbers. Chronically, cortisol may contribute to the variance in functional and structural consequences of repeated ecstasy usage.

Cannabis and Ecstasy/ MDMA: empirical measures of creativity in recreational users.

This study investigated the associations between chronic cannabis and Ecstasy/MDMA use and one objective and two subjective measure of creativity. Fifteen abstinent Ecstasy users, 15 abstinent cannabis users, and 15 nondrug-user controls, completed three measures of creativity: the Consequences behavioral test of creativity, self-assessed performance on the Consequences test, and Gough's Trait Self-Report Creative Adjective Checklist. The Consequences test involved five scenarios where possible consequences had to be devised; scoring was conducted by the standard blind rating (by two independent judges) for "remoteness" and "rarity," and by a frequency and rarity of responses method. Cannabis users had significantly more "rare-creative" responses than controls (Tukey, p < 0.05); this effect remained significant with gender as a covariate. There were no significant differences between the groups on the number of standard scoring "remote-creative" ideas or for fluency of responses. On self-rated creativity, there was a significant ANOVA group difference (p < 0.05), with Ecstasy users tending to rate their answers as more creative than controls (Tukey comparison; p = 0.058, two-tailed). Ecstasy users did not differ from controls on the behavioral measures of creativity, although there was a borderline trend for self-assessment of greater creativity. Cannabis users produced significantly more "rare-creative" responses, but did not rate themselves as more creative.

Dance clubbing on MDMA and during abstinence from Ecstasy/MDMA: prospective neuroendocrine and psychobiological changes.

BACKGROUND/AIMS: The present study is the first to prospectively compare a group of recreational Ecstasy users when dance clubbing on 3,4-methylenedioxymethamphetamine (MDMA) and when clubbing during abstinence from Ecstasy/MDMA. METHODS: Twelve normal healthy volunteers (mean age = 23.2 years) were assessed at a Saturday night dance club under self-administered MDMA. On the other weekend they went to the same dance club without taking MDMA (order counterbalanced). Both conditions involved 5 test sessions conducted at similar times: pre-drug baseline, 1 h post-drug clubbing, 2.5 h post-drug clubbing, and 2 and 4 days later. The assessments included body and ambient temperature, physical activity (pedometer), as well as self-ratings for mood state, physical activity, thermal comfort and thirst. Saliva samples were analyzed for MDMA, cortisol and testosterone. RESULTS: The cortisol levels increased significantly by 800% when dance clubbing on MDMA, while testosterone increased significantly by 75%; neither neuroendocrine measure was altered during abstinence. Saliva analyses confirmed the presence of MDMA when dancing on Ecstasy and its absence when dancing off Ecstasy. The pedometer values and self-rated levels of dancing were similar at both weekends. Hot and cold flushes and feeling hot increased significantly under MDMA. The mean body temperature did not change significantly, although there was a borderline trend for increased values after MDMA. Feelings of happiness and excitement increased under MDMA, although they were not significantly greater than when clubbing during abstinence. CONCLUSIONS: Neurohormonal release may be an important part of the acute MDMA experience. The large cortisol increase provides further data on the bioenergetic stress model of recreational Ecstasy/MDMA.

Cannabis and Ecstasy/MDMA (3,4-methylenedioxymethamphetamine): an analysis of their neuropsychobiological interactions in recreational users.

The majority of recreational Ecstasy/MDMA users (90-98%) also take cannabis. This co-drug usage is often viewed as a methodological confound, which needs to be removed statistically. Here we take a rather different approach, and debate the potential complexities of their psychobiological interactions. The ring-substituted amphetamine derivate MDMA (3,4-methylendioxymethamphetmaine, or 'Ecstasy') is a powerful CNS stimulant, whereas cannabis is a relaxant. Their co-usage may reflect opposing effects in three psychobiological areas: arousal, body temperature, and oxidative stress. Firstly MDMA is alerting whereas cannabis is sedating. Secondly MDMA is hyperthermic whereas cannabis is hypothermic. Thirdly MDMA increases oxidative stress whereas cannabinoids are antioxidant. Hence cannabis may modulate the acute and sub-acute reactions to MDMA, reduce the acute hyperthermia induced by MDMA, and ameliorate the oxidative stress caused by MDMA. The limited empirical evidence on each topic will be critically examined. In terms of chronic effects each drug is functionally damaging, so that polydrug users generally display cumulative neurobiological impairments. However in certain aspects their neuropsychobiological effects may interactive rather than additive. In particular, the combined use of cannabis and MDMA may have rather different neuropsychobiological implications, than their separate usage. In order to investigate these potential complexities, future research will need better empirical data on the exact patterns of co-drug usage.

The psychotherapeutic potential of MDMA (3,4-methylenedioxymethamphetamine): an evidence-based review.

UNLABELLED: AIMS AND RATIONALE: The purpose of this study was to review whether methylenedioxymethamphetamine (MDMA) has the appropriate pharmacodynamic profile to be a therapeutic agent. MATERIALS AND METHODS: Empirical descriptions of MDMA's subjective effects in humans will be reviewed to evaluate the proposal that MDMA has psychotherapeutic properties. The focus will be published evidence on its functional effects in therapeutic, medical, and other situations. RESULTS: MDMA is a powerful central nervous system (CNS) stimulant which affects several neurotransmitter systems and intensifies a range of psychobiological functions. Its acute mood effects can be very positive and life enhancing, and the affirmative cognitions engendered during MDMA therapy may well endure afterwards. However, MDMA also has a number of potential anti-therapeutic characteristics. Acutely, it can also intensify negative cognitions, and these may similarly endure over time. Psychotherapists have found that setting, intention, and expectancy are crucial for a positive outcome, but these factors cannot be guaranteed. Post-MDMA, there is a period of neurotransmitter recovery when low moods predominate, and these may exacerbate psychiatric distress. The explanations proposed for MDMA-assisted therapy are all psychodynamic, and a neurochemical model needs to be outlined. It has been suggested that enduring therapeutic gains can follow a single session, but again, this lacks a clear psychopharmacological rationale. Finally, diathesis-stress models suggest that psychiatric individuals are more prone to acute and chronic abreactions to CNS stimulants such as MDMA. CONCLUSIONS: There are a number of issues which need to be addressed before it can be argued that MDMA might be clinically useful for psychotherapy.

Dancing hot on Ecstasy: physical activity and thermal comfort ratings are associated with the memory and other psychobiological problems reported by recreational MDMA users.

BACKGROUND: Non-drug factors such as ambient temperature can heighten the adverse effects of MDMA (3,4-methylendioxymethamphetamine) in animals. We assessed whether dancing and feeling hot on Ecstasy would be associated with more psychobiological problems in recreational users. METHODS: In an internet study, 206 unpaid participants (modal age 16-24) reported that they had used recreational Ecstasy/MDMA. They completed a drug use questionnaire, the Prospective Memory Questionnaire (PMQ), questions about dancing and feeling hot when on Ecstasy, and psychobiological problems afterwards. RESULTS: Those who danced 'all the time' when on Ecstasy, reported significantly more PMQ memory problems than the less intensive dancers. Prolonged dancing was also associated with more complaints of depression, memory problems, concentration and organizational difficulties afterwards. Feeling hot when on Ecstasy was associated with poor concentration in the comedown period, and with mood fluctuation and impulsivity off-drug. PMQ long-term problems demonstrated a significant curvilinear relationship with thermal self-ratings; more memory problems were noted by those who felt very hot, and by those who did not feel hot when on Ecstasy. CONCLUSIONS: Non-drug factors such as dancing and feeling hot are associated with the incidence of psychobiological problems reported by recreational Ecstasy/MDMA users.

Problematic versus non-problematic ecstasy/MDMA use: the influence of drug usage patterns and pre-existing psychiatric factors.

Recreational ecstasy (3,4-methylenedioxymethamphetamine; MDMA) use has been increasingly associated with a number of psychiatric symptoms and psychological problems. However, previous studies assessing possible psychopathological effects have not identified whether users consider their ecstasy use "problematic" or not. In addition, research has generally failed to address the potential role of premorbid psychiatric status. This study aimed to assess whether premorbid psychiatric history and/or patterns of ecstasy use would be associated with the degree of self-reported problems attributable to ecstasy. Problematic ecstasy users (n = 53) who had reported problems attributable to their ecstasy use were compared with non-problematic ecstasy users (n = 62), polydrug controls (n = 62) and illegal drug-naive controls (n = 111) on a recreational drug use questionnaire; a questionnaire, which ascertained personal and family psychiatric histories, and the Brief Symptom Inventory (BSI). Problematic ecstasy users exhibited significantly higher scores on a number of dimensions of the BSI compared to illegal drug-naive and/or polydrug controls. Problematic ecstasy users also exhibited significantly elevated scores on somatization, depression, anxiety and negative psychobiology compared to non-problematic ecstasy users. BSI scores for the non-problematic ecstasy users did not differ from polydrug or illegal drug-naive controls. Problematic ecstasy users reported significantly higher levels of ecstasy use, including lifetime consumption, average dosage and binge consumption compared to non-problematic ecstasy users. Additionally, a greater number of problematic ecstasy users reported personal and family psychiatric histories compared to controls and non-problematic ecstasy users. This study demonstrates two distinct ecstasy using groups: non-problematic ecstasy users who are not showing signs of psychopathology and problematic ecstasy users who are showing evidence of a range of symptoms. This data therefore partially supports the link between ecstasy dosage and negative psychological sequelae, but highlights the importance of the need to consider ecstasy-related attributions, pre-existing mental health status and vulnerability.

Self-rated everyday and prospective memory abilities of cigarette smokers and non-smokers: a web-based study.

The present study examined self-ratings of two aspects of everyday memory performance: long-term prospective memory-measured by the prospective memory questionnaire (PMQ), and everyday memory-measured by the everyday memory questionnaire (EMQ). Use of other substances was also measured and used as covariates in the study. To ensure confidentiality and to expand the numbers used in previous studies, an Internet study was carried out and data from 763 participants was gathered. After controlling for other drug use and strategy use, the data from the PMQ revealed that smokers reported a greater number of long-term prospective memory errors than non-smokers. There were also differences between light and heavier smokers in long-term prospective memory, suggesting that nicotine may have a dose-dependent impact upon long-term prospective memory performance. There was also a significant ANOVA group effect on the EMQ, although the trend for more memory errors amongst the heavier smokers was statistically only borderline (p=.057). These findings suggest there are selective memory deficits associated with smoking and that long-term prospective memory deficits should be added to the growing list of problems associated with cigarette use.

Pattern of cannabis use in ecstasy polydrug users: moderate cannabis use may compensate for self-rated aggression and somatic symptoms.

Cannabis is one of the most common 'co-drugs' for ecstasy users. The aim of the present study was to explore self-reported psychobiological problems in ecstasy polydrug users in relation to their pattern of cannabis use. Two hundred and eighty ecstasy polydrug users were allocated into five cannabis groups according to the frequency of their cannabis use. The control group comprised 121 alcohol-tobacco users. There were no significant group differences with regard to age, diagnosed family psychiatric history and level of self-rated stress experienced during 6 months prior to the study. The present study produced three main findings: (a) Ecstasy users with no concomitant use of cannabis displayed more self-rated aggression and somatic symptoms compared with ecstasy users who were smoking cannabis on a monthly or weekly basis. (b) Ecstasy users who reported heavy cannabis use in the past displayed higher paranoid symptoms compared with ecstasy weekly and daily cannabis users. (c) Former heavy cannabis users were the most likely to complain of a variety of ecstasy related long-term problems. In conclusion, moderate cannabis use may help to ameliorate or mask MDMA-induced aggressivity and somatic symptoms. However, this study confirms that heavy cannabis and ecstasy use is associated with several psychobiological problems, which may emerge after a period of abstinence from both drugs.

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.