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CORK Bibliography: The Dissociative Drugs (ketamine, gamma-hydroxybutyrate, ecstasy)

86 citations. January 2011 to present

Prepared: March 2012

Abdon JG; Wallin E; Andreasson S. The "Clubs against Drugs" program in Stockholm, Sweden: Two cross-sectional surveys examining drug use among staff at licensed premises. Substance Abuse, Treatment, Prevention and Policy 6: article 2, 2011. (38 refs.)

Background: The objective of this study is to examine self-reported drug use among staff at licensed premises, types of drugs used, attitudes towards drugs, and observed drug use among guests. Results are presented from two measurement points (in 2001 and 2007/08). This study was carried out within the framework of the "Clubs against Drugs" program, which is a community-based multi-component intervention targeting licensed premises in Stockholm, Sweden. Methods: Two cross-sectional surveys were conducted, the first in 2001 and the second in 2007/08. Staff at licensed premises attending server training were asked to participate in the anonymous survey. A survey was administered in a classroom setting and consisted of four sections: 1) demographics, 2) respondents' own drug use experience, 3) respondents' attitudes towards drug use, and 4) observed drug use among guests at licensed premises. Results: Data were collected from 446 staff in 2001 and 677 staff in 2007/08. The four most commonly used drugs among staff were cannabis, cocaine, amphetamine, and ecstasy. The highest rates of drug use were reported by staff in the two youngest age groups, i.e., those younger than 25 and those between the ages of 25 and 29. In 2007/08 staff reported significantly lower rates of drug use than staff in 2001. Last year drug use for the sample in 2007/08 was 19% compared to 27% for the 2001 sample. While drug-using staff compared to non drug-using staff reported more observations of drug use among guests, they were less inclined to intervene. Overall, staff reported restrictive attitudes towards drugs. Conclusions: The prevalence of life-time and last year drug use among staff at licensed premises is high compared to the general population in Sweden. Lower rates of self-reported drug use among staff were reported in 2007/08. The results of this study highlight that staff at licensed premises represent an important target population in club drug prevention programs.

Andolfatto G; Willman E. A prospective case series of single-syringe ketamine-propofol (Ketofol) for emergency department procedural sedation and analgesia in adults. Academic Emergency Medicine 18(3): 237-245, 2011. (52 refs.)

Objectives: The objective was to evaluate the effectiveness, recovery time, and adverse event profile of intravenous (IV) mixed 1:1 ketamine-propofol (ketofol) for adult procedural sedation and analgesia (PSA) in the emergency department (ED). Methods: Prospective data were collected on all PSA events over a 4.5-year period in a trauma-receiving suburban teaching hospital. PSAs using a 1:1 single-syringe mixture of 10 mg/mL ketamine and 10 mg/mL propofol in patients over 21 years of age were analyzed. Physiologic data, drug doses, adverse events, recovery time, patient satisfaction, and staff satisfaction were recorded. Results: Ketofol PSA was used in 728 patients for primarily orthopedic procedures. Median patient age was 53 years (range = 21 to 99 years, interquartile range [IQR] = 36-70 years). The median dose of ketamine and propofol was 0.7 mg/kg each (range = 0.2 to 2.7 mg/kg, IQR = 0.5-0.9 mg/kg), and median recovery time was 14 minutes (range = 3 to 50 minutes, IQR = 10-17 minutes). PSA was effective in 717 cases (98%). Bag-mask ventilation occurred in 15 patients (2.1%; 95% confidence interval [CI] = 1.0% to 3.1%). Recovery agitation occurred in 26 patients (3.6%; 95% CI = 2.2% to 4.9%), of whom 13 (1.8%; 95% CI = 0.8% to 2.7%) required treatment. One patient experienced vomiting and one patient was admitted to the hospital for monitoring of transient dysrhythmia and hypotension. No sequelae were identified. The median staff satisfaction scores were 10 (IQR = 9-10) on a scale of 1 to 10, and 97% of patients would have chosen the same method of PSA in the future. Conclusions: Ketofol is an effective PSA agent in adult ED patients. Recovery times are short and adverse events are few. Patients and ED staff were highly satisfied.

Arendt M; Munk-Jorgensen P; Sher L; Jensen SOW. Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: A nationwide follow-up study of Danish substance users in treatment. Drug and Alcohol Dependence 114(2-3): 134- 139, 2011. (74 refs.)

This is a register-based cohort study of 20,581 individuals in treatment for illicit substance use disorders in Denmark between 1996 and 2006. All in all, 1441 deaths were recorded during 111,445 person-years of follow-up. Standardized mortality ratios (SMRs) associated with different primary substance types were calculated and Cox-regression analyses were performed in order to establish hazard ratios (HR) associated with injection drug use and psychiatric comorbidity. SMRs for primary users of specific substances were: cannabis: 4.9 (95% confidence interval (Cl): 4.2-5.8), cocaine: 6.4 (Cl: 3.9-10.0), amphetamine: 6.0 (Cl: 4.2-8.3), heroin: 9.1 (Cl: 8.5-9.8), and other opioids 7.7 (Cl: 6.6-8.9). For MDMA ('ecstasy') the crude mortality rate was 1.7/1000 person-years (Cl: 0.4-7.0) and the SMR was not significantly elevated. Injection drug use was associated with significantly increased hazard ratios in users of opioids and cocaine/amphetamine. Overall, psychiatric comorbidity was not associated with increased mortality (HR: 1.1 [Cl: 0.9-1.2], p = .28), but an association was found specifically among cocaine/amphetamine users (HR: 3.6 [Cl: 2.1-6.4], p <.001).

Arroyo-Novoa CM; Figueroa-Ramos MI; Miaskowski C; Padilla G; Paul SM; Rodriguez-Ortiz P et al. Efficacy of small doses of ketamine with morphine to decrease procedural pain responses during open wound care. Clinical Journal of Pain 27(7): 561-566, 2011. (32 refs.)

Objective: The purpose of this study was to evaluate differences in pain intensity, pain quality, physiological measures, and adverse effects when patients received morphine with saline (MS) compared with morphine and a small dose of ketamine (MK) before an open wound care procedure (WCP). Methods: A randomized, cross-over design was used to determine whether the addition of a small dose of ketamine would potentiate morphine's analgesic effects and decrease WCP pain intensity. Patients were randomized to receive either 0.1 mg/kg of morphine (8 mg maximum) plus saline intravenously (IV) or 0.05 mg/kg of morphine (4 mg maximum) plus ketamine 0.25 mg/kg IV before the WCP. Patients were crossed-over to receive the alternate treatment during the next WCP. Results: Eleven male patients participated in the study. Mean rank of pain intensity during WCP-MK was significantly less than during WCP-MS (P = 0.005). Mean +/- standard error of mean pain intensity during the WCP-MK was 3.09 +/- 0.99, whereas it was 6.82 +/- 0.92 during the WCP-MS. However, 91% of the patients had adverse effects (eg, strange sensations, hallucinations, blurred vision) with MK versus 0% with MS. Diastolic blood pressure was significantly higher during the WCP-MK. Discussion: Ketamine with morphine significantly reduced procedural wound pain intensity during WCP. Adverse effects and higher diastolic BP occurred with MK. Further research is warranted to determine the optimal analgesic dose of ketamine or if the addition of a benzodiazepine would mitigate the psychotomimetic effects of ketamine.

Brown PC; Alfonso J; Dunn ME. Gamma hydroxybutyrate use: Exploring the influence of outcome expectancies through memory modeling. American Journal on Addictions 20(2): 127-136, 2011. (64 refs.)

Gamma hydroxybutyrate (GHB) has been linked to overdose, criminal surreptitious administration, the need for emergency medical care, and fatalities worldwide. To begin to identify and understand the motivational factors that lead to the use of GHB, the present investigation utilized methods that have been successful in identifying potential expectancy targets and have been incorporated into prevention and intervention strategies successful in reducing high-risk alcohol use. In the present investigation, GHB expectancies were elicited from 926 voluntary participants aged 18-60 at a university in the southeastern United States to develop the GHB Expectancy Questionnaire (GHBEQ). The GHBEQ was subsequently administered to a different sample of 1,373 participants aged 18-55 in order to empirically derive the possible organization of GHB expectancies in memory, including likely paths of GHB expectancy activation. Findings suggest differences in GHB expectancies based on use history and sex. These results can be used to understand differences in GHB use for men and women, and to develop expectancy-based prevention and intervention programing to prevent and reduce its use in high-risk populations.

Burgess AP; Venables L; Jones H; Edwards R; Parrott AC. Event related potential (ERP) evidence for selective impairment of verbal recollection in abstinent recreational methylenedioxymethamphetamine ("Ecstasy")/polydrug users. Psychopharmacology 216(4): 545-556, 2011. (39 refs.)

Ecstasy is a recreational drug whose active ingredient, 3,4-methylenedioxymethamphetamine (MDMA), acts predominantly on the serotonergic system. Although MDMA is known to be neurotoxic in animals, the long-term effects of recreational Ecstasy use in humans remain controversial but one commonly reported consequence is mild cognitive impairment particularly affecting verbal episodic memory. Although event-related potentials (ERPs) have made significant contributions to our understanding of human memory processes, until now they have not been applied to study the long-term effects of Ecstasy. The aim of this study was to examine the effects of past Ecstasy use on recognition memory for both verbal and non-verbal stimuli using ERPs. We compared the ERPs of 15 Ecstasy/polydrug users with those of 14 cannabis users and 13 non-illicit drug users as controls. Despite equivalent memory performance, Ecstasy/polydrug users showed an attenuated late positivity over left parietal scalp sites, a component associated with the specific memory process of recollection. This effect was only found in the word recognition task which is consistent with evidence that left hemisphere cognitive functions are disproportionately affected by Ecstasy, probably because the serotonergic system is laterally asymmetrical. Experimentally, decreasing central serotonergic activity through acute tryptophan depletion also selectively impairs recollection, and this too suggests the importance of the serotonergic system. Overall, our results suggest that Ecstasy users, who also use a wide range of other drugs, show a durable abnormality in a specific ERP component thought to be associated with recollection.

Cagnin A; Pompanin S; Manfioli V; Briani C; Zambon A; Saladini M et al. gamma-Hydroxybutyric acid-induced psychosis and seizures. Epilepsy & Behavior 21(2): 203-205, 2011. (7 refs.)

Disulfiram and gamma-hydroxybutyric acid (GHB) are used to treat alcohol dependence and may both increase dopamine brain levels and modulate GABAergic transmission. We describe a patient affected by bipolar disorder (on valproate as mood-stabilizing treatment) and alcohol dependence who developed a disulfiram-induced hypomanic episode and in whom the switch from disulfiram to GHB induced recurrent convulsive seizures, not responsive to treatment with diazepam, and psychosis. Seizures and psychiatric symptoms ceased after GHB discontinuation. We outline the deregulation of the neurotransmitter systems (GABAergic and dopaminergic networks) that are involved in these drug-drug interactions and that might be responsible for both psychosis and generalized tonic-clonic seizures resistant to standard treatments.

Calafat A; Blay NT; Hughes K; Bellis M; Juan M; Duch M et al. Nightlife young risk behaviours in Mediterranean versus other European cities: are stereotypes true? European Journal of Public Health 21(3): 311-315, 2011. (25 refs.)

Background: Mediterranean lifestyle has long been hailed as protective against certain risk behaviours and diseases. Mediterranean drinking patterns of moderate alcohol consumption as part of daily life have often been assumed to protect young people from harmful alcohol consumption, in contrast to Northern European drinking patterns. Nightlife environments are strong related to alcohol and drugs use, and other health risk behaviours but few cross-national studies have been undertaken amongst young Europeans frequenting bars and nightclubs. This study aims to understand differences in nightlife risk-taking behaviours between young nightlife users from Mediterranean and non-Mediterranean cultures, including alcohol and illicit drug use, unprotected sex, violence and driving under the influence of alcohol. Methods: A total of 1363 regular nightlife users aged 16-35 years were surveyed in nine European cities by means of a self-reported questionnaire. Sample selection was done through respondent driven sampling techniques. Results: after controlling for demographic variables, no differences among the Mediterranean and non-Mediterranean samples were found in current alcohol, tobacco, cannabis, or cocaine use, neither in violent behaviours, but Northern people were more likely to get drunk [adjusted odds ratio (AOR) = 0.53], while Mediterranean were more likely to have unprotected sex (AOR = 2.01) and to drive drunken (AOR = 5.86). Conclusion: Our data suggest that stereotypes are partially confirmed, and that Mediterranean lifestyle is protective for some risk behaviours (drunkenness, ecstasy and amphetamines current use), but not for all of them. Further research in depth is needed in order to clarify the relations between cultural patterns, social norms and nightlife risk behaviours assumed by the young people.

Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. The DAWN Report: Emergency Department Visits Involving Ecstasy. (March 24, 2011). Rockville MD: Substance Abuse and Mental Health Administration, 2011. (4 refs.)

The number of drug-related emergency department (ED) visits involving 3,4-methylenedioxymeth-amphetamine (MDMA), commonly known as "Ecstasy," increased significantly from 10,220 visits in 2004 to 17,865 visits in 2008, representing a 74.8%increase. Most ED visits involving Ecstasy in 2008 (69.3 percent) were made by patients aged 18 to 29. An estimated 77.8 percent of these ED visits involved Ecstasy in combination with alcohol or other drugs (including pharmaceuticals or illicit drugs); in fact, 31.3% involved one other drug, 15.0% involved two other drugs, 14.0 percent involved three other drugs, and 17.5 percent involved four or more other drugs. Ecstasy-related ED visits among patients aged 21 or older were more likely than those made by patients aged 20 or younger also to involve alcohol (50.1 vs. 20.4%) or cocaine (43.4 vs. 14.7%). Because it provides psychedelic and stimulant side effects, Ecstasy is associated with dynamic social environments, such as parties or raves, where there is loud music and dancing. Yet the benign nicknames and the lively social environments in which the drug often is used belie the serious health and mental consequences that can result from casual to heavy Ecstasy use. Aside from addiction, Ecstasy use can cause anxiety, agitation, recklessness, increased blood pressure, dehydration, heat stroke, muscle cramping, blurred vision, hyperthermia, heart failure, and kidney failure.2 The social and environmental contexts in which Ecstasy often is used-prolonged vigorous activity in warm environments, such as dancing at crowded parties-can amplify associated cardiovascular health risks.3 Because it also compromises metabolic functioning, Ecstasy taken in combination with other drugs may place users at increased risk for additional and life-threatening drug interactions.3

Public Domain

Chan YC; Tse ML; Lau FL. Hong Kong Poison Information Centre: Annual Report 2009. Hong Kong Journal of Emergency Medicine 18(4): 221-231, 2011. (9 refs.)

Objective: To report and analyse the poisoning data of Hong Kong Poison Information Centre (HKPIC) in 2009. Methods: In 2009, all poisoning cases received by HKPIC were retrieved from its database (PICMS) for analysis. Results: Totally 4338 poisoned cases were analysed. There were 1955 male patients (45.1%), 2,367 female patients (54.6%) and 16 patients with no gender specified. More than two-third of cases (68.6%) were between 20 and 59 years old. Common causes of exposure were suspected self harm/suicidal attempt, abusive use and unintentional exposure. Paracetamol, ketamine, zopiclone, benzodiazepine and household products were the common poisons exposed. Majority of the patients were managed supportively, with 13.6% and 13.1% treated by decontamination and antidotes respectively. Most cases had uneventful recovery; about 1% of the poison exposure resulted in death and about 5% of the exposure had major outcomes. Conclusions: The 2009 annual report provides updated epidemiological information on poisoning pattern in Hong Kong and emphasized some changes in comparing with our previous reports.

Chen TT; Yen CF. Sexual intercourse experience and engagement in unprotected sex in adolescent MDMA users in Taiwan. Substance Use & Misuse 46(4): 398-403, 2011. (27 refs.)

This study aimed to examine the multidimensional correlates of having sexual intercourse experience and engaging in unprotected sex among adolescent ecstasy (3,4-methylenedioxyamphetamine or MDMA) users in Taiwan. The rates of having sexual intercourse and engaging in unprotected sex in 200 adolescent ecstasy users were calculated. Individual, family, and peer correlates of sexual intercourse and engagement in unprotected sex were examined. The results found that 124 (62%%) had had sexual intercourse and 79 (39.5%%) had engaged in unprotected sex at least once. Adolescent ecstasy users who were female, had used ketamine, had parents with habitual alcoholic problems, and more actively interacted with their peers were more likely to have had sexual intercourse. Those who were higher in novelty seeking and more actively interacted with peers were more likely to have engaged in unprotected sex. Sexual intercourse and engaging in unprotected sex in adolescent ecstasy users were correlated to multidimensional factors; the findings could provide a basis for interventions of prevention and reduction of harm.

Ciorciari J; Marotte A. Implications of MDMA use for prospective memory function and substance use patterns in an Australian sample: A web-based pilot study. Australian Journal of Psychology 63(3): 142-149, 2011. (30 refs.)

The use of amphetamine type stimulants, particularly MDMA, is a global concern. Little research has been conducted on the association between MDMA use and everyday memory function-prospective memory. Twenty-five MDMA users, 37 cannabis users, and 43 illicit substance-naive controls were assessed on their substance use history and reported prospective memory performance as measured by the Prospective Memory Questionnaire (PMQ) using a web-based survey. There were significant differences between MDMA users and controls and cannabis users and controls on long-term episodic subscale of the PMQ. However, given the high prevalence of cannabis co-use by MDMA users, it was not possible to determine if MDMA use alone is associated with prospective memory performance. The substance use patterns of the sample were evaluated. Alcohol was the most used substance followed by tobacco, cannabis, and MDMA. The incidence of polydrug use was high, with all illicit substance use reporting having used at least two substances in their lifetime. The present study supports previous research into prospective memory deficits associated with substance use, and provides a basis for future research, particularly for elucidation of prospective memory deficits specific to MDMA use and further evaluation of substance use patterns.

Cohen BMZ; Butler R. BZP-party pills: A review of research on benzylpiperazine as a recreational drug. (review). International Journal of Drug Policy 22(2): 95- 101, 2011. (41 refs.)

Background: BZP-party pills are yet another 'designer drug' which mimics the stimulant qualities of amphetamines and MDMA/Ecstasy. As legal markets for the substance have developed in the last decade (especially amongst young people) so has public and governmental concern. Methods: This article provides a summary of the available international research on benzylpiperazine (BZP) and its popular use in the compound form known as 'party pills'. Through performing an analysis of the available medical and social scientific literature, the review outlines current knowledge on the compound, the prevalence of usage of BZP-party pills, as well as the associated harms, risks and rationales for use of the drug. Results: Despite moves towards legislative control of BZP-party pills, the evidence presented suggests limited social and health harms associated with the drug, although research on long term effects is a significant gap in the literature. It also remains inconclusive as to whether BZP-party pills act as a 'gateway' to illegal drugs or, conversely, play a role in harm reduction with illegal drug users turning to legal alternatives; there is some evidence for both positions. Conclusion: With increasing controls of BZP-party pills, and with the increasing numbers of 'legal highs' and new designer drugs on the market, we conclude that new legal alternatives will continue to surface to replace the drug in the future. Considering a harm reduction approach to drug taking, it is suggested that policy makers consider the creation of a legal holding category which restricts and regulates the market in legal highs whilst the social and health harms associated with each drug can be thoroughly investigated.

Cuyas E; Verdejo-Garcia A; Fagundo AB; Khymenets O; Rodriguez J; Cuenca A et al. The influence of genetic and environmental factors among MDMA users in cognitive performance. PLoS ONE 6(11): e27206, 2011. (56 refs.)

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (> 100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

Davey M. Theme: Ketamine use and abuse. (editorial). Emergency Medicine Journal 28(7): 552-636, 2011. (13 refs.)

den Hollander B; Schouw M; Groot P; Huisman H; Caan M; Barkhof F et al. Preliminary evidence of hippocampal damage in chronic users of ecstasy. Journal of Neurology, Neurosurgery and Psychiatry 83(1): 83-85, 2012. (13 refs.)

Various studies have shown that ecstasy (3,4-methylenedioxymethamphetamine) users display significant memory impairments, whereas their performance on other cognitive tests is generally normal. The hippocampus plays an essential role in short-term memory. There are, however, no structural human data on the effects of ecstasy on the hippocampus. The objective of this study was to investigate whether the hippocampal volume of chronic ecstasy users is reduced when compared with healthy polydrug-using controls, as an indicator of hippocampal damage. The hippocampus was manually outlined in volumetric MRI scans in 10 male ecstasy users (mean age 25.4 years) and seven healthy age- and gender-matched control subjects (21.3 years). Other than the use of ecstasy, there were no statistically significant differences between both groups in exposure to other drugs of abuse and alcohol. The ecstasy users were on average drug-free for more than 2 months and had used on average 281 tablets over the past six and a half years. The hippocampal volume in the ecstasy using group was on average 10.5% smaller than the hippocampal volume in the control group (p=0.032). These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage, in line with previous reports of acute hippocampal sclerosis and subsequent atrophy in chronic users of this drug.

Dowse MS; Shaw S; Cridge C; Smerdon G. The use of drugs by UK recreational divers: Illicit drugs. Diving and Hyperbaric Medicine 41(1): 9-15, 2011. (24 refs.)

Aims: Anecdotal observations suggest the use of illicit drugs takes place amongst recreational divers but, to date, there has been little open debate within the diving community concerning possible prevalence. This study investigated the prevalence and type of illicit drugs used by recreational divers in the United Kingdom (UK). Methods: Anonymous questionnaires were circulated via UK dive clubs, dive schools, dive shows and conferences. Questions incorporated diver and diving demographics and general health, which included anxiety, depression and panic attacks, alcohol use, smoking and illicit drug use since learning to dive and closest time to a dive. Questions pertaining to over-the-counter and prescription drug use were also asked. Results: 479 divers responded (66% males and 34% females) in the age range 16 to 59 years. Of the respondents, 22% had used one or more illicit drug since learning to dive, reporting benzodiazepines, amphetamines, cocaine, ecstasy, LSD, cannabis, heroin, and 'magic mushrooms'. Illicit drugs had been used by 3.5% of respondents in the last 12 months, and 3% in the last month. Cannabis, cocaine and ecstasy use was reported within 6 hours of a dive. Logistic regression confirmed a relationship between illicit drug use and depression (P = 0.014), and also between illicit drug use and anxiety (P = 0.024). Conclusion: These data support anecdotal reports that recreational divers use a range of illicit drugs. The significant relationship between illicit drug use and depression and anxiety supports the literature in non-diving populations.

Dunn M; Thomas JO. A risk profile of elite Australian athletes who use illicit drugs. Addictive Behaviors 37(1): 144-147, 2012. (25 refs.)

Much of the literature investigating the relationship between sports participation and substance use has focused upon student populations, with little focus being given to athletes who participate at elite levels. Identifying why some athletes may be at a greater risk for substance use can help in the design and implementation of prevention initiatives. Data for the current study was from 1684 self-complete surveys with elite Australian athletes. Eight percent (n = 134) of the sample reported the use of at least one of the six illicit drugs under investigation (ecstasy, cannabis, cocaine, meth/amphetamine, ketamine and GHB) in the past year. Having been offered or having had the opportunity to use illicit drugs in the past year, knowing other athletes who use drugs and identifying as a 'full-time athlete' were significant predictors of past-year illicit drug use, while having completed secondary education or a post-school qualification was associated with a lower likelihood of past-year illicit drug use. Athletes are part of a sportsnet that includes family, coaches, support staff and other athletes, and these relationships may encourage the use, supply and demand for drugs. The current findings suggest that relationships with some of those in the sportsnet may play an important role when understanding illicit drug use among elite athletes. As education appears to be associated with a lower likelihood of illicit drug use among this group, initiatives should encourage athletes to engage in off-field pursuits which may also help prepare them for life after sport.

Fakier N; Wild LG. Associations among sleep problems, learning difficulties and substance use in adolescence. Journal of Adolescence 34(4): 717-726, 2011. (68 refs.)

This study investigated the relationships among sleep problems, learning difficulties and substance use in adolescence. Previous research suggests that these variables share an association with executive functioning deficits, and are intertwined. The sample comprised 427 adolescents (M age = 16 years) attending remedial schools and 276 adolescents (M age = 15 years) attending a mainstream school in Cape Town, South Africa. Participants completed anonymous self-report questionnaires. Results indicated that adolescents without learning difficulties were more likely to use tobacco, methamphetamine and cannabis, whereas those with learning difficulties engaged in more inhalant use. Adolescents who had more sleep problems were more likely to use tobacco, alcohol, methamphetamine, cannabis, inhalants, cocaine, ecstasy and any other illegal drug. Adolescents with learning difficulties had more sleep problems than those without learning difficulties. However, sleep problems remained independently associated with tobacco, cannabis and inhalant use when learning difficulties were taken into account.

Fisk JE; Murphy PN; Montgomery C; Hadjiefthyvoulou F. Modelling the adverse effects associated with ecstasy use. Addiction 106(4): 798-805, 2011. (41 refs.)

Aims: Ecstasy, the street name for 3,4-meththylenedioxymethamphetamine, has been associated with a range of psychiatric symptoms and impaired psychological health in both problem and recreational users. The purpose of the present paper is to determine how these impairments are related to the history of polydrug use, and the conditions under which individuals ingest ecstasy. Design: Associations between the variables of interest were investigated utilizing negative binomial regression. Setting: Liverpool and Preston in the North West of England. Participants: A convenience sample of 159 recreational ecstasy/polydrug users (80 males, 79 females). The sample was composed primarily of undergraduates. Measurements: The dependent variable was the number of reported ecstasy-related adverse effects. Independent variables included quantitative aspects of ecstasy and other drug use, and the various beliefs and behaviours associated with ecstasy use. Findings: The number of adverse effects was associated positively with life-time exposure to ecstasy and negatively with period of abstinence from the drug. Adverse effects were more common among those who consumed ecstasy and alcohol concurrently, but were unrelated to other aspects of polydrug use. They were unaffected by whether the user took precautions when using the drug, and only weakly related to prior beliefs concerning the effects of ecstasy. Conclusions: Greater life-time exposure to ecstasy and consuming the drug concurrently with alcohol increase the likelihood of experiencing adverse effects, including paranoia, poor general health, irritability, confusion and moodiness. Adverse effects decrease with the period of abstinence from the drug.

Fogger SA. Update on ecstasy. Journal of Psychosocial Nursing and Mental Health Services 49(4): 16-18, 2011. (14 refs.)

After years of declining use in the United States, youth consumption of ecstasy has increased significantly. Although ecstasy (3, 4-methylenedioxymethamphetamine) is known to be a drug with detrimental effects, users view the drug as a safe and attractive social lubricant. To update and clarify misperceptions, this article reviews current evidence regarding ecstasy's side effects and risks and encourages honest discussion focusing on risk-reduction behaviors.

Fulceri F; Ferrucci M; Lenzi P; Soldani P; Paparelli ABA; Gesi M. MDMA (Ecstasy) enhances loud noise-induced morphofunctional alterations in heart and adrenal gland. (review). Microscopy Research and Technique 74(9): 874-887, 2011. (169 refs.)

Noise is an environmental stressor increasingly more present in modern life and, in particular, in a variety of recreational contexts. The aim of this work is to show the effects of noise on the myocardium and adrenal gland, through a careful review of the literature dealing with the peripheral effects of noise exposure in experimental and clinical studies. Noise induces adverse effects in human health, principally involving the cardiovascular and autonomic nervous systems, and the endocrine apparatus. Several factors in recreational environments potentially worsen the effects induced by loud noise. Among these, the intake of 3,4-methylenedioxymethamphetamine (MDMA) is frequently associated with noise exposure in recreational situations, because of its high compliance within social and relaxation settings. For this reason, MDMA is defined as a club drug-as its intake by young people often occurs in association with other factors, such as aggregation, high temperatures, and noise. It is known that self-administration of MDMA by humans causes severe toxicity. In particular, the myocardium is affected early after MDMA intake-resulting in tachycardia, hypertension, and arrhythmia. Furthermore, MDMA alters the activity of the adrenal glands by elevating catecholamines and corticosterone levels. This review shows that combining MDMA and loud noise exposure potentiates the effects that are produced by each single stimulant alone as seen in experimental animal models. The convergence of the effects of prolonged loud noise exposure and the consumption of MDMA on the same system might explain the sudden fatal events that happen in recreational situations.

Galicia M; Nogue S; Miro O. Liquid ecstasy intoxication: Clinical features of 505 consecutive emergency department patients. Emergency Medicine Journal 28(6): 462- 466, 2011. (25 refs.)

Background: To describe the epidemiological profile and clinical manifestations of liquid ecstasy (GHB) poisonings. Methods All cases of GHB poisoning or overdose admitted to the Emergency Department (ED) of the Hospital Clinic (Barcelona) between 2000 and 2007 were recorded. Results: A total of 505 patients (mean age 24.7 years, 68% men) were included. Most patients were brought to the hospital by ambulance (98%), during the weekend (89%) and during the early morning (75%). Symptoms began in a public place in 97%. Reduced consciousness was the most important clinical manifestation: 72% of patients had a Glasgow Coma Score of <= 12. 76% of patients had consumed other drugs: ethanol (64%), amphetamines and derivates (30%), cocaine (28%), ketamine (11%), cannabis (9%) and others (5%). Treatment was required in 26% of cases and an antidote was administered in 35 cases with no response. There were no deaths. The combined GHB group had a longer time to complete recovery of consciousness (71 +/- 40 vs 59 +/- 40 min, p<0.001) and a higher percentage of patients with severely reduced consciousness at ED arrival (54% vs 37%, p=0.01), need for treatment (29% vs 16%, p<0.01) and need for mechanical ventilation (3% vs 0%, p<0.05) compared with the pure GHB group. Conclusions: GHB intoxication leading to reduced consciousness is a frequent reason for ED admission, above all in young people and in the early morning at the weekend. Symptoms are more severe in patients who have taken GHB in combination with other substances of abuse.

George AM; Windsor TD; Rodgers B. Are ecstasy users biased toward endorsing somatic mental health symptoms? Results from a general community sample. Psychopharmacology 214(4): 901-909, 2011. (34 refs.)

Whether the reported poorer mental health of ecstasy users is due to a bias in endorsement of somatic symptoms has been postulated, but rarely examined. The purpose of this study is to investigate whether levels of ecstasy use were associated with differential probabilities of endorsing somatic mental health symptoms. Current ecstasy users aged 24-30 years (n = 316) were identified from a population-based Australian study. Measures included frequency of ecstasy, meth/amphetamine, and cannabis use and the Goldberg anxiety/depression symptom scales. Multiple indicator, multiple cause models demonstrated no bias towards endorsing somatic symptoms with higher ecstasy use, both with and without adjustment for gender, cannabis, and meth/amphetamine use. Other studies using alternate measures of mental health should adopt this approach to determine if there is a bias in the endorsement of somatic symptoms among ecstasy users.

Goodwin AK; Kaminski BJ; Griffiths RR; Ator NA; Weerts EM. Intravenous self-administration of gamma-hydroxybutyrate (GHB) in baboons. Drug and Alcohol Dependence 114(2-3): 217- 224, 2011. (60 refs.)

Background: Abuse of gamma-hydroxybutyrate (GHB) poses a public health concern. In previous studies, intravenous (IV) self-administration of GHB doses up to 10 mg/kg was not maintained in non-human primates under limited-access conditions, which was inconsistent with the usual good correspondence between drugs abused by humans and those self-injected by laboratory animals. Methods: Self-administration of GHB was studied in 10 baboons using procedures standard for our laboratory to assess drug abuse liability. Each self-injection depended on completion of 120 or 160 lever responses. Sessions ran continuously; a 3-h timeout limited the number of injections per 24 h to 8. Self-injection was established at 6-8 injections/day with cocaine (0.32 mg/kg/injection) prior to substitution of each GHB dose (3.2-178 mg/kg/injection) or vehicle for 15 days. Food pellets were available 24 h/day. Results: GHB maintained significantly greater numbers of injections when compared to vehicle in 6 of the 9 baboons that completed GHB evaluations that included 32 mg/kg/injection or higher. The baboons that self-administered GHB at high rates were ones for which GHB was the first drug each had tested under the 24-h/day cocaine baseline procedure. Self-injection of the highest doses of GHB decreased food-maintained responding. Conclusions: High-dose GHB can function as a reinforcer in non-human primates under 24-h access, but self-administration history may be important. The findings are consistent with the demonstrated abuse liability of GHB in humans, and remove GHB as an exception to the typical good correspondence between those drugs abused by humans and those self-administered by nonhuman primates.

Gorun G; Curca GC; Hostiuc S; Buda O. "Legal highs" in Romania: Historical and present facts. Romanian Journal of Legal Medicine 19(1): 73-76, 2011. (7 refs.)

In the modern history of our country, the subject of psychoactive substances was banned as being against the socialist-communist political ideology, and consequently the research and knowledge on the historical evolution of the use of plants and substances for medical, hedonistic and/or ritual purposes in our country was not given any encouragement. In this context of a diluted and outdated knowledge on the psychoactive substances which had been maintained for decades, the explosion of the drug addiction phenomenon encountered an idealistic perception ("it is a problem of the Western world", "we are just a transit country", etc.), which lead to a fast increase in the number of young people who tried to consume illegal drugs. The political/administrative organisations, the civil society, the NGOs and particularly the scientific experts in Romania had all a very slow and laggard response, which has lead to the current situation when drug addiction is finally recognized as a very serious issue. Particular features of the Romanian phenomenon surprisingly not due to the local tradition or spontaneous flora (as long as currently marketed products are imported) are presented in this publication, giving examples from the criminal investigation experience. An alarming issue which has been highlighted by our research points to the fact that "classical drugs", such as opioids, methadone, ketamine, MDMA, are likely to be used in Romania for "spicing up" the so-called "legal" marketed products. In the following, we shall trace the historical evolution of the use of plants and substances for medical, hedonistic and/or ritual purposes in our country. We shall also reflect on the related legislative and medical issues, and the suggested measures.

Green SM; Roback MG; Kennedy RM; Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. (review). Annals of Emergency Medicine 57(5): 449- 461, 2011. (112 refs.)

We update an evidence-based clinical practice guideline for the administration of the dissociative agent ketamine for emergency department procedural sedation and analgesia. Substantial new research warrants revision of the widely disseminated 2004 guideline, particularly with respect to contraindications, age recommendations, potential neurotoxicity, and the role of coadministered anticholinergics and benzodiazepines. We critically discuss indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, recovery issues, and future research questions for ketamine dissociative sedation.

Hadjiefthyvoulou F; Fisk JE; Montgomery C; Bridges N. Everyday and prospective memory deficits in ecstasy/polydrug users. Journal of Psychopharmacology 25(4): 453-464, 2011. (52 refs.)

The impact of ecstasy/polydrug use on real-world memory (i.e. everyday memory, cognitive failures and prospective memory [PM]) was investigated in a sample of 42 ecstasy/polydrug users and 31 non-ecstasy users. Laboratory-based PM tasks were administered along with self-reported measures of PM to test whether any ecstasy/polydrug-related impairment on the different aspects of PM was present. Self-reported measures of everyday memory and cognitive failures were also administered. Ecstasy/polydrug associated deficits were observed on both laboratory and self-reported measures of PM and everyday memory. The present study extends previous research by demonstrating that deficits in PM are real and cannot be simply attributed to self-misperceptions. The deficits observed reflect some general capacity underpinning both time-and event-based PM contexts and are not task specific. Among this group of ecstasy/polydrug users recreational use of cocaine was also prominently associated with PM deficits. Further research might explore the differential effects of individual illicit drugs on real-world memory.

Hadjiefthyvoulou F; Fisk JE; Montgomery C; Bridges N. Prospective memory functioning among ecstasy/polydrug users: Evidence from the Cambridge Prospective Memory Test (CAMPROMPT). Psychopharmacology 215(4): 761- 774, 2011. (50 refs.)

Prospective memory (PM) deficits in recreational drug users have been documented in recent years. However, the assessment of prospective memory has largely been restricted to self-reported measures that fail to capture the distinction between event-based and time-based prospective memory. The aim of the present study is to address this limitation. Extending our previous research, we augmented the range laboratory measures of prospective memory by employing the CAMPROMPT test battery to investigate the impact of illicit drug use on prospective remembering in a sample of cannabis only, ecstasy/polydrug and non-users of illicit drugs, separating event and time-based prospective memory performance. We also administered measures of executive function and retrospective memory in order to establish whether ecstasy/polydrug deficits in prospective memory were mediated by group differences in these processes. Ecstasy/polydrug users performed significantly worse on both event and time-based prospective memory tasks in comparison to both cannabis only and non-user groups. Furthermore, it was found that across the whole sample, better retrospective memory and executive functioning was associated with superior prospective memory performance. Nevertheless, this association did not mediate the drug-related effects that were observed. Consistent with our previous study, recreational use of cocaine was linked to prospective memory deficits. prospective memorP deficits have again been found among ecstasy/polydrug users, which appear to be unrelated to group differences in executive function and retrospective memory. However, the possibility that these are attributable to cocaine use cannot be excluded.

Halpern P; Moskovich J; Avrahami B; Bentur Y; Soffer D; Peleg K. Morbidity associated with MDMA (ecstasy) abuse: A survey of emergency department admissions. Human & Experimental Toxicology 30(4): 259-266, 2011. (35 refs.)

Methods: We conducted a prospective, representative-sample nationwide study on morbidity related to 3,4, methylenedioxymethamphetamine (MDMA; 'ecstasy') as determined from admissions to 5 geographically representative emergency departments (EDs) and from data from the poison information center (PIC). MDMA-related ED admissions were analyzed over a 7-month period and the records of all PIC calls were reviewed. Results: There were 52 (age 15-44 years, 32 males) ecstasy-related ED admissions during the study period. Most (68%) admissions presented to the ED at night, 52% on weekends and 44% consumed the drug at clubs and parties. Forty-six percent of the patients took between 1/2 to 3 tablets and 29 patients (56%) had taken ecstasy before. Twenty-two subjects (42%) reported poly-drug use. Fifteen subjects (29%) required hospitalization, six of them (11%) to the intensive care unit. The most common manifestations were restlessness, agitation, disorientation, shaking, high blood pressure, headache and loss of consciousness. More serious complications were hyperthermia, hyponatremia, rhabdomyolysis, brain edema and coma. Conclusion: The image of ecstasy as a safe party drug is spurious. The results of this study confirm that the drug bears real danger of physical harm and of behavioral, psychological and psychiatric disturbances.

Halpern JH; Sherwood AR; Hudson JI; Gruber S; Kozin D; Pope HG. Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs. Addiction 106(4): 777-786, 2011. (63 refs.)

Aims: In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias. Design: We compared illicit ecstasy users and non-users while (1) excluding individuals with significant life-time exposure to other illicit drugs or alcohol; (2) requiring that all participants be members of the 'rave' subculture; and (3) testing all participants with breath, urine and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons. Setting: Field study. Participants: Fifty-two illicit ecstasy users and 59 non-users, aged 18-45 years. Measurements: Battery of 15 neuropsychological tests tapping a range of cognitive functions. Findings: We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. However, this finding might have reflected a pre-morbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions: In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users.

Hayatbakhsh MR; Kingsbury AM; Flenady V; Gilshenan KS; Hutchinson DM; Najman JM. Illicit drug use before and during pregnancy at a tertiary maternity hospital 2000-2006. Drug and Alcohol Review 30(2): 181-187, 2011. (26 refs.)

Introduction and Aims. To study the prevalence of use of illicit drugs by women of reproductive age before and during pregnancy and the changes in rates of illicit drug use in pregnancy over recent years. Design and Methods. All pregnant women attending the public antenatal clinic over a 7 year period (2000-2006) were routinely interviewed about their use of illicit drugs by a midwife at the antenatal booking visit. Measurements. Records for 25 049 women, who self-reported previous and current use of cannabis, amphetamines, ecstasy and heroin, were included in the study. Results. Cannabis was the most common illicit drug used before and during pregnancy; 9.3% of women were engaged in regular use prior to pregnancy and 2.5% were users during pregnancy. A very low proportion of women reported use of amphetamines, ecstasy or heroin in pregnancy. There was an increase in ever regular use and any past use of cannabis, amphetamines and ecstasy over time. Conclusions. The prevalence of illicit drug use by young women prior to becoming pregnant is of concern. While pregnancy appears to be a strong motivator for women to cease substance use, there is a need to study whether women resume drug use after their baby is born.

Hirota K; Lambert DG. Ketamine: New uses for an old drug? (editorial). British Journal of Anaesthesia 107(2): 123-126, 2011. (35 refs.)

Hondebrink L; Meulenbelt J; van Kleef RGDM; van den Berg M; Westerink RHS. Modulation of human GABA(A) receptor function: A novel mode of action of drugs of abuse. Neurotoxicology 32(6): 823-827, 2011. (30 refs.)

Drugs of abuse are known to mainly affect the dopaminergic and serotonergic system, although behavioral studies indicated that the GABA-ergic system also plays a role. We therefore investigated the acute effects of several commonly used drugs of abuse (methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP)) on the function of the human alpha(1)beta(2)gamma(2) GABA(A) receptor (hGABA(A)-R), expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique. Although none of the tested drugs acted as full agonist on the hGABA(A)-R, some drugs induced differential modulation of hGABA(A)-R function, depending on the degree of receptor occupancy. Methamphetamine did not affect the GABA-evoked current at high receptor occupancy, but induced a minor inhibition at low receptor occupancy. Its metabolite amphetamine slightly potentiated the GABA-evoked current. MDMA and its metabolite MDA both inhibited the current at low receptor occupancy. However, MDMA did not affect the current at high occupancy, whereas MDA induced a potentiation. mCPP induced a strong inhibition (max. similar to 80%) at low receptor occupancy, but similar to 25% potentiation at high receptor occupancy. Competitive binding to one of the GABA-binding sites could explain the drug-induced inhibitions observed at low receptor occupancy, whereas an additional interaction with a positive allosteric binding site may play a role in the observed potentiations at high receptor occupancy. This is the first study to identify direct modulation of hGABA(A)-Rs as a novel mode of action for several drugs of abuse. Consequently, hGABAA-Rs should be considered as target for psychiatric pharmaceuticals and in developing treatment for drug intoxications.

Huang YS; Tang TC; Lin CH; Yen CF. Effects of Motivational Enhancement Therapy on readiness to change MDMA and methamphetamine use behaviors in Taiwanese adolescents. Substance Use & Misuse 46(4): 411-416, 2011. (28 refs.)

The aim of this study was to examine the effect of brief modified motivational enhancement therapy (MET) on readiness to change patterns of methylenedioxymethamphetamine (MDMA) and methamphetamine (MAMP) use behaviors in adolescents. A total of 94 adolescents who used MDMA or MAMP were consecutively recruited from a juvenile abstinence center; 46 received a three-session MET intervention (intervention group), and 48 received educational materials only and no MET intervention (control group). Analysis of covariance was performed to examine the effect of motivational interviewing on the readiness of change scores on the University of Rhode Island Change Assessment and on the scores of its subscales. By using the pretreatment scores as covariates, the intervention group demonstrated higher posttreatment scores of readiness to change and of the contemplation subscale on the University of Rhode Island Change Assessment than the control group. The results of this study support the finding that brief modified MET is effective in promoting readiness to change MAMP and MDMA use behaviors in adolescents who receive short-term treatment programs.

Hughes CE; Lancaster K; Spicer B. How do Australian news media depict illicit drug issues? An analysis of print media reporting across and between illicit drugs, 2003-2008. International Journal of Drug Policy 22(4): 285-291, 2011. (35 refs.)

Background: Media reporting on illicit issues has been frequently criticised for being sensationalised, biased and narrow. Yet, there have been few broad and systematic analyses of the nature of reporting. Using a large sample and methods commonly adopted in media communications analysis this paper sought to identify the dominant media portrayals used to denote illicit drugs in Australian newspapers and to compare and contrast portrayals across drug types. Methods: A retrospective content analysis of Australian print media was carried out over the period 2003-2008 from a sample comprised of 11 newspapers. Articles that contained one or more mention of five different drugs (or derivatives) were identified: cannabis, amphetamines, ecstasy, cocaine and heroin. A sub-sample of 4397 articles was selected for media content analysis (with 2045 selected for full content analysis) and a large number of text elements coded for each. Key elements included topic, explicit or implicit messages about the consequences of drugs/use and three value dimensions: overall tone, whether drugs were portrayed as a crisis issue and moral evaluations of drugs/use. Results: The dominant media portrayals depicted law enforcement or criminal justice action (55%), but most articles were reported in a neutral manner, in the absence of crisis framings. Portrayals differed between drugs, with some containing more narrow frames and more explicit moral evaluations than others. For example, heroin was disproportionately framed as a drug that will lead to legal problems. In contrast, ecstasy and cocaine were much more likely to emphasise health and social problems. Conclusion: Media reporting on illicit drugs is heavily distorted towards crime and deviance framings, but may be less overtly sensationalised, biased and narrowly framed than previously suggested. This is not to suggest there is no sensationalism or imbalance, but this appears more associated with particular drug types and episodes of heightened public concern.

Hughes RR; Walker GS. Rapid screening for the detection and differentiation of gamma-hydroxybutyrate using ion chromatography. Journal of Forensic Sciences 56(5): 1256-1260, 2011. (36 refs.)

The analysis of gamma-hydroxybutyric acid (GHB) is problematic because it is hygroscopic, it lacks a good UV chromophore, and it undergoes heat-induced cyclization. This paper presents a new method utilizing ion-exchange chromatography (IC) with conductivity detection. The simple sample preparation, rapid analysis time, and inorganic anion detection capabilities are all advantages over the current methods. The detection of inorganic salts (formed during GHB synthesis) gives insight into the synthetic route utilized and can aid in drug seizure comparison. The developed method has a detection limit for GHB anions of 0.57 mg/L and chloride of 0.22 mg/L. A comparison of this technique with a current gas chromatography-mass spectrometry technique is presented, and a t-test found that the two methods' results are not statistically different at the 99.9% confidence level demonstrating the merits of this fast, simple, and informative IC method as a routine screening tool.

Hungerbuehler I; Buecheli A; Schaub M. Drug checking: A prevention measure for a heterogeneous group with high consumption frequency and polydrug use. Evaluation of Zurich's Drug Checking services. Harm Reduction Journal 8: article 16, 2011. (9 refs.)

Background: The increasing party culture in Zurich presents new challenges, especially regarding the consumption of alcohol and so-called party drugs. Streetwork, the youth advisory service of the city of Zurich, has provided onsite and stationary Drug Checking facilities since 2001 and 2006, respectively. Drug Checking always involves filling out an anonymous questionnaire, which allows the collection of important information about a largely unknown group of users and their consumption patterns. Methods: The questionnaires assessed sociodemographic characteristics, consumption patterns, Drug Checking experiences, information behavior and social support. The collected data were statistically analyzed by the Research Institute for Public Health and Addiction (RIPHA). Results: The majority of Drug Checking service patrons were male and between 20 and 35 years old. These patrons reported high lifetime prevalences and high consumption frequencies of legal and illegal substances, and they often reported polydrug use. Aside from tobacco and alcohol, the most consumed drugs during typical party nights were ecstasy, amphetamines, cannabis and cocaine. Party drug consumers using Drug Checking services form a heterogeneous group with respect to sociodemographic characteristics and consumption patterns. Users of the onsite Drug Checking facilities were significantly younger, were less experienced with drug testing, and reported more polydrug use than users of the stationary Drug Checking service. Conclusions: Drug Checking combined with a consultation appears to be an important harm reduction and prevention measure that reaches a group of consumers with high consumption frequency and polydrug use. Because of the heterogeneity of the target group, different prevention measures must be offered and embedded in an overall local concept.

Hysek CM; Simmler LD; Ineichen M; Grouzmann E; Hoener MC; Brenneisen R et al. The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("Ecstasy") in humans. Clinical Pharmacology & Therapeutics 90(2): 246-255, 2011. (49 refs.)

This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans.

Irvine RJ; Kostakis C; Felgate PD; Jaehne EJ; Chen C; White JM. Population drug use in Australia: A wastewater analysis. Forensic Science International 210(1-3): 69-73, 2011. (26 refs.)

Accurate information on drug use in communities is essential if health, social and economic harms associated with illicit drug use are to be addressed efficiently. In most countries population drug use is estimated indirectly via surveys, medical presentations and police and custom seizures. All of these methods have at least some problems due to bias, small samples and/or long time delays between collecting the information and analysing the results. Recently the direct quantification of drug residues in wastewater has shown promise as a means of monitoring drug use in defined geographical areas. In this study we measured 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine and benzoylecgonine in sewage inflows in metropolitan and regional areas of Australia and compared these data with published European data. Cocaine use was small compared to European cities (p < 0.001) but was compensated for by much greater consumption of methamphetamine (p < 0.001) and MDMA (p < 0.05). MDMA was more popular in regional areas (p < 0.05) whereas methamphetamine and cocaine were mainly consumed in the city (p < 0.05). Greater than 5-fold increases in MDMA use were detected on weekends (p < 0.001). This approach has the potential to improve our understanding of drug use in populations and should be further developed to improve prevention and treatment programs.

Jennings PA; Cameron P; Bernard S. Ketamine as an analgesic in the pre-hospital setting: A systematic review. (review). Acta Anaesthesiologica Scandinavica 55(6): 638-643, 2011. (19 refs.)

Background: Pain is a common presenting complaint and there is considerable debate regarding the best practice for analgesia in the pre-hospital environment for trauma patients with severe pain. Methods: A review of the literature was conducted using a number of electronic medical literature databases from their earliest record to the latest available at the time the search was conducted (May 2010). Medical Subject Headings, keywords and a pre-hospital search filter were used to yield relevant literature. Results: The search strategy yielded a total of 837 references. Seven hundred and fifty of these references were excluded as they did not meet the inclusion criteria. Of the 87 articles short listed for abstract or full-text review, six reported on ketamine use as an analgesic agent in the pre-hospital setting. Two papers were prospective randomized-controlled trials, and the number of patients included in the studies ranged from 4 to 164. Three studies aimed to report on the effectiveness of ketamine for pain intensity reduction; two concluded that ketamine provided safe and effective pain relief and one reported that ketamine reduced the amount of morphine required but was not associated with a reduction in pain intensity. One study identified a significantly higher prevalence of adverse effects following ketamine administration. The other studies reported no significant side effects and concluded that ketamine was safe. Conclusion: Ketamine is a safe and effective analgesic agent. The addition of ketamine as an analgesic agent may improve the management of patients presenting with acute traumatic pain in the pre-hospital setting.

Khajeamiri AR; Kobarfard F; Ahmadkhaniha R; Mostashari G. Profiling of ecstasy tablets seized in Iran. Iranian Journal of Pharmaceutical Research 10(2): 211-220, 2011. (9 refs.)

In this study 50 samples of ecstasy tablets seized in Iran during the period of 2007 through 2008 were examined and their physical characteristics (appearance, marking, scored/not scored, color, weight, diameter, thickness) were determined. In order to determine the chemical characteristics of these tablets, color tests (Marquis test, Simon's test, Chen's test and Gallic acid test), Thin Layer Chromatography (TLC), anion test, residual solvents, Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were carried out on the tablets. The range of tablets weight was 96-308 mg and the range of 3,4-methylenedioxymethamphetamine (MDMA) hydrochloride content in these tablets was 60180 mg. No good correlation was found between the tablets weight and their MDMA contents. All of the tablets containing MDMA had this compound in hydrochloride form. Ketamine, phenmetrazine and ephedrine (or pseudoephedrine) were found in some of the tablets along with MDMA. No MDMA was found in 10% of the tablets. Some of these tablets contained compounds such as caffeine or tramadol as their active ingredient.

Khan U; Nicell JA. Refined sewer epidemiology mass balances and their application to heroin, cocaine and ecstasy. Environment International 37(7): 1236-1252, 2011. (153 refs.)

The detection of illicit drugs in environmental matrices may be a cause for concern, both from the perspective of their potential environmental impacts and the fact that their presence in detectable concentrations would be an indicator of significant drug use. The primary goal behind recent studies on this subject has been to use measured influent concentrations of selected illicit drugs or their in vivo metabolites in the environment as a means of estimating the abuse level of these drugs and patterns of consumption. Thus-far, such calculations have hinged on the use of solitary excretion estimates from single studies of limited scope and/or studies of limited applicability. Therefore, the need exists to conduct a comprehensive meta-analysis of metabolic disposition studies to construct excretions profiles for the various illicit drugs and their in vivo metabolites. The constructed excretory profiles should not only provide mean excretion values but also indicate the expected variations in excreted fractions that arise due to differences not only in the metabolic capacity of users but also in the efficiencies of various routes of administration for a given illicit drug. Therefore, the primary goal of the research presented here was to refine sewer epidemiology extrapolation mass balances for various illicit drugs of interest by constructing their excretory profiles segregated by route-of-administration. After conducting such a study with a multi-national scope on illicit drugs including cocaine, heroin and ecstasy, the results obtained clearly indicate that extrapolation factors currently being used in literature for these drugs to enumerate prevalence of abuse required significant refinement to increase their reliability.

Kim J; Fan B; Liu XH; Kerner N; Wu P. Ecstasy use and suicidal behavior among adolescents: Findings from a national survey. Suicide and Life-Threatening Behavior 41(4): 435-444, 2011. (49 refs.)

The relationship between ecstasy use and suicidal behavior among adolescents in the United States was examined. Data from the adolescent subsample (ages 12-17, N = 19,301) of the 2000 National Household Survey on Drug Abuse were used in the analyses. Information on adolescent substance use, suicidal behaviors, and related sociodemographic, family, and individual factors was obtained in the survey. The rate of past year suicide attempt among adolescents with lifetime ecstasy use was almost double that of adolescents who had used other drugs only, and nine times that of adolescents with no history of illicit drug use. In multinomial logistic regression analyses controlling for related factors, the effect of ecstasy use remained significant. Adolescent ecstasy users may require enhanced suicide prevention and intervention efforts.

Krul J; Girbes ARJ. Gamma-hydroxybutyrate: Experience of 9 years of gamma-hydroxybutyrate (GHB)-related incidents during rave parties in The Netherlands. Clinical Toxicology 49(4): 311- 315, 2011. (31 refs.)

Objective. The objective of this study was to determine the health disturbances and to assess the severity of the incidents as reported during a 9-year experience of gamma-hydroxybutyrate (GHB)-related First Aid Attendees attending First Aid Stations at rave parties. Design. This study was a prospective observational study of self-referred patients from the year 2000 to 2008. During rave parties, First Aid Stations were staffed with specifically trained medical and paramedical personnel. Patients were diagnosed and treated, and data were recorded using standardized methods. Results. During a 9-year period with 202 rave parties, involving approximately three million visitors, 22 604 First Aid Attendees visited the First Aid Stations, of which 771 reported GHB-related health problems. The mean age of the GHB-using First Aid Attendees was 25.7 +/- 6.1 years, most of them (66.4%) were male. Approximately one-third (32.7%) of them used one substance, while 48.1% combined GHB with ecstasy, alcohol, or cannabis. One of five (19.2%) combined GHB with other substances or more than one substance. One case was categorized as severe/life-threatening and 202 (26.2%) cases as moderate, requiring further medical care. In total, 43 (5.6%) First Aid Attendees needed hospital care. The most encountered health disturbance was altered consciousness. Combinations of altered consciousness, vomiting, and/or low body temperature were found in 186 cases (24.1%) and considered to be potentially dangerous. GHB-related First Aid Attendees required a longer stay at the First Aid Stations than the total group First Aid Attendees did (median 45 min vs 10 min). Conclusion. We found very little, severe short-term GHB-related health disturbances during rave parties in The Netherlands. Hospital referrals were rare. The most found symptom was altered consciousness, sometimes accompanied by vomiting and low body temperature. At events where the visitors use GHB, a well-trained and qualified medical team, including nurses and physicians, is recommendable. They must be able to recognize GHB intake and prevent secondary problems such as aspiration and hypothermia.

Kuypers KPC; Wingen M; Heinecke A; Formisano E; Ramaekers JG. MDMA intoxication and verbal memory performance: A placebo-controlled pharmaco-MRI study. Journal of Psychopharmacology 25(8): 1053-1061, 2011. (35 refs.)

The aim of the present study was to identify the neural substrate underlying memory impairment due to a single dose of MDMA (3,4-methylenedioxymethamphetamine) by means of pharmaco-MRI. Based on previous behavioral results it was hypothesized that this deficit could be attributed to a specific influence of MDMA on encoding. Fourteen Ecstasy users participated in this double-blind, placebo-controlled, within-subject study with two treatment conditions: MDMA (75 mg) and placebo. Memory performance was tested by means of a word learning task including two words lists, one addressing reading processes (control task, CWL) and a second (experimental task, EWL) addressing encoding and reading processes. Behavioral data showed that under the influence of MDMA, EWL performance was worse than placebo. Imaging data showed that Encoding was situated mainly in (pre)frontal, temporal and parietal areas. MDMA by Encoding interaction was situated in three areas: the left middle frontal gyrus (BA10), the right fusiform gyrus (BA19), and the left cuneus (BA18). Behavioral and functional data only correlated in BA10. It appeared that EWL performance caused BOLD signal change in BA10 during placebo treatment but not during MDMA intoxication. It is concluded that MDMA influences middle frontal gyrus processes resulting in impoverished memory encoding.

Lee HKH; Ng HW; Tse ML; Lau FL. A retrospective survey on the clinical presentation of ketamine abusers in a Hong Kong emergency department. Hong Kong Journal of Emergency Medicine 18(4): 210-216, 2011. (12 refs.)

Objective: Ketamine is one of the commonest abusing agents in Hong Kong. Our study aims to identify their clinical pattern of presentations to emergency departments. Method: This is a retrospective survey study. The studied group was ketamine abusers being referred to us from a source out of emergency department (ED). Control group was randomly selected from patients attending our ED. The electronic records of the ketamine abusers and the controls in the past 3 years (1st April 2004-31st March 2007) were reviewed and analysed. Result: Total 91 subjects (48 in ketamine group, 43 in control group) were included. The mean age of ketamine abusers and control group are 21 and 22.2 year-old respectively. Most of them (97.9%) did not declare their background of ketamine abuse. The mean 3-year attendance rate for the ketamine group was 2.38 and for control group was 0.91, with a difference of 1.47 (95% CI 0.54-2.41, p=0.003). Most of their illnesses were diagnosed as epigastric pain (25%), followed by upper respiratory tract infection (18.8%), head injury (10.4%) and urinary tract infection (10.4%). Significantly higher number of ketamine abusers presented with epigastric pain compared with control group (odds ratio 143, p<0.001). Conclusion: Most teenage ketamine abusers do not declare their background of drug abuse when they present to emergency departments. They tend to have a higher frequency of attendances. Most of their presenting problems are related to gastrointestinal system.

Lee JP; Battle RS; Soller B; Brandes N. Thizzin': Ecstasy use contexts and emergent social meanings. Addiction Research & Theory 19(6): 528-541, 2011. (113 refs.)

The drug "Ecstasy" has been most commonly associated with raves, or electronic music dance events, and attributed with sexual disinhibition. In an ethnographic investigation of drug use among second-generation Southeast Asian youth in Northern California conducted in 2003, respondents described little use of or interest in using Ecstasy; yet in a second study, Ecstasy was the fourth most commonly used substance. This article investigates the social contexts for this change in use patterns. Respondents were second-generation Southeast Asian youths and young adults between the ages of 15 and 26 who were currently or recently drug-involved. We compared qualitative data from the two studies and found emerging patterns of meaning and context related to the observed change in use patterns. Ecstasy use among co-resident African American youth within the context of the local "hyphy" hip-hop music subculture had influenced Southeast Asian youths' uptake of the drug, known as "thizz." Respondents referred to the effects of the drug as "thizzin'," described as energizing, disinhibiting, numbing, and emotion enhancing. Reported consequences of "thizzin'" included violence and aggression as well as fun, while sexual disinhibition was rarely mentioned. The meanings assigned to drugs, including the effects ascribed to them, may be relative to the social contexts within which users are exposed to and consume drugs. The findings indicate the susceptibility of youths to local trends in drug use, particularly associated with popular cultural movements and music. Second-generation youths may be particularly susceptible relative to the conditions of their immigration and processes of identity formation unique to them.

Lyne JP; O'Donoghue B; Clancy M; O'Gara C. Comorbid psychiatric diagnoses among individuals presenting to an addiction treatment program for alcohol dependence. Substance Use & Misuse 46(4): 351-358, 2011. (31 refs.)

A retrospective patient record review was conducted to examine comorbid psychiatric diagnoses, and comorbid substance use, among 465 patients below 45 years of age, presenting to a national alcohol addiction treatment unit in Dublin, between 1995 and 2006. Rates were high for depressive disorder (25.3%%) particularly among females (35.4%%). Lifetime reported use of substances other than alcohol was 39.2%%, and further analysis showed significantly higher rates of deliberate self-harm among this group. Lifetime reported use of ecstasy was also significantly associated with depression in this alcohol-dependent population using logistic regression analysis. Implications and limitations of the findings are discussed.

Lyvers M. Commentary on Halpern et al. (2011): Strengthening the case against functionally significant serotonergic neurotoxicity in human MDMA (ecstasy) users. (commentary). Addiction 106(4): 787-788, 2011. (18 refs.)

Macias MS; Furton KG. Availability of target odor compounds from seized ecstasy tablets for canine detection. Journal of Forensic Sciences 56(6): 1594-1600, 2011. (14 refs.)

The aim of this study was to compare seized samples of 3,4-methylenedioxy-N-methylamphetamine (MDMA) pills, used to train law enforcement detection canine teams, to determine what differences exist in the chemical makeup and headspace odor and their effect on detectability. MDMA solutions were analyzed by liquid chromatography-mass spectrometry. Analysis of these samples showed a wide variance of MDMA (8-25%). Headspace SPME-GC/MS analysis showed that several compounds such as 3,4-methylenedioxyphenylacetone and 1-(3,4-methylenedioxyphenyl)-2-propanol are common among these MDMA samples regardless of starting compound and synthesis procedure. However, differences, such as the level of the various methylenedioxy starting compounds, were shown to affect the overall outcome of canine detection, indicating the need for more than one MDMA training aid. Combinations of compounds such as the primary odor piperonal in conjunction with a secondary compound such as MDP-2-OH or isosafrole are recommended to maximize detection of different illicit MDMA samples.

Maremmani AGI; Pani PP; Rovai L; Pacini M; Dell'Osso L; Maremmani I. Long-term gamma-hydroxybutyric acid (GHB) and Disulfiram combination therapy in GHB treatment-resistant chronic alcoholics. International Journal of Environmental Research and Public Health 8(7): 2816-2827, 2011. (48 refs.)

Leading Italian studies support the use of gamma-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30-40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of 'antagonist' effect by using the 'psychological threat' of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its 'non-blockade' effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

Martins SS; Carlson RG; Alexandre PK; Falck RS. Perceived risk associated with ecstasy use: A latent class analysis approach. Addictive Behaviors 36(5): 551-554, 2011. (23 refs.)

This study aims to define categories of perceived health problems among ecstasy users based on observed clustering of their perceptions of ecstasy-related health problems. Data from a community sample of ecstasy users (n = 402) aged 18 to 30, in Ohio, was used in this study. Data was analyzed via Latent Class Analysis (LCA) and Regression. This study identified five different subgroups of ecstasy users based on their perceptions of health problems they associated with their ecstasy use. Almost one third of the sample (28.9%) belonged to a class with "low level of perceived problems" (Class 4). About one fourth (25.6%) of the sample (Class 2), had high probabilities of "perceiving problems on sexual-related items", but generally low or moderate probabilities of perceiving problems in other areas. Roughly one-fifth of the sample (21.1%. Class 1) had moderate probabilities of perceiving ecstasy health-related problems in all areas. A small proportion of respondents (11.9%, Class 5) had high probabilities of reporting "perceived memory and cognitive problems", and of perceiving "ecstasy related-problems in all areas" (12.4%. Class 3). A large proportion of ecstasy users perceive either low or moderate risk associated with their ecstasy use. It is important to further investigate whether lower levels of risk perception are associated with persistence of ecstasy use.

McCann UD; Edwards RR; Smith MT; Kelley K; Wilson M; Sgambati F; Ricaurte G. Altered pain responses in abstinent (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") users. Psychopharmacology 217(4): 475-484, 2011. (56 refs.)

Rationale: (+/-) 3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has potential to damage brain serotonin (5-HT) neurons in humans. Brain 5-HT neurons play a role in pain modulation, yet little is known about long-term effects of MDMA on pain function. Notably, MDMA users have been shown to have altered sleep, a phenomenon that can lead to altered pain modulation. Objectives: This study sought to assess pain processing in MDMA users using objective methods, and explore potential relationships between pain processing and sleep indices. Methods: Forty-two abstinent MDMA users and 43 age-matched controls participated in a 5-day inpatient study. Outcome measures included standardized measures of pain, sleep polysomnograms, and power spectral measures of the sleep EEG. When differences in psychophysiological measures of pain were found, the relationship between pain and sleep measures was explored. Results: MDMA users demonstrated lower pressure pain thresholds, increased cold pain ratings, increased pain ratings during testing of diffuse noxious inhibitory control, and decreased Stage 2 sleep. Numerous significant relationships between sleep and pain measures were identified, but differences in sleep between the two groups were not found to mediate altered pain perception in MDMA users. Conclusions Abstinent MDMA users have altered pain perception and sleep architecture. Although pain and sleep outcomes were related, differences in sleep architecture in MDMA users did not mediate altered pain responses. It remains to be determined whether alterations in pain perception in MDMA users are secondary to neurotoxicity of 5-HT-mediated pain pathways or alterations in other brain processes that modulate pain perception.

Middela S; Pearce I. Ketamine-induced vesicopathy: A literature review. (review). International Journal of Clinical Practice 65(1): 27-30, 2011. (26 refs.)

Ketamine consumption in on the increase as a recreational abuse substance. It is reported to cause lower urinary tract symptoms (LUTS), and published accounts of its deleterious effects are increasing. We reviewed the available literature regarding the urological impact of ketamine abuse and its management. Twenty-two publications were found in total after a search of all databases including Pubmed, Medline and Google Scholar using the words 'ketamine', 'bladder' and 'cystitis' with no limits imposed. There are approximately 110 cases reported in the literature in the form of case series, case reports and letters. The effect of ketamine abuse on the bladder is universally similar; however, there is no uniform method adopted in reporting the symptoms, diagnosis and management. Very little is known regarding the pathogenesis of its effects on the urinary tract. Patients with severe irritative LUTS, a positive history of ketamine abuse and the absence of any other aetiology should be considered to have ketamine-induced vesicopathy. Effort must be made to elicit the history of drug abuse in those with no found cause of LUTS, especially in the young. Presently, ketamine cessation is the only effective treatment modality to prevent deterioration of the renal function and indeed offer the possibility of symptom resolution. Management akin to that formulated for interstitial cystitis patients would appear to offer the greatest opportunity for effective treatment.

Milani HS; Abadi AR; Helmzadeh Z; Abachizadeh K. Prevalence of ecstasy use and predisposing factors among Iranian female high school students. Journal of the Pakistan Medical Association 61(6): 566- 571, 2011. (22 refs.)

Objectives: To determine prevalence of ecstasy use and its predisposing factors among Iranian high school female students in Tehran, capital of Iran. Methods: In this cross-sectional study, 2350 female students of 36 high schools from Tehran, were selected by multi-stage cluster sampling to determine prevalence of ecstasy use and its predisposing factors. SPSS- version 13 was employed to conduct analysis through chi-square, fisher's exact test and logistic regression methods. Results: The prevalence of ecstasy use was 2.3% (95 A,Cl: 1.7-2.9%). Party was the most prevalent place of first use (65%) and access was easy for most users (63%). In multivariate analysis, smoking (P-V=0.005), alcohol use (P-V=003), use of other substances (P-V < 0.001), being in relationship with boys (P-V=0.015), families without one or two parents (P-V=0.020), night spending at friends home without parents' permission (P.V=0.001) were associated with ecstasy use. Conclusion: Due to relation of ecstasy use with other substances, designed programmes should be comprehensive, with different strategies and collaboration of several sectors. The main strategies are to improve students' health literacy, family support, to limit supply and access, and to legislate appropriate regulatory laws.

Mitrevski B; Veleska B; Engel E; Wynne P; Song SM; Marriott PJ. Chemical signature of ecstasy volatiles by comprehensive two-dimensional gas chromatography. Forensic Science International 209(1-3): 11-20, 2011. (42 refs.)

A method for ecstasy volatiles 'signature' analysis based on two-dimensional gas chromatography separation and time-of-flight mass spectrometry detection (GC x GC-TOFMS) is presented. Organic impurity volatiles were extracted by head space solid phase microextraction (HS-SPME). The final column phase choice of the four different column combinations tested was a low-polarity 5% phenyl polysilphenylene-siloxane coupled with a polyethylene glycol phase, which best displayed the complex impurity profile. Second dimension (D-2) retention time reproducibility was found to be about 1% RSD, and area reproducibility of SPME sampling was just over 5% RSD for compounds with S/N ratio of about 100. High similarity of TOFMS spectra of impurities was obtained against commercial MS libraries. 16 components from the two-dimensional profiles were selected for comparison of the 24 ecstasy tablets, most of which proved to be benzodioxole derived compounds. All tablets were correctly classified in eight groups according to their post-tabletting characteristics, when appropriate data pre-treatment was applied. Principal component analysis revealed clustering of samples according to the country of origin. Samples from Macedonia were elevated in N-formyl-MDMA and N-acetyl-MDMA while samples from Australia were elevated in 3,4-methylenedioxypropane and 3,4-methylenedioxyacetophenone. Furthermore, three components were found to be unique for one of the source countries. The additional separation of components on the 2D column, increased response due to modulation, high acquisition rate with full mass spectra using TOFMS detection, and MS deconvolution extend the possibility of detecting additional markers and route-specific components, especially of low abundant, polar components.

Mohamed WMY; Ben Hamida S; Cassel JC; de Vasconcelos AP; Jones BC. MDMA: Interactions with other psychoactive drugs. (review). Pharmacology, Biochemistry And Behavior 99(4): 759-774, 2011. (335 refs.)

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most widely abused illegal drugs. Some users self-report euphoria and an increased perception and feeling of closeness to others. When taken in warm environments. MDMA users may develop acute complications with potential fatal consequences. In rodents, MDMA increases locomotor activity and, depending on ambient temperature, may produce a dose-dependent, potentially lethal hyperthermia. Like most other recreational drugs, MDMA is frequently taken in combination with other substances including tobacco, EtOH, marijuana, amphetamines, cocaine and, caffeine. Although polydrug use is very common, the understanding of the effects of this multiple substance use, as well as the analysis of consequences of different drug-drug associations, received rather little attention. The purpose of this review is to summarize our current knowledge about the changes on MDMA-related behavior, pharmacology, and neurotoxicity associated with co-consumption of other drugs of abuse and psychoactive agents.

Moonzwe LS; Schensul JJ; Kostick KM. The role of MDMA (ecstasy) in coping with negative life situations among urban young adults. Journal of Psychoactive Drugs 43(3): 199-210, 2011. (77 refs.)

This article examines the role of Ecstasy (MDMA or 3, 4-methylenedioxymethamphetamine) as a drug used for self-medication and coping with both short- and long-term negative life situations. We show that urban youth who do not have a specific diagnosed mental illness are more likely than those who have been diagnosed and have received treatment to use Ecstasy to cope with both situational stress and lifetime trauma. Diagnosed and treated youth sometimes self-medicate with other drugs, but do not choose Ecstasy for mediation of their psychological stress. We discuss the implications of self-medication with Ecstasy for mental health services to urban youth experiencing mental health disparities, and for the continued testing and prescription of MDMA for therapeutic use in controlled clinical settings.

Morefield KM; Keane M; Felgate P; White JM; Irvine RJ. Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users. Addiction 106(7): 1293-1300, 2011. (50 refs.)

Aims: To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. Design, setting and participants: A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Measurements: Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Findings: Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-methylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. Conclusions: MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies.

Newton TF. A perhaps unexpected role of norepinephrine in actions of MDMA. (editorial). Clinical Pharmacology & Therapeutics 90(2): 215-216, 2011. (8 refs.)

In this issue, Hysek and colleagues present new data describing the impact of treatment with reboxetine on the effects produced by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in human volunteers. They demonstrate that several effects of MDMA are mediated by reboxetine's actions on norepinephrine (NE) transporters, an unexpected finding. Building on earlier work, their new data provide new insights into the pharmacodynamics of MDMA and other monoamine-releasing agents.

Nulsen C; Fox A; Hammond G. Electrophysiological indices of altered working memory processes in long-term ecstasy users. Human Psychopharmacology: Clinical and Experimental 26(7): 488-497, 2011. (41 refs.)

Objective: The aim of this study was to determine the effect of light long-term ecstasy consumption on verbal short-term and working memory and to identify the cognitive processes contributing to task performance. Method: Electroencephalogram was recorded while ecstasy users (N=11), polydrug users (N=13), and non-users (N=13) completed forward and backward serial recognition tasks designed to engage verbal short-term memory and verbal working memory, respectively. Results All three groups displayed significantly lower digit-backward span than digit-forward span with ecstasy users displaying the greatest difference. The parietally distributed P3b was significantly smaller in the digits backward task than in the digits forward task in non-ecstasy-using controls. Ecstasy users did not show the reduced P3b component in the backward task that was seen in both non-ecstasy-using control groups. Conclusions: Ecstasy users' performance was suppressed more by the concurrent processing demands of the working memory task than that of the non-ecstasy-using controls. Non-ecstasy-using controls showed differential event-related potential wave forms in the short-term and working memory tasks, and this pattern was not seen in the ecstasy users. This is consistent with a reduction in the cognitive resources allocated to processing in working memory in ecstasy users.

Ogeil RP; Rajaratnam SMW; Phillips JG; Redman JR; Broadbear JH. Ecstasy use and self-reported disturbances in sleep. Human Psychopharmacology: Clinical and Experimental 26(7): 508-516, 2011. (40 refs.)

Objective: Ecstasy users report a number of complaints after its use including disturbed sleep. However, little is known regarding which attributes of ecstasy use are associated with sleep disturbances, which domains of sleep are affected or which factors may predict those ecstasy users likely to have poor sleep quality and/or excessive daytime sleepiness. Methods: This study examined questionnaire responses of social drug users (n = 395) to the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Results: A significant proportion of ecstasy users (69.5%) had Pittsburgh Sleep Quality Index scores above the threshold used to identify sleep disturbance. Although frequency of ecstasy use did not affect the degree of reported sleep disturbance, participants who used larger amounts of ecstasy had poorer sleep. In addition, participants who perceived harmful consequences arising from their ecstasy use or had experienced remorse following ecstasy use had poorer sleep. Clinically relevant levels of sleep disturbance were still evident after controlling for polydrug use. Risk factors for poor sleep quality were younger age, injury post-ecstasy use and having been told to cut down on ecstasy use. Conclusions: Many ecstasy users report poor sleep quality, which likely contributes to the negative effects reported following ecstasy use.

Palamar JJ; Kiang MV; Halkitis PN. Development and psychometric evaluation of scales that assess stigma associated with illicit drug users. Substance Use & Misuse 46(12): 1457-1467, 2011. (36 refs.)

This study established validity evidence for scales that assess perceived public stigma and stigmatization of illicit drug use. These concepts were measured with respect to five commonly used drugs: marijuana, powder cocaine, ecstasy, and nonmedical use of opioids and amphetamine. Data were collected from a diverse sample of 1,048 emerging adults in New York City in 2009. Exploratory and confirmatory factor analyses suggested two distinct factors, which were inversely related to exposure to users and recent use of each drug. These measures demonstrated good criterion, construct, and incremental validity and effectiveness in analyzing predictors of use. Study limitations were discussed.

Parrott AC; Gibbs A; Scholey AB; King R; Owens K; Swann P et al. MDMA and methamphetamine: Some paradoxical negative and positive mood changes in an acute dose laboratory study. Psychopharmacology 215(3): 527- 536, 2011. (58 refs.)

This study investigated the acute mood effects of oral MDMA, methamphetamine, and placebo in a double-blind laboratory study. Fifty-two healthy participants comprised abstinent recreational users of stimulant drugs, 27 female and 25 male, mean age 24.8 years. Three test sessions involved acute 100 mg oral 3.4-methylendioxymethamphetamine (MDMA), 0.42 mg/kg oral methamphetamine, and matching placebo. Drug administration was counterbalanced, testing was double-blind, and medical supervision was present throughout. Car-driving performance on a laboratory simulator was assessed after 3 and 24 h, with the findings being presented elsewhere. Positive and negative moods (PANAS self-ratings) were completed before drug administration, 3, 4.5, and 24 h later. Blood samples were taken to monitor drug plasma levels. Following MDMA, there were no significant increases in positive moods, whereas negative moods were significantly higher than under placebo. Methamphetamine led to significant increases in both positive and negative moods. The MDMA findings contrast with the elated moods, typically noted by dance clubbers on Ecstasy. However, they are consistent with some previous laboratory findings, since a wide array of positive and negative mood changes have been demonstrated. One possible explanatory factor was the neutral environmental situation, particularly if a primary action of MDMA is to intensify ongoing psychological states. Other explanatory factors, such as dosage, gender, post-drug timing, neurohormonal aspects, and social factors, are also discussed. In the laboratory, acute methamphetamine led to significantly higher positive moods. However, against expectations, MDMA did not generate a significant increase in positive moods.

Roberts DM; Smith MWH; Gopalakrishnan M; Whittaker G; Day RO. Extreme gamma-butyrolactone overdose with severe metabolic acidosis requiring hemodialysis. Annals of Emergency Medicine 58(1): 83-85, 2011. (14 refs.)

gamma-Hydroxybutyrate (GHB) and its precursor gamma-butyrolactone (GBL) are commonly abused drugs with a narrow therapeutic index. Therefore, overdoses occur readily with recreational use, and severe poisoning can occur after deliberate self-poisoning. We report the sequelae in a patient who ingested a massive dose of GBL, with suicidal intent. Severe metabolic acidosis and an asystolic cardiac arrest were successfully treated with standard resuscitation, supportive care, and continuous venovenous hemodiafiltration. Plasma GHB concentrations were the highest reported to date. The acidosis was attributed to rapid systemic absorption of GBL, followed by rapid metabolism to GHB.

Romero-Sandoval EA. Depression and pain: Does ketamine improve the quality of life of patients in chronic pain by targeting their mood? (editorial). Anesthesiology 115(4): 687-688, 2011. (10 refs.)

Sawyer-Kurian KM; Browne FA; Carney T; Petersen P; Wechsberg WM. Exploring the intersecting health risks of substance abuse, sexual risk, and violence for female South African teen dropouts. Journal of Psychology in Africa 21(1): 15- 25, 2011. (41 refs.)

The study sought to better understand the cultural contexts of the risks for adolescent females who have dropped out of school. Focus groups were conducted with 37 Black and Coloured females aged 13 to 17 in Cape Town, South Africa. Data were analysed using content analysis. Methamphetamine, cannabis, and alcohol were used by both, however, Black teens also used methaqualone and Coloured teens used heroin and ecstasy. Some teens traded sex for drugs and others did so at the request of their drug-addicted mothers. Teens revealed high rates of violence, including rape, and many myths and barriers about condom use, revealing risky sex behaviours. Conclusion: Cultural nuances between the two groups will help inform the adaptation of an HIV prevention intervention.

Schwaninger AE; Meyer MR; Barnes AJ; Kolbrich-Spargo EA; Gorelick DA; Goodwin RS et al. Stereoselective urinary MDMA (ecstasy) and metabolites excretion kinetics following controlled MDMA administration to humans. Biochemical Pharmacology 83(1): 131-138, 2012. (36 refs.)

The R- and S-enantiomers of racemic 3,4-methylenedioxymethamphetamine (MDMA) exhibit different dose-concentration curves. In plasma, S-MDMA was eliminated at a higher rate, most likely due to stereoselective metabolism. Similar data were shown in various in vitro experiments. The aim of the present study was the in vivo investigation of stereoselective elimination of MDMA's phase I and phase II metabolites in human urine following controlled oral MDMA administration. Urine samples from 10 participants receiving 1.0 and 1.6 mg/kg MDMA separated by at least one week were analyzed blind by liquid chromatography-high resolution-mass spectrometry and gas chromatography-mass spectrometry after chiral derivatization with S-heptafluorobutyrylprolyl chloride. R/S ratios at C(max) were comparable after low and high doses with ratios >1 for MDMA, free DHMA, and HMMA sulfate, and with ratios <1 for MDA, free HMMA, DHMA sulfate and HMMA glucuronide. In the five days after the high MDMA dose, a median of 21% of all evaluated compounds were excreted as R-stereoisomers and 17% as S-stereoisomers. Significantly greater MDMA, DHMA, and HMMA sulfate R-enantiomers and HMMA and HMMA glucuronide S-stereoisomers were excreted. No significant differences were observed for MDA and DHMA sulfate stereoisomers. Changes in R/S ratios could be observed over time for all analytes, with steady increases in the first 48 h. R/S ratios could help to roughly estimate time of MDMA ingestion and therefore, improve interpretation of MDMA and metabolite urinary concentrations in clinical and forensic toxicology.

Shram MJ; Sellers EM; Romach MK. Oral ketamine as a positive control in human abuse potential studies. Drug and Alcohol Dependence 114(2-3): 185- 193, 2011. (46 refs.)

The selection of a relevant and appropriate positive control is of key importance in the design of a clinical abuse potential study. Ketamine is a N-methyl-n-aspartate receptor antagonist used clinically as an anaesthetic, yet also abused for its euphoric and perceptual properties. The current study sought to identify 2 doses of oral ketamine that are safe and produce subjective effects that would make them suitable for use as positive controls in abuse potential studies. A single-center, partially double-blind, placebo-controlled, ascending dose (65,100 and 150 mg)study was carried out in 11 healthy recreational polydrug users who first passed a pharmacologic qualification session to ensure they could distinguish and like the effects of a psychoactive drug (20 mg n-amphetamine) compared to placebo. Subjective data were collected through questionnaires (e.g., Addiction Research Center Inventory [ARCI] scales) and visual analog scales (VAS). Generally, oral ketamine was well tolerated and could be used safely at 65 mg and 100 mg. Peak responses to ketamine were significantly different (p < 0.05) from placebo on measures of positive (e.g., drug liking VAS), perceptual (e.g., VAS of floating, detached, hallucinating) and sedative (e.g., ARCI phenobarbital-chlorpromazine-alcohol group scale) effects. Effects were generally not dose-dependent, though significant differences for some subjective effects measures were observed between 65 mg and 100 mg ketamine. The current study indicates that oral ketamine doses of 65 mg and 100 mg are useful positive controls for future abuse potential studies of compounds with a similar mechanism of action, or with possible perception-altering and euphoric effects.

Singer EO; Schensul JJ. Negotiating ecstasy risk, reward, and control: A qualitative analysis of drug management patterns among ecstasy-using urban young adults. Substance Use & Misuse 46(13): 1675-1689, 2011. (37 refs.)

This paper is based on qualitative in-depth interviews conducted from 2008 to 2009 with 118 ethnically diverse Ecstasy users from the greater Hartford area, CT, USA. Participants were urban, primarily Black and Hispanic, aged 18 to 36, and had limited higher education compared with samples in previous Ecstasy research. Interviews focused on personal background, history of Ecstasy and other drug use, and recent sexual events. In this paper, we examine: participants' negotiation of perceived risks and benefits of Ecstasy use, behavioral strategies employed to minimize risks, and the relationship of risk-benefit analysis, motivation for use, frequency of use, and polydrug use to participants' sense of control over their Ecstasy use. We conclude with recommendations for intervention approaches and suggestions for future research.

Sircar R; Wu LC; Reddy K; Sircar D; Basak AK. GHB-Induced cognitive deficits during adolescence and the role of nmda receptor. Current Neuropharmacology 9(1): 240-243, 2011. (29 refs.)

We have earlier reported that-hydroxybutyric acid (GHB) disrupts the acquisition of spatial learning and memory in adolescent rats. GHB is known to interact with several neurotransmitter systems that have been implicated in cognitive functioning. The N-methyl-D-aspartate receptor (NR)-type of glutamate receptor is considered to be an important target for spatial learning and memory. Molecular mechanisms governing the neuroadptations following repeated GHB treatment in adolecent rats remain unknown. We examined the role of NMDA receptor in adolescent GHB-induced cognitive deficit. Adolescent rats were administered with GHB on 6 consecutive days, and surface-expressed NMDA receptor subunits levels were measured. GHB significantly decreased NR1 levels in the frontal cortex. Adolescent GHB also significantly reduced cortical NR2A subunit levels. Our findings support the hypothesis that adolescent GHB-induced cogntive deficits are associated with neuroadaptations in glutamatergic transmission, particulaly NR functioning in the frontal cortex.

Smerdon MJ; Francis AJP. Reward sensitivity and outcome expectancies as predictors of ecstasy use in young adults. Addictive Behaviors 36(12): 1337-1340, 2011. (31 refs.)

Extending recent studies showing that sensitivity to reward and outcome expectancies are associated with problematic alcohol and cannabis use, we undertook to determine if similar relationships would hold for ecstasy. One hundred and twenty five males and females aged between 18 and 35 years were recruited from RMIT University and through snowball sampling. Participants completed a questionnaire package measuring frequency, amount and first age of ecstasy use, sensitivity to reward and punishment as well as outcome expectancies relating to ecstasy use. Frequency of ecstasy use was significantly related to reward sensitivity (p<.05) and positive outcome expectancies (p<.01). Regression analysis revealed significant prediction of ecstasy use by study variables, with expectations of increased confidence making the largest individual contribution. Multiple intervention points are suggested by the results of this study, within a largely cognitive-based framework.

Susnjara IM; Smoljanovic A; Gojanovic MD. Drug related deaths in the Split-Dalmatia County 1997-2007. Collegium Antropologicum 35(3): 823-828, 2011. (40 refs.)

Drug overdoses are a major cause of mortality for drug users and, in many countries, are the leading cause of death in this group. The aim of the present study is to explore the frequency of all drug related deaths in the Split-Dalmatia County in the period between 1997 and 2007 and to analyze some of the characteristics of these deaths to help target preventive policies. The data on drug related deaths were collected using records from the Department of Forensic Medicine, Clinical Hospital Centre Split, University of Split, School of Medicine. There were 190 drug related deaths in the observed period of 11 years. Statistically significant difference (p=0.004, chi(2)-test for trend) was found in the number of deaths in 1997 in comparison with the number of deaths in 2007. The majority of 105 (55%) the decedents were 25-34 years old, and 92.1% (175) of them were male. There was a 94% higher probability of mortality in the 25-34 years group (chi(2)=5.55, p=0.064). Average age of all dead people was 31.01 +/- 7.59 years (median 31.0 years; range 18-49). Almost three quarters of the decedents were single and more than three fifths hadn't been employed. The most common location of death was at home. Approximately, 80% were autopsied followed by full histological and toxicological analyses. Out of all examined cases, the majority of drug related deaths (93 or 60.8%) were attributed to heroin. Heroin was the sole cause of death in 35(22.9%) cases. Methadone was cause of death in 24 (15.7%) cases. 3.4-methylenedioxy-methamphetamine (MDMA) deaths were rare (3.3%). Cocaine deaths were also rare (1.3%). Three fifths (55.6%) of the cases involved includes multi-substance use. During the investigation there was an evident trend towards multi-substance abuse patterns. These data suggest that interventions to prevent drug related mortality should address the use of drugs such as heroin and alcohol in combination.

Temple JR; Freeman DH. Dating violence and substance use among ethnically diverse adolescents. Journal of Interpersonal Violence 26(4): 701-718, 2011. (61 refs.)

Teen dating violence is a serious public health concern with numerous and long-lasting consequences. Although alcohol and drug use have been associated with dating violence, little is known about the role of specific substances, especially the use of club drugs and the nonmedical use of prescription drugs. Thus, the authors examined the association between dating violence victimization and the use of a variety of licit and illicit substances among 1,565 ethnically diverse and economically disadvantaged high school students in southeast Texas. Past year dating violence victimization was reported by 14.1% of boys and 11.3% of girls. Compared to their nonabused counterparts, youth who experienced dating violence were more likely to smoke cigarettes, drink alcohol, binge drink alcohol, sniff glue to get high, use marijuana, use ecstasy, use Vicodin, and use Xanax. However, with the exception of alcohol and cigarettes, all substances were reduced to nonsignificance in multivariate analyses. No differences were found in the rate of dating violence between African American, White, and Hispanic adolescents.

Uchaipichat V; Raungrut P; Chau N; Janchawee B; Evans AM; Miners JO. Effects of ketamine on human udp-glucuronosyltransferases in vitro predict potential drug-drug interactions arising from ketamine inhibition of codeine and morphine glucuronidation. Drug Metabolism and Disposition 39(8): 1324-1328, 2011. (25 refs.)

In this study, the selectivity of UDP-glucuronosyltransferase (UGT) enzyme inhibition by ketamine (KTM) and the kinetics of KTM inhibition of human liver microsomal morphine (MOR) and codeine (COD) glucuronidation were characterized to explore a pharmacokinetic basis for the KTM-opioid interaction. With the exception of UGT1A4, KTM inhibited the activities of recombinant human UGT enzymes in a concentration-dependent manner. However, IC(50) values were < 100 mu M only for UGT2B4, UGT2B7, and UGT2B15. UGT2B7 catalyzes MOR 3- and 6-glucuronidation and the 6-glucuronidation of COD, with an additional substantial contribution of UGT2B4 to the latter reaction. Consistent with the effects of KTM on the activities of recombinant UGT2B enzyme activities, KTM competitively inhibited human liver microsomal MOR and COD glucuronidation. K(i) values for KTM inhibition of MOR 3- and 6-glucuronidation and COD 6-glucuronidation by human liver microsomes supplemented with 2% bovine serum albumin were 5.8 +/- 0.1, 4.6 +/- 0.2, and 3.5 +/- 0.1 mu M, respectively. Based on the derived inhibitor constants, in vitro-in vivo extrapolation was used to predict the effects of anesthetic and analgesic doses of KTM on MOR and COD clearances. Potentially clinically significant interactions (>50% increases in the in vivo area under the curve ratios) with MOR and COD were predicted for anesthetic doses of KTM and for a subanesthetic dose of KTM on COD glucuronidation.

Van Havere T; Vanderplasschen W; Lammertyn J; Broekaert E; Bellis M. Drug use and nightlife: More than just dance music. Substance Abuse Treatment, Prevention and Policy 6: e-article 18, 2011. (58 refs.)

Background: Research over the last decade has focused almost exclusively on the association between electronic music and MDMA (3,4-Methylenedioxymethamphetamine or "ecstasy") or other stimulant drug use in clubs. Less attention has been given to other nightlife venues and music preferences, such as rock music or southern/funky music. This study aims to examine a broader spectrum of nightlife, beyond dance music. It looks at whether certain factors influence the frequency of illegal drug and alcohol use: the frequency of going to certain nightlife venues in the previous month (such as, pubs, clubs or goa parties); listening to rock music, dance music or southern and funky music; or sampling venues (such as, clubs, dance events or rock festivals). The question of how these nightlife variables influence the use of popular drugs like alcohol, MDMA, cannabis, cocaine and amphetamines is addressed. Methods: The study sample consisted of 775 visitors of dance events, clubs and rock festivals in Belgium. Study participants answered a survey on patterns of going out, music preferences and drug use. Odds ratios were used to determine whether the odds of being an illegal substance user are higher for certain nightlife-related variables. Furthermore, five separate ordinal regression analyses were used to investigate drug use in relation to music preference, venues visited during the last month and sampling venue. Results: Respondents who used illegal drugs were 2.5 times more likely to report that they prefer dance music. Goa party visitors were nearly 5 times more likely to use illegal drugs. For those who reported visiting clubs, the odds of using illegal drugs were nearly 2 times higher. Having gone to a pub in the last month was associated with both more frequent alcohol use and more frequent illegal substance use. People who reported liking rock music and attendees of rock festivals used drugs less frequently. Conclusions: It was concluded that a more extended recreational environment, beyond dance clubs, is associated with frequent drug use. This stresses the importance of targeted prevention in various recreational venues tailored to the specific needs of the setting and its visitors.

Venancio C; Magalhaes A; Antunes L; Summavielle T. Impaired spatial memory after ketamine administration in chronic low doses. Current Neuropharmacology 9(1): 255-259, 2011. (29 refs.)

Ketamine is a noncompetitive antagonist of the NMDA-receptors, used as a dissociative anesthetic, presently included in the category of the psychoactive substances known as "club drugs". Ketamine administration was associated with impaired working memory and increased psychopathological symptoms, but there is a lack of information regarding the effects of chronic sub-anesthetic doses. Adult Wistar rats were administered ketamine, 5 and 10 mg/kg twice daily, subcutaneously for 14 days. One week later, rats were tested in an object recognition/object location task and in the open field arena. There was altered performance in both the object recognition/location and in the open field tests by the group chronically exposed to the lower dose of ketamine. These animals displayed a decreased discrimination index (p<0.05) in the object recognition task, were unable to recognize the displacement of a familiar object and displayed decreased activity across open filed sessions. Importantly, these alterations were not observed in animals administered a higher dose of ketamine. Collectively, these results consistently show that chronic administration of ketamine in sub-anesthetic doses may lead to decreased habituation and inability to update spatial representations.

Watson C; Wilkinson J. The intensive care management of common and uncommon drugs of misuse. (review). British Journal of Hospital Medicine 72(4): 211-218, 2011. (33 refs.)

With an ever-expanding field of illicit drugs available, doctors working in the acute specialties will inevitably be involved in the management of the serious and life-threatening side effects of drug misuse, as outlined in this article.

Wilkins LK; Girard TA; Cheyne JA. Ketamine as a primary predictor of out-of-body experiences associated with multiple substance use. Consciousness and Cognition 20(3): 943-950, 2011. (33 refs.)

Investigation of "out-of-body experiences" (OBEs) has implications for understanding both normal bodily-self integration and its vulnerabilities. Beyond reported associations between OBEs and specific brain regions, however, there have been few investigations of neurochemical systems relevant to OBEs. Ketamine, a drug used recreationally to achieve dissociative experiences, provides a real-world paradigm for investigating neurochemical effects. We investigate the strength of the association of OBEs and ketamine use relative to other common drugs of abuse. Self-report data (N = 192) from an online survey indicate that both lifetime frequency of ketamine use and OBEs during ketamine intoxication were more strongly related to the frequency of OBEs and related phenomena than other drugs. Moreover, the apparent effects of other drugs could largely be explained by associated ketamine use. The present results, consistent with the role of NMDA receptors in OBEs, should encourage future studies of the role of neurochemical systems in OBEs.

Wilkins C; Sweetsur P; Griffiths R. Recent trends in pharmaceutical drug use among frequent injecting drug users, frequent methamphetamine users and frequent ecstasy users in New Zealand, 2006-2009. Drug and Alcohol Review 30(3): 255- 263, 2011. (22 refs.)

Aims. To examine the rates of pharmaceutical drug use, and level of prescription use and injection of pharmaceutical drugs, by frequent injecting drug users (IDU), frequent methamphetamine users and frequent ecstasy users in New Zealand for 2006-2009. Design: and method. The paper draws on findings from the 2006, 2007, 2008 and 2009 Illicit Drug Monitoring System (IDMS). The IDMS interviews three groups of frequent illegal drug users (i.e. IDU, methamphetamine users and ecstasy users) from the three main cities of New Zealand using purposive sampling and 'snowballing'. Results. Pharmaceutical morphine rather than heroin was the principal opioid used by the IDU. Few of the IDU or frequent methamphetamine users had prescriptions to use morphine. A lower proportion of the IDU had a prescription to use morphine in 2009 compared to 2008. The injection of methadone by IDU and methamphetamine users was common. A higher proportion of the IDU had injected methadone in 2009 compared to previous years. A higher proportion of the IDU had used oxycodone in 2009 compared to 2008 and prescription use of oxycodone by IDU was very low. All three groups of frequent drug users were involved in the extra-medical use of methylphenidate and benzodiazepines. Discussion and conclusion. Extra-medical use of pharmaceuticals occurred among all three groups of frequent illegal drug users to varying degrees. Differences between the three groups in the level and type of extra-medical pharmaceutical drug use suggest that different control strategies may be effective for each group.

Wimmer K; Schneider S. Screening for illicit drugs on Euro banknotes by LC-MS/MS. Forensic Science International 206(1-3): 172-177, 2011. (22 refs.)

A method for the simultaneous quantification of illicit drugs on Euro banknotes, using an ultra-performance liquid chromatography tandem mass spectrometry, was developed and validated. The method included cocaine, benzoylecgonine, MDMA, MDEA, MDA, methamphetamine, diacetylmorphine, 6-MAM, morphine and Delta(9)-THC. Drug residues were monitored and quantified via positive ESI mode using multiple reaction monitoring. Banknotes were extracted with methanol by vigorous shaking. Recovery rates were in the range of 60-80%. Calibration was performed with spiked banknotes in the range of 10-100 ng/note (R-2 0.98-0.99). Intra-day analysis showed fair precision and accuracy (<= 15%). Matrix effects were in the range from 27% to 235%. 7-15 samples of each denomination were analyzed. The calculated median values per note were 106 ng cocaine, 43 ng benzoylecgonine, 41 ng heroin, 15.5 ng 6-MAM, 16.5 ng morphine, 9 ng MDMA and 7 ng methamphetamine. Delta(9)-THC was detected on 4 banknotes. MDEA and MDA were not detected on any note. A widespread background contamination for cocaine and opiates was demonstrated.

Wood DM; Brailsford AD; Dargan PI. Acute toxicity and withdrawal syndromes related to gamma-hydroxybutyrate (GHB) and its analogues gamma-butyrolactone (GBL) and 1,4-butanediol(1,4-BD)(1). (review). Drug Testing and Analysis 3(7-8, special issue): 417-425, 2011. (123 refs.)

Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues gamma-butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues.

Wood DM; Stribley V; Dargan PI; Davies S; Holt DW; Ramsey J. Variability in the 3,4-methylenedioxymethamphetamine content of 'ecstasy' tablets in the UK. Emergency Medicine Journal 28(9): 764-765, 2011. (9 refs.)

Background Toxicity, such as hyperpyrexia, associated with the use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') appears to be related to serum MDMA concentrations. However, there does not appear to be a similar association with the number of tablets ingested, suggesting variation in the tablet content of MDMA. Although work has shown this variation in other areas of the world, no studies have reported on the variation of MDMA content in UK ecstasy tablets. Methods Ecstasy tablets seized from individuals attending nightclubs were analysed qualitatively to determine if they contained MDMA and quantitatively to determine the MDMA content per tablet. Results: The mean amount of MDMA hydrochloride in 101 seized ecstasy tablets was 58.7 +/- 22.9 mg per tablet, with a range of 20 mg to 131 mg per tablet. The majority (96.0%) of tablets contained less than 100 mg MDMA per tablet. There appeared to be a bimodal distribution of MDMA content at approximately 20-40 mg per tablet and 60-80 mg per tablet. Conclusion: There is variability in the MDMA content of ecstasy tablets in the UK. This variability could potentially put users at increased risk of acute harm due to inadvertent excess ingestion of MDMA, as they are unaware of the differences in the MDMA content. Repeat sampling and quantification of MDMA content of ecstasy tablets in the UK will allow better education of users about the potential harms associated with the variability in the MDMA content. In addition, it will provide information to allow the monitoring of changes in not only the MDMA content, but also other adulterants, in ecstasy tablets.

Wu ZH; Grady JJ; Rosales S; Berenson AB. Ecstasy use and its correlates among young, low-income women. Substance Use & Misuse 46(4): 404-410, 2011. (43 refs.)

We examined the association of illicit drug use with stress and sexual behaviors among 407 women, aged 18-31, who attended family-planning clinics in southeast Texas between June 2002 and May 2003 (n = 407). Paired comparisons of each of three types of drug users (of ecstasy, marijuana only, and other illicit drugs except ecstasy) with nonusers were assessed by logistic regressions. After controlling for demographics, both ecstasy users and marijuana-only users had a higher score on the stress scale than nonusers. All drug users were at higher risk of more lifetime sexual partners than those who had never used drugs, while those who had used ecstasy were more than twice as likely to have had prior sexually transmitted infections as those who had never used drugs. This study demonstrates that young, low-income women who use ecstasy experience higher levels of stress than nonusers. Stress level is correlated with drug use and participation in risky sexual behaviors. If stress is associated with drug use and risky sexual behavior, interventions designed to reduce substance use and risky sexual behavior in these women may need to also address factors that lead to increased stress. The study's limitations were noted.

Zvosec DL; Smith SW; Porrata T; Strobl AQ; Dyer JE. Case series of 226 gamma-hydroxybutyrate-associated deaths: Lethal toxicity and trauma. (review). American Journal of Emergency Medicine 29(3): 319-332, 2011. (97 refs.)

gamma-Hydroxybutyrate (GHB) and its prodrugs are drugs of abuse that were also sold as "dietary supplements." Users present to emergency departments with overdose, impaired driving, withdrawal, and associated trauma. We compiled a series of GHB-associated deaths to elucidate lethal risks, GHB concentrations, cointoxicants, products, uses, and medical interventions. Death records were reviewed for toxicology, autopsy findings, and history. Inclusion cutoffs were as follows: 5/10 mg/L of GHB (antemortem blood/urine) and 50/20/7 mg/L of GHB (postmortem blood/urine/vitreous). 01226 deaths included, 213 had cardiorespiratory arrest and 13 had fatal accidents. Seventy-eight deaths (35%) had no cointoxicants. Sixteen deaths involved "supplements" and 1 involved pharmaceutical GHB (Xyrem, jazz Pharmaceuticals, Palo Alto, CA). Postmortem blood GHB was 18 to 4400 mg/L (median, 347 mg/L) in deaths negative for cointoxicants. Cardiorespiratory arrest occurred prehospital in 100% of 184 cases with available history. Of 72 cases with antemortem adverse effects reported, medical assistance was delayed or absent in 66; of these, acute GHB ingestion was known in 51, including 40 left to "sleep off" adverse effects. Thirty others were left "sleeping" and found dead. gamma-Hydroxybutyrate is lethal even without cointoxicants, directly and through fatal accidents. Medical interventions were frequently delayed or absent despite known GHB ingestion, and witnessed adverse events and cardiorespiratory arrest occurred prehospital. Education is needed about the lethality of GHB and the necessity for prompt medical intervention.