MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') toxicity: a brief overview and update.

OBJECTIVES: MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') is a psychoactive substance, sold primarily over the Internet and in 'head' shops as a 'legal high'. Synthesised and used as a research chemical in the 1990s, MDAI has structural similarities to MDMA (3,4-methylenedioxy-N-methylamphetamine) and shares its behavioural properties. Recreational use of MDAI appears to have started in Europe around 2007, with a noticeable increase after 2009 in the UK and other countries. Calls to National Poisons Information Services started in 2010, although there were few presentations to emergency departments by patients complaining of undesirable physical and psychiatric effects after taking MDAI. Recreational use of this drug has been reported only occasionally by online user fora. There is little scientifically based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of this drug. METHODS: Recent literature (including 'grey') was searched to update what is known about MDAI, especially on its toxicity. RESULTS: The resultant information is presented, including on the first three UK deaths involving MDAI use in 2011 and 2012. 'Serotonin syndrome' appears to be a possible factor in these fatalities. CONCLUSION: It is vital that any other cases, including non-fatal overdoses, are documented so that a scientific evidence base can be established for them.

Suspected and confirmed fatalities associated with mephedrone (4-methylmethcathinone, "meow meow") in the United Kingdom.

BACKGROUND: International media have been reporting about fatalities allegedly related to mephedrone, a popular recreational stimulant, but now a proportion of them have been confirmed. We aimed here at analyzing information relating to the circumstances of mephedrone-related deaths in the United Kingdom. METHODS: Descriptive analysis of information was mainly extracted from the UK National Programme on Substance Abuse Deaths database. With an average annual response rate of 95%, UK National Programme on Substance Abuse Deaths receives information from coroners on drug-related deaths among both addicts and nonaddicts in the United Kingdom, the Channel Islands, and the Isle of Man. RESULTS: So far, 128 alleged mephedrone-associated fatalities have been reported; mephedrone was identified at postmortem in 90 cases; inquests have been concluded in 69 cases, 62 of which are analyzed here. Typical mephedrone victims were young (mean age, 28.8 years), male, and with a previous history of drug misuse. There was a notable number (18 cases [29%], 11 being from hanging) of deaths involving self-harm. Mephedrone alone was identified at postmortem on 8 occasions (13% of the inquests' sample). CONCLUSIONS: Present mortality data may suggest a significant level of caution when ingesting mephedrone. Limitations include an inability to determine the exact extent of risks associated with mephedrone consumption.

The recreational tryptamine 5-MeO-DALT (N,N-diallyl-5-methoxytryptamine): a brief review.

5-MeO-DALT (N,N-diallyl-5-methoxytryptamine) is a psychoactive substance, sold primarily over the Internet as a 'research chemical' or 'plant food'. Although details for the synthesis of this tryptamine have been available since 2004, its use as a hallucinogenic drug has been reported only occasionally in on-line user fora. It is controlled in only a few countries world-wide. There is little scientifically-based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of 5-MeO-DALT. Here we review what is known about these aspects. We also report what we believe to be the first death involving the use of this substance. The case involved a man in his mid-20s who died in mid-2010. The coroner concluded that the deceased "died from injuries sustained after being hit by a lorry whilst under the influence of 5-MeODALT". It is critical that any other cases, including non-fatal instances, are documented so that a scientific evidence-base can be established for this drug.

2-DPMP (desoxypipradrol, 2-benzhydrylpiperidine, 2-phenylmethylpiperidine) and D2PM (diphenyl-2-pyrrolidin-2-yl-methanol, diphenylprolinol): A preliminary review.

2-DPMP (desoxypipradrol, 2-benzhydrylpiperidine, 2-phenylmethylpiperidine) and D2PM (diphenyl-2-pyrrolidin-2-yl-methanol, diphenylprolinol) are psychoactive substances, sold primarily over the Internet and in 'head' shops as 'legal highs', 'research chemicals' or 'plant food'. Originally developed in the 1950s for the treatment of narcolepsy and ADHD, 2-DPMP's use soon became very limited. Recreational use of 2-DPMP and D2PM appears to have started in March 2007, but only developed slowly. However, in the UK their popularity grew in 2009, increasing rapidly during summer 2010. At this time, there were many presentations to UK Emergency Departments by patients complaining of undesirable physical and psychiatric effects after taking 2-DPMP. In spring 2011 there were similar presentations for D2PM. Recreational use of these drugs has been reported only occasionally in on-line user fora. There is little scientifically-based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of these drugs. Here we describe what is known about them, especially on their toxicity, including what we believe to be the first three deaths involving the use of 2-DPMP in August 2010. There are no international controls imposed on 2-DPMP or D2PM. However, a ban on their UK importation was imposed in November 2011 and they became Class C drugs on 13 June 2012. It is critical that any other cases, including non-fatal overdoses, are documented so that a scientific evidence-base can be established for them.

Overview of literature and information on "khat-related" mortality: a call for recognition of the issue and further research.

During the past 20 years or so, more has become known about the properties of khat, its pharmacology, physiological and psychological effects on humans. However, at the same time its reputation of social and recreational use in traditional contexts has hindered the dissemination of knowledge about its detrimental effects in terms of mortality. This paper focuses on this particular deficit and adds to the knowledge-base by reviewing the scant literature that does exist on mortality associated with the trade and use of khat. We sought all peer-reviewed papers relating to deaths associated with khat. From an initial list of 111, we identified 15 items meeting our selection criteria. Examination of these revealed 61 further relevant items. These were supplemented with published reports, newspaper and other media reports. A conceptual framework was then developed for classifying mortality associated with each stage of the plant's journey from its cultivation, transportation, consumption, to its effects on the human body. The model is demonstrated with concrete examples drawn from the above sources. These highlight a number of issues for which more substantive statistical data are needed, including population-based studies of the physiological and psychological determinants of khat-related fatalities. Khat-consuming communities, and health professionals charged with their care should be more aware of the physiological and psychological effects of khat, together with the risks for morbidity and mortality associated with its use. There is also a need for information to be collected at international and national levels on other causes of death associated with khat cultivation, transportation, and trade. Both these dimensions need to be understood.

Deaths of opiate/opioid misusers involving dihydrocodeine, UK, 1997-2007.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Dihydrocodeine (DHC) is an opioid analgesic sometimes prescribed as an alternative to other medications (e.g. methadone and buprenorphine) for opioid misuse. Its effectiveness is, however, still controversial. DHC prescription rates seem to be related to levels of DHC fatalities, possibly in relation to levels of disregard of the availability of supervised or interval dispensing of opioids, but no large-scale analysis of DHC fatalities has been carried out. We analysed here involvement of DHC in fatalities that occurred between 1997 and 2007 among individuals with a history of opiate/opioid misuse reported to the National Programme on Substance Abuse Deaths (np-SAD). WHAT THIS STUDY ADDS: DHC, either alone or in combination, was identified in 584 fatalities. Typical cases identified were males in their early thirties. In accidental overdoses, DHC, which had been prescribed to 45% of the victims, was typically identified in combination with other drugs, such as heroin/morphine, methadone and hypnotics/sedatives. Both paracetamol and antidepressants were more typically identified in combination with DHC in suicides. Opiate/opioid misusers should be educated about risks associated with polydrug intake and prescribers should carefully consider a pharmacological intervention alternative to DHC (e.g. methadone, buprenorphine) when managing and treating opiate addiction. AIMS: Although its effectiveness is somewhat controversial, it appears that dihydrocodeine (DHC) is still prescribed in the UK as an alternative to both methadone and buprenorphine for the treatment of opiate addiction. METHODS: Data covering the period 1997-2007 voluntarily supplied by coroners were analysed. All cases pertaining to victims with a clear history of opiate/opioid misuse and in which DHC, either on its own or in combination, was identified at post-mortem toxicology and/or implicated in death, were extracted from the database. RESULTS: Dihydrocodeine, either alone or in combination, was identified in 584 fatalities meeting the selection criteria. In 44% of cases it was directly implicated in the cause of death. These cases represented about 6.8% of all opiate/opioid-related deaths during this period. Typical DHC cases identified were White males in their early thirties. Accidental deaths (96%) were likely to involve DHC in combination with other psychoactives, mainly heroin/morphine, hypnotics/sedatives and methadone. Both paracetamol and antidepressants were found in proportionately more suicide cases than in accidental overdoses. DHC had been prescribed to the decedent in at least 45% of cases. CONCLUSIONS: Opiate/opioid misusers should be educated about risks associated with polydrug intake. More in particular, co-administration of DHC with heroin, methadone and benzodiazepines may increase the risk of accidental fatal overdose. Prescribers should carefully consider pharmacological intervention alternative to DHC (e.g. methadone, buprenorphine) when managing and treating opiate addiction. More resources are required to do prospective research in this area.

Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues.

BACKGROUND: Recently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; 'meow meow' and others) has been seen by some as a cheaper alternative to other classified recreational drugs. AIMS: We aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry, pharmacology, legal status, product market appearance, clinical/management and related fatalities. METHODS: Because of the limited evidence, some of the information here presented has been obtained from user reports/drug user-orientated web sites. The most common routes for mephedrone recreational use include insufflation and oral ingestion. It elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem. DISCUSSION AND CONCLUSIONS: Within the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs.

A survey of staff attitudes to smoking-related policy and intervention in psychiatric and general health care settings.

BACKGROUND: Although the move to smoke-free hospital settings is generally a popular initiative, it may be a more challenging and controversial issue in mental health care. A survey was carried out to investigate differences in attitudes between clinical staff in psychiatric and general medical settings to smoke-free policy and intervention. METHOD: The sample comprised 2574 NHS staff working in two Acute Hospital Trusts and one Mental Health Trust in England. Attitudes were examined on two factors: health care settings as smoke-free environments and the role of staff in stop smoking intervention. RESULTS: The findings indicated that attitudes on the two factors were only moderately correlated. Psychiatric staff expressed significantly less favourable attitudes than general staff to smoke-free health care settings and also to the role of staff in stop smoking intervention. The largest difference between the settings concerned the implementation of smoking bans. While approximately 1 in 10 staff in the general setting disagreed with a smoking ban in their wards or clinics, nearly one in three psychiatric staff was against such a ban in their setting. CONCLUSIONS: Staff attitudes need to be carefully considered, particularly in psychiatric settings, in attempts to implement smoke-free policies in health care settings.

Ecstasy (MDMA, MDA, MDEA, MBDB) consumption, seizures, related offences, prices, dosage levels and deaths in the UK (1994-2003).

In the last decade, a global trend of escalating ecstasy (MDMA, MDA, MDEA, MBDB) use was observed. Mentions on medical death certificates, last year's ecstasy use, number of drug offenders, seizures, prices and dosage levels figures were used for this descriptive and correlational study. Figures (1994-2003) were taken from the UK General Mortality Registers, from the Home Office Statistical Bulletins, from the British Crime Survey and from those reported to both the National Crime Intelligence and Forensic Science Services. A total of 394 ecstasy deaths mentions were here identified from the UK; in 42% of cases ecstasy was the sole drug mentioned. Overall, number of fatalities showed a year-per-year increase and positively correlated with: prevalence of last year's use (p < 0.01); number of offenders (p < 0.01) and number of seizures (p < 0.01) but negatively correlated with ecstasy price (p < 0.05). Price negatively correlated with: prevalence of last year's use (p < 0.001) and number of seizures (p < 0.01); but positively correlated with average MDMA dosage per tablet (p < 0.01). MDA, MDEA and MBDB accounted for a significant proportion of tablets only up to 1997, but not afterwards. Increasing production with a concomitant decrease in ecstasy price may have facilitated an increase in consumption levels and this, in turn, may have determined an increase in number of ecstasy deaths mentions. Only medical death certificates and not coroners' reports at the end of their inquests were here analysed; no data were available in respect of other drugs use and toxicology results.

Drugs on the web; the Psychonaut 2002 EU project.

PURPOSE: Only a few formal assessments of websites with drug-related contents have been carried out. We aimed here at fostering collection and analysis of data from web pages related to information on consumption, manufacture and sales of psychoactive substances. GENERAL METHODS: An 8-language, two-engine, assessment of the information available in a purposeful sample of 1633 unique websites was carried out. FINDINGS: A pro-drug and a harm reduction approach were evident, respectively, in 18% and 10% of websites accessed. About 1 in 10 websites offered either psychoactive compounds for sale or detailed data on drugs' synthesis/extraction procedures. Information on a number of psychoactive substances and on unusual drugs' combinations not found in the Medline was elicited. CONCLUSIONS: This represents the first review which is both comprehensive and multilingual of the online available information on psychoactive compounds. Health professionals may need to be aware of the web being a new drug resource for information and possibly purchase.

Buprenorphine mortality, seizures and prescription data in the UK, 1980-2002.

Buprenorphine safety in overdose has been debated recently, but no mortality data related to this compound from the UK have been published. To gather together all of the buprenorphine mortality figures, a number of different sources have been checked. To inform on buprenorphine safety issues, accessible information related to its availability indicators (i.e. prescriptions; seizures) data for the 1980-2002 time frame have been sought. In the UK, during this period, buprenorphine was mentioned in 43 fatalities. Typically, victims were males in the 25-44 age group. In 12 cases (28% of total), a verdict of suicide was given. Buprenorphine was detected on its own in seven cases; more frequently, it was found together with benzodiazepines and other opiates. Large quantities of buprenorphine were prescribed both in England in 1985-1989 and in 1991-1992 in Scotland, where seizures reached their highest levels. Buprenorphine prescriptions seemed to peak again after 1999, when high dose buprenorphine formulations entered the UK market. No positive correlation was found between the number of buprenorphine deaths over the years and either buprenorphine dispensings/prescriptions or seizures. However, an increase in buprenorphine-related deaths since 1999 was identified and this may be an issue which should be carefully monitored over the next few years.

The effects of methadone and its role in fatalities.

Methadone is a synthetic opioid, used both as an analgesic in severe pain relief and now mainly in the treatment of opiate dependence. Such use of the drug has increased as its advantages have become widely recognized. There are undesirable outcomes from its greater use, including a substantial market in diverted methadone and a high number of deaths where the drug has been implicated. It is important to understand how and why methadone causes death so that such fatalities can be minimized, and to disseminate such information. This paper presents an overview of the chief effects of methadone on the human body, considering its metabolism, drug interactions and tolerance. The principal mechanisms by which methadone causes death are discussed: respiratory depression, aspiration of vomit, pulmonary oedema, bronchopneumonia, cardiac problems and renal failure. Many such deaths are preventable, if drug interactions and polydrug use are avoided, its longer period of metabolism and individuals' tolerance levels are considered. It is hoped that this paper will (a) help guide health professionals in their management and treatment of patients participating in methadone treatment programmes, and (b) provide some basic information for those dealing with individuals who have consumed methadone.

Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998-2000.

BACKGROUND: Deaths from antidepressants continue to account for a substantial proportion of drug-related deaths. AIMS: To investigate the relative toxicity of the major classes of antidepressant drugs, with the specific objective of assessing this in relation to the cause of death; and to analyse the deaths where there were multiple mentions of antidepressant drugs or other psychoactive drugs with antidepressants. METHOD: Mortality data were collected from the National Programme of Substance Abuse Deaths, and antidepressant prescription data were collected. RESULTS: Most deaths from antidepressant drugs were suicides (80%). Tricyclic antidepressants (TCAs) accounted for more drug mentions than did other antidepressant drugs (12 per million prescriptions). Selective serotonin reuptake inhibitors (SSRIs) were associated with a significantly lower risk of toxicity, but 93% of deaths from SSRIs occurred in combination with other drugs, especially TCAs (24.5%). In 'combination' deaths patients were significantly more likely to have had a history of drug misuse. CONCLUSIONS: The efficacy and safety of augmentation therapy with TCAs in SSRI-resistant patients should be monitored carefully, and patients prescribed antidepressants should be screened for drug use/misuse.

Cause and manner of death in drug-related fatality: an analysis of drug-related deaths recorded by coroners in England and Wales in 2000.

This study investigated causes and manner of drug-related fatalities recorded in 2000 in the United Kingdom, measuring the 'masked' manner of death in cases typically recorded as overdose. A retrospective cohort study was used of 1037 cases of accidental drug-related fatalities reported by coroners in England and Wales to the National Programme of Substance Abuse Deaths. Whilst 802 cases were identified as direct acute overdose, representing 77% of the total accidental deaths, 23% of 'overdose' fatalities were caused by asphyxiation (7%), drug-related medical conditions (7%), non-drug-related conditions (4%), traumatic accidents (3%) and infections (2%). Younger people show higher risk of overdose and asphyxiation; older people show higher risk from pre-existing medical conditions. This study not only confirmed the high risk of overdose associated with heroin and polydrug use, but it also identified other high fatality risk factors for heroin/morphine users such as contracting an acute infection leading to septicaemia or endocarditis, or contracting a chronic infection such as HIV, HBV or HCV. In contrast, stimulants particularly featured in traumatic accidents, with amphetamine use most associated with cardio-vascular fatality. These findings highlight the 'masked' manner of death in cases commonly recorded as overdose and demonstrate the need for a more-detailed and systematic method of recording drug-related deaths in order to inform drug education and harm reduction strategies.

Treating an opiate-dependent inpatient population: a one-year follow-up study of treatment completers and noncompleters.

INTRODUCTION: The aim of this study was to compare the characteristics of patients who completed (completers) inpatient treatment of drug dependence with those who failed to complete this programme (noncompleters). METHOD: Participants were assessed at admission using the Substance Abuse Assessment Questionnaire (SAAQ) to obtain information about the sociodemographic background, history of drug and alcohol use, physical health, mental health, offending behaviour, and interpersonal relationships. Follow-up interviews were carried out 3, 6, 9, and 12 months after discharge using the SAAQ-Follow-up. To form the three comparison groups, participants were divided on the basis of completion of detoxification and receipt of aftercare. RESULTS AND CONCLUSIONS: Significantly better treatment outcome was observed amongst those who completed detoxification and went on to spend at least 6 weeks in a recovery and/or residential rehabilitation unit. In contrast, there were no significant differences between noncompleters and completers who had no aftercare on the majority of measures of drug use during follow-up.