John Corkery

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

BackgroundRecently, 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.AimsWe 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.MethodsBecause 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 ConclusionsWithin 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.

Novel psychoactive substances of interest for psychiatry

Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine‐like dissociatives, piperazines, GABA‐A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA‐A/B, 5‐HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed.

Phenomenon of new drugs on the Internet: The case of ketamine derivative methoxetamine

On the basis of the material available both in the scientific literature and on the web, this paper aims to provide a pharmacological, chemical and behavioural overview of the novel compound methoxetamine. This is a dissociative drug related to ketamine, with a much longer duration of action and intensity of effects. A critical discussion of the availability of information on the web of methoxetamine as a new recreational trend is here provided. Those methodological limitations, which are intrinsically associated with the analysis of online, non‐peer reviewed, material, are here discussed as well. It is concluded that the online availability of information on novel psychoactive drugs, such as methoxethanine, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast‐growing phenomenon. Copyright

Promoting innovation and excellence to face the rapid diffusion of Novel Psychoactive Substances in the EU: the outcomes of the ReDNet project

The recent emergence of new psychoactive compounds (novel psychoactive substances (NPS)) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS by identifying online products and disseminating relevant information through technological tools.

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.

Cocaine/crack cocaine consumption, treatment demand, seizures, related offences, prices, average purity levels and deaths in the UK (1990—2004):

A recent trend of escalating use of cocaine/crack cocaine was observed in the UK. The number of mentions on death certificates; last year use of cocaine; treatment demand, number of drug offenders, seizures, prices and average purity levels were the indicators used for this descriptive and correlational study. Figures (1990—2004) were taken from official UK sources. A total of 1022 cocaine/crack cocaine death mentions (i.e. deaths from any cause where the presence of cocaine/crack cocaine was also detected) were identified, with cocaine/crack cocaine being the sole drug mentioned in 36% of cases. The number of cocaine/crack cocaine death mentions showed a year-on-year increase and correlated positively with the following cocaine (powder) figures: last year use (p < 0.001); number of offenders (p < 0.001) and number of seizures (p < 0.001), but correlated negatively with price (p < 0.001). Furthermore, the number of cocaine/crack cocaine death mentions correlated positively with the number of crack offenders (p < 0.001) and seizures (p < 0.001), but correlated negatively with both crack purity ( p < 0.001) and price (p < 0.05). With conditions of increasing drug availability having been met in the UK, decrease in cocaine prices were associated with higher consumption levels and this, in turn, contributed to the increase in number of cocaine-related fatalities. There are limitations with the information collected, since no distinction is usually made on medical death certificates between cocaine and crack cocaine. The present study being an ecological one, it proved difficult to address the role of confounding variables that may well explain some of the associations observed.

Overview of Amphetamine-Type Stimulant Mortality Data – UK, 1997–2007

Background/Aims: Despite being amphetamine derivatives, MDMA and its analogues show a number of clinical pharmacological differences with respect to both amphetamine (AMP) and methylamphetamine (METH). We aimed here at reporting and analysing information relating to the socio-demographics and clinical circumstances of the AMP-type stimulant-related deaths for the whole of the UK. Methods: Data (1997–2007) were taken from the National Programme on Substance Abuse Deaths (np-SAD) database, collecting information from UK coroners/procurators fiscal. To calculate rates of fatalities per 100,000 users, appropriate AMP/METH and ecstasy users’ numbers were taken from the 2001–2007 British Crime Survey. Results: Overall, 832 AMP/METH- and 605 ecstasy (mostly MDMA and methylenedioxyamphetamine/MDA)-related deaths were respectively identified. In comparison with AMP/METH victims, the ecstasy ones were more likely to be younger (28.3 vs. 32.7 years; p < 0.0001) and less likely to be known as drug users (PR = 1.9; CI 1.5–2.6). Ecstasy was more likely to be identified on its own than AMP/METH (p = 0.0192). Contributory factors were more frequently mentioned by coroners in the ‘AMP/METH-only’ (106 cases) group than in the ‘ecstasy-only’ (104 cases) one (p = 0.0043). Both poly- and monodrug AMP/METH fatalities per 100,000 16- to 59-year-old users were significantly more represented than ecstasy fatalities (respectively 17.87 ± 4.77 deaths vs. 10.89 ± 1.27; p = 0.000; 2.09 ± 0.88 vs. 1.75 ± 0.56; p = 0.0096). However, mono-intoxication ecstasy fatalities per 100,000 16- to 24-year-old users were significantly more represented than AMP/METH fatalities (1.67 ± 0.52 vs. 0.8 ± 0.65; p = 0.0007). Conclusion: With respect to AMP/METH, ecstasy was here more typically identified in victims who were young, healthy, and less likely to be known as drug users. AMP/METH high mortality rates may be explained by users’ high levels of physical co-morbidity; excess ecstasy-related fatality rates in young users may be a reason for concern. Although the coroners’ response rate was of 90–95%, study limitations include both reporting inconsistency over time and lack of routine information on drug intake levels prior to death.

“Spice,” “Kryptonite,” “Black Mamba”: An Overview of Brand Names and Marketing Strategies of Novel Psychoactive Substances on the Web

Abstract Introduction: Novel Psychoactive Substances (NPSs) are often sold online as “legal” and “safer” alternatives to International Controlled Drugs (ICDs) with captivating marketing strategies. Our aim was to review and summarize such strategies in terms of the appearance of the products, the brand names, and the latest trends in the illicit online marketplaces. Methods: Scientific data were searched in PsychInfo and Pubmed databases; results were integrated with an extensive monitoring of Internet (websites, online shops, chat rooms, fora, social networks) and media sources in nine languages (English, French, Farsi, Portuguese, Arabic, Russian, Spanish, and Chinese simplified/traditional) available from secure databases of the Global Public Health Intelligence Network. Results: Evolving strategies for the online diffusion and the retail of NPSs have been identified, including discounts and periodic offers on chosen products. Advertisements and new brand names have been designed to attract customers, especially young people. An increased number of retailers have been recorded as well as new Web platforms and privacy systems. Discussion: NPSs represent an unprecedented challenge in the field of public health with social, cultural, legal, and political implications. Web monitoring activities are essential for mapping the diffusion of NPSs and for supporting innovative Web-based prevention programmes.

5,6-Methylenedioxy-2-aminoindane: from laboratory curiosity to 'legal high'.

The fully synthetic ‘legal high’ 5,6‐methylenedioxy‐2‐aminoindane (MDAI) is an analogue of 3,4‐methylenedioxymethamphetamine. Although developed in the 1990s, it was not widely abused until 2010. However, mephedrone was banned in the UK in April 2010, and almost immediately, MDAI was widely advertised as a legal alternative. This paper provides both an overview of the current state of knowledge of MDAI and a critical analysis of online available information relating to its psychoactive effects, adverse reactions and use in combination with other drugs.

Gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD; BDO): A literature review with a focus on UK fatalities related to non-medical use

Misuse of gamma hydroxybutrate (GHB) and gamma butyrolactone (GBL) has increased greatly since the early 1990s, being implicated in a rising number of deaths. This paper reviews knowledge on GHB and derivatives, and explores the largest series of deaths associated with their non-medical use. Descriptive analyses of cases associated with GHB/GBL and 1,4-butanediol (1,4-BD) use extracted from the UKs National Programme on Substance Abuse Deaths database. From 1995 to September 2013, 159 GHB/GBL-associated fatalities were reported. Typical victims: White (92%); young (mean age 32 years); male (82%); with a drug misuse history (70%). Most deaths (79%) were accidental or related to drug use, the remainder (potential) suicides. GHB/GBL alone was implicated in 37%; alcohol 14%; other drugs 28%; other drugs and alcohol 15%. Its endogenous nature and rapid elimination limit toxicological detection. Post-mortem blood levels: mean 482 (range 0-6500; SD 758)mg/L. Results suggest significant caution is needed when ingesting GHB/GBL, particularly with alcohol, benzodiazepines, opiates, stimulants, and ketamine. More awareness is needed about risks associated with consumption.