Tibor M. Brunt

Instability of the ecstasy market and a new kid on the block: mephedrone

Recently, several reports have indicated instability of the ecstasy market in the Netherlands and other EU countries. In the current study, we demonstrate this instability in the Netherlands, showing a decrease of ecstasy tablets containing 3,4-methylenedioxymetamphetamine (MDMA) by more than 50% in 2009. In addition, we describe a partial replacement of MDMA in tablets sold as ecstasy by a previously unseen substance, mephedrone (or 4-methylmethcathinone). Mephedrone was quantified and ecstasy tablets contained between 96 and 155 mg of this new compound. So far, no studies about mephedrone’s effects have been published. For this study, we gathered information on the acute subjective effects of mephedrone from 70 regular ecstasy users. Overall, the majority of users considered the effects enjoyable. Mephedrone seemed to evoke effects similar to other amphetamine type psychostimulants, including MDMA. In contrast to MDMA, however, mephedrone induced strong feelings of craving in most users. If the unstable ecstasy market situation persists, the potential of mephedrone to substitute for MDMA might be substantial. Mephedrone, sold as ecstasy, is therefore likely to be a valid cause for health concern.

Content of ecstasy in the Netherlands: 1993-2008.

AIMS The present paper outlines the results of analyses carried out on the content of tablets sold as ecstasy, collected in the Netherlands by the Drugs Information Monitoring System (DIMS) from January 1993 to December 2008. METHODS During a period of 16 years, the DIMS analysed the content of 33 006 tablets sold as ecstasy that were handed in by numerous individual (potential) substance users. The DIMS results were compared with the results from various seized tablets to determine whether the DIMS is a monitor of the ecstasy consumer market. RESULTS The DIMS system appears to be a market monitor that gives an accurate reflection of what is actually available on the hidden Dutch ecstasy market. During 16 years of monitoring, the purity [tablets containing only 3,4-methylenedioxymethamphetamine (MDMA)] was lowest around 1997. During this time-period many tablets contained other substances in addition to or instead of MDMA [e.g. 3,4-methylene-dioxyamphetamine (MDA), 3,4-methylene-dioxyethylamphetamine (MDEA) and N-methyl-a-(1,3-benzodixol-5-yl)-2-butamine (MBDB), amphetamine and caffeine]. From 1998 to 2008, the number of high-dose tablets (> or =106 mg MDMA per tablet) gradually increased. The same holds true for the proportion of tablets that contained only MDMA, reaching the highest levels in 2000 and 2004. After 2004, the purity of ecstasy tablets decreased again, caused mainly by a growing proportion of tablets containing meta-chlorophenylpiperazine (mCPP). CONCLUSIONS The DIMS results provide valuable qualitative information on the content of ecstasy tablets in the Netherlands, and its changes throughout the years. Moreover, the results were used for national and international risk assessments and important warning and prevention activities.

The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects

Cannabis use is associated with an increased risk of psychosis in vulnerable individuals. Cannabis containing high levels of the partial cannabinoid receptor subtype 1 (CB1) agonist tetrahydrocannabinol (THC) is associated with the induction of psychosis in susceptible subjects and with the development of schizophrenia, whereas the use of cannabis variants with relatively high levels of cannabidiol (CBD) is associated with fewer psychotic experiences. Synthetic cannabinoid receptor agonists (SCRAs) are full agonists and often more potent than THC. Moreover, in contrast to natural cannabis, SCRAs preparations contain no CBD so that these drugs may have a higher psychosis-inducing potential than cannabis. This paper reviews the general toxicity profile and the adverse effects of SCRAs with special emphasis on their psychosis-inducing risk. The review shows that, compared with the use of natural cannabis, the use of SCRAs may cause more frequent and more severe unwanted negative effects, especially in younger, inexperienced users. Psychosis and psychosis-like conditions seem to occur relatively often following the use of SCRAs, presumably due to their high potency and the absence of CBD in the preparations. Studies on the relative risk of SCRAs compared with natural cannabis to induce or evoke psychosis are urgently needed.

Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study

BACKGROUND AND AIMS Increased delta-9-tetrahydrocannabinol (THC) concentrations in cannabis may lead to higher THC exposure, cannabis dependence and treatment need, but users may also adapt the actual intake of THC through reduced inhalation of THC containing smoke (titration). We investigated whether consumers of stronger cannabis use less cannabis per joint or inhale less smoke than those using less potent cannabis and whether these factors predict cannabis dependence severity. METHODS Heavy cannabis users (n = 98) brought their own cannabis, rolled a joint and smoked it ad libitum in a naturalistic setting. We analysed the content of the joint, its association with smoking behaviour and the cross-sectional and prospective (1.5-year follow-up) relations between smoking behaviour and cannabis dependence severity (total number of DSM-IV dependence symptoms). RESULTS THC concentration in cannabis (range 1.10-24.70%) was correlated positively with cannabis dose per joint (b = 0.008, P = 0.01), but the resulting THC concentration per joint (range 0.24-15.72%) was associated negatively with inhalation volume (b = -0.05, P = 0.03). Smoking behaviour measures (number of puffs, inhaled volume, reduction of puff volume and puff duration while smoking) predicted follow-up dependence severity, independently of baseline dependence severity and monthly THC dose (number of joints × cannabis dose × cannabis THC concentration). Monthly THC dose only predicted follow-up dependence severity when unadjusted for baseline severity. CONCLUSIONS Cannabis users titrate their delta-9-tetrahydrocannabinol intake by inhaling lower volumes of smoke when smoking strong joints, but this does not fully compensate for the higher cannabis doses per joint when using strong cannabis. Thus, users of more potent cannabis are generally exposed to more delta-9-tetrahydrocannabinol. Smoking behaviour appears to be a stronger predictor for cannabis dependence severity than monthly delta-9-tetrahydrocannabinol dose.

Monitoring new psychoactive substances (NPS) in The Netherlands: Data from the drug market and the Poisons Information Centre

BACKGROUND In recent years, the number of new psychoactive substances (NPS) appearing on the illicit drug market strongly increased. However, little is known about their toxic effects and risks. Therefore, we determined the most frequently occurring NPS in The Netherlands and combined this with data regarding drug-related intoxications. METHODS Data from the Drugs Information and Monitoring System (DIMS) and the Dutch Poisons Information Centre (DPIC) were combined and jointly analyzed. RESULTS The number of drug samples submitted to DIMS for analysis containing NPS increased from 22 in 2007 to 431 samples in 2013. The most frequently submitted NPS in 2013 included 4-bromo-2,5-dimethoxyphenethylamine (2C-B), 4-fluoroamphetamine (4-FA), methoxetamine (MXE) and 6-(2-aminopropyl)benzofuran (6-APB). From 2012 onwards, the number of NPS bought as drug of choice exceeded those appearing as adulterants in established drugs. The DPIC was consulted about 35 NPS exposures in 2013, most frequently involving 4-FA, mephedrone, MXE, 2C-B and 6-APB. Following NPS exposure, neurological and psychological symptoms were most frequently reported, like agitation and hallucinations. In addition, cardiovascular symptoms like hypertension and tachycardia often occurred. CONCLUSIONS NPS are currently being purchased as drug of choice in The Netherlands and their availability and use is increasing. Although pharmacological and toxicological data are scarce, NPS can induce pronounced clinical effects. Therefore, the monitoring of trends in NPS prevalence needs to be continued, combined with reported clinical effects, and preferably supported by analytical confirmation of exposures in such patients.

Drug testing in Europe: monitoring results of the Trans European Drug Information (TEDI) project

Drug testing is a harm reduction strategy that has been adopted by certain countries in Europe. Drug users are able to hand in their drugs voluntarily for chemical analysis of composition and dose. Drug users will be alerted about dangerous test results by the drug testing systems directly and through warning campaigns. An international collaborative effort was launched to combine data of drug testing systems, called the Trans European Drug Information (TEDI) project. Drug testing systems of Spain, Switzerland, Belgium, Austria, Portugal, and the Netherlands participated in this project. This study presents results of some of the main illicit drugs encountered: cocaine, ecstasy and amphetamine and also comments on new psychoactive substances (NPS) detected between 2008 and 2013. A total of 45 859 different drug samples were analyzed by TEDI. The drug markets of the distinct European areas showed similarities, but also some interesting differences. For instance, purity of cocaine and amphetamine powders was generally low in Austria, whilst high in Spain and the Netherlands. And the market for ecstasy showed a contrast: whereas in the Netherlands and Switzerland there was predominantly a market for ecstasy tablets, in Portugal and Spain MDMA (3,4-methylenedioxymethamphetamine) crystals were much more prevalent. Also, some NPS appearing in ecstasy seemed more specific for one country than another. In general, prevalence of NPS clearly increased between 2008 and 2013. Drug testing can be used to generate a global picture of drug markets and provides information about the pharmacological contents of drugs for the population at risk. Copyright

The Drug Information and Monitoring System (DIMS) in the Netherlands: Implementation, results, and international comparison

The Ministry of Health in the Netherlands has made illicit drug testing for drug users possible since the 1990s, in order to prevent serious health hazards associated with unexpected dangerous substances. This system of illicit drug testing is called the Drug Information and Monitoring System (DIMS). In nearly two decades, more than 100 000 drug samples have been handed in at DIMS testing facilities. This review describes the DIMS methodology and overviews results of the three main psychostimulant drug markets that have been monitored, i.e. ecstasy, amphetamine (speed), and cocaine. Additionally, monitoring results of hallucinogens are also described for the first time. For comparison, alternative international monitoring systems are described briefly alongside some of their results. Finally, drug monitoring is discussed from the perspectives of policy, prevention, and the drug users themselves.

Possible long-term effects of γ-hydroxybutyric acid (GHB) due to neurotoxicity and overdose.

In several countries, including the Netherlands, the use of GHB seems to be rising. GHB is regarded by recreational users as an innocent drug without any side effects. Recently, the number of patients in treatment due to GHB addiction sharply increased. In addition, various studies report incidents following risky GHB use or GHB overdosing. Other sedative drugs, like ketamine and alcohol have been shown to result in unintended neurotoxic harm at the level of memory and cognitive function. As outlined in the present review, GHB and ketamine have a common mode of action, which suggests that GHB may also lead to similar neurotoxicity as ketamine. GHB overdosing, as well as binge drinking (and high ketamine doses), induce profound coma which is probably neurotoxic for the brain especially in the maturing brain of young adults. It is therefore advocated to investigate possible long-term neurotoxic effects in recreational GHB users e.g. by studying the residual effects on cognition and memory.

Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15.

BACKGROUND AND AIMS Between 2000 and 2005 the average percentage of Δ(9) -tetrahydrocannabinol (THC) in marijuana as sold in Dutch coffeeshops has increased substantially; the potency of domestic products (Nederwiet and Nederhasj) has particularly increased. In contrast with imported marijuana, Nederwiet hardly contained any cannabidiol (CBD), a cannabinoid that is thought to offset some of the adverse effects of THC. In 2005, the THC content in Nederwiet was significantly lower than in 2004. This study investigates the further decrease or increase of cannabinoids in these cannabis products. METHODS From 2005 to 2015 five different cannabis products were bought anonymously in 50 coffeeshops that were selected randomly each year from all coffeeshops in the Netherlands. A total of 2126 cannabis samples were bought, consisting of 664 Nederwiet samples (most popular), 537 Nederwiet samples (supposed strongest varieties), 183 imported herbal cannabis samples, 140 samples of cannabis resin made of Nederwiet and 602 samples of imported cannabis resin. All samples were analysed chemically for their THC, CBD and cannabinol (CBN) content. RESULTS Between 2005 and 2015, the mean potencies of the most popular and the strongest Nederwiet and of imported cannabis resin were 16.0±4.0%, 17.0±3,9% and 16.5±6.3%, respectively. Imported herbal cannabis (6.5±3.5%) and cannabis resin made from Nederwiet (30.2±16.4%) contained, respectively, less (β=-10.0, P<0.001) and more (β=13.7, P<0.001) THC than imported cannabis resin. Linear regression models were used to study the trends in THC of the different cannabis products over time. A marginal, but significant (P<0.001), overall decline of THC per year of 0.22% was found in all cannabis products. However, no significant difference was found between the five products in the THC linear trajectories across time. Of all the cannabis products, only imported cannabis resin contained a relatively high CBD/THC ratio (median 0.42). CONCLUSION The average tetrahydrocannabinol (THC) content of the most popular herbal cannabis products in the Netherlands has decreased slightly since 2005. The popular Nederwiet type still has a relatively high THC to cannabidiol ratio.

4-Fluoroamphetamine in the Netherlands: more than a one-night stand

AIMS To investigate the temporal pattern of appearance of a new psychoactive substance (4-fluoroamphetamine) on the Dutch drug market, as well as its patterns of use and effects. DESIGN Data from the Drug Information and Monitoring System (DIMS) was used to investigate the emergence of 4-fluoroamphetamine on the Dutch drug market. An on-line questionnaire was used to study its patterns of use and effects. SETTING Dutch drug-related websites and social media. PARTICIPANTS A convenience sample of 249 life-time 4-fluoroamphetamine users was recruited through the internet. MEASUREMENTS Samples containing 4-fluoroamphetamine were extracted from the DIMS database for further investigation. Patterns of use, settings of use and the subjective effects of 4-fluoroamphetamine, amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) were investigated with the on-line questionnaire. FINDINGS 4-Fluoroamphetamine was first encountered on the Dutch drug market, sold mainly as amphetamine or ecstasy (MDMA), between 2007 and 2009. These misrepresented drug samples declined when the MDMA and amphetamine markets recovered after a period of shortage, whereas purposefully bought 4-fluoroamphetamine samples showed an increase. Survey results showed that 4-fluoroamphetamine is used predominantly [77.1%, 95% confidence interval (CI) = 72.0-82.3] for its specific effects, rather than its legal status (17.7%, 95% CI = 10.7-22.1). The subjective effects of 4-fluoroamphetamine were compared with those of amphetamine and MDMA. Subjective effect scores of 4-fluoroamphetamine ranged between those of amphetamine and MDMA. CONCLUSIONS The stimulant 4-fluoroamphetamine is increasingly popular in the Netherlands, which might be due to its subjective effects profile, which lies intermediate between amphetamine and MDMA.