Changes in cannabis potency and first-time admissions to drug treatment: a 16-year study in the Netherlands.

BACKGROUND: The number of people entering specialist drug treatment for cannabis problems has increased considerably in recent years. The reasons for this are unclear, but rising cannabis potency could be a contributing factor. METHODS: Cannabis potency data were obtained from an ongoing monitoring programme in the Netherlands. We analysed concentrations of δ-9-tetrahydrocannabinol (THC) from the most popular variety of domestic herbal cannabis sold in each retail outlet (2000-2015). Mixed effects linear regression models examined time-dependent associations between THC and first-time cannabis admissions to specialist drug treatment. Candidate time lags were 0-10 years, based on normative European drug treatment data. RESULTS: THC increased from a mean (95% CI) of 8.62 (7.97-9.27) to 20.38 (19.09-21.67) from 2000 to 2004 and then decreased to 15.31 (14.24-16.38) in 2015. First-time cannabis admissions (per 100 000 inhabitants) rose from 7.08 to 26.36 from 2000 to 2010, and then decreased to 19.82 in 2015. THC was positively associated with treatment entry at lags of 0-9 years, with the strongest association at 5 years, b = 0.370 (0.317-0.424), p < 0.0001. After adjusting for age, sex and non-cannabis drug treatment admissions, these positive associations were attenuated but remained statistically significant at lags of 5-7 years and were again strongest at 5 years, b = 0.082 (0.052-0.111), p < 0.0001. CONCLUSIONS: In this 16-year observational study, we found positive time-dependent associations between changes in cannabis potency and first-time cannabis admissions to drug treatment. These associations are biologically plausible, but their strength after adjustment suggests that other factors are also important.

Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabis.

In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for medicinal purposes as commissioned by the Ministry of Health. Few studies have thus far described its therapeutic efficacy or subjective (adverse) effects in patients. The aims of this study are to assess the therapeutic satisfaction within a group of patients using prescribed pharmaceutical-grade cannabis and to compare the subjective effects among the available strains with special focus on their delta-9-tetrahydrocannabinol and cannabidiol content. In a cross-sectional and natural design, users of pharmaceutical-grade cannabis were investigated with questionnaires. Medical background of the patients was asked as well as experienced therapeutic effects and characteristics of cannabis use. Subjective effects were measured with psychometric scales and used to compare among the strains of cannabis used across this group of patients. One hundred two patients were included; their average age was 53 years and 76% used it for more than a year preceding this study. Chronic pain (53%; n = 54) was the most common medical indication for using cannabis followed by multiple sclerosis (23%; n = 23), and 86% (n = 88) of patients (almost) always experienced therapeutic satisfaction when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation were found to differ among the 3 strains of cannabis. These results show that patients report therapeutic satisfaction with pharmaceutical cannabis, mainly pain alleviation. Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different tetrahydrocannabinol/cannabidiol content. These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.

Experience during adolescence shapes brain development: From synapses and networks to normal and pathological behavior.

Adolescence is a period of dramatic neural reorganization creating a period of vulnerability and the possibility for the development of psychopathology. The maturation of various neural circuits during adolescence depends, to a large degree, on one's experiences both physical and psychosocial. This occurs through a process of plasticity which is the structural and functional adaptation of the nervous system in response to environmental demands, physiological changes and experiences. During adolescence, this adaptation proceeds upon a backdrop of structural and functional alterations imparted by genetic and epigenetic factors and experiences both prior to birth and during the postnatal period. Plasticity entails an altering of connections between neurons through long-term potentiation (LTP) (which alters synaptic efficiency), synaptogenesis, axonal sprouting, dendritic remodeling, neurogenesis and recruitment (Skaper et al., 2017). Although most empirical evidence for plasticity derives from studies of the sensory systems, recent studies have suggested that during adolescence, social, emotional, and cognitive experiences alter the structure and function of the networks subserving these domains of behavior. Each of these neural networks exhibits heightened vulnerability to experience-dependent plasticity during the sensitive periods which occur in different circuits and different brain regions at specific periods of development. This report will summarize some examples of adaptation which occur during adolescence and some evidence that the adolescent brain responds differently to stimuli compared to adults and children. This symposium, "Experience during adolescence shapes brain development: from synapses and networks to normal and pathological behavior" occurred during the Developmental Neurotoxicology Society/Teratology Society Annual Meeting in Clearwater Florida, June 2018. The sections will describe the maturation of the brain during adolescence as studied using imaging technologies, illustrate how plasticity shapes the structure of the brain using examples of pathological conditions such as Tourette's' syndrome and attention deficit hyperactivity disorder, and a review of the key molecular systems involved in this plasticity and how some commonly abused substances alter brain development. The role of stimulants used in the treatment of attention deficit hyperactivity disorder (ADHD) in the plasticity of the reward circuit is then described. Lastly, clinical data promoting an understanding of peer-influences on risky behavior in adolescents provides evidence for the complexity of the roles that peers play in decision making, a phenomenon different from that in the adult. Imaging studies have revealed that activation of the social network by the presence of peers at times of decision making is unique in the adolescent. Since normal brain development relies on experiences which alter the functional and structural connections between cells within circuits and networks to ultimately alter behavior, readers can be made aware of the myriad of ways normal developmental processes can be hijacked. The vulnerability of developing adolescent brain places the adolescent at risk for the development of a life time of abnormal behaviors and mental disorders.

Is online information on ecstasy tablet content safe?

BACKGROUND AND AIMS: In recent years, the prevalence of ecstasy use has increased in most European countries. Users can acquire information on ecstasy tablet composition through the internet. This study compares online information from two websites, Pillreports and Partyflock, to the validated Dutch Drugs Information and Monitoring System (DIMS) database, and aims to measure its accuracy and potential danger or value. DESIGN, SETTING, PARTICIPANTS: The drug-related information posted on Pillreports.net and Partyflock.nl between 1 January 2014 and 31 December 2015 was investigated for accuracy and several information characteristics such as picture inclusion and dose range inclusion. In total, 471 informatory statements on ecstasy tablet content were analysed relative to the Dutch ecstasy market. MEASUREMENTS: Informatory statements on the content of specific ecstasy tablets were scored as 'too high' or 'too low' if their concentrations deviated > 10 mg from the entries in the DIMS database within a 12-week time-frame, and scored as 'dangerous' if their concentration was > 40 mg too low. Unreported substances were scored as 'dangerous' if listed as an illegal or dangerous substance in the DIMS database and if present in relevant quantities. Also scored were the report characteristics 'picture inclusion', 'spread inclusion' and 'website source', which were tested for their association with report safety/danger. FINDINGS: On average, reports on ecstasy tablets from Pillreports and Partyflock show concentrations which are 10.6 mg too high [95% confidence interval (CI) = 6.7-14.4]. Qualitatively, 39.7% of the reports scored as 'too high' (95% CI = 35.2-44.4), 17.6% scored as 'too low' (95% CI = 14.0-21.2) and 15.5% had 'unreported substances' (95% CI = 12.3-18.9), resulting overall in 15.3% of the reports being scored as 'dangerous' (95% CI = 11.9-18.5). The report characteristic 'spread inclusion' associated inversely with report danger [Exp(b) = 0.511, 95% CI = 0.307-0.850, P = 0.01]. CONCLUSION: Information from the popular Pillreports and Partyflock websites tends to overestimate 3,4-methylenedioxymethamphetamine (MDMA) concentrations in ecstasy tablets. In addition, 15.3% of the reports omit the relevant concentration spread, fail to report additional illegal or dangerous substances contained in the tablets or underestimate MDMA concentration by > 40 mg.

Limitations to the Dutch cannabis toleration policy: Assumptions underlying the reclassification of cannabis above 15% THC.

The Netherlands has seen an increase in Δ9-tetrahydrocannabinol (THC) concentrations from approximately 8% in the 1990s up to 20% in 2004. Increased cannabis potency may lead to higher THC-exposure and cannabis related harm. The Dutch government officially condones the sale of cannabis from so called 'coffee shops', and the Opium Act distinguishes cannabis as a Schedule II drug with 'acceptable risk' from other drugs with 'unacceptable risk' (Schedule I). Even in 1976, however, cannabis potency was taken into account by distinguishing hemp oil as a Schedule I drug. In 2011, an advisory committee recommended tightening up legislation, leading to a 2013 bill proposing the reclassification of high potency cannabis products with a THC content of 15% or more as a Schedule I drug. The purpose of this measure was twofold: to reduce public health risks and to reduce illegal cultivation and export of cannabis by increasing punishment. This paper focuses on the public health aspects and describes the (explicit and implicit) assumptions underlying this '15% THC measure', as well as to what extent these are supported by scientific research. Based on scientific literature and other sources of information, we conclude that the 15% measure can provide in theory a slight health benefit for specific groups of cannabis users (i.e., frequent users preferring strong cannabis, purchasing from coffee shops, using 'steady quantities' and not changing their smoking behaviour), but certainly not for all cannabis users. These gains should be weighed against the investment in enforcement and the risk of unintended (adverse) effects. Given the many assumptions and uncertainty about the nature and extent of the expected buying and smoking behaviour changes, the measure is a political choice and based on thin evidence.

Pharmacological aspects of the combined use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and gamma-hydroxybutyric acid (GHB): a review of the literature.

Epidemiological studies show that the use of club drugs is on the rise. Furthermore, the last few decades have seen a rise in patterns of polydrug use. One of the combinations frequently used is ecstasy (MDMA) with gammahydroxybutyrate (GHB). For effective prevention it is important to be aware of this phenomenon and of the pharmacology of these drugs. The effects of the combination extend to different neurotransmitter systems, including serotonin, dopamine and noradrenaline. Studies investigating the effects of combinations of psychoactive substances are limited. In this review we describe the subjective effects of the MDMA/GHB combination. Furthermore, we review the individual actions of MDMA on serotonin, dopamine and noradrenaline systems. In addition, actions of GHB on these systems are discussed as a possible pharmacological basis for the interaction of both drugs. It is postulated that GHB attenuates the unpleasant or dysphoric effects of MDMA by its effect on the central dopaminergic system.

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 (ß=-10.0, P<0.001) and more (ß=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.

[A patient in a methoxetamine-induced dissociative psychosis]. / Dissociatieve psychose door methoxetamine.

BACKGROUND: The international drug market has dramatically changed with the emergence of various new psychoactive substances that are mostly being sold on the internet. One of those new psychoactive substances is methoxetamine (MXE), a structural analogue of ketamine. CASE DESCRIPTION: A 30-year-old man with no history of illness was presented to the accident and emergency department. He had lost his balance and could not move. He was in a dissociative psychosis, felt he had no control over his body and was extremely frightened. Most of this symptoms disappeared within two hours of arrival. The next day there were no indications of a psychosis, and only headache and nausea remained. The state of dissociative psychosis was caused by MXE, which was sold to him as an ecstasy tablet. CONCLUSION: Whether mixed with alcohol and other drugs or not, MXE can cause serious feelings of dissociation resulting in extreme anxiety and psychosis. This might cause severely lowered consciousness in these patients. Currently, use of MXE in the Netherlands is limited, but ketamine or MXE intoxication should be considered in patients with these symptoms.

Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword "cannabidiol." After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.

Impact of a transient instability of the ecstasy market on health concerns and drug use patterns in The Netherlands.

BACKGROUND: A recent decline in MDMA-like substances in ecstasy tablets has been reported by a number of countries in the European Union. This study describes the instability of the ecstasy market in The Netherlands during 2008 and 2009, and investigates whether this had any impact on drug testing or patterns of drug use. METHODS: The health concerns of drug users handing in drug samples at drug testing facilities was measured using intervention time-series analysis. In addition, these ecstasy users were asked about changes in their drug use. RESULTS: Nationally, the unstable market situation for ecstasy has increased the number of users handing in ecstasy tablets for testing because of health concern. There was no change in the number of users handing in cocaine or gamma hydroxybutyrate (GHB). Respondents reported no major changes in their drug use resulting from the shortage of MDMA-like substances. CONCLUSIONS: These findings provide further insight in drug policy based on both harm reduction and use reduction. In the event of reduced ecstasy quality, ecstasy users in The Netherlands have increasingly used drug testing as a potential harm reduction tool, rather than changing their patterns of drug use. This might indicate that a transient reduction of drug quality does not serve as a good drug use reduction strategy for ecstasy users.

Linking the pharmacological content of ecstasy tablets to the subjective experiences of drug users.

RATIONALE: Most studies on the subjective effects of ecstasy are based on the assumption that the substance that was taken is 3,4-methylenedioxymethamphetamine (MDMA). However, many tablets sold as ecstasy contain other substances and MDMA in varying doses. So far, few attempts have been made to take this into account while assessing subjective effects. OBJECTIVES: This study aims to link the pharmacological content of tablets sold as ecstasy to the subjective experiences reported by ecstasy users. METHODS: Self-reported effects on ecstasy tablets were available from 5,786 drug users who handed in their tablets for chemical analysis at the Drug Information and Monitoring System (DIMS) in the Netherlands. Logistic regression was employed to link the pharmacological content of ecstasy tablets to the self-reported subjective effects and compare effects with MDMA to other substances present. RESULTS: MDMA showed a strong association with desirable subjective effects, unparalleled by any other psychoactive substance. However, the association of MDMA was dose-dependent, with higher doses (>120 mg/tablet) likely to evoke more adverse effects. The novel psychostimulants mephedrone and p-fluoroamphetamine were considered relatively desirable, whereas meta-chlorophenylpiperazine (mCPP) and p-methoxymethamphetamine (PMMA) were strongly associated with adverse subjective effects. Also, 3,4-methylene-dioxyamphetamine (MDA) and benzylpiperazine (BZP) were not appreciated as replacement for MDMA. CONCLUSION: Linking the pharmacological content of ecstasy sold on the street to subjective experiences contributes to a better understanding of the wide range of subjective effects ascribed to ecstasy and provides a strong rationale for the prolonged endurance of MDMA as the key ingredient of the ecstasy market.

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.

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.

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.

Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia.

Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose-time-effect relationship should be central.

The relationship of quality and price of the psychostimulants cocaine and amphetamine with health care outcomes.

A major component of the illicit drug market can be subcategorized as the psychostimulant drug market, with cocaine and amphetamine as popular constituents. In The Netherlands, an increase in both health care outcomes addiction treatment and hospital admissions was noted for both amphetamine and cocaine throughout a period of 17 years (1992-2008). Both cocaine price and quality showed a decrease in The Netherlands during the studied period. We used time-series regression analysis to investigate whether price or quality of the drugs were associated with health care outcomes. Drug seizures were also added to the time-series regressions in order to check for possible effects of drug availability and supply. Price and quality of cocaine were strongly associated with health care outcomes of addiction treatment and hospital admissions. Price of amphetamine also showed a decrease during these 17 years, but was associated with an increase in addiction treatment only. Other amphetamine market variables did not show any relationship with the health care outcomes. It could be stated that following basic market logics does not apply equally to all psychostimulants of abuse. Other factors might play a role, such as the addictiveness or desirability of a specific drug in question. This finding is supportive of the dynamics of the illicit psychostimulant market affecting actual use and thereby health care outcomes.

An analysis of cocaine powder in the Netherlands: content and health hazards due to adulterants.

AIMS: To report on trends in the content and adulterants present in street cocaine (powder) in the Netherlands and to describe the associated health hazards. DESIGN AND PARTICIPANTS: Drug consumers handed in samples of cocaine powder from 1999 to 2007 for analysis. Reports were compiled of users' experiences with the samples received. MEASUREMENTS AND ANALYSIS: Linear regression analysis was used to assess the trend in adulterated cocaine powder across the study period, and comparison of reported adverse effects of adulterated with those of unadulterated cocaine by Fisher's exact test. FINDINGS: There has been a statistically significant upward trend in the occurrence of adulterated cocaine powder over the years. Adulterated cocaine was associated more frequently with reported adverse effects than unadulterated cocaine. Phenacetin, hydroxyzine and diltiazem appeared to be three adulterants contributing to these adverse effects. CONCLUSIONS: An increase in adulterants was detected in the analysed cocaine powder between 1999 and 2007. This increase is associated with relatively more adverse effects with cocaine use. The cardiac and hallucinatory effects that were reported more frequently are not understood clearly. Adverse effects are likely to be due to several factors, including interactions of adulterants with cocaine and the route of administration.

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.