Developing a new national MDMA policy: Results of a multi-decision multi-criterion decision analysis.

BACKGROUND: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) has a relatively low harm and low dependence liability but is scheduled on List I of the Dutch Opium Act ('hard drugs'). Concerns surrounding increasing MDMA-related criminality coupled with the possibly inappropriate scheduling of MDMA initiated a debate to revise the current Dutch ecstasy policy. METHODS: An interdisciplinary group of 18 experts on health, social harms and drug criminality and law enforcement reformulated the science-based Dutch MDMA policy using multi-decision multi-criterion decision analysis (MD-MCDA). The experts collectively formulated policy instruments and rated their effects on 25 outcome criteria, including health, criminality, law enforcement and financial issues, thematically grouped in six clusters. RESULTS: The experts scored the effect of 22 policy instruments, each with between two and seven different mutually exclusive options, on 25 outcome criteria. The optimal policy model was defined by the set of 22 policy instrument options which gave the highest overall score on the 25 outcome criteria. Implementation of the optimal policy model, including regulated MDMA sales, decreases health harms, MDMA-related organised crime and environmental damage, as well as increases state revenues and quality of MDMA products and user information. This model was slightly modified to increase its political feasibility. Sensitivity analyses showed that the outcomes of the current MD-MCDA are robust and independent of variability in weight values. CONCLUSION: The present results provide a feasible and realistic set of policy instrument options to revise the legislation towards a rational MDMA policy that is likely to reduce both adverse (public) health risks and MDMA-related criminal burden.

Fatal and non-fatal health incidents related to recreational ecstasy use.

BACKGROUND: The recreational drug ecstasy (3,4-methylenedioxymethamphetamine) is currently used world-wide. Severe (including fatal) health incidents related to ecstasy have been reported but a risk assessment of acute non-fatal and fatal ecstasy-related health incidents has never been performed. METHODS: In the current risk assessment review, national data of non-fatal health incidents collected in the Netherlands were combined with the nationwide exposure to ecstasy, that is, last-year prevalence of ecstasy use. In addition, the annual number of ecstasy-related deaths in Great Britain (Scotland, Wales and England) was used to assess the risk of fatal ecstasy-related cases. RESULTS: In the Netherlands, the estimated risk of a moderate to severe acute health incident following the use of ecstasy is one in 900 pills (0.11%), whereas for cocaine it is one in 1600 doses (0.06%) and for gamma-hydroxybutyrate one in 95 doses (1.05%). With respect to ecstasy-related deaths in Great Britain, the estimated risk of ecstasy alone per user is 0.01-0.06%, which is close to the range of the fatality risk in chronic alcohol users (0.01-0.02%), amphetamine users (0.005%) and cocaine users (0.05%), but much lower than that of opiate use (heroin and morphine: 0.35%). CONCLUSION: The current review shows that almost no data are available on the health risks of ecstasy use. The few data that are available show that ecstasy is not a safe substance. However, compared to opiates (heroin, morphine), the risk of acute ecstasy-related adverse health incidents per ecstasy user and per ecstasy use session is relatively low.

Adverse effects of levamisole in cocaine users: a review and risk assessment.

The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.

Levamisole-contaminated cocaine: a hairy affair.

Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse. Symptoms included ulcerating skin lesions, arthralgia and myalgia, and the occurrence of an ileal intussusception. The definitive diagnosis was made using hair testing for toxins. She recovered through cocaine abstinence, but re-exposure resulted in a severe relapse with glomerulonephritis. Importantly, at time of the relapse, the patient became positive for both myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA. Cocaine-levamisole-induced vasculitis poses a great clinical challenge. The proper diagnostic strategy and therapy is still controversial. We highlight our diagnostic and therapeutic considerations, including hair testing for definitive proof of exposure.

Risk assessment of GBL as a substitute for the illicit drug GHB in the Netherlands. A comparison of the risks of GBL versus GHB.

In the Netherlands, γ-hydroxybutyric acid (GHB) was recently banned, but γ-butyrolactone (GBL) was not. As such, GBL remained a legal alternative to GHB. This review compares the risks of GBL and GHB. Pure GBL is per unit of volume about threefold stronger and therefore threefold more potent than currently used GHB-preparations in the Netherlands. Like GHB, GBL use hardly leads to organ toxicity, although, as with GHB, frequent GBL use may lead to repeated comas that may result in residual impairments in cognitive function and memory. Little is known about the prevalence of GBL use in Europe, but the recent increase in improper trading in GBL confirms that users of GHB gradually switch to the use of GBL. This shift may result in an increase in the number GBL dependent users, because the dependence potential of GBL is as great as that of GHB. Severe withdrawal symptoms and a high relapse rate are seen following cessation of heavy GBL use. GBL-dependent users seem to be severe (dependent, problematic) GHB users who started using GBL, the legal GHB substitute. Subjects who are solely dependent to GBL are rarely reported. About 5-10% of the treatment seeking GHB dependent subjects also use GBL and this subpopulation forms a vulnerable group with multiple problems. Fatal accidents with GBL are rarely reported, but non-fatal GHB (or GBL) overdoses frequently occur for which supportive treatment is needed. It is recommended to monitor the recreational use of GBL, the rate of GBL dependence treatment, and the improper trading of GBL.

Rapid analysis of Δ-9-tetrahydrocannabinol in hair using direct analysis in real time ambient ionization orbitrap mass spectrometry.

RATIONALE: Forensic hair analysis methods are laborious, time-consuming and provide only a rough retrospective estimate of the time of drug intake. Recently, hair imaging methods using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) were reported, but these methods require the application of MALDI matrix and are performed under vacuum. Direct analysis of entire locks of hair without any sample pretreatment and with improved spatial resolution would thus address a need. METHODS: Hair samples were attached to stainless steel mesh screens and scanned in the X-direction using direct analysis in real time (DART) ambient ionization orbitrap MS. The DART gas temperature and the accuracy of the probed hair zone were optimized using Δ-9-tetrahydrocannabinol (THC) as a model compound. Since external contamination is a major issue in forensic hair analysis, sub-samples were measured before and after dichloromethane decontamination. RESULTS: The relative intensity of the THC signal in spiked blank hair versus that of quinine as the internal standard showed good reproducibility (26% RSD) and linearity of the method (R(2) = 0.991). With the DART hair scan THC could be detected in hair samples from different chronic cannabis users. The presence of THC was confirmed by quantitative liquid chromatography/tandem mass spectrometry. Zones with different THC content could be clearly distinguished, indicating that the method might be used for retrospective timeline assessments. Detection of THC in decontaminated drug user hair showed that the DART hair scan not only probes THC on the surface of hair, but penetrates deeply enough to measure incorporated THC. CONCLUSIONS: A new approach in forensic hair analysis has been developed by probing complete locks of hair using DART-MS. Longitudinal scanning enables detection of incorporated compounds and can be used as pre-screening for THC without sample preparation. The method could also be adjusted for the analysis of other drugs of abuse.

Physical harm due to chronic substance use.

Chronic use at high dose of illicit drugs, alcohol and tobacco is associated with physical disease. The relative physical harm of these substances has not been described before, but will benefit the guiding of policy measures about licit and illicit substances. The physical harm of 19 addictive substances (including alcohol and tobacco), consisting of toxicity and the risk and severity of somatic disease (not psychiatric disease) was assessed based on literature data and the professional opinion of experts using scores ranging from 0 (no physical harm) to 3 (very serious physical harm). For alcohol, tobacco and some illicit drugs strong associations between long-term use or use in high dose versus the risk of somatic disease have been described, whereas for other substances such data are not available. Magic mushrooms, LSD and methylphenidate obtained relatively low scores (0.45-0.65) for physical harm, whereas relatively high scores were given for heroin (2.09), crack (2.32), alcohol (2.13) and tobacco (2.10). For cannabis, tobacco, and alcohol the estimated societal disease burden was higher than at individual level. The present ranking solely based on their physical harm was very similar to a previous ranking based on a combination of dependence liability, physical harm and social impairments.

Saccadic peak velocity and EEG as end-points for a serotonergic challenge test.

UNLABELLED: We previously reported that a single dose of the serotonin receptor agonist meta-chlorophenylpiperazine increased the peak velocity of saccadic eye movements and decreased low-frequency electroencephalographic activity. METHODS: We administered a single dose of the serotonin releaser dexfenfluramine in a double blind, placebo controlled randomised cross-over design and measured saccadic eye movements and EEG every hour up to 6 h. Subjects were 62 males (18-30 years) with a history of no, moderate or heavy use of ecstasy tablets. RESULTS: Dexfenfluramine increased saccadic peak velocity and decreased alpha, delta and theta electroencephalographic activity, the latter predominantly in heavy users of ecstasy. CONCLUSIONS: This study supports the idea that saccadic peak velocity and EEG can be useful endpoints of a serotonergic challenge. This could be an important anatomical extension of these end-points, which until now were limited to the effect on hypothalamic serotonergic projections.

Effects of concurrent use of alcohol and cocaine.

The combination of alcohol and cocaine is popular among drug users, perhaps because of more intense feelings of 'high' beyond that perceived with either drug alone, less intense feelings of alcohol-induced inebriation and tempering of discomfort when coming down from a cocaine 'high'. A review is presented of the medical literature on psychological and somatic effects and consequences of combined use of alcohol and cocaine in man. The search was carried out with Medline, the Science Citation Index/Web of Science and Toxline. Exclusion and inclusion criteria for this search are identified. There is generally no evidence that the combination of the two drugs does more than enhance additively the already strong tendency of each drug to induce a variety of physical and psychological disorders. A few exceptions must be noted. Cocaine consistently antagonizes the learning deficits, psychomotor performance deficits and driving deficits induced by alcohol. The combination of alcohol and cocaine tends to have greater-than-additive effects on heart rate, concomitant with up to 30% increased blood cocaine levels. Both prospective and retrospective data further reveal that co-use leads to the formation of cocaethylene, which may potentiate the cardiotoxic effects of cocaine or alcohol alone. More importantly, retrospective data suggest that the combination can potentiate the tendency towards violent thoughts and threats, which may lead to an increase of violent behaviours.