Radiological detection of dissolved cocaine

Introduction: Smuggling dissolved drugs, especially cocaine, in bottled liquids is a problem at borders nowadays. Common fluoroscopy of packages at the border cannot detect contaminated liquids. To find a dissolved drug, an immunological test using a drug-test panel has to be performed. This means that a control sample of the cargo must be opened to perform the test. As it is not possible to open all boxes, and as smugglers hide the drugcontaining boxes between regularly filled boxes, contaminated cargos can be overlooked. Investigators sometimes cannot perform the drug-test panel because they try not to arouse the smugglers' suspicion in order to follow the cargo and to find the recipient. Aims: The objective of our studies was to define non-invasive examination techniques to investigate cargos that are suspicions to contain dissolved cocaine without leaving traces on the samples. We examined vessels containing cocaine by radiological cross-section techniques such as multidetector computed tomography (MDCT) and magnetic resonance spectroscopy (MRS). Methods: In a previous study, we examined bottles of wine containing dissolved cocaine in different quantities using an MDCT unit. To distinguish between bottles containing red wine and those where cocaine was solved in the wine, cross sectional 2D-images have been reconstructed and the absorption of X-rays was quantified by measuring the mean density of the liquid inside the bottles. In our new study, we investigated phantoms containing cocaine dissolved in water with or without ethanol as well as cocaine dissolved in different sorts of commercially available wine by the use of a clinical magnetic resonance unit (3 tesla). To find out if dissolved cocaine could be detected, magnetic resonance spectroscopy (1H MRS) was performed. Results: By using a MDCT-unit and measuring the mean attenuation of X-rays, it is possible to distinguish weather substances are dissolved in a liquid or not, if a comparative liquid without any solutions is available. The increase of the mean density indicates the presence of dissolved substances without the possibility to identify the substance. By using magnetic resonance spectroscopy, dissolved cocaine can be clearly identified because it produces distinctive resonances in the spectrum. In contrast to MDCT, this technique shows a high sensitivity (detection of 1 mM cocaine in wine). Conclusions: Cross-sectional imaging techniques such as MDCT and MRS appropriated to examine cargos that are suspicious to contain dissolved cocaine. They allow to perform non-invasive investigations without leaving any trace on the cargo. While an MDCT scan can detect dissolved substances in liquids, identification of cocaine can be obtained by MR-spectroscopy. Acknowledgment: This work was supported by the Centre d'Imagerie BioMédicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the University of Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the Hôpitaux Universitaire de Genève (HUG) and the Leenaards and the Jeantet Foundations.

Differentiation of heroin and cocaine using dual-energy CT-an experimental study.

OBJECTIVE: To evaluate if heroin and cocaine can be distinguished using dual-energy CT. MATERIALS AND METHODS: Twenty samples of heroin and cocaine at different concentrations and standardized compression (SC) were scanned in dual-energy mode on a newest generation Dual Energy 64-row MDCT scanner. CT number, spectral graphs, and dual-energy index (DEI) were evaluated. Results were prospectively tested on six original samples from a body packer. Wilcoxon's test was used for statistical evaluation. RESULTS: Values are given as median and range. Under SC, the CT number of cocaine samples (-29.87 Hounsfield unit (HU) [-125.85; 16.16 HU]) was higher than the CT number of heroin samples (-184.37 HU [-199.81; -159.25 HU]; p < 0.01). Slope of spectral curves for cocaine was -2.36 HU/keV [-7.15; -0.67 HU/keV], and for heroin, 1.75 HU/keV [1.28; 2.5 HU/keV] (p < 0.01). DEI was 0.0352 [0.0081; 0.0528] for cocaine and significantly higher than for heroin samples (-0.0127 [-0.0097; -0.0159]; p < 0.001). While CT number was inconclusive, all six original packs were correctly classified after evaluation of the spectral curve and DEI. In contrast to the CT number, slope of the spectral curve and DEI were independent of concentration and compression. CONCLUSION: The slope of the spectral curve and the DEI from dual-energy CT data can be used to distinguish heroin and cocaine in vitro; these results are independent of compression and concentration in the measured range.

Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity.

Overactivation of the sympatho-adrenergic system is an essential mechanism providing short-term adaptation to the stressful conditions of critical illnesses. In the same way, the administration of exogenous catecholamines is mandatory to support the failing circulation in acutely ill patients. In contrast to these short-term benefits, prolonged adrenergic stress is detrimental to the cardiovascular system by initiating a series of adverse effects triggering significant cardiotoxicity, whose pathophysiological mechanisms are complex and only partially elucidated. In addition to the development of myocardial oxygen supply/demand imbalance induced by the sustained activation of adrenergic receptors, catecholamines can damage cardiomyocytes by fostering mitochondrial dysfunction, via two main mechanisms. The first one is calcium overload, consecutive to β-adrenergic receptor-mediated activation of protein kinase A and subsequent phosphorylation of multiple Ca(2+)-cycling proteins. The second one is oxidative stress, primarily related to the transformation of catecholamines into "aminochromes," which undergo redox cycling in mitochondria to generate copious amounts of oxygen-derived free radicals. In turn, calcium overload and oxidative stress promote mitochondrial permeability transition and cardiomyocyte cell death, both via the apoptotic and necrotic pathways. Comparable mechanisms of myocardial toxicity, including marked oxidative stress and mitochondrial dysfunction, have been reported with the use of cocaine, a common recreational drug with potent sympathomimetic activity. The aim of the current review is to present in detail the pathophysiological processes underlying the development of catecholamine and cocaine-induced cardiomyopathy, as such conditions may be frequently encountered in the clinical practice of cardiologists and ICU specialists.

Detection of smuggled cocaine in cargo using MDCT.

OBJECTIVE: Smuggling dissolved drugs, especially cocaine, in bottled liquids is an ongoing problem at borders. Common fluoroscopy of packages at the border cannot detect contaminated liquids. The objective of our study was to develop an MDCT screening method to detect cocaine-containing vessels that are hidden between uncontaminated ones in a shipment. MATERIALS AND METHODS: Studies were performed on three wine bottles containing cocaine solutions that were confiscated at the Swiss border. Reference values were obtained by scans of different sorts of commercially available wine and aqueous solutions of dissolved sugar. All bottles were scanned using MDCT, and data evaluation was performed by measuring the mean peak of Hounsfield units. To verify the method, simulated testing was performed. RESULTS: Using measurements of the mean peak of Hounsfield units enables the detection of dissolved cocaine in wine bottles in a noninvasive and rapid fashion. Increasing opacity corresponds well with the concentration of dissolved cocaine. Simulated testing showed that it is possible to distinguish between cocaine-contaminated and uncontaminated wine bottles. CONCLUSION: The described method is an efficacious screening method to detect cocaine-contaminated bottles that are hidden between untreated bottles in cargo. The noninvasive examination of cargo allows a questionable delivery to be tracked without arousing the suspicion of the smugglers.

Hypocretin/orexin in addiction: a mediator of stress-induced reinstatement of cocaine-seeking behaviour

The importance of the lateral hypothalamus in the pursuit of reward has long been recognized. However, the hypothalamic neuronal network involved in the regulation of reward still remains partially unknown. Hypocretins (aka orexins) are neuropeptides synthesized by a few thousand neurons restricted to the lateral hypothalamus and the perifornical area. Compelling evidence indicates that hypocretin neurons receive inputs from sensory and limbic systems and drive hyper-arousal possibly through modulation of stress responses. Major advances have been made in the elucidation of the hypocretin involvement in the regulation of arousal, stress, motivation, and reward seeking, without clearly defining the role of hypocretins in addictionrelated behaviors. We have recently gathered substantial evidence that points to a previously unidentified role for hypocretin-1 in driving relapse for cocaine seeking through activation of brain stress pathways. Meanwhile, several authors published concordant observations rather suggesting a direct activation of the mesolimbic dopamine system. In particular, hypocretin-1 has been shown to be critically involved in cocaine sensitization through the recruitment of NMDA receptors in the ventral tegmental area. Overall, on can conclude from recent findings that activation of hypocretin/orexin neurons plays a critical role in the development of the addiction process, either by contributing to brain sensitization (which is thought to lead to the unmanageable desire for drug intake) or by modulating the brain reward system that, in coordination with brain stress systems, leads to a vulnerable state that may facilitate relapse for drug seeking behavior.

Extended access cocaine self-administration differentially activates dorsal raphe and amygdala corticotropin-releasing factor systems in rats.

Cocaine-induced neuroadaptation of stress-related circuitry and increased access to cocaine each putatively contribute to the transition from cocaine use to cocaine dependence. The present study tested the hypothesis that rats receiving extended versus brief daily access to cocaine would exhibit regional differences in levels of the stress-regulatory neuropeptide corticotropin-releasing factor (CRF). A secondary goal was to explore how CRF levels change in relation to the time since cocaine self-administration. Male Wistar rats acquired operant self-administration of cocaine and were assigned to receive daily long access (6 hours/day, LgA, n = 20) or short access (1 hour/day, ShA, n = 18) to intravenous cocaine self-administration (fixed ratio 1, ∼0.50 mg/kg/infusion). After at least 3 weeks, tissue CRF immunoreactivity was measured at one of three timepoints: pre-session, post-session or 3 hours post-session. LgA, but not ShA, rats showed increased total session and first-hour cocaine intake. CRF immunoreactivity increased within the dorsal raphe (DR) and basolateral, but not central, nucleus of the amygdala (BLA, CeA) of ShA rats from pre-session to 3 hours post-session. In LgA rats, CRF immunoreactivity increased from pre-session to 3 hours post-session within the CeA and DR but tended to decrease in the BLA. LgA rats showed higher CRF levels than ShA rats in the DR and, pre-session, in the BLA. Thus, voluntary cocaine intake engages stress-regulatory CRF systems of the DR and amygdala. Increased availability of cocaine promotes greater tissue CRF levels in these extrahypothalamic brain regions, changes associated here with a model of cocaine dependence.

Millepertuis, corticoïdes, cocaïne, alcool ... et un premier épisode maniaque. Femme, 36 ans, artiste [St. John's Wort, corticosteroids, cocaine, alcohol ... and a first manic episode].

We describe an alcohol and cocaine abusing female patient who developed a first manic episode in the context of a corticosteroid prescription. The differential diagnoses are discussed on the basis of the available literature on secondary manias.

Interpretation of lesions of the cardiac conduction system in cocaine-related fatalities.

This study examines cases of chronic drug users who died suddenly after drug administration. Victims were young subjects, aged from 19 to 35 from Switzerland and known to the police as long-term drug users. The circumstances of death suggested the occurrence of a sudden, unexpected death. Some victims were undergoing methadone treatment. In each case, a forensic autopsy and toxicological analyses were performed at the Institute of Forensic Medicine in Lausanne in Switzerland between 2002 and 2004, including hair analysis as a means to establish chronic drug use in general, and cocaine use in particular. The conduction system was examined histologically and cases showing potentially lethal changes were chosen for this report. The most frequent lesions found were severe thickening of the atrioventricular node artery, intranodal and perinodal fibrosis, and microscopic foci of chronic inflammatory infiltration. The authors conclude that pathological lesions in the conduction tissue may play a role in the occurrence of death attributed to intoxication consecutive to cocaine ingestion.

First systematic chemical profiling of cocaine police seizures in Finland in the framework of an intelligence-led approach

For the first time in Finland, the chemical profiling of cocaine specimens was performed at the National Bureau of Investigation (NBI). The main goals were to determine the chemical composition of cocaine specimens sold in the Finnish market and to study the distribution networks of cocaine in order to provide intelligence related to its trafficking. An analytical methodology enabling through one single GC-MS injection the determination of the added cutting agents (adulterants and diluents), the cocaine purity and the chemical profile (based on the major and minor alkaloids) for each specimen was thus implemented and validated. The methodology was found to be efficient for the discrimination between specimens coming from the same source and specimens coming from different sources. The results highlighted the practical utility of the chemical profiling, especially for supporting the investigation through operational intelligence and improving the knowledge related to the cocaine trafficking through strategic intelligence.

The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.

Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulation of reward and addiction are still unknown. In this study, we showed that disruption of the gene that encodes VGLUT3 (Slc17a8) markedly increased cocaine self-administration in mice. Concomitantly, the amount of dopamine (DA) release was strongly augmented in the NAc of VGLUT3(-/-) mice because of a lack of signaling by metabotropic glutamate receptors. Furthermore, dendritic spines and glutamatergic synaptic transmission on medium spiny neurons were increased in the NAc of VGLUT3(-/-) mice. Increased DA and glutamate signaling in the NAc are hallmarks of addiction. Our study shows that TANs use glutamate to reduce DA release and decrease reinforcing properties of cocaine in mice. Interestingly, we also observed an increased frequency of rare variations in SLC17A8 in a cohort of severe drug abusers compared with controls. Our findings identify VGLUT3 as an unexpected regulator of drug abuse.

Qualitative, quantitative and temporal study of cutting agents for cocaine and heroin over 9 years

Forensic laboratories mainly focus on the qualification and the quantitation of the illicit drug under analysis as both aspects are used for judiciary purposes. Therefore, information related to cutting agents (adulterants and diluents) detected in illicit drugs is limited in the forensic literature. This article discusses the type and frequency of adulterants and diluents detected in more than 6000 cocaine specimens and 3000 heroin specimens, confiscated in western Switzerland from 2006 to 2014. The results show a homogeneous and quite unchanging adulteration for heroin, while for cocaine it could be characterised as heterogeneous and relatively dynamic. Furthermore, the results indicate that dilution affects more cocaine than heroin. Therefore, the results provided by this study tend to reveal differences between the respective structures of production or distribution of cocaine and heroin. This research seeks to promote the systematic analysis of cutting agents by forensic laboratories. Collecting and processing data related to the presence of cutting agents in illicit drug specimens produces relevant information to understand and to compare the structure of illicit drug markets.

The cutting of cocaine and heroin: a critical review

The illicit drug cutting represents a complex problem that requires the sharing of knowledge from addiction studies, toxicology, criminology and criminalistics. Therefore, cutting is not well known by the forensic community. Thus, this review aims at deciphering the different aspects of cutting, by gathering information mainly from criminology and criminalistics. It tackles essentially specificities of cocaine and heroin cutting. The article presents the detected cutting agents (adulterants and diluents), their evolution in time and space and the analytical methodology implemented by forensic laboratories. Furthermore, it discusses when, in the history of the illicit drug, cutting may take place. Moreover, researches studying how much cutting occurs in the country of destination are analysed. Lastly, the reasons for cutting are addressed. According to the literature, adulterants are added during production of the illicit drug or at a relatively high level of its distribution chain (e.g. before the product arrives in the country of destination or just after its importation in the latter). Their addition seems hardly justified by the only desire to increase profits or to harm consumers' health. Instead, adulteration would be performed to enhance or to mimic the illicit drug effects or to facilitate administration of the drug. Nowadays, caffeine, diltiazem, hydroxyzine, levamisole, lidocaïne and phenacetin are frequently detected in cocaine specimens, while paracetamol and caffeine are almost exclusively identified in heroin specimens. This may reveal differences in the respective structures of production and/or distribution of cocaine and heroin. As the relevant information about cutting is spread across different scientific fields, a close collaboration should be set up to collect essential and unified data to improve knowledge and provide information for monitoring, control and harm reduction purposes. More research, on several areas of investigation, should be carried out to gather relevant information.