Aerosol microparticles in exhaled breath carry non-volatile compounds from the deeper parts of the lung. When captured and analyzed, these aerosol microparticles constitute a non-invasive and readily available specimen for drugs of abuse testing. The present study aimed to evaluate a simple breath collection device in a clinical setting. The device divides a breath sample into three parallel \"collectors\" that can be individually analyzed. Urine was used as the reference specimen, and parallel specimens were collected from 99 patients undergoing methadone maintenance treatment. Methadone was used as the primary validation parameter. A sensitive multi-analyte method using tandem liquid chromatography - mass spectrometry was developed and validated as part of the project. The method was successfully validated for 36 analytes with a limit of detection of 1 pg/collector for most compounds. Based on the validation results tetrahydrocannabinol THC), cannabidiol (CBD), and lysergic acid diethylamide (LSD) are suitable for qualitative analysis, but all other analytes can be quantitively assessed by the method. Methadone was positive in urine in 97 cases and detected in exhaled breath in 98 cases. Median methadone concentration was 64 pg/collector. The methadone metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was detected in 90 % of the cases but below 10 pg/collector in most. Amphetamine was also present in the urine in 17 cases and in exhaled breath in 16 cases. Several other substances were detected in the exhaled breath and urine samples, but at a lower frequency. This study concluded that the device provides a specimen from exhaled breath, that is useful for drugs of abuse testing. The results show that high analytical sensitivity is needed to achieve good detectability and detection time after intake.

A straightforward approach for creating fast and novel potentiometric sensors that are modified with multi-walled nanotubes (MWCNTs) was described. The impact of the selective sensor\'s material was studied. The suggested sensors were successfully fabricated for instant and fast detection of the prohibited β-adrenoreceptor blocking agent acebutolol hydrochloride (AC) in commercial products. Acebutolol-phosphomolybdate (AC-PM) carbon paste sensor was formed by mixing AC and phosphomolybdic acid and graphite powder in the presence of o-nitrophenyl octyl ether (o-NPOE) as a plasticizing agent. The functionalized AC-PM-MWCNTs and AC-PM-MWCNTs-Al2O3 nanocomposite sensors were prepared and all parameters affecting the sensors\' potential responses have been investigated as well as the green synthesis of Al2O3NPs has been characterized using various microscopic and spectroscopic techniques. AC-PM-MWCNTs and AC-PM-MWCNTs-Al2O3 nanocomposite sensors demonstrated linearity of 1.0 × 10-7-1.0 × 10-2 and 1.0 × 10-8-1.0 × 10-2 mol L-1, respectively with regression equations -53.571x + 423.24 (r = 0.999) and -57.107x + 518.54 (r = 0.999). It also revealed excellent selectivity and sensitivity for the determination and quantification of AC. The developed potentiometric system was suitable for the determination of AC in bulk powder and commercial products.

During the last decade, substance use disorders (SUDs) have been increasingly recognized as neuroinflammation-related brain diseases. Various types of abused drugs (cocaine, methamphetamine, alcohol, opiate-like drugs, marijuana, etc.) can modulate the activation status of microglia and neuroinflammation levels which are involved in the pathogenesis of SUDs. Several neuroimmune signaling pathways, including TLR/NF-кB, reactive oxygen species, mitochondria dysfunction, as well as autophagy defection, etc., have been implicated in promoting SUDs. Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation induced by abused drugs. Among the family of inflammasomes, NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) serves the primary research target due to its abundant expression in microglia. NLRP3 has the capability of integrating multiple external and internal inputs and coordinately determining the intensity of microglia activation under various pathological conditions. Here, we summarize the effects of abused drugs on NLRP3 inflammasomes, as well as others, if any. The research on this topic is still at an infant stage; however, the readily available findings suggest that NLRP3 inflammasome could be a common downstream effector stimulated by various types of abused drugs and play critical roles in determining abused-drug-mediated biological effects through enhancing glia-neuron communications. NLRP3 inflammasome might serve as a novel target for ameliorating the development of SUDs.

Atomic-level understanding of the dynamic feature of host-guest interactions remains a central challenge in supramolecular chemistry. The remarkable guest binding behavior of the Cucurbiturils family of supramolecular containers makes them promising drug carriers. Among Cucurbit[n]urils, Cucurbit[8]uril (CB8) has an intermediate portal size and cavity volume. It can exploit almost all host-guest recognition motifs formed by this host family. In our previous work, an extensive computational investigation of the binding of seven commonly abused and structurally diverse drugs to the CB8 host was performed, and a general dynamic binding picture of CB8-guest interactions was obtained. Further, two widely used fixed-charge models for drug-like molecules were investigated and compared in great detail, aiming at providing guidelines in choosing an appropriate charge scheme in host-guest modelling. Iterative refitting of atomic charges leads to improved binding thermodynamics and the best root-mean-squared deviation from the experimental reference is 2.6 kcal/mol. In this work, we focus on a thorough evaluation of the remaining parts of classical force fields, i.e., the bonded interactions. The widely used general Amber force fields are assessed and refitted with generalized force-matching to improve the intra-molecular conformational preference, and thus the description of inter-molecular host-guest interactions. The interaction pattern and binding thermodynamics show a significant dependence on the modelling parameters. The refitted system-specific parameter set improves the consistency of the modelling results and the experimental reference significantly. Finally, combining the previous charge-scheme comparison and the current force-field refitting, we provide general guidelines for the theoretical modelling of host-guest binding.

Psychological disorders and dramatic social problems are serious concerns regarding the abuse of amphetamine and its stimulant derivatives worldwide. Consumers of such drugs experience great euphoria along with serious health problems. Determination and quantification of amphetamine-type stimulants are indispensable skills for clinical and forensic laboratories. Analysis of low drug doses in bio-matrices necessitates applications of simple and also effective preparation steps. The preparation procedures not only eliminate adverse matrix effects, but also provide reasonable clean-up and pre-concentration benefits. The current review presents different methods used for sample preparation of amphetamines from urine as the most frequently used biological matrix. The advantages and limitations of various sample preparation methods were discussed focusing on the miniaturized methods.

This review highlights literature relating the anatomy, physiology, and behavioral contributions by projections between rodent prefrontal cortical areas and the basolateral amygdala. These projections are robustly modulated by both environmental experience and exposure to drugs of abuse including ethanol. Recent literature relating optogenetic and chemogenetic dissection of these circuits within behavior both compliments and occasionally challenges roles defined by more traditional pharmacological or lesion-based approaches. In particular, cortico-amygdala circuits help control both aversive and reward-seeking. Exposure to pathology-producing environments or abused drugs dysregulates the relative \'balance\' of these outcomes. Modern circuit-based approaches have also shown that overlapping populations of neurons within a given brain region frequently govern both aversion and reward-seeking. In addition, these circuits often dramatically influence \'local\' cortical or basolateral amygdala excitatory or inhibitory circuits. Our understanding of these neurobiological processes, particularly in relation to ethanol research, has just begun and represents a significant opportunity. This article is part of the special Issue on \'Neurocircuitry Modulating Drug and Alcohol Abuse\'.

Synthetic cannabinoids are a new class of chemical drugs capable of modifying human behavior. These products do not contain cannabis, but produce similar effects after consumption. The fact that they are easily accessed, and are many times considered to be harmless, justifies their widespread use among young people. This fact, together with the difficulty in their detection by routine drug tests, makes it extremely important to develop new procedures able to detect and monitor their consumption. The aim of this work is to perform a critical review regarding the human biological samples that can be used for the determination of synthetic cannabinoids, paying special attention to analytical methods and sample preparation techniques. The reviewed articles deal with the determination of synthetic cannabinoids in the context of forensic and toxicological analysis.

The consumption of illicit drugs such as cannabis, cocaine, and amphetamines is still a major health and social problem, creating an abuse in adults especially. Novel techniques which estimate the drug of abuse are needed for the detection of newly revealed psychoactive drugs. Herein, we have constructed a combinatorial platform by using quantum dots (QDs) and gold nanoparticles (AuNPs) as well as a functional aptamer which selectively recognizes cocaine and its metabolite benzoylecgonine (BE). We have called it an aptamer folding-based sensory device (AFSD). For the fabrication of AFSD, QDs were initially immobilized onto the poly-L-lysine coated μ-well surfaces. Then, the AuNP-aptamer conjugates were bound to the QDs. The addition of cocaine or BE caused a change in the aptamer structure which induced the close interaction of AuNPs with the QDs. Hence, quenching of the fluorescence of QDs was observed depending on the analyte amount. The linearity of cocaine and BE was 1.0-10 nM and 1.0-25 μM, respectively. Moreover, the limits of detection for cocaine and BE were calculated as 0.138 nM and 1.66 μM. The selectivity was tested by using different interfering substances (methamphetamine, bovine serum albumin, codeine, and 3-acetamidophenol). To investigate the use of AFSD in artificial urine matrix, cocaine/BE spiked samples were applied. Also, confirmatory analyses by using high performance liquid chromatography were performed. It is shown that AFSD has a good potential for testing the cocaine abuse and can be easily adapted for detection of various addictive drugs by changing the aptamer according to desired analytes. Copyright © 2016 John Wiley & Sons, Ltd.

Numerous commonly abused drugs exist in two enantiomeric forms. Identifying the exact enantiomeric form is essential when only one of these two enantiomers is a controlled substance. Enantiomeric composition data may also help the investigation of clandestine laboratory activities. Although generally not as convenient as gas chromatographic methods, liquid chromatographic methods (LC) allow for the selection of larger and hopefully more effective derivatizing groups and the use of an \"active\" mobile phase. LC-based enantiomeric resolution approaches include derivatization with chiral agents, incorporation of chiral additives in the mobile phase, and the use of chiral stationary phases. Various applications of these approaches are reviewed.Unique detection procedures that were adopted in enantiomeric analysis are also reviewed.

Although abused drugs are administered most often by preferred routes, unconventional routes also may be employed. In addition, unsuspected drug exposure can occur by \"unusual\" routes, e.g., oral ingestion, passive inhalation, transcutaneous absorption, and in utero exposure. Urine testing is often used to document recent drug exposure. Much of the scientific literature on urine testing concerns studies of conventional routes of drug administration. This article reviews current data on urine testing following unconventional means of administration of drugs of abuse. In each section, a brief review of the principles involved in each unusual route is followed by a discussion of studies and case reports in which urine was tested for drugs of abuse. Special mention is made of the danger of passive inhalation to small children and in utero exposure to fetuses. It is hoped that this review will sensitize those involved in interpretation of urine test data to the many possible ways drugs can enter the human organism.