新精神活性物质发展与管制综述

新精神活性物质具有更迭快、种类多、毒性强的特点,业已成为继传统毒品和合成毒品之后的"第三代毒品".新精神活性物质的出现对个人和公众健康构成越来越严峻的威胁,也对传统的毒品管制制度提出了巨大的挑战.为应对新精神活性物质问题,以联合国为平台的国际组织与国际社会均进行了一系列措施,我国于2015年出台《非药用类麻醉药品和精神...     

新精神活性物质检验鉴定面临的挑战和对策

新精神活性物质更新快,种类繁多,缺乏国际条约的监管,列入联合国管控目录困难,加之一些国家和国际社会对大麻等毒品管控降低,给我国在新精神活性物质类毒品的监管带来困难.具有成瘾性和社会危害性的新精神活性物质才能成为列管对象,毒物分析技术人员在列管程序中扮演极为重要的角色.我国对新精神活性物质的监管法规规定了相关列管程序,毒...     

Determining the Toxicological Significance of Pregabalin in Fatalities

Pregabalin has become more widely prescribed and abused in recent years but is still not always included in laboratory analysis. An LC‐MS‐MS method has been developed and applied to measure pregabalin in 93 postmortem cases, including drug‐related deaths, alternative causes of death, and fatalities where pregabalin was likely to have contributed to death. Other drugs or alcohol was detected, and the most common drug types (in decreasing frequency) were antidepressants, opioids, benzodiazepines, opiates, alcohol, antipsychotics, cocaine, cardiac drugs, amphetamines, cannabis, anticonvulsants, and antihistamines. New psychoactive substances (methoxphenidine and synthetic cannabinoids) were only found in two cases. The results provide further data to assist in evaluating the significance of postmortem pregabalin concentrations and a toxicologically significant concentration of 25 mg/L is proposed. Pregabalin, especially with concomitant use of other CNS depressant drugs, presents a significant toxicological risk and existing laboratory protocols should be reviewed for their suitability to detect pregabalin.     

Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive drug poisoning

A suicide caused by ingestion of multiple psychoactive drugs is reported. A 42-year-old man with a history of psychosis was found dead in a blood pool in his room. The forensic autopsy revealed two stab wounds on his chest. However, these wounds could not explain the cause of death. Eighty-six tablets were found in his stomach. Four psychoactive drugs; clocapramine (CC), chlorpromazine (CP), promethazine (PM) and clotiazepam (CT) were detected in blood and tissues. The concentrations of CC, CP, PM and CT in the femoral vein (FV) blood were 0.39, 0.61, 1.23 and 0.09 microg/ml, respectively. The cause and manner of death were attributed to suicidal multiple psychoactive drug poisoning.Postmortem drug redistribution showed great site-dependent variations with the lowest level in the FV blood. Remarkable variations were observed in CC, CP and PM, but not in CT compared to other three drugs. The variations were dependent on the volume of distribution (Vd) of the drugs. Our human case has demonstrated drugs with higher Vd values showed higher degree of postmortem redistribution of the drug and vice versa.     

The use of 13C NMR spectroscopy in forensic drug analysis

¹³C NMR spectroscopy has been used for analysis of fourteen compounds which, according to Swedish laws are defined as narcotic drugs or are substances often found in combination with these drugs. The carbon-13 NMR method seems to be well suited for analysis of complex forensic drug mixtures because no preliminary separation of components is required.     

Awareness of Novel Drug Legality in a Young Adult Population

In recent years, use of substances commonly referred to as ‘legal highs’ has become a significant concern to policy makers and public health officials. Though legislation banning the use and possession of these novel and synthetic drugs often follows the initial media attention and public outcry, potential users may often be unaware of the legislation. A survey including self-reported drug use and perceptions of the legality of various psychoactive substances was administered to 2,346 students in randomly selected classes at a large public university to determine what portion accurately knew four types of novel drugs were locally illegal. Results indicated that numerous potential and current users incorrectly believed that the former ‘legal highs’ remained unrestricted. This sample did include a number of novel drug users; lifetime use of at least one novel drug was reported by 17.1 %, many of which reported using multiple types of novel drugs. Approximately one-third of the overall sample inaccurately believed that Salvia divinorum (34.7 %), K2/Spice (36.5 %), and Mr. Miyagi/Pot-pourri (32.1 %) were legal in the state and over half (50.3 %) inaccurately believed ‘bath salts’ (synthetic cathinones, MDPV, and other synthetic stimulants) remained legal. As these misperceptions have the potential to influence substance use decisions, they may need to be corrected through educational campaigns as widespread as the preceding media coverage that labeled the drug as ‘legal highs.’ Results also indicated that Blacks and previous users of the substances were more likely to hold inaccurate legal beliefs.     

Occupational workplace and traffic fatalities in Alsace, France (2000–2005): Results of toxicological investigations

France ranks as leader country in Europe for the consumption of cannabis as well as of psychoactive medications. Whereas the relationship between psychotropics and road accidents is now well-established, few data are still available on the influence of drugs on occupational accidents. The purpose of the present study was to measure the prevalence of psychoactive drug intake (alcohol excepted) among victims of occupational fatalities (including workplace accidents + traffic accidents, i.e. on the way to and from work) occurred in the region Alsace over the period 2000–2005. Data were collected by compiling files on occupational accidents from two different public agencies (CRAM, Regional Sickness Fund Alsace-Moselle; DRTEFP, Regional Department of Work, Employment and Professional Training) together with those from the Medico-Legal Institute of Strasbourg over the period tested. Data analysis showed that 3% of the victims of workplace fatalities were under the influence of drugs (alcohol excluded) at the time of accident, as well as 5% of the victims of occupational traffic accidents. Our results also highlight a low rate of toxicological analyses, since these investigations were requested by the authorities in 41% of traffic victims and only 15% of workplace victims. In France, the relevance of psychoactive drug intake in occupational deaths is much better targeted in the case of traffic fatalities (due to the existence of specific regulations, e.g. compulsory urinalysis for drugs of abuse in drivers involved in a road accident) than in those occurred at workplace (no specific regulations).     

Drugs and chronic alcohol abuse in drivers

Blood specimens from 210 drivers (179 male and 31 female) apprehended in Luxembourg from autumn 2001 to spring 2002 and requested for the determination of their blood alcohol concentration (BAC) were tested for medicinal drugs, illicit drugs, and chronic alcohol abuse (by quantification of the carbohydrate-deficient transferrin: CDT). These additional analyses were performed anonymously and with permission of state prosecutor. The 22.8% had consumed medicinal drugs, with benzodiazepines and antidepressants (10.9 and 7.6%, respectively) as main psychoactive classes. Cannabis was the most detected illicit drug (9.5%) but only one in three had THC detectable in their blood. Association of two or more psychoactive substances (poly-drug use) was observed in 27.6% of drivers (90.6% of drug consumers). On the basis of CDT values, 29.5% of drivers investigated were assumed to be chronic alcohol abusers. Statistical analysis revealed that chronic alcohol abuse and medicinal psychoactive drugs were associated with significantly higher BAC. Medicinal psychoactive drugs were clearly associated with poly-drug use, and were furthermore detected at supra-therapeutic levels in 34.9%.     

"Legal highs"-Toxicity in the clinical and medico-legal aspect as exemplified by suicide with bk-MBDB administration

The easily available "legal highs", which are products containing psychoactive substances, such as cathinones, piperazines and synthetic cannabinoids, are abused by adolescents in Poland and in the world as alternatives to classic drugs, such as amphetamines or marijuana. The majority of these potentially dangerous substances are still legal and they are associated with a risk of severe poisoning or even death, and provide new challenges in clinical and forensic toxicological practice. Investigations in the field of "designer drugs" may be well illustrated by the case of a suicide of a 21-year old male who ingested a specified dose of a preparation called "Amphi-bi-a" that contains bk-MBDB, chemically 2-methylamino-1-(3,4-methylenedioxyphenyl) butan-1-one, which belongs to the cathinone group, as a synthetic euphoric empathogen and psychoactive stimulant that is chemically similar to MDMA. It is one of more common components of "legal highs" examined in Poland and other countries. The documentation of the case includes a clinical assessment of the patient's health status performed during his almost 4-h hospitalization before death, autopsy and histological examinations supported by toxicological findings revealing bk-MBDB at extremely high concentrations (at 20mg/l in the blood and 33mg/kg in the liver); hence, this body of evidence contributes to knowledge in the field of "designer drugs". Inventions of designers of new psychoactive xenobiotics, which are much in demand, especially in view of the dynamic Internet marketing, which drums up narcobusiness, must be balanced by a national strategy developed by medical, legal and educational circles in the modern civilized world in order to prevent the spreading of the phenomenon.     

GC–MS analysis of eight aminoindanes using three derivatization reagents

Aminoindanes are a class of novel psychoactive substances (NPSs) that have become more prevalent over the past decade. GC–MS is often utilized for identifying seized drugs and is well regarded for its ability to separate mixtures. However, certain aminoindanes have similar mass spectral data and require specific gas chromatographic stationary phases for separation. Derivatization is an alternative method that can be applied to GC–MS to enhance chromatographic results, providing more selective analysis in seized-drug identification. This study investigates derivatization techniques to provide options for forensic science laboratories in accurately identifying aminoindanes. Three derivatization reagents, N-methyl-bis(trifluoroacetamide) (MBTFA), heptafluorobutyric anhydride (HFBA), and ethyl chloroformate (ECF) were evaluated for the analysis of eight aminoindanes by GC–MS using two common gas chromatographic stationary phases, Rxi®-5Sil MS and Rxi®-1Sil MS. All three derivatization methods successfully isolated eight aminoindanes, including the isomers 4,5-methylenedioxy-2-aminoindane (4,5-MDAI), and 5,6-methylenedioxy-2-aminoindane (5,6-MDAI) that could not be differentiated prior to derivatization. Reduced peak tailing and increased abundance were observed after derivatization for all the compounds, and mass spectra of the derivatives contained individualizing fragment ions that allowed for further characterization of the aminoindanes. This excluded 4,5-MDAI and 5,6-MDAI as they shared the same characteristic ions and were only distinguishable by their retention times. All three derivatization techniques used in this study allow for successful characterization of the aminoindanes and give forensic science laboratories flexibility in their analysis approach when they encounter these compounds.     

Prodrugs of New Psychoactive Substances (NPS): A New Challenge

The concept of a substance acting as a prodrug for an intended drug is not new and has been known and utilized with particular benefits within medicine for efficacy and patient safety. Prodrugs of psychoactive substances are also not particularly new but this has also extended to considerations of prodrugs of new psychoactive substances (NPS). The continuing evolution of NPS has been a constant forensic challenge. In some countries, this constant evolution has led to the introduction of various alternative methods of drug control. Whether for this reason or in the pursuit of user experimentation, prodrugs of NPS have been discussed, developed, and exploited, posing some distinct forensic challenges. This is especially the case within toxicological analysis of biological fluids and for some substances, also forensic chemical analysis, through inherent instability of the prodrug or metabolism in the body. Particular examples of NPS prodrugs include 1-propanoyl-LSD, 1-butanoyl-LSD, 1-acetyl-LSD, and 2C-B-AN. This is in addition to associated substances and medicines that may be used for an intended pharmacological effect. Various prodrugs for stimulant and hallucinogenic substances in particular have appeared in the literature and have been discussed within drug user forums and made available for purchase online. Presently, drug monitoring data from national and international systems indicate that prodrugs are not widely available or problematic. Nevertheless, it is important that there is sufficient awareness of the prodrug concept and potential impact and associated forensic implications, not just for chemical analysis but also for toxicological considerations when a substance has been used.     

In silico toxicity as a tool for harm reduction: A study of new psychoactive amphetamines and cathinones in the context of criminal science

The emergence of new psychoactive substances (NPS) has raised many issues in the context of law enforcement and public drug policies. In this scenario, interdisciplinary studies are crucial to the decision-making process in the field of criminal science. Unfortunately, information about how NPS affect people's health is lacking even though knowledge about the toxic potential of these substances is essential: the more information about these drugs, the greater the possibility of avoiding damage within the scope of a harm reduction policy. Traditional analytical methods may be inaccessible in the field of forensic science because they are relatively expensive and time-consuming. In this sense, less costly and faster in silico methodologies can be useful strategies. In this work, we submitted computer-calculated toxicity values of various amphetamines and cathinones to an unsupervised multivariate analysis, namely Principal Component Analysis (PCA), and to the supervised techniques Soft Independent Modeling of Class Analogy and Partial Least Square-Discriminant Analysis (SIMCA and PLS-DA) to evaluate how these two NPS groups behave. We studied how theoretical and experimental values are correlated by PLS regression. Although experimental data was available for a small amount of molecules, correlation values reproduced literature values. The in silico method efficiently provided information about the drugs. On the basis of our findings, the technical information presented here can be used in decision-making regarding harm reduction policies and help to fulfill the objectives of criminal science.     

Concentrations of Opiates and Psychotropic Agents in Polydrug Overdoses: A Surprising Correlation Between Morphine and Antidepressants

Abstract: The relationship between postmortem concentrations of morphine and co‐detected psychoactive drugs in fatal overdoses is examined. Morphine and other drugs were detected in 161 medicolegal autopsy cases. Subsets of these morphine‐positive cases based on drug class were established, including opioids, antidepressants, ethanol, benzodiazepines, and “other.” Each subset was split into high or low concentration groups based on median drug concentrations. Morphine concentrations of the [high] and [low] groups were compared, with no significant difference in morphine concentration identified in the opioid, ethanol, or benzodiazepine subsets. The “other” drug class was too heterogeneous for statistical assessment. Morphine concentrations did show a significant direct relationship (p = 0.01) with antidepressants, namely increased concentrations of antidepressant drugs are associated with an increased concentration of morphine. This trend probably remains even after excluding cocaine‐positive cases. The unsuspected finding that postmortem concentrations of antidepressants positively correlate with morphine levels may be important in the treatment of depression in drug addicts.     

Toxicology and Circumstances of Death of Homicide Victims in New South Wales, Australia 1996–2005

Abstract:  To determine the prevalence and circumstances of psychoactive substances amongst homicide victims, 485 consecutive cases autopsied at the NSW Department of Forensic Medicine (1/1/1996–12/31/2005) were analyzed. Substances were detected in 62.6% of cases, and illicit drugs in 32.8%. Alcohol, cannabis, opioids, and psychostimulants were most commonly detected. Alcohol and cannabis were both more prevalent amongst males. Mean ages were significantly younger for decedents who tested positive for a substance and for an illicit drug. Cases where death resulted from a physical altercation were more likely to have had alcohol and cannabis present. Illicit drugs were prominent amongst firearms deaths. The proportion of alcohol positive cases increased from 25.0% on Monday to 49.4% for Saturdays/Sundays. Alcohol was more common in incidents in the 0001–0600 h and 1800–2400 h periods. Psychoactive substances appear to substantially increase the risk of homicide, although there are important differences between drug classes in the circumstances of such incidents.     

Drug abuse in western Denmark during the eighties. II. Fatal poisonings among drug abusers.

Cases of fatal poisoning among drug addicts (n = 246) and abusers of medical drugs (n = 138) are discussed on the basis of the availability of illicit and medical drugs during the eighties. Propoxyphene was frequently the cause of death among both drug addicts and abusers of medical drugs. Deaths caused by analgesics and psychoactive drugs, mainly barbiturates and antidepressants, predominated among abusers of medical drugs. During the late eighties the number of deaths caused by barbiturates and propoxyphene declined as a result of changes in the distribution regulations for both drugs. Heroin/morphine accounted for only one-third of the poisonings in drug addicts. No trends concerning the prevalence of deaths caused by these drugs were observed throughout the decade. The number of deaths caused by the synthetic opiates methadone and ketobemidone, however, increased during the late eighties, probably due to an increased availability of these drugs in the illicit drug market. Alcohol was detected in half of all the poisoning cases and benzodiazepines in one-third.     

Postmortem citalopram concentrations: alone or along with other compounds

Citalopram, an antidepressant whose use has become more widespread in Spain in recent years participates directly and indirectly in the lethal mechanism in voluntary and involuntary poisonings. There were 30 cases of autopsies in the Madrid region where citalopram and other psychoactive substances (psychotropic drugs, alcohol, opiates) were detected in the corpses. The postmortem citalopram levels in relation to the manner and mechanism of death were evaluated, and a significant difference between the toxic and nontoxic cases (p < 0.01) was found. We studied the citalopram blood levels alone and along with other psychoactive products, and these cases were then further divided into those where the compounds were at deadly levels and those which were not. We found a range of citalopram levels between 0.37 and 0.83 microg/mL in which some cases were associated with citalopram toxicity and others were not. Citalopram blood levels of less than 0.35 microg/mL did not lead to fatal poisoning when it was the sole substance detected.     

Psychoactive substances in seriously injured drivers in Denmark

This study assesses the presence of a number of psychoactive substances, including alcohol, based on blood samples from 840 seriously injured drivers admitted to five selected hospitals located in five different regions of Denmark. The study was a part of the EU 6th framework program DRUID (Driving Under the Influence of Drugs, Alcohol and Medicines). Blood samples were screened for 30 illegal and legal psychoactive substances and metabolites as well as ethanol. Danish legal limits were used to evaluate the frequency of drivers violating the Danish legislation while limit of quantification (LOQ) was used for monitoring positive drivers. Tramadol is not included in the Danish legislation therefore the general cut off, as decided in the DRUID project was used. Overall, ethanol (18%) was the most frequently identified compound (alone or in combination with other drugs) exceeding the legal limit, which is 0.53 g/l in Denmark. The percentage of seriously injured drivers testing positive for medicinal drugs at levels above the Danish legal limit was 6.8%. Benzodiazepines and Z-drugs (6.4%) comprised the majority of this group. One or more illegal drugs (primarily amphetamines and cannabis) were found to be above the Danish legal limit in 4.9% of injured drivers. Young men (median age 31 years) were over-represented among injured drivers who violated Danish law for alcohol and drugs.Diazepam (4.4%), tramadol (3.2%), and clonazepam (3.0%) were the medicinal drugs most frequently detected at levels above LOQ, whereas amphetamines (5.4%) (amphetamine [5.2%] and methamphetamine [1.5%]), tetrahydrocannabinol (3.7%), and cocaine (3.3%), including the metabolite benzoylecgonine, were the most frequently detected illegal drugs. A driver could be positive for more than one substance; therefore, percentages are not mutually exclusive. Poly-drug use was observed in 112 (13%) seriously injured drivers. Tramadol was detected above DRUID cutoffs in 2.1% of seriously injured drivers. This is 3.5 times that observed in a Danish survey of randomly selected drivers. Moreover, illegal and medicinal drug levels above the Danish legal limit were present more than 10 times as frequently as in injured drivers, whereas ethanol was present more than 30 times as frequently than in randomly selected drivers. The results indicate that there is an increased risk in traffic when driving under the influence of psychoactive drugs, especially alcohol in young male drivers.