Synthetic cathinones - From natural plant stimulant to new drug of abuse.

As recreational substances, synthetic cathinones started to be used at the beginning of the 21st century. There is still limited data on these compounds, introduced to the illicit drug market for the most part after 2009. Considering that synthetic cathinones are currently the second largest group of new psychoactive and dangerous substances among over 670 new psychoactive substances identified in Europe and monitored by the EMCDDA, research on them should be regarded as extremely important. This review focuses on the availability of synthetic cathinones on the illicit drug market, presentation of current trends in the use of these substances, and their mechanisms of action and toxicity. The authors discuss cases of intoxication with synthetic cathinones and post-mortem diagnostics as well as the problem of combined used of synthetic cathinones with other psychoactive substances. Literature as well as clinical and forensic data indicate the need for further research on the metabolism, toxicokinetics, toxicodynamics, clinical effects, and addictive potential of synthetic cathinones, especially in the context of potential threats caused by increased consumption of this group of drugs in future.

Chemical profiling of the synthetic cannabinoid MDMB-CHMICA: Identification, assessment, and stability study of synthesis-related impurities in seized and synthesized samples.

In this work, the most discriminating synthesis-related impurities found in samples from seizures and controlled synthesis of the synthetic cannabinoid MDMB-CHMICA (methyl (S)-2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate) were characterized. Based on 61 available powder samples of MDMB-CHMICA, 15 key-impurities were assessed, isolated in larger quantities via flash chromatography and structurally elucidated and characterized via high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Apart from verifying the relation of the impurities to the major component, the interpretation of their chemical structures with distinct structural elements provided first insights into the manufacturing process and the precursor compounds used. Following liquid chromatography mass spectrometry analysis of the 15 key-impurities, the 61 seized samples of MDMB-CHMICA were evaluated and classified via multivariate data analysis based on the corresponding relative peak areas. In a second part of this work, stability tests and multiple controlled syntheses of MDMB-CHMICA were carried out to better understand variations in impurity signatures and to assess the significance of variations in the impurity patterns of seized samples. The last coupling step of the amino acid with 1-(cyclohexylmethyl)-1H-indole-3-carboxylic acid was performed using the coupling agents oxalyl chloride, thionyl chloride, and HATU. Furthermore, the impact of reaction time and temperature on the impurity profile were investigated. Overall, eight new impurities were found in the controlled syntheses and two degradation products of MDMB-CHIMCA were found in the course of the stability tests. Replicates of a synthesis conducted on the same day showed similar impurity signatures; on different days they showed discriminable signatures. The use of different coupling reagents or conditions gave clearly distinguishable impurity signatures.

Narcotic Analgesics and Common Drugs of Abuse: Clinical Correlations and Laboratory Assessment.

Pain management is an evolving discipline. New formulations mature with promises of improved pain control, better dosing, and fewer side effects. These agents also have an equal risk for abuse. Street chemists are adept at manipulating drugs to more potent versions and creating new compositions of matter. The clinical assessment of the patient is paramount to developing an index of suspicion of overdose, toxicity, or illicit drug use; the clinical laboratory can be a resource to support investigations and guide therapy. The clinical toxicology laboratory needs to keep in step, adapting technology and methodology to facilitate detection of such substances.

[Synthetic drugs: the new low-cost landscape of drugs]. / Drogues de synthèse: le nouveau cadre low-cost des drogues.

Designer drugs include, among others, synthetic cannabinoids and synthetic cathinones. These new "legal highs" drugs are sold on line for recreational public or private use. Synthetic cannabinoids are a psychoactive herbal and chemical product that, when used, mimics the effects of cannabis. Cathinone is a naturally occurring betaketone amphetamine analogue found in the leaves of the Catha edulis plant. Synthetic cathinones are phenylalkylamines derivatives, and may possess both amphetamine-like properties. They are often sold as "bath salts" or "plant food" and labeled "not for human consumption" to circumvent drug abuse legislation. The absence of legal risks, the ease of obtaining these drugs, the moderate cost, and the avaibility via Internet are the main criteria attracting the user. There is evidence that negative health and social consequences may occur in recreational and chronic users. The addictive potential of designer drugs is not weak. Furthermore, there is a lack of epidemiological, pharmacological, animal, clinical, psychological and therapeutic data concerning these new synthetic agents.

Analysis of synthetic cannabinoids in "spice-like" herbal highs: snapshot of the German market in summer 2011.

In this study, seven commercial "spice-like" products available on the German market were analyzed. They all contained significant amounts of synthetic cannabinoids and had distinctly different compositions of these adulterants. All synthetic cannabinoids were extracted and purified by different chromatographic techniques from the respective product. The structures of all compounds were elucidated by nuclear magnetic resonance spectroscopy and further characterized by mass spectrometry (MS) and ultraviolet and infrared spectroscopy to generate a full data set of each compound. Altogether, eight compounds were identified, and one deuterium-labeled cannabinoid was used as internal standard. Four products contained only one individual compound, while three products contained mixtures of two compounds. Among the eight isolated compounds, six were already known from recent publications (JWH-081, JWH-210, JWH-122, AM2201, RCS-4, and JWH-203), but the published data were not always complete. In addition, two unknown compounds (AM2201-pMe, RCS-4-(N-Me)) were isolated. Overall, compounds from three distinct classes of synthetic cannabinoids could be identified, characterized, and compared. The MS data of the different subclasses allowed the postulation of some general key fragmentations to distinguish between these subclasses. In addition, we established a general method using an isotopically labeled internal standard (JWH-018-D(3)) to quantify synthetic cannabinoids in herbal mixtures. The total content of the synthetic cannabinoids ranged from 77.5 to 202 mg/g, while individual compounds were detected from 19.3 to 202 mg/g in these products. The spectroscopic data for all compounds mentioned here were collected and added en bloc as Electronic supplementary material to this manuscript.

Let it snow! Let it snow! Let it snow! Estimating cocaine production using a novel dataset based on reported seizures of laboratories in Colombia.

BACKGROUND: Data on the cocaine market appear inconsistent, as they tend to show declining prices vis-a-vis steady or increasing demand and a declining supply. This paper proposes an explanation for this trend by providing evidence of an under-estimation of the supply of cocaine. METHODS: We propose a conservative estimate of cocaine production in Colombia for 2008, using data based on all reported seizures from 328 laboratories made by the counteracting organisations operating within the Colombian territory. RESULTS: Our conservative estimate of 935 tons from the seized laboratories is at least twice the estimate declared in official statistics of 295-450 tons. We are careful to keep all variables to their minimum boundary values. Our methodology could prove to be a useful tool, especially if used in parallel with the standard tools. Moreover, its characteristics (affordability, ease of use and potential for worldwide adoption) make it a powerful instrument to counteract cocaine production.

Arylethylamine psychotropic recreational drugs: a chemical perspective.

The arylethylamines substituted in the aryl ring, side-chain carbons and on the terminal amine, comprise a large number of human mood and behaviour altering chemicals. Some of these psychotropic drugs have been used since pre-history, but in many states are proscribed and are consequently subject to clandestine synthesis and illegal traffic world-wide in the forms particularly of amphetamines and to a lesser extent tryptamines. The chemistry employed in the synthesis of these compounds is dictated often by the available precursors and relies usually on relatively simple, unsophisticated conversion reactions to a suitable product. The internet web sites and documentation of the recreational drug culture have been studied alongside the professional scientific and regulatory literature. The review demonstrates the great complexity of the chemistry and neuro-pharmacology of these chemicals and the challenge faced by legislative bodies to control their traffic and use for the sake of social welfare.

Commerce in drugs and chemicals and the detection of clandestine laboratories.

There were 225 clandestine laboratories seized in the United States of America in 1982, an increase of 23 per cent over 1981. These laboratories most commonly produced methamphetamines, phencyclidine (PCP), lysergic acid diethylamide (LSD), amphetamine and methaqualone. In order to determine whether a seized drug has been clandestinely manufactured and to identify the source of the drug, special techniques are used, involving detailed physical and chemical examinations. The results of such examinations are computerized and compared with reference samples to provide indications of the drug source. Undercover techniques are also effectively used for the detection of clandestine laboratories. Chemicals necessary for the illegal production of drugs of abuse were often diverted from legitimate sources through international commerce, which, together with clandestine laboratories, are recognized as an international problem that requires monitoring through international co-operation.