The term 'club drug' can be loosely defined as any substance used to enhance social settings. Such drugs are commonly found at raves or similar all-night dance parties and include methamphetamine, 3,4-methylenedioxymethamphetamine, gamma-hydroxybutyrate (GHB), ketamine (KET), and flunitrazepam (FLU). These drugs have potentially dangerous side effects including hallucinations, paranoia, amnesia and hyperthermia. In addition, GHB, KET and FLU are considered predatory drugs due to their roles in drug-facilitated sexual assault. Forensic and regulatory agencies routinely have the need for determination and accurate quantification of these drugs in biological fluids, especially in cases of mortality or criminal investigations. This review presents the chromatographic and spectroscopic methods published for such analyses over the last decade, including sample preparation techniques and validation data.

A pesar del uso terapéutico de GHB y de un aumento en la percepción de su toxicidad, el conocimiento sobre los efectos fisiológicos, subjetivos y sobre el rendimiento psicomotor inducidos por el GHB en humanos era limitado. Si bien se habían descrito casos de abuso y dependencia, no se habían realizado estudios controlados evaluando el potencial de abuso de la sustancia. El objetivo más importante de este trabajo fue la caracterización de los efectos del GHB en humanos. En este contexto se pusieron en marcha una serie de estudios controlados para evaluar los efectos del GHB y su potencial de abuso. Los estudios fueron randomizados, a doble ciego, de tipo cruzado y controlados. Las variables estudiadas incluyeron constantes vitales (presión arterial, frecuencia cardiaca, temperatura oral, diámetro pupilar), efectos sobre el rendimiento psicomotor (test de sustitución de símbolos por dígitos, tarea de balance, ala de maddox) efectos subjetivos (cuestionario Addiction Research Center Inventory reducido de 49 items, 13 escalas visuales analógicas, cuestionario de valoración de efectos subjetivos de sustancias con potencial de abuso‐VESSPA) y evaluación farmacocinética. En una primera fase se realizó un estudio piloto de farmacología humana de fase I, donde fueron administradas diferentes dosis de GHB sódico (40, 50, 60 y72 mg/kg) por vía oral a 8 voluntarios en una pauta de dosis ascendente. Las concentraciones de GHB en plasma, fluido oral, orina y sudor fueron analizadas mediante cromatografía de gases acoplada a espectrometría de masas. El método de detección de GHB en plasma, fluido oral y orina fue validado para su posterior uso durante los estudios. Los efectos fisiológicos, subjetivos y sobre el rendimiento psicomotor del GHB fueron evaluados simultáneamente. El GHB produjo efectos de tipo mixto estimulante y sedante, con un incremento inicial de las puntuaciones en los efectos subjetivos de euforia y"colocón", seguido de efectos moderados de tipo sedante asociados a una alteración del rendimiento psicomotor. La administración de GHB se siguió de una rápida absorción y eliminación.El estudio definitivo se realizó con la intención de confirmar los efectos fisiológicos y subjetivos del GHB y su impacto sobre el rendimiento psicomotor, así como pare evaluar su potencial de abuso en comparación con etanol y flunitrazepam, en usuarios de "Club Drugs". Con estos objetivos se evaluaron 12 voluntarios sanos con experiencia previa en el uso de GHB durante 5 sesiones experimentales. Las diferentes condiciones de tratamiento fueron, 2 dosis únicas de GHB (40 o 60 mg/kg), etanol (0.7 g/kg), flunitrazepam (1.25 mg), y placebo, todos administrados por vía oral.Todos los tratamientos activos indujeron efectos de tipo positivo relacionados con su potencial de abuso. La administración de GHB indujo efectos de tipo euforizantes y placenteros ligeramente superiores a los observados tras la administración de flunitrazepam y etanol. El perfil de efectos inducidos por el GHB fue de tipo bifásico, inicialmente de tipo estimulante‐euforizante en relación con el incremento simultáneo de las concentraciones plasmáticas, seguido de un efecto de tipo sedante no relacionado con la cinética plasmática. La administración de GHB produjo asimismo efectos adversos dosis dependientes, pero sin una coincidencia intra‐sujeto de efectos positivos y negativos. Las concentraciones plasmáticas de GHB y las concentraciones de etanol en sangre se correlacionaron significativamente con los efectos subjetivos estimulantes, mientras que las concentraciones plasmáticas de flunitrazepam se correlacionaron significativamente con efectos de tipo sedante. Las concentraciones plasmáticas de GHB se correlacionaron significativamente con las variables relacionadas con el potencial de abuso. En cuanto a los efectos fisiológicos, el GHB indujo un aumento significativo de la presión arterial y del diámetro pupilar, mientras el etanol indujo sus efectos prototípicos y flunitrazepam produjo una marcada sedación. GHB y flunitrazepam produjeron un empeoramiento significativo del rendimiento psicomotor (tareas de sustitución de símbolos por dígitos y del balance), mientras que el etanol únicamente indujo un leve empeoramiento de la tarea del balance.Como conclusión, a las dosis investigadas, la administración de GHB indujo efectos de tipo euforizantes y placenteros, sedación y efectos estimulantes de tipo moderado, similares a los descritos previamente por los usuarios de las sustancia. El perfil de efectos inducidos por el GHB fue de tipo bifásico, inicialmente de tipo estimulante‐eufórico y relacionado con el incremento simultáneo de las concentraciones plasmáticas, seguido de un efecto de tipo sedante no relacionado con la cinética plasmática. La tolerabilidad del GHB difirió substancialmente entre los diferentes sujetos, sin coincidencia intra‐sujeto de efectos positivos y negativos. La administración de GHB se sigue de una rápida absorción y eliminación con una gran variabilidad inter‐indiviudal. Si bien se encontraron concentraciones de GHB todas las matrices biológicas analizadas, tanto el fluido oral como el sudor no parecen convenientes para monitorizar el consumo de GHB. Los resultados sugieren un alto potencial de abuso de GHB en usuarios de "Club Drugs" y aportan los fundamentos científicos del aumento en el abuso de la sustancia en humanos. / Despite GHB therapeutic uses and the increasing concern about the toxicity of this drug, little was known about the physiologic and subjective effects and alterations in psychomotor performance induced by GHB in humans. Furthermore, a number of cases of GHB abuse and dependence have been reported, but no abuse liability studies had been performed. The main aim of this work was characterising the actual behavioural effects of GHB in humans. Within this context, a series of controlled studies to evaluate the effects of GHB and its relative abuse liability were set up. The studies were double blind, randomized, crossover and controlled. Study assessments included vital signs (BP, HR, oral temperature, pupil diameter), psychomotor performance (digit-symbol-substitution-test, balance, maddox‐wing), subjective effects (a set of 13 visual analogue scales, Addiction Research Center Inventory‐49 items, and Evaluation of the Subjective Effects of Substances with Potential of Abuse questionnaires), and pharmacokinetics. Firstly, a pilot pharmacology phase I study was performed where different oral doses of sodium GHB (40, 50, 60, and 72 mg/kg) were given to 8 volunteers in a dose escalation schedule. GHB concentrations in plasma, oral fluid, urine, and sweat were analyzed by gas chromatography-mass spectrometry. The method of detection of GHB in plasma, urine and oral fluid used throughout the studies was validated. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB showed a mixed stimulant‐sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild‐moderate symptoms of sedation with impairment of psychomotor performance. GHB was readily absorbed after oral administration and rapidly eliminated. The final study was performed to confirm GHB‐induced subjective and physiological effects, and to evaluate its relative abuse liability compared to flunitrazepam and ethanol, and its impact on psychomotor performance in 'Club Drug' users. Twelve healthy male recreational users of GHB participated in 5 experimental sessions. Drug conditions were a single oral dose of GHB (40 or 60 mg/kg), ethanol (0.7 g/kg), flunitrazepam (1.25 mg), and placebo. All active conditions induced positive effects related to their abuse potential. The administration of GHB produced euphoria and pleasurable effects with slightly higher ratings than those observed for flunitrazepam and ethanol. GHB induced a biphasic time profile with an initial stimulant‐like effect related to the simultaneous rise of plasma concentrations and a latter sedative effect not related to GHB kinetics. GHB administration also induced dose‐dependent mild unpleasant effects, with no within‐subject coincidence of positive and negative GHB related effects. GHB plasma concentrations and ethanol blood concentrations were well correlated to subjective effects related with stimulation whereas flunitrazepam plasma concentrations were better correlated to sedative‐like effects. GHB plasma concentrations were also well correlated to different VAS related to abuse potential. GHB increased blood pressure and pupil diameter. Ethanol induced its prototypical effects, and flunitrazepam produced marked sedation. GHB and flunitrazepam impaired psychomotor performance (digit symbol substitution test and balance task), whereas ethanol, at the dose tested, induced only mild effects exclusively affecting the balance task.In conclusion, at the doses tested GHB was capable of inducing euphoria, pleasurable feelings, sedation and slight stimulant‐like effects as previously reported by GHB users. GHB induced a biphasic time profile with an initial stimulant‐like, euphoric and pleasurable effect related to the simultaneous rise of plasma drug concentrations and ulterior sedative effect collateral to a decrease in GHB plasma concentrations. GHB tolerability highly differ between subjects with no within‐subject coincidence of positive and negative GHB related effects. Following oral administration, GHB is rapidly absorbed and eliminated with high interindiviidual variability. Measurable plasma, urine, oral fluid and sweat were observed. However, oral fluid and sweat appear not to be suitable biological matrices for monitoring GHB consumption. The results suggest a high abuse liability of GHB in 'Club Drug' users, providing the scientific rationale for the increased abuse of the drug in humans.

As chamadas club drugs compreendem um vasto grupo de substâncias frequentemente utilizadas em bares, festas e raves, com a finalidade de intensificar o contato social e a estimulação sensorial. Englobam desde substâncias sintéticas comumente conhecidas, como a anfetamina, a metanfetamina, o MDMA, até moléculas de surgimento mais recente, denominadas novas substâncias psicoativas. Isoladas ou associadas a outras drogas, é possível que sejam causa de morte per se, ou que predisponham o usuário a envolver-se em situações potencialmente fatais, sendo necessário que os órgãos de Perícia Criminal (Institutos Médico Legais e Institutos de Criminalística) estejam aptos a detectar e quantificar essas substâncias em amostras biológicas. O presente trabalho teve como objetivo desenvolver um método analítico para identificação e quantificação de club drugs em sangue total, utilizando cromatografia líquida acoplada a espectrometria de massas com analisador híbrido quadrupolotempo de voo (LC-QTOF). Após o desenvolvimento do método, este foi validado utilizando as diretrizes do guia de validação do Scientific Working Group for Forensic Toxicology (SWGTOX), sendo analisados de linearidade, limite de detecção, limite de quantificação, efeito matriz, precisão intradia, precisão interdia, exatidão e integridade de diluição, além de recuperação e eficiência do processo. O método desenvolvido compreendeu a determinação de MDA, MDMA, 2C-B, DOB, cetamina, mCPP, cocaína e cocaetileno. Amostras provenientes de casos reais de morte não natural, oriundas do Instituto Médico Legal Aristoclides Teixeira de Goiânia - GO foram analisadas pelo método desenvolvido. 56 casos foram selecionados, em sua maioria com histórico de morte por projétil de arma de fogo e acidente de transito. Das 56 amostras analisadas, 28,5% (n=16) foram positivas para cocaína e/ou cocaetileno. As demais substâncias pesquisadas não foram encontradas nas amostras. / Club drugs are a large group of substances consumed in pubs, parties and raves, aiming to intensify social contact and sensorial stimulation. The term comprises largely known substances such as amphetamine, methamphetamine, 3,4-methylenodioxymethamphetamine (MDMA), as well as so-called new psychoactive substances, which are synthetic drugs recently developed or recently introduced in drug market. Club drugs can be taken alone, combined with each other or, most frequently, with alcohol or other commonly abused drugs such as cocaine. In any of these situations, club drugs can possibly be the cause of death or potentialize the involvement of the user with crime and potentially fatal behavior. Thus, official organisms in charge of criminal investigation must be capable of identifying and quantifying these substances in biological samples. The present work aimed the development of an analytical method to identify and quantify club drugs in whole blood, using liquid chromatography - mass spectrometry with hybrid analyzer quadrupole - time of flight (LC-QTOF). After analytical development, the method was validated according to do Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines, evaluating linearity, limit of detection, limit of quantification, matrix effect, precision, intermediate precision, bias and dilution integrity, besides recovery and process efficiency. The developed method comprised MDA, MDMA, 2C-B, DOB, ketamine, mCPP, cocaine and cocaethylene determination. Real samples related to non-natural deaths were collected at Institute of the Legal Medicine Aristoclides Teixeira, Goiânia, Goiás, Brazil, and analyzed by the developed method. 56 cases were selected, most of them related to fire gun injury and traffic events, 28,5% (n=16) of them being positive for cocaine and/or cocaethylene. None of the other drugs comprised in the analysis were detected in these samples.

As chamadas club drugs compreendem um vasto grupo de substâncias frequentemente utilizadas em bares, festas e raves, com a finalidade de intensificar o contato social e a estimulação sensorial. Englobam desde substâncias sintéticas comumente conhecidas, como a anfetamina, a metanfetamina, o MDMA, até moléculas de surgimento mais recente, denominadas novas substâncias psicoativas. Isoladas ou associadas a outras drogas, é possível que sejam causa de morte per se, ou que predisponham o usuário a envolver-se em situações potencialmente fatais, sendo necessário que os órgãos de Perícia Criminal (Institutos Médico Legais e Institutos de Criminalística) estejam aptos a detectar e quantificar essas substâncias em amostras biológicas. O presente trabalho teve como objetivo desenvolver um método analítico para identificação e quantificação de club drugs em sangue total, utilizando cromatografia líquida acoplada a espectrometria de massas com analisador híbrido quadrupolotempo de voo (LC-QTOF). Após o desenvolvimento do método, este foi validado utilizando as diretrizes do guia de validação do Scientific Working Group for Forensic Toxicology (SWGTOX), sendo analisados de linearidade, limite de detecção, limite de quantificação, efeito matriz, precisão intradia, precisão interdia, exatidão e integridade de diluição, além de recuperação e eficiência do processo. O método desenvolvido compreendeu a determinação de MDA, MDMA, 2C-B, DOB, cetamina, mCPP, cocaína e cocaetileno. Amostras provenientes de casos reais de morte não natural, oriundas do Instituto Médico Legal Aristoclides Teixeira de Goiânia - GO foram analisadas pelo método desenvolvido. 56 casos foram selecionados, em sua maioria com histórico de morte por projétil de arma de fogo e acidente de transito. Das 56 amostras analisadas, 28,5% (n=16) foram positivas para cocaína e/ou cocaetileno. As demais substâncias pesquisadas não foram encontradas nas amostras. / Club drugs are a large group of substances consumed in pubs, parties and raves, aiming to intensify social contact and sensorial stimulation. The term comprises largely known substances such as amphetamine, methamphetamine, 3,4-methylenodioxymethamphetamine (MDMA), as well as so-called new psychoactive substances, which are synthetic drugs recently developed or recently introduced in drug market. Club drugs can be taken alone, combined with each other or, most frequently, with alcohol or other commonly abused drugs such as cocaine. In any of these situations, club drugs can possibly be the cause of death or potentialize the involvement of the user with crime and potentially fatal behavior. Thus, official organisms in charge of criminal investigation must be capable of identifying and quantifying these substances in biological samples. The present work aimed the development of an analytical method to identify and quantify club drugs in whole blood, using liquid chromatography - mass spectrometry with hybrid analyzer quadrupole - time of flight (LC-QTOF). After analytical development, the method was validated according to do Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines, evaluating linearity, limit of detection, limit of quantification, matrix effect, precision, intermediate precision, bias and dilution integrity, besides recovery and process efficiency. The developed method comprised MDA, MDMA, 2C-B, DOB, ketamine, mCPP, cocaine and cocaethylene determination. Real samples related to non-natural deaths were collected at Institute of the Legal Medicine Aristoclides Teixeira, Goiânia, Goiás, Brazil, and analyzed by the developed method. 56 cases were selected, most of them related to fire gun injury and traffic events, 28,5% (n=16) of them being positive for cocaine and/or cocaethylene. None of the other drugs comprised in the analysis were detected in these samples.

The use of methylenedioxymethamphetamine (MDMA) or Ecstasy is a phenomenon that has established itself in the widespread Rave culture. Ecstasy use causes not only physical, social and psychological problems in the development of the adolescent but may also influence his concentration and learning abilities. To prevent these problems educators should be well informed regarding current drug use trends and also be capable of assisting adolescents. Research regarding the nature of Ecstasy use and the characteristics of its users is lacking nationally. The increase in use amongst school going adolescents and young adults and the fact that there are side effects and unknown long term effects has made it imperative that educators learn as much as possible about this drug. The purpose of this research is therefore to furnish the educator with accurate information that will enable him to obtain a reference point from which assistance can be offered to the young Ecstasy user. / Psychology of Education / M.Ed.(Guidance and Counselling)

The use of methylenedioxymethamphetamine (MDMA) or Ecstasy is a phenomenon that has established itself in the widespread Rave culture. Ecstasy use causes not only physical, social and psychological problems in the development of the adolescent but may also influence his concentration and learning abilities. To prevent these problems educators should be well informed regarding current drug use trends and also be capable of assisting adolescents. Research regarding the nature of Ecstasy use and the characteristics of its users is lacking nationally. The increase in use amongst school going adolescents and young adults and the fact that there are side effects and unknown long term effects has made it imperative that educators learn as much as possible about this drug. The purpose of this research is therefore to furnish the educator with accurate information that will enable him to obtain a reference point from which assistance can be offered to the young Ecstasy user. / Psychology of Education / M.Ed.(Guidance and Counselling)