Drug Interactions With New Synthetic Opioids

Fentanyl, fentanyl analogs, and other new synthetic opioids (NSO) have burst onto the illegal drug market as new psychoactive substances (NPS). They are often sold as heroin to unsuspecting users and produce euphoria through their agonist action on μ- opioid receptors. Their high consumption, often combined with other substances, has led to multiple intoxications during recent years. In some countries, such as the United States, the consumption of opioids, whether for medical or recreational purposes, has become epidemic and is considered a public health problem. Fentanyl analogs are more potent than fentanyl which in turn is 50 times more potent than morphine. Furthermore, some fentanyl analogs have longer duration of action and therefore interactions with other substances and medicines can be more serious. This review is focused on the potentially most frequent interactions of opioid NPS taking into account the drugs present in the reported cases of poly-intoxication, including other illegal drugs of abuse and medication. Substances involved are mainly antidepressants, antihistamines, antipsychotics, benzodiazepines, analgesics, anesthetics, psychostimulants, other opioids, alcohol, and illegal drugs of abuse. The interactions can be produced due to pharmacokinetic and pharmacodynamic mechanisms. Naloxone can be used as an antidote, although required doses might be higher than for traditional opioid intoxications. It is crucial that doctors who habitually prescribe opioids, which are often misused by patients and NPS users, be aware of designer opioids' potentially life-threatening drug-drug interactions in order to prevent new cases of intoxication

Cannabis Use in Patients with Fibromyalgia: Effect on Symptoms Relief and Health-Related Quality of Life

BACKGROUND: The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users. METHODS: Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36). RESULTS: Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI. CONCLUSIONS: The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted

Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

Background. 2C-B (Nexus) is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen. Objectives. To evaluate the emotional, subjective, and cardiovascular effects of 2C-B. Methods. Twenty healthy recreational 2C-B users (12 women) self-administered a 20 mg dose of 2C-B. Evaluations included emotional (IAPS, FERT, and speech), subjective (visual analog scales, ARCI, VESSPA, HRS, and POMS questionnaires), and cardiovascular effects (blood pressure and heart rate). Results. Positive subjective effects predominated with a reduction of anger under the influence of 2C-B. It did, however, increase reactivity to negative emotional stimuli and decrease the ability to recognize expressions of happiness. Augmented emotionality in speech could be appreciated by others. 2C-B induced euphoria and wellbeing, changes in perceptions, and slight hallucinogenic states. Mild sympathetic actions were observed. Conclusions. The specific profile that 2C-B exerts on emotions suggests its classification as an entactogen with psychedelic properties

La fisiología en las películas: Coma, CO y la comprensión del intercambio gaseoso

[ES]El presente artículo analiza la película Coma dirigida por Michael Chricton en 1978 e inspirada en la novela del mismo nombre de Robin Cook. Bajo el formato de thriller médico, muestra una serie de casos de coma que suceden en pacientes jóvenes y sanos sometidos a intervenciones quirúrgicas menores. La protagonista descubre que los afectados son traslados a una institución donde se les extraen los órganos para su comercio ilegal. También investiga la causa del coma, consecuencia de la intoxicación homicida con monóxido de carbono mientras los pacientes se encuentran en quirófano. La película tiene el interés docente de estimular la comprensión de los fenómenos de transporte de oxígeno por la hemoglobina, así como su afinidad por diversos gases, como el dióxido de carbono y el monóxido de carbono. Los estudiantes deben aplicar sus conocimientos fisiológicos para comprender cómo se realiza la intoxicación y sus características clínicas, así como las bases de su tratamiento.[EN]We analyze the movie Coma directed by Michael Chricton in 1978 and inspired in the novel of the same name that was written by Robin Cook. The film is a medical thriller that shows several cases of patients who dropped in coma in a hospital during simple surgical procedures of minimal risk. Patients were young and healthy and the appearance of coma was unexpected and unexplainable. The heroine is a resident from surgery who discovers that affected patients are moved to the same long care institution. There, their organs are illegally removed to be used in patients who need them and who pay huge amounts of money. She also investigates the cause of coma and discovers that patients are poisoned with carbon monoxide during surgical procedures. The film has a teaching interest to stimulate the understanding of blood oxygen transport by hemoglobin, as well as the knowledge of affinity to this molecule by several gases, as oxygen, carbon monoxide and carbon dioxide. Students may also learn how to apply physiological concepts to understand the carbon monoxide intoxication, the clinical signs and symptoms, and the scientific bases of its treatment

And the Band Played On: Epidemiological Research and Bioethical and Psychological Aspects in the HIV Pandemic

The HIV pandemic and the spectrum of diseases associated with its syndrome (AIDS) were noted for the first time in the early 1980s in the United States, with cases of death from pneumonia associated with Kaposi's sarcoma. The epidemiological investigation carried out by different teams in the United States –but mainly focusing on the Centers for Disease Control and Prevention– is portrayed in the film And the band played on (1993), by Roger Spottiswoode. Almost 30 years after its release, the film is still iconic and closely portrays the events of the investigation. This article presents a detailed analysis of the research process, the bioethical issues involved, and the psychological factors that allows to analyze the group and social confrontations of the epidemiological event that marked a before and after in the 20th century. It is suggested to use the film as a teaching tool.La pandemia de VIH (virus de inmunodeficiencia humana) y el espectro de enfermedades de su síndrome (SIDA) se registran por primera vez a principios de los años 1980 en Estados Unidos, con casos de muerte por neumonías asociados con el sarcoma de Kaposi. La investigación epidemiológica llevada a cabo por distintos equipos en los Estados Unidos –haciendo foco principalmente en el Centro para el Control y Prevención de Enfermedades– aparece retratada en la película En el filo de la duda / And the band played on (1993), de Roger Spottiswoode. Casi 30 años luego de su estreno, la película es sumamente actual y retrata de manera muy ajustada los hechos sucedidos en la investigación. En este artículo se presenta un análisis detallado del proceso investigativo, las cuestiones bioéticas implicadas y los factores psicológicos que permiten analizar los enfrentamientos grupales y sociales del acontecimiento epidemiológico que marcó un antes y un después en el siglo XX. Se sugiere utilizar la película como herramienta docente

Neuroimagen y adicción I: Correlatos neuroanatómicos y funcionales de la administración aguda, el craving y el consumo crónico de psicoestimulantes

En los últimos años ha aumentado el interés por el estudio de los correlatos neurobiológicos del consumo de drogas psicoestimulantes, como la cocaína o el éxtasis. La aplicación de las técnicas de neuroimagen ha permitido examinar in vivo los efectos agudos de la administración de estas sustancias, los correlatos cerebrales del deseo intenso por consumirlas (craving), o las alteraciones funcionales o morfológicas asociadas al consumo crónico. Los objetivos de esta revisión son: (1) explicar brevemente las técnicas de neuroimagen utilizadas en la investigación de drogodependencias (2) presentar los hallazgos más actualizados de neuroimagen en el estudio de los correlatos cerebrales del consumo de cocaína y MDMA, teniendo en cuenta (i) la administración aguda de la sustancia, (ii) el craving, y (iii) los efectos asociados al consumo crónico (3) discutir las implicaciones de estos hallazgos para una mejor comprensión de los procesos adictivos y su tratamiento. Los resultados sugieren que ambas sustancias producen alteraciones cerebrales comunes en regiones como el cortex frontal, estructuras límbicas (ínsula, amígdala e hipocampo) y ganglios basales, predominantemente lateralizadas en el hemisferio derecho. Mientras que la administración aguda se asocia a hiperactivación en estas regiones, que también tienden a activarse en experimentos de inducción de craving, durante la abstinencia permanecen hipoactivadas o se evidencian cambios estructurales.La funcionalidad de estas regiones se corresponde con los deficits neuropsicológicos observados en individuos drogodependientes; incluyendo alteraciones de la motivación por reforzadores naturales, el procesamiento emocional, la memoria, las funciones ejecutivas y la toma de decisiones

Neuroimagen y adicción II: Correlatos neuroanatómicos y funcionales de la administración aguda, el craving y el consumo crónico de opiáceos, alcohol y cannabis

En las últimas décadas las técnicas de neuroimagen han contribuido en gran medida al estudio in vivo de los efectos neurobiológicos del consumo agudo y crónico de sustancias de abuso. El incremento en los últimos años del consumo de alcohol y cannabis, así como las graves consecuencias asociadas al consumo de opiáceos han contribuido al aumento del interés por estudiar los efectos de estas sustancias en el sistema nervioso central. Los objetivos de esta revisión son: (1) presentar los hallazgos más actualizados de neuroimagen en el estudio de los correlatos cerebrales del consumo de opiáceos, alcohol y cannabis, teniendo en cuenta: (i) la administración aguda de estas sustancias, (ii) el craving, y (iii) los efectos asociados al consumo crónico (2) discutir las implicaciones de estos hallazgos para una mejor comprensión de los procesos adictivos y su tratamiento. Los resultados sugieren que el consumo de estas tres drogas está asociado con alteraciones estructurales y funcionales en varias regiones del córtex frontal y el sistema límbico, con sutiles diferencias en la intensidad y extensión de estas alteraciones. A su vez, estas regiones muestran una mayor activación durante la inducción de estados de craving, y muestran alteraciones durante la neuroactivación mediante tareas cognitivas. Las alteraciones cerebrales observadas se han relacionado con síntomas clínicos, como la co-ocurrencia de trastornos psquiátricos, la intensidad del craving en condiciones naturales, o la probabilidad de recaídas. Por tanto, el uso de técnicas basadas en la modulación del funcionamiento cerebral puede contribuir a mejorar el tratamiento de estas adicciones

UHPLC-HRMS and GC-MS Screening of a Selection of Synthetic Cannabinoids and Metabolites in Urine of Consumers

Background and Objectives : The use of synthetic cannabinoids has increased around the world. As a result, the implementation of accurate analysis in human biological matrices is relevant and fundamental. Two different analytical technologies, ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and high-sensitivity gas chromatography-mass spectrometry (GC-MS) were used for the determination of three synthetic cannabinoids JWH-122, JWH 210, UR-144 and their metabolites in urine of consumers. Materials and Methods : Sample preparation included an initial hydrolysis with β-glucuronidase and liquid-liquid extraction. The UHPLC-HRMS method included a Kinetex 2.6 u Biphenyl 100A (100 × 2.1 mm, 2.6 μm) (Phenomenex, Italy) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode was used (mass range 100-1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m × 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40-550 m/z). Results: Both methods have been successfully used for screening of parent synthetic cannabinoids and their metabolites in urine samples of consumers. Conclusions: The screening method applied JWH-122, JWH-210, UR-144 and their metabolites in urine of consumers can be applied to other compounds of the JWH family