Estudo da influência do metabolismo na toxicidade das novas substâncias psicoativas pertencentes ao grupo dos canabinóides sintéticos

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The synthetic cannabinoids phenomenon: from structure to toxicological properties. A review

Publication . Alves, Vera L.; Gonçalves, João L.; Aguiar, Joselin; Teixeira, Helena M.; Câmara, José S.

The word “cannabinoid” refers to every chemical substance, regardless of structure or origin, that joins the cannabinoid receptors of the body and brain and that have similar effects to those produced by the Cannabis plant and based on their source of production, cannabinoids can be classified into endocannabinoids, phytocannabinoids and synthetic cannabinoids. Synthetic cannabinoids represent the largest class of drugs detected through the EU Early Warning System with a total of 190 substances notified from 2008 to 2018 and about 280 have been reported worldwide to the United Nations Office on Drugs and Crime. Sprayed on natural herb mixtures with the aim to mimic the euphoria effect of cannabis and sold as “herbal smoking blends” or “herbal incense” under brand names like “Spice” or “K2”, synthetic cannabinoids are available from websites for the combination with herbal materials or more recently, for the use in e-cigarettes. Currently labeled as “not for human consumption” to circum vent legislation, their legal status varies by country with many government institutions currently push ing for their control. However, due to the emergence of new substances, it requires a constant update of the list of controlled drugs. Little is known about how these substances work and their toxic effects in humans and the same product could vary not only in the amount and in the type of substance added. In the last years, synthetic cannabinoids have been associated with deaths and acute intoxica tions in Europe and, despite a range of new measures introduced in this area, continue to represent a challenge to current drug policy models. These synthetic substances are much more potent than nat ural cannabis, as well as displayed greater efficacy, acting as full agonists at the cannabinoid receptors. It is possible that, along with being highly potent, some may also have long half-lives, potentially lead ing to a prolonged psychoactive effect. The present work provides a review on existing literature about the development of synthetic cannabinoids as substances of abuse, current patterns of abuse and their legal status, chemical classification, and some pharmacological and toxicological properties.

2020Journal article

Open access

Relationship between Volatile Composition and Bioactive Potential of Vegetables and Fruits of Regular Consumption—An Integrative Approach

Publication . Aguiar, Joselin; Gonçalves, João L.; Alves, Vera L.; Câmara, José S.

In recent years, there has been a growing interest in studying and exploring the potential health benefits of foods, mainly from vegetables and fruits from regular intake. The presence of secondary metabolites, namely polyphenols, carotenoids and terpenes, in certain food matrices seems to contribute to their functional properties, expressed through an increased prevention in the development of certain chronic diseases, namely coronary heart diseases, neurodegenerative diseases, cancer and diabetes. However, some foods’ volatile secondary metabolites also present important bioactive properties, although this is a poorly scientifically explored field. In this context, and in order to explore the potential bioactivity of volatile metabolites in different vegetables and fruits from regular consumption, the volatile composition was established using a green extraction technique, solid phase microextraction in headspace mode (HS-SPME), combined with gas chromatography tandem mass spectrometry (GC-MS). A total of 320 volatile metabolites, comprising 51 terpenic compounds, 45 organosulfur compounds, 31 aldehydes, 37 esters, 29 ketones, 28 alcohols, 23 furanic compounds, 22 hydrocarbons, 19 benzene compounds, 13 nitrogenous compounds, 9 carboxylic acids, 7 ethers, 4 halogenated compounds and 3 naphthalene derivatives, were positively identified. Each investigated fruit and vegetable showed a specific volatile metabolomic profile. The obtained results revealed that terpenic compounds, to which are associated antimicrobial, antioxidant, and anticancer activities, are the most predominant chemical family in beetroot (61%), orange carrot (58%) and white carrot (61%), while organosulfur compounds (antiviral activity) are dominant in onion, garlic and watercress. Broccoli and spinach are essentially constituted by alcohols and aldehydes (enzyme-inhibition and antimicrobial properties), while fruits from the Solanaceae family are characterized by esters in tamarillo and aldehydes in tomato.

2021Journal article

Open access

Structure assignment of seized products containing cathinone derivatives using high resolution analytical techniques

Publication . Gonçalves, João L.; Alves, Vera L.; Aguiar, Joselin; Caldeira, Maria J.; Teixeira, Helena M.; Câmara, José S.

The innovation of the new psychoactive substances (NPS) market requires the rapid identification of new substances that can be a risk to public health, in order to reduce the damage from their use. Twelve seized products suspected to contain illicit substances were analyzed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), gas chromatography coupled to mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). Synthetic cathinones (SCat) were found in all products, either as a single component or in mixtures. Infrared spectra of all products were consistent with the molecular structure of SCat, showing an intense absorption band at 1700–1674 cm−1 , corresponding to the carbonyl stretching, a medium/strong peak at 1605–1580 cm−1 , indicating stretching vibrations in the aromatic ring (C=C) and bands with relative low intensity at frequencies near 2700–2400 cm−1 , corresponding to an amine salt. It was possible to identify a total of eight cathinone derivatives by GC-MS and NMR analysis: 40 -methyl-α pyrrolidinohexanophenone (MPHP), α-pyrrolidinohexanophenone (α-PHP), 3-fluoromethcathinone (3-FMC), methedrone, methylone, buphedrone, N-ethylcathinone, and pentedrone. Among the adulterants found in these samples, caffeine was the most frequently detected substance, followed by ethylphenidate. These results highlight the prevalence of SCat in seized materials of the Portuguese market. Reference standards are usually required for confirmation, but when reference materials are not available, the combination of complementary techniques is fundamental for a rapid and an unequivocal identification of such substances.

2021Journal article

Open access

Analytical and in vitro cytotoxicity studies of synthetic cannabinoids found in seized ‘herbal incenses’

Publication . Alves, Vera Lúcia Gouveia; Câmara, José Sousa; Teixeira, Helena Maria de Sousa Ferreira e

Initially developed as therapeutic agents, synthetic cannabinoids rapidly appeared on drug market as recreational drugs with over 200 substances notified in Europe. Marketed as ‘synthetic marijuana’, they are usually sold in herbal mixtures, as smoking products. Cheaper, accessible, and with stronger effects compared to cannabis, have led to a dramatic increase in its consumption. New compounds emerge constantly, and the side effects and toxicity of these products have not yet been properly studied, being a challenge for laboratories. In our study, nineteen seized herbal products provided by the criminal police were analysed by gas chromatography – mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) techniques. Ten synthetic cannabinoids (JWH-018, JWH-073, JWH-122, JWH-210, MAM-2201, APINACA, XLR-11, UR-144, CP47,497-C8 and 3-epi-CP47,497-C8), and three adulterants (oleamide, vitamin E and vitamin E acetate) were identified. Subsequently, the determination of eight cannabinoids (MAM-2201, JWH-073, JWH-018, JWH-122, JWH-210, UR-144, XLR-11 and APINACA) in oral fluid samples using microextraction by packed sorbent (MEPS) and μSPEed techniques combined with ultra-high performance liquid chromatography (UHPLC) analysis was developed. Both methodologies were validated, presenting good recovery values (above 70%) and low detection limits (9.5 – 13.2 and 4.4 – 10.3 ng/mL, respectively) and applied to two real samples. Finally, the cytotoxicity of eight seized herbal extracts and damiana extract was evaluated in A549 lung cell line. A significant concentration-dependent decrease in cell viability was observed after 48h and 72h exposure. Damiana extract and JWH-018 (single compound of one of the samples) significantly induced more reactive species formation and a significant decline in ATP synthesis was observed in damiana and in sample with XLR-11 and APINACA compounds. In summary, the applied methodologies revealed as promising approaches. Inconsistency in composition was verified among the analysed samples, and in vitro results highlighted the potential harmful effects of these synthetic drugs.

2023-04-20Doctoral thesis

Embargoed access

Beer volatile fingerprinting at different brewing steps

Publication . Alves, Vera; Gonçalves, João; Figueira, José A.; Ornelas, Laura P.; Branco, Ricardo N.; Câmara, José S.; Pereira, Jorge A. M.

Volatile fingerprints of a lager beer were carried out throughout five brewing steps to characterize the changes encompassing this process. Overall, 60 volatile organic metabolites (VOMs) were identified by headspace solid phase microextraction followed by gas chromatography mass spectrometry (HS-SPME/GC–MS). Specific profiles were observed at different brewing steps - aldehydes and furans dominate in wort, whereas the aliphatic esters and alcohols predominate in the following steps. Such variations can be assigned to specific VOMs, as 3-me thylbutanal (wort), ethyl alcohol and ethyl octanoate (fermentation, maturation and filtration), or ethyl alcohol and isoamyl acetate (final product). These VOMs can influence the beer final flavour. Ethyl alcohol contributes to its strong and pungent smell and taste, while isoamyl acetate adds intense ‘fruity’ and ‘banana’ odours. These beer volatile fingerprints constitute a valuable tool to obtain insights on the impact of each brewing step on the final product, being also very useful for certification purposes.

2020Journal article

Open access